REVIEW of the Literature on Antimicrobial Resistance in Zoonotic Bacteria from Livestock in East, South and Southeast Asia

FAO Regional Office for Asia and the Pacific

Animal Production and Health Commission for Asia and the Pacific

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REVIEW of the Literature on

Antimicrobial Resistance in Zoonotic Bacteria from

Livestock in East, South and Southeast Asia

Prepared by

R. Chuanchuen, N. Pariyotorn, K. Siriwattanachai, S. Pagdepanichkit, S. Srisanga, W. Wannaprasat, W. Phyo Thu, S. Simjee and J. Otte

FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS

REGIONAL OFFICE FOR ASIA AND THE PACIFIC

Bangkok, 2014

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TABLE OF CONTENTS

Executive Summary .......................................................................................................................... iv Introduction ...................................................................................................................................... 1

Bacteria of particular concern in AMR monitoring ........................................................................ 2 Salmonella ...................................................................................................................................... 3 Campylobacter ................................................................................................................................ 3 Escherichia coli ............................................................................................................................... 4 Enterococcus .................................................................................................................................. 4

AMR selection and transfer ........................................................................................................... 4 AMR Selection................................................................................................................................. 4 AMR transfer .................................................................................................................................. 5

Methods ............................................................................................................................................ 6 Findings ............................................................................................................................................. 9

Prevalence of AMR in bacteria of concern ..................................................................................... 9 Salmonella .................................................................................................................................... 10 Campylobacter .............................................................................................................................. 15 Escherichia coli ............................................................................................................................. 19 Enterococcus ................................................................................................................................ 23

AMU in livestock and national AMR surveillance and control programs ..................................... 26 East Asia ........................................................................................................................................ 26 South Asia ..................................................................................................................................... 27 Southeast Asia .............................................................................................................................. 30

Discussion ........................................................................................................................................ 33 AMR in East, South and Southeast Asia and in other countries ................................................... 33

Salmonella .................................................................................................................................... 33 Campylobacter .............................................................................................................................. 35 E. coli ............................................................................................................................................. 36 Enterococcus ................................................................................................................................ 39

AMU and AMR management in East, South and Southeast Asian countries and in the USA and the EU ............................................................................................................................................... 41

East Asia ........................................................................................................................................ 41 South Asia ..................................................................................................................................... 42 Southeast Asia .............................................................................................................................. 43 USA ............................................................................................................................................... 44 European Union ............................................................................................................................ 44

Conclusions and Recommendations ................................................................................................ 45 References ....................................................................................................................................... 48 Annexes ........................................................................................................................................... 60

Annex 1: Study inclusion and exclusion criteria ........................................................................... 60 Annex 2: AMR studies and summary statistics for Salmonella spp. ............................................. 61 Annex 3: AMR studies and summary statistics for Campylobacter spp. ....................................... 64 Annex 4: AMR studies and summary statistics for E. coli ............................................................. 67 Annex 5: AMR studies and summary statistics for Enterococcus spp. .......................................... 70

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ABBREVIATIONS AND ACRONYMS

AB Antibiotic

ADR Adverse drug reaction

AMR Antimicrobial resistance

AMU Antimicrobial use

APHCA Animal Production and Health Commission for Asia and the Pacific

AST Antimicrobial susceptibility testing

APR Asia-Pacific region

ECDC European Center for Disease Control

EFSA European Food Safety Agency

FDA Food and Drug Administration

MDR Multi-drug resistant

MT Metric tonne

PBP Penicillin-binding protein

USD United States dollar

VRE Vancomycin-resistant enterococcus

Country abbreviations

BGD Bangladesh BHU Bhutan

CAM Cambodia CHI China, People’s Republic

IND India IRA Iran

JAP Japan LAO Lao PDR

MAL Malaysia NEP Nepal

PAK Pakistan PHI Philippines

ROK Korea, Republic SRI Sri Lanka

TAI Taiwan Province of China THA Thailand

VIE Viet Nam

Abbreviations of antimicrobial classes

AMI Aminoglycosides CEP Cephalosporins

MAC Macrolides PEN Penicillins

PHE Phenicols POL Polymyxins

QUI Quinolones SUL Sulfonamides

TET Tetracylines TRI Trimethoprim

OTH Other

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ACKNOWLEDGEMENTS

The authors thank Dr. Manoonsak Wongpatcharachai, University of Minnesota, College of Biological

Sciences, for providing data and Dr. Benjama Saelim for assistance in data analysis.

We are also indebted to APHCA focal points and their colleagues for relevant information on national

regulation of AMU and institutional arrangements for AMU and AMR monitoring.

Staff of the Department of Veterinary Public Health, Faculty of Veterinary Science, Chulalongkorn

University, are gratefully acknowledged for assistance in the preparation of the report.

Finally, we would like to thank the anonymous reviewers for their insightful comments and

constructive suggestions that have substantially improved the document.

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EXECUTIVE SUMMARY

INTRODUCTION Antimicrobial resistance (AMR) has become one of the main public health issues in many parts of the

world. Based on data from the Study for Monitoring Antimicrobial Resistance Trends (SMART), the

prevalence of AMR in pathogens causing human illness varies across geographic regions but is highest

in Asia-Pacific countries and food borne diseases caused by AMR micro-organisms harbored by food

animals are increasingly emerging as a public health challenge in the region.

Worldwide, large amounts of antimicrobials are used in food animal production for: (i) treatment of

infection, (ii) disease prevention and (iii) growth promotion. This practice provides favorable conditions

for the selection, spread and maintenance of AMR bacteria, and emergence and increased prevalence

of AMR in bacteria associated with food animals has been linked to antimicrobial use (AMU) in food

animal production.

In many Asian countries, AMU in humans and food animals is not well regulated and existing

regulations are poorly enforced. In conjunction with the strong and growing demand for animal source

food, the lack of effective regulation of AMU in livestock production is likely to accelerate the

development and distribution of AMR in bacteria associated with food animals. Few Asian countries

have systematic AMR monitoring systems in place and consequently data on the actual burden of AMR

is scant or absent.

The aim of this study is to enhance current knowledge on the extent and patterns of AMR, AMU and its

regulation in food animal production in East, South and Southeast as basis for devising strategies for

AMR monitoring and management in the livestock sector. It is intended to serve as a reference

document for international organizations, public health agencies, regulatory authorities and policy

makers for their future discussion and action.

METHODS This study reviews and synthesizes the available literature on the prevalence of AMR in selected

zoonotic bacteria associated with livestock and livestock products, regulations, guidelines and policies

on antimicrobial use (AMU) in livestock and monitoring/surveillance and control/prevention programs

for AMR in bacteria carried by livestock and livestock products in East, South and Southeast Asia. The

review focuses on the major livestock species groups in the Asia-Pacific region, namely poultry, pigs,

and ruminants and is limited to the following four important zoonotic bacterial species found in

livestock and livestock products: Salmonella spp., Campylobacter spp., Escherichia coli and

Enterococcus spp.

Publications were identified through online database searches, references in scientific literature and

included written resources known to the authors through other means. Peer-reviewed scientific

literature was preferentially included to ensure the quality of documents. Searches were restricted to

English language publications and preferentially to papers published from 2008 onwards. Studies not

reporting the number of isolates examined and those performed on isolates from ‘mixed’ sources were

excluded from the analysis.

Fifty-six, 24, 39 and 5 studies were available for the analysis for Salmonella spp., Campylobacter spp.,

Escherichia coli and Enterococcus spp, respectively. For all microorganism – host class – antibacterial

compound combinations a ‘weighted average prevalence’ of AMR was calculated across studies and

subsequently converted into a qualitative score following a simplification of the ‘ratings’ provided by

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the European Food Safety Authority (EFSA) as follows: resistance level ≤10% = ‘low’; >10% to 20% =

‘moderate’; >20% to 50% = ‘high’; >50% to 70% = ‘very high’; and >70% = ‘extremely high’.

FINDINGS The method of testing for antimicrobial susceptibility and the selection of the isolates to be tested

varied markedly between the countries. Monitoring and surveillance schemes for antimicrobial

resistance in food borne pathogens and commensal bacteria covered in this report are not harmonised

among the countries reported. The data presented may not have necessarily been derived from

sampling plans that were statistically designed, and, thus, findings may not accurately represent the

national situation regarding antimicrobial resistance in food borne pathogens and commensal bacteria.

Additionally, there may not be harmonization in the interpretive criteria (clinical breakpoints) used

between, or even within, the countries covered in this report. The findings presented in this report

must, therefore, be interpreted with great care and no direct comparison between countries should

be made.

Despite the limitations in the data, the results obtained for the same bacterium isolated from poultry

and pigs (in overlapping but different sets of studies) as well as those of related but different bacterial

species (e.g. C. jejuni and C coli; E. faecalis and E faecium; Salmonella and E. coli) isolated from the

same host class were very consistent. The classification into the broad categories of AMR level to

selected compounds thus appear quite robust although some misclassification will still occur and the

approach masks differences that may well exist between countries.

Salmonella spp.: For Salmonella isolates from poultry, the pooled estimate of AMR across countries in

the study region fell into the categories of ‘high’ to ‘extremely high’ for 10 of 15 compounds

(representing eight antimicrobial classes) used to compare the prevalence of AMR in this study with

findings from AMR monitoring programs in high-income countries. A very similar pattern of AMR was

found for Salmonella isolates from pigs, with overall ‘high’ to ‘extremely high’ AMR levels to 11 of the

15 compounds used for comparison. In both sets of isolates ‘low’ levels of AMR were only found for

the two cephalosporins cefotaxime and ceftriaxone, while for ciprofloxacin both estimates of AMR

prevalence were borderline between ‘low’ and ‘moderate’. The pattern of AMR in Salmonella isolates

from ruminants showed some differences to those observed in poultry and pigs. ‘High’, ‘very high’ and

‘extremely high’ levels of resistance were only found for six of 13 compounds for which sufficient data

was available, while for the remaining seven compounds only ‘low’ levels of resistance were recorded.

Comparison of the pooled AMR estimates for East, South and Southeast Asian countries with those

from systematic AMR monitoring efforts in high income countries revealed that, with very few

exceptions, the highest estimates of AMR were found in the Asian isolates from all livestock groups

and for all compounds included in the comparison.

Campylobacter spp.: AMR patterns in C. coli and C. jejuni isolates from poultry were very similar and,

overall, it appears that in the Asian countries from which studies were available Campylobacter

populations harbored by poultry have developed ‘high’, ‘very high’ or ‘extremely high’ levels of

resistance to ciprofloxacin, nalidixic acid, and tetracycline while they still showed ‘low’ levels of

resistance to gentamicin, erythromycin, and chloramphenicol. Although for C. jejuni the number of

ruminant isolates tested was comparatively low, the observed pattern of AMR was similar to that of

C. jejuni isolates from poultry. C. coli isolates from pigs in China displayed high rates of resistance to

gentamicin (and kanamycin) and to erythromycin in addition to ‘high’ resistance to nalixic acid and

‘extremely high’ resistance to ciprofloxacin and tetracycline. ‘High’ levels of resistance to erythromycin

in C. coli isolates from pigs were also found in Japan, where isolates were also highly resistant to tylosin

and chloramphenicol.

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E. coli: The extent and pattern of AMR resistance in E. coli was very similar to that in Salmonella

isolates. For E. coli isolates from poultry, the pooled estimate of AMR across the study region fell into

the categories of ‘high’ to ‘extremely high’ for 15 of the 17 compounds (from nine classes) used for

comparison. ‘Low’ levels of AMR were only found for the 3rd

generation cephalosporin ceftiofur and for

colistin, representative of the polymyxin class. The pattern of AMR in E. coli isolates from pigs was very

similar to that in poultry isolates and ‘high’ to ‘extremely high’ rates of AMR were found for 14 of the

17 compounds in the comparison. Resistance to chloramphenicol was estimated as ‘high’ and

resistance to trimethoprim-sulfa as ‘extremely high’ both in isolates from poultry and from pigs. AMR

rates in E. coli isolates from ruminants were considerably lower than those found in poultry and pig

isolates and the pooled estimate of AMR prevalence only fell in to the ‘high’ category for four out of 15

compounds for which data was available. Comparison of the pooled AMR estimates in E. coli isolates

from poultry and pigs in East, South and Southeast Asia with those from systematic AMR monitoring

efforts in high income countries revealed that for most compounds used for comparison they fell into

the highest observed resistance category. Only in three of 64 comparisons was the AMR category for

isolates from poultry higher in one of the countries in the comparison, namely for streptomycin,

sulfamethoxazole and trimethoprim in the Netherlands. In E. coli isolates from pigs this was only the

case for one compound (out of 73 comparisons), namely oxytetracycline in Australia (‘extremely high’

vs. ‘very high’).

Enterococcus spp.: Only three studies on AMR were available for E. faecalis and E. faecium isolates, two

of which from Japan and the remaining from Taiwan Province of China. However, given the large

number of isolates tested, the results are likely to adequately reflect the situation in Japan and Taiwan

Province of China and a cross-country comparison was carried out as for the other microorganisms

included in this review. Similar to the findings with the other microorganisms, AMR rates found in

E. faecalis isolated from poultry in Japan and Taiwan Province of China always fell into the highest

category seen for all eight compounds (from seven classes) used for comparison. AMR was found to be

‘high’ or ‘extremely high’ for six of the eight compounds, resistance being ‘low’ to ampicillin, while no

isolate (of 251 tested) was found to be resistant to vancomycin. In E. faeciu, ‘high’ to ‘extremely high’

levels of resistance were found for six of the nine compounds included in the comparison, resistance

being rated as ‘low’ for gentamicin and ampicillin, while no isolate (of 523 tested) was found to be

resistant to vancomycin. AMR rates in E. faecium isolates from poultry in Japan and Taiwan Province of

China also nearly always fell into the highest category observed for the compound, the only exception

being ampicillin, where isolates from the Netherlands exhibited a ‘high’ level of resistance while the

corresponding estimate for the isolates from the two Asian countries was ‘low’.

In most of East, South and Southeast Asia AMU in food animal production is not well regulated and the

capacity to enforce existing regulations and to monitor AMR are often poor. As in the human medical

sector, the high levels of AMR provide strong evidence for the widespread and ‘non-responsible’ use of

antimicrobials. Lack of awareness of the extent and consequences of AMR and the contribution of

uncontrolled AMU in food animal production by policy makers appear to be at the root of the rather

low level of policy concern and relative regulatory inertia seen in many of the countries in the region.

RECOMMENDATIONS This review has provided a first insight into the likely extent of AMR in selected pathogens and

commensals associated with food animal production in East, South and Southeast Asia and although it

appears that the levels of AMR are high in comparison to a number of countries with systematic AMR

monitoring programs, the true extent and impact of AMR in the region remain largely unknown. There

is an urgent necessity to produce comparable data from national monitoring and surveillance programs

in different countries in the region and to combine the results at the regional level to support the

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formulation of rational and cost-effective AMR programs across the region. Better communication and

collaboration and among Asian countries (e.g. at ASEAN and SAARC level) is a prerequisite for the

development of harmonized and standardized schemes for AMR monitoring and regional approaches

to conserve antibiotic effectiveness for human and animal health protection.

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INTRODUCTION Many bacteria are increasingly becoming resistant to antimicrobial compounds commonly used to control

bacterial infections in humans and animals and antimicrobial resistance (AMR) has become one of the main

public health issues in many parts of the world, including the Asia-Pacific region (APR).

Based on data from the Study for Monitoring Antimicrobial Resistance Trends (SMART), the prevalence of AMR

in pathogens causing human illness varies across geographic regions but is highest in Asia-Pacific countries and

food borne diseases caused by AMR micro-organisms harbored by food animals are increasingly emerging as a

public health challenge in the region 121. Previous studies from several parts of the Asia-Pacific region

showed the emergence of drug resistant Salmonella in both humans and animals, e.g. Cambodia 120,

Pakistan 5, Thailand 159, 161, and Viet Nam 151. Fluoroquinolone-resistant Salmonella have been

reported across Asia (Bangladesh, China, India, Indonesia, Lao PDR, Nepal, Pakistan, and central Viet Nam)

35. Antibiotic-resistant Campylobacter species have been increasingly reported in diarrhea patients 36, 160,

187. Recently, several reviews demonstrated that the rate of ESBL-positive Escherichia coli isolated from intra-

abdominal infections in the Asia-Pacific region doubled from 20 percent in 2002 to 40.8 percent in 2010 39,

99, 100, 121. The prevalence of carbapenem-resistant Enterobacteriaceae isolates also increased sharply, in

particular, imipenem resistance increased from 0.2 percent to 6.3 percent 39, 99, 100, 121. These data

highlight that AMR is a serious and growing health problem in the region in need of immediate action.

Mis- and overuse of antimicrobial agents in humans and animals creates selective pressures leading to the

emergence and subsequent spread of AMR. Worldwide, large amounts of antimicrobials are used in food

animal production for: (i) treatment of infection, (ii) disease prevention and (iii) growth promotion. This

practice provides favorable conditions for the selection, spread and maintenance of AMR bacteria, and

emergence and increased prevalence of AMR in bacteria associated with food animals has been linked to

antimicrobial use (AMU) in livestock production 26, 109.

In response to growing demand for animal source food, food animal populations and production have grown

tremendously across East, South and Southeast Asia over the past decade (Table 1). Chicken populations have

exhibited the largest increases, growth between 2000 and 2010 reaching 42, 147 and 62 percent in East, South

and Southeast Asia respectively. The three Asian sub-regions now account for around 52 percent of the global

chicken population. Pig numbers have also increased dramatically in East and Southeast Asia (respectively by

18 and 35 percent) while pig numbers have declined in South Asia. Overall, East, South and Southeast Asia

account for 60 percent of global pig stocks. Cattle and buffalo populations have exhibited the slowest growth

rate (between 10 and 20 percent) but populations have shifted from draft and beef cattle towards dairy

animals. Increasing livestock numbers has been accompanied by growth in individual livestock holdings and

increasing intensification of food animal production. The latter entails higher usage rates of antimicrobials for

all above-mentioned purposes.

Published information on the use of antimicrobials in food animal production in Asia is scarce but the size of

the Asia-Pacific market for in-feed antibiotics has been estimated at USD1.8 billion in 2011, accounting for 48

percent of estimated global in-feed antibiotic sales 157. Around 70 percent of in-feed antibiotics are used in

pig and poultry production while use in cattle is estimated to account for approximately 20 percent.

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Table 1. Livestock populations and population growth in East, South and Southeast Asia between 2000 and

2010

Sub-region Species 2000 2010 Growth (%)

East Asia Chicken 4.01 5.70 42.0

Pigs 413.76 487.35 17.8

Cattle & buffalo 128.42 141.97 10.6

South Asia Chicken 0.95 2.34 147.2

Pigs 14.39 10.92 -24.1

Cattle & buffalo 377.67 437.59 15.9

SE. Asia Chicken 1.51 2.44 61.5

Pigs 53.29 72.05 35.2

Cattle & buffalo 52.60 62.91 19.6

* Chicken: billion head; pigs, cattle & buffalo: million head; Source: FAOSTAT, accessed on 27.01.2014

In many Asian countries, AMU in humans and food animals is currently not well regulated and existing

regulations are poorly enforced. In conjunction with the strong and growing demand for animal source food,

the lack of regulation of AMU in livestock production is likely to accelerate the development and distribution of

AMR in bacteria associated with food animals.

However, few Asian countries have systematic AMR monitoring systems in place and consequently data on the

actual burden of AMR is scant or absent. Public health systems in the region differ from one country to

another and most work independently, leading to a wide variation in AMR surveillance and control systems.

This lack of coordination is one of the major hindrances for the development and implementation of effective

and efficient AMR control and prevention strategies in the region.

The relationship between AMU and the development of AMR is complex. AMU in some food animal species

may result in AMR in some species of bacteria under certain conditions but the same outcome does not

necessarily occur in other animal species and the bacteria they harbor. Application of the same antimicrobial

may lead to different resistance rates in the same bacterial species in different animals as well as to different

resistance rates in different species of bacteria from the same animal species. To date, efforts to control AMR

have been based solely on regulation of AMU and variable responses have been obtained due to poorly

understood biological differences in AMR development 176. This phenomenon suggests the requirement for

detailed interdisciplinary and international studies 177. Epidemiological data and current practices pertaining

to AMU and AMR in the region need to be assessed for forthcoming risk assessments, harmonization of the

control and prevention strategies and formulation of evidence-based policies for AMR management.

The aim of this review is to enhance current knowledge on the extent and patterns of AMR, AMU and its

regulation, and AMR monitoring programs in different countries in East, South and Southeast as basis for

devising strategies for AMR monitoring and management. It is intended to serve as a reference document for

international organizations, public health agencies, regulatory authorities and policy makers for their future

discussion and action.

BACTERIA OF PARTICULAR CONCERN IN AMR MONITORING

Bacteria of particular concern with respect AMR monitoring in food animals are zoonotic bacteria, namely

Salmonella spp. and Campylobacter spp., and commensal (indicator) bacteria, namely E. coli and Enterococcus

spp. 64. Pathogenic bacteria, particularly when resistant to antimicrobials, directly affect human and animal

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health, while resistant commensal bacteria indirectly contribute to the AMR problem by possessing and

transferring resistance genes to other bacteria belonging to the normal microflora and to bacterial pathogens

of humans. As commensal bacteria are prevalent in healthy food animals, in particular in pigs and poultry,

extensive AMU can result in selective pressure for AMR in their populations.

Commensal bacteria are ubiquitous in healthy animals and can contaminate carcasses during slaughter and

processing. Compared to foodborne pathogens, commensal bacteria represent the larger share of the total

possible transfer of resistance genes to bacteria of humans through food. Although the transmission rates

remain unknown, the commensal AMR gene reservoir may pose a risk to humans, which may be equal to or

even greater than that posed by resistant-pathogenic bacteria. It is important that indicator bacteria for AMR

monitoring should be derived from healthy animals that are randomly sampled to provide data on the

selective pressure exerted by the use of antimicrobials in food-producing animals 64.

SALMONELLA

Non-typhoidal Salmonella are among the most common and widely distributed food-borne pathogens

worldwide. Infection with Salmonella, or salmonellosis, is of significant public health and economic importance

and impacts on international food trade. The incidence and predominant serovars of Salmonella differ

depending on type of food and geographical area. The food items most commonly associated with Salmonella

infection include foods of animal origin, such as eggs, chicken meat, pork, beef, and milk. The prevalence of

the various serovars in food animals can change over time but livestock such as pigs, cattle, and poultry serve

as a major reservoir of the pathogen. Most cases of Salmonella infection in humans are self-limiting, but

severe cases can become invasive and cause extra-intestinal infections. Problems related to Salmonella have

become more complicated due to the rapid emergence of the strains resistant to clinically important

antimicrobial agents, usually to many drugs simultaneously.

Salmonella strains that are resistant to a range of antimicrobials are now a serious public health concern

worldwide. Assessment of the presence of Salmonella is mandatory in determination of microbiological food

quality and the monitoring of AMR in Salmonella is suggested in food-producing animals and meat 64.

Although a number of studies on AMR in Salmonella in the region have been published, these are often of

qualitative nature and limited to a few countries and therefore do not provide a comprehensive overview.

In the EFSA-harmonised panel of antimicrobials for antimicrobial susceptibility testing (AST) of Salmonella, up

to 13 antimicrobial agents were recommended to be included. It is highly recommended to determine ESBL-

AmpC phenotypes 64. This can provide clearer picture regarding resistance mechanisms involved. It is also to

investigate the possible link between AMR in bacteria from different sources and to measure zoonotic risks

64.

CAMPYLOBACTER Campylobacter is the leading cause of bacterial food-borne diseases in many countries. It is very common in

developed nations. Campylobacter species that are most common in food animals include C. coli and C. jejuni.

Campylobacter are part of the normal intestinal flora of food animals. Pigs are the primary reservoirs of C. coli

while poultry are usually colonised with C. jejuni. In general, the numbers of Campylobacter are higher in

young animals than in older animals. In the latter, the bacteria can only be sporadically detected in feces,

possibly due to low numbers or intermittent shedding 153. Contamination of animal products with

Campylobacter usually occurs during the slaughter process.

AMR monitoring in Campylobacter spp. preferentially focuses on C. coli in pigs and on C. jejuni in poultry.

However, C. coli also occurs regularly in poultry and may be more resistant to antibiotics than C. jejuni.

Accordingly, it is advisable to also test antimicrobial susceptibility of C. coli strains isolated from poultry 153.

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Most Campylobacter infections are self-limiting. However, severe infections and prolonged cases of enteritis

require antibiotic treatment. Antibiotics used for clinical therapy of campylobacteriosis are erythromycin,

fluoroquinolones (e.g. ciprofloxacin), tetracycline and gentamicin. The last two antibiotics are commonly used

in cases of systemic infection with Campylobacter 28.

ESCHERICHIA COLI E. coli are commensal bacteria that are ubiquitous in healthy animals and humans. E. coli exist in the gut and

usually do not cause disease. However, some E. coli strains can be pathogenic, e.g. extra-intestinal pathogenic

E. coli (ExPEC), uro-pathogenic E. coli 110. E. coli bacteria have been used as an indicator for fecal

contamination of food. E. coli isolates from healthy animals are now accepted as indicator species for AMR in

Gram-negative bacteria. E. coli have the ability to accept and transfer resistance genes and therefore serve as

a model for studying the emergence of AMR and the health risks posed by AMU. The antibiotics suggested for

susceptibility testing in AMR monitoring in E. coli are similar to those suggested for Salmonella.

ENTEROCOCCUS Enterococcus spp. are proposed to be included in AMR monitoring programs. They serve as Gram-positive

indicator organisms 64. Enterococci are ubiquitous in healthy animals. Enterococcus spp, particularly

E. faecalis and E. faecium, though commensal bacteria in animal and human intestinal tracts, are among the

most important opportunistic pathogens in humans. Enterococci are intrinsically resistant to many antibiotics,

e.g. β-lactams (penicillins, cephalosporins, carbapenems) and aminoglycosides 97. As a commonly isolated

nosocomial pathogen, such natural resistance phenotype adversely affects treatment protocols. Enterococci

can survive after release from their animal host and constitute a reservoir of transferable resistance genes. For

these reasons, Enterococcus spp. are considered important for AMR monitoring 62.

Antimicrobials recommended for inclusion in AMR monitoring include ampicillin streptomycin, gentamicin,

chloramphenicol, vancomycin, teicoplanin quinupristin/dalfopristin, tetracycline, tigecycline, linezolid and

daptomycin 64.

AMR SELECTION AND TRANSFER

The development and spread of AMR in bacteria is a complex dynamic process that depends on the type of

antimicrobial selective pressure and the availability and transferability of resistance genes. Currently, the

majority of bacteria are multidrug-resistant (MDR).

AMR SELECTION Antimicrobials can select for MDR bacteria in two common ways: co-selection and cross-resistance.

Co-selection: Co-selection occurs when different resistance determinants are present on the same genetic

element 24. A single antibiotic can co-select for several resistance genes encoding resistance to completely

unrelated drugs. The bacteria can become resistant to many drugs simultaneously, including drugs that are not

used. Co-selection is a simple direct selection process and the best example of mobile genetic elements

associated with co-selection are integrons 75.

At least nine classes of integrons have been described in clinical isolates and class 1 integrons are the most

predominant integron type. The significance of class 1 integrons arises from their ability to simultaneously

contain many resistance gene cassettes in their variable regions. Class 1 integrons are frequently located on

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conjugative plasmids. Therefore, they are efficiently transferred among bacteria both within and between

species and play an important role in the dissemination of AMR genes among bacteria.

Cross-resistance: Cross-resistance is another common phenomenon creating multi-drug resistant phenotypes.

In this case, the same genetic determinant is responsible for resistance to many classes of antibiotics 32.

Therefore, selection through a single antibiotic can promote cross-resistance to a number of drugs at the same

time. The best example of cross-resistance mechanisms is the multidrug efflux system.

Bacterial efflux systems are active transporters localized in the cytoplasmic membrane of all bacterial species.

Efflux systems function via an energy-dependent process that pumps out unwanted toxic substances, including

antimicrobial agents, from the interior to the exterior of the cells. As a result, the intracellular drug

concentration remains below the necessary bacteriostatic / bactericidal and the bacteria. Some efflux systems

are drug-specific, whereas most are multiple drug transporters, also referred to as multidrug efflux systems.

Exposure to an antimicrobial agent may cause over-expression of a multidrug efflux pump and promote cross-

resistance to other structurally-unrelated antimicrobial drugs.

Both co-selection and cross-resistance are important factors contributing to the persistence of resistance to

certain antimicrobials that are no longer used.

AMR TRANSFER AMR spreads through bacteria populations by vertical and horizontal transfer.

Vertical transfer: Bacteria can develop resistance through the process of mutation, a trait that is then directly

passed on to all offspring during DNA replication 60. This process is known as vertical gene transfer or

vertical evolution. Originally, the resistance conferring mutation is rare, but, in the presence of antibiotic

selective pressure, disseminates throughout a bacterial population as the susceptible wild type without the

mutation will be eliminated and the resistant mutant will multiply. This resistance is stably maintained even in

the absence of antibiotic selective pressure and, eventually, the resistant mutants will be predominant.

Horizontal transfer: Horizontal gene transfer is a process through which resistance genes can be transferred

from donor to recipient cells, a process that can occur among bacteria of the same or different species 60.

Conjugation, transformation and transduction are the primary methods of horizontal gene transfer in bacteria.

Horizontal transfer of resistance genes is a major factor that causes wide distribution of resistant bacteria.

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METHODS This study reviews and synthesizes the available literature on the prevalence of AMR in selected zoonotic

bacteria associated with livestock and livestock products, regulations, guidelines and policies on antimicrobial

use (AMU) in livestock and monitoring/surveillance and control/prevention programs for AMR in bacteria

carried by livestock and livestock products in East, South and Southeast Asia. The review comprises official

government documents, journal articles and online-news articles published over the past 5 years (from 2008-

2013) to cover the most current developments in the field. However, as the quantity and quality of available

publications vary between countries, the search was extended to the past ten years (from 2003-2013) for

countries with a very limited number (one or less) of publications, e.g. Afghanistan, Democratic People's

Republic of Korea, Maldives, Mongolia, Myanmar, and Timor-Leste.

The Asian countries covered by the review, grouped by sub-regions as defined by FAO, are listed in Table 2

below.

Table 2. Countries covered in the literature search by Asian sub-region as defined by FAO

Sub-region Countries

East Asia China PR, Japan, Democratic People's Republic of Korea, Republic of Korea, Mongolia, Taiwan (Province of China)

South Asia Afghanistan, Bangladesh, Bhutan, India, Iran, Maldives, Nepal, Pakistan, Sri Lanka

Southeast Asia Cambodia, Indonesia, Lao PDR, Malaysia, Myanmar, Philippines, Thailand, Timor-Leste, Viet Nam

Throughout this review, the term ‘antimicrobial agent or antimicrobials’ is defined as, “any substance of

natural, semi-synthetic, or synthetic origin that at in vivo concentrations kills or inhibits the growth of a

microorganism but causes little or no damage to the host”. Anthelmintics, antiseptics and disinfectants are

excluded 154.

The review focuses on the major livestock species in the Asia-Pacific region, namely poultry (chicken, ducks,

geese, quail, etc.), pigs, and ruminants (buffalo, cattle, sheep and goats), their environment / excreta, and

products (i.e. chicken meat, pork, beef, mutton and milk).

Following the EFSA technical specifications for the harmonised monitoring and reporting of antimicrobial

resistance in bacteria transmitted through food 64, the review is limited to the following four most important

bacterial species found in livestock and livestock products: Salmonella spp., Campylobacter spp., Escherichia

coli and Enterococcus spp.. The guideline recommends to cover the combinations of bacterial species including

zoonotic agents specific for the animal species (Salmonella and Campylobacter) and indicator (commensal)

E. coli and Enterococcus bacteria (E. faecium and E. faecalis) that serve as reservoirs for AMR determinants 61,

62, 64.

Publications were identified through online database searches, references in scientific literature and included

written resources (e.g. government documents and publications of universities or relevant agencies) known to

the authors. Peer-reviewed scientific literature was preferentially included to ensure the quality of documents.

Searches were restricted to English publications. The full publications were acquired and the relevant sections

were reviewed. When full / original scientific publications were unavailable, alternatives (e.g. conference

proceedings with methods and results, government statements, meeting/country reports, and dissertations)

and websites were utilized. Ad hoc searches of online databases, websites and grey literature were

occasionally conducted to obtain additional information.

Internet searches were performed using Google and Yahoo search engines. The online databases PubMed,

ScienceDirect, Scopus, MEDLINE (Ts), MEDLINE (OvidSP), LISTA, Web of Science and Library catalogues, e.g.

7

National Agricultural Library, were searched systematically using consistent algorithms. Online information and

websites provided by national agencies in each country including academic institutions, governmental

departments, relevant ministries, respective national and international NGOs, and scientific journal databases

were searched. Some publications were obtained directly via personal contact. Persons with existing

collaboration in certain countries i.e. University of Veterinary Science, Nay Pyi Taw, Myanmar; Faculty of

Agriculture, National University of Laos, Vientiane, Lao PDR were asked to kindly provide documents.

The “Keyword relevancy algorithm” was used for the search and the results were displayed as a ranked

keyword using “Search result ranking algorithm”. Combinations of key words were used for each of the subject

areas. The algorithms (keywords) used are listed in Table 3.

Table 3. Search algorithms used for identification of relevant literature on AMU, AMR and their regulation in

East, South and Southeast Asia

Search Nr. Search algorithm (Keyword)

1 Antimicrobial use? (Country name)

2 Antimicrobial use? Livestock (Country name) e.g. Antimicrobial resistance? Thailand

3 Antimicrobial use? Food animals (Country name)

4 Antimicrobial resistance?

5 Antimicrobial resistance? (Country name) e.g. Antimicrobial resistance? Thailand

6 Antimicrobial resistance?, Food animals, and (Country name)

7 Antimicrobial resistance?, (Animal species), and (Country name)

8 Antimicrobial resistance?, (Bacterial species), and (Country name)

9 Antimicrobial resistance?, (Bacterial species), (Animal species), and (Country name)

10 (Resistance specific antimicrobial agent), Food animals, and (Country name)

11 (Resistance specific antimicrobial agent), Food animals, and (Country name)

12 (Resistance specific antimicrobial agent), (Animal species), and (Country name)

13 (Resistance specific antimicrobial agent), (Bacterial species), and (Country name)

14 Prudent use, antibiotics, and (Country name)

15 Responsible use, antibiotics, and (Country name)

16 Judicious use, antibiotics, and (Country name)

17 (Bacterial species)? (Country name) e.g. Salmonella? Thailand

18 (Bacterial species) Antibiotic Resistance (Country name)

19 MICs (Bacterial species)(Country name)

20 MICs (Food animals)(Country name)

21 Control antimicrobial resistance? (Country name)

22 Regulation antimicrobial resistance? (Country name)

23 Policy antimicrobial resistance? (Country name)

24 Law, antibiotics, and (Country name)

25 Monitoring antimicrobial resistance? (Country name)

26 Surveillance antimicrobial resistance? (Country name)

8

The full publications were acquired and reviewed by the working team comprising five veterinary

microbiologists and two microbiology research scientists. The team independently reviewed citation titles,

abstracts and full texts to exclude citations that did not meet the inclusion criteria (Annex 1). Publications

meeting inclusion criteria were organized by microorganism and country, and relevant information (e.g. source

of isolate, number of isolates tested, antimicrobials used, etc) was extracted and compiled in MS-EXCEL

databases.

For the descriptive analysis, all farmed poultry types were grouped as poultry (e.g. broiler, layer, duck, geese,

etc = POU); all ruminant types were grouped as ruminants (cattle, calf, goat, etc = RUM); all pig types (e.g.

weaners, growers, etc) were grouped as PIG. Studies on isolates from various host groups were classified as

‘MIX’. Studies were classified into the above four groups, irrespective of whether the isolates were obtained

from live animals, their products, feces or their environment. Studies not reporting the number of isolates

examined and those performed on isolates from ‘mixed’ sources were excluded from the analysis.

The overall, ‘cross-study weighted1 average prevalence’ of AMR is presented in summary tables for selected

compound – pathogen – host species combinations in the main text. Given the limitations in comparability of

different studies, qualitative levels of AMR were used following a simplification of the ‘ratings’ provided in

EFSA 2013: resistance level ≤10% = ‘low’; >10% to 20% = ‘moderate’; >20% to 50% = ‘high’; >50% to 70% =

‘very high’; and >70% = ‘extremely high’. More details for each compound – micro-organism – host class

combination, such as number of studies, number of isolates, lowest and highest AMR prevalence are provided

in respective annexes 63.

1 The number of isolates tested were used as weights

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FINDINGS The stage of development and effectiveness of AMR monitoring programs and AMU regulation and policy in

countries in East, South and Southeast Asia is highly variable and to a large extent linked to the country’s

general level of economic development. Almost all countries in the study region (with the exception of Japan)

suffer from a scarcity of reliable and systematic antimicrobial resistance monitoring data. Many of the

countries in the study region are classified as low or medium income countries, in which antimicrobial agents

are easily accessible and often used as a surrogate for good animal husbandry practices.

Irrational use of antimicrobials appears to be a common and significant practice in livestock production in the

region and is considered a major cause of the development and spread of antimicrobial-resistant bacteria.

Unfortunately, most of the countries covered by this study lack effective national AMR control and prevention

programs. AMU policies and regulation in livestock production are not well established and even where

legislation to control the use of antibiotics exists, it may not be implemented properly or effectively.

PREVALENCE OF AMR IN BACTERIA OF CONCERN

AMR monitoring in food animals, their environment and in derived food product is the starting point for the

assessment of the prevalence of AMR, understanding its source and subsequent spread. The resulting data

provides important, basic information for policymakers to identify potential areas for action and further

investigation and for the evaluation of specific prevention strategies. None of the countries covered by the

review has an established systematic AMR monitoring program and this review therefore had to build on a

review of studies conducted and published by researchers from different institutions following different

protocols and producing results of diverse quality.

The number of AMR studies retrieved for each of the four bacterial species by country is displayed in Table 4.

Most (56) studies on AMR in bacterial isolates from food animals were found for Salmonella spp. from 14

countries in East, South and Southeast Asia. E. coli followed as the bacterial species for which the second most

(39) AMR studies could be identified, covering 12 countries of the region. Only 24 AMR studies could be found

for Campylobacter spp., 13 of which originated from two countries only (Iran and Japan). Enterococcus spp.

were the least covered bacterial group with only five studies found through the literature search, with no

studies from South and Southeast Asian countries.

Table 4. Country of origin and number of studies (in parenthesis) on AMR in selected bacteria included in the

review

Sub-region Salmonella Campylobacter E. coli Enterococcus

South Asia BGD (2); IND (1); IRA (4); NEP (1); PAK (2)

IRA (6); BGD (6); IND (3); IRA (2); NEP (1); SRI (1)

East Asia CHI (7); JAP (12); ROK (1); TAI (5)

CHI (4); JAP (7) CHI (9); JAP (6); ROK (3); TAI (1)

CHI (1); JAP (2); ROK (1); TAI (1)

Southeast Asia

CAM (1); LAO (2); MAL (4); THA (11); VIE (3)

CAM (1); MAL (2); PHI (1); THA (2); VIE (1)

MAL (1); THA (4); VIE (2)

TOTAL 56 24 39 5

No studies on AMR in any of the four bacterial groups were found for Bhutan (one study of AMR in isolates

from imported livestock products was identified), Democratic Peoples’ Republic of Korea, Indonesia, Maldives,

Mongolia, Myanmar or Timor-Leste.

10

The quality of the publications was quite variable. Precise information on sampling techniques, sample

collection, antimicrobial susceptibility testing was seldom provided. The number of bacterial isolates in some

studies was rather limited (n<30). While the qualitative antimicrobial susceptibility tests (i.e. mostly disk

diffusion test) were performed in most studies, breakpoints used for defining ‘susceptible’ and ‘resistant’ were

not provided. These inconsistencies seriously affect the comparability of the data and the results of the

descriptive quantitative analysis have to be interpreted as indicative. Qualitative resistance categories were

used to mitigate against these limitations in comparability and to reduce the probability and degree of

‘misclassification’.

SALMONELLA A relatively large body of literature on AMR could be assembled for bacteria of the Salmonella enterica, which

contains a vast amount of serovars. In some studies AST was carried out on isolates for which the serovars had

been determined while most studies reported on AMR in ‘Salmonella spp.’. The number of studies available for

different Salmonella serovars, broken down by host from which the isolates were obtained and the country in

which the study was carried out are presented in Table 5.

Table 5. Number of AMR studies on Salmonella enterica by serovar and origin of isolate

Salmonella serovar

Host species Studies Countries

S. Enteritidis Poultry 4 CAM (1); CHI (1); IRA (1); MAL (1)

Mixed 1 JAP (1)

S. Gallinarum Poultry 2 BGD (1); MAL (1)

S. Infantis Poultry 3 IRA (1); JAP (2)

Mixed 1 VIE (1)

S. Pullorum Poultry 2 BGD (1); CHI (1)

S. Typhimurium Poultry 4 BGD (1); CAM (1); CHI (1); MAL (1)

Pigs 2 CHI (1); TAI (1)

Ruminants 2 CHI (1); JAP (1)

Mixed 1 VIE (1)

Other serovars Poultry 4 CAM (1); CHI (1); MAL (1); TAI (1)

Pigs 1 TAI (1)

Mixed 4 JAP (1); LAO (1); THA (1); VIE (1)

‘Salmonella spp.’ Poultry 22 CAM (1); CHI (4); IND (1); IRA (1); JAP (5); MAL (2); NEP (1); PAK (2); TAI (1); THA (3); VIE (1)

Pigs 14 CHI (3); JAP (3); MAL (1); ROK (1); THA (5); VIE (1)

Ruminants 5 BGD (1); CHI (1); IRA (1); JAP (2)

Mixed 10 IRA (1); JAP (2); LAO (2); TAI (1); THA (4)

Antimicrobial agents that were most commonly tested included ampicillin, ciprofloxacin, gentamicin, nalidixic

acid, streptomycin, sulfonamides, tetracycline and trimethoprim. These drugs are very commonly used in

livestock production in the region because they are readily available and of low cost in comparison to drugs of

newer generations.

As AMR in Salmonella is usually not serovar-specific and as few studies were available for specific Salmonella

serovars, the prevalence of AMR for the most frequently tested antimicrobial compounds was estimated

across all Salmonella isolates, irrespective of serovars, for each of the three host groups, i.e. poultry (mainly

chicken and ducks), pigs, and ruminants (mainly cattle and sheep). The number of studies, countries, number

of isolates tested, etc. are detailed in Annex 2 while an overview of the prevalence of AMR in Salmonella spp.

to selected antimicrobial compounds is presented in Table 6.

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Table 6. Proportion (%) of Salmonella isolates from poultry, pigs and ruminants in East, South and Southeast

Asia resistant to selected antimicrobial compounds

Class Compound Poultry Pigs Ruminants

AMI

Gentamicin 17 24 3

Kanamycin 28 24 35

Streptomycin 62 58 65

CEP

Cefotaxime 2 0 0

Ceftriaxone 4 1 0

Cephalothin 29 7 7

MAC Erythromycin 86

28

PEN Amoxicillin 36 22 80

Ampicillin 25 60 77

PHE Chloramphenicol 23 47 56

Florfenicol 26 12

POL Colistin 12 6 0

QUI

Ciprofloxacin 10 11 3

Nalidixic acid 44 40 5

Norfloxacin 18 9 0

SUL Sulfamethoxazole 77 85

Sulfonamide 16 55 90

TET Oxytetracycline 82 83 72

Tetracycline 48 83 76

TRI Trimethoprim 59 38 0

Trim-Sulfa 39 44 7

OTH Imipenem 0 0 0

Meropenam 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

The review the literature reveals widespread and diverse AMR in different serovars of Salmonella from

livestock and livestock products in the East, South and Southeast Asia, confirming the important role of food

animals as common reservoirs of AMR Salmonella. Overall, a wide variation of AMR prevalence and patterns

was observed between different animal species and food categories either from the same or different

countries. Resistance to drugs of some classes that are used in human medicine is rather high.

Aminoglycosides: Aminoglycosides have been commonly used in livestock for a long time and, therefore, it is

not surprising to observe high resistance to these drugs in Salmonella. However, the percentage of resistance

varied greatly even in the Salmonella collections in the same study. In China, the prevalence of gentamicin-

resistance varied from 0% to >90% 128. When considering the source of the Salmonella isolates, the

prevalence of gentamicin resistance was usually higher in chicken and pigs than in other food animals and their

products. For example, the isolates from ducks in Malaysia 4 and from raw milk in Iran 200, 201 were all

susceptible to gentamicin. However, the Salmonella isolates from cattle, pigs, broilers and layers in Japan were

susceptible to gentamicin but resistant to dihydrostreptomycin and kanamycin 16, 18. In general, resistance

to aminoglycosides in Salmonella is mainly due to the presence of aminoglycoside-modifying enzymes.

Therefore, the variation in aminoglycoside resistance is most likely due to different usage of antibiotics in

different countries, resulting in selection of different genes encoding for aminoglycoside-modifying enzymes.

12

Cephalosporins: Extended-spectrum cephalosporins (e.g. ceftriaxone) have been recommended for treatment

of invasive and severe Salmonella infections as well. Unfortunately, ESBL-producing Salmonella have been

increasingly reported from livestock, e.g. pigs and poultry, worldwide 93, 173. The ESBL genes are usually

located on plasmids that can be horizontally transferred 98. This is a particular concern in antibiotic therapy

for humans. Among drugs in this group, susceptibility to cephalothin is most commonly studied. Cephalothin is

a first generation cephalosporin that may be legally prescribed by veterinarians for use in pet animals (e.g.

dogs, cats) but is not approved for use in food animals 181. Nevertheless, high resistance rates to

Cephalothin were observed in isolates from poultry from China 128, 215, Taiwan (Province of China) 37,

and Nepal 188 and in isolates from pigs from Malaysia 40. The poultry isolates tested in the study from

China 215 exhibited resistance to cephalothin (74%), cefoxitin (second generation, 13%) and ceftriaxone

(third generation, 61%). The lower prevalence of resistance to cefoxitin was suggested to be due to less

frequent use of this drug. Particular note should be made of the very high resistance (94.9%) to cephalothin in

the poultry isolates in Nepal 188. This could be a result of widespread use of this antibiotic for veterinary

therapeutic and preventive purposes in Nepal.

Macrolides: As Salmonella are intrinsically resistant to erythromycin 84, the high prevalence of resistance to

this drug is not surprising. Azithromycin is an azalide antimicrobial agent that has been recommended as

treatment alternative for invasive Salmonella infections, especially in case of decreased susceptibility to

ciprofloxacin 77. A study suggested that azithromycin is useful in treatment of bovine mastitis caused by

S. aureus 129. Its efficacy in calves with diarrhea due to Cryptosporidium parvum has also been

demonstrated 47. However, the drug is not commonly used in food animals and, at present, no clinical

azithromycin breakpoints have been defined for Enterobacteriaceae, including Salmonella. Nevertheless,

resistance to azithromycin was reported in the Salmonella isolates from cattle in Bangladesh 210.

Penicillins: Penicillins have been used in livestock for a long time. It is thus not surprising to observe high

resistance rates to drugs in this particular group. High ampicillin-resistance rates (>60%) were reported in

Salmonella isolates from food animals in many countries, for example, poultry in China 128, Taiwan 37,

Nepal 188, Pakistan 194; cattle in Bangladesh [2]; pigs in China 163, Taiwan 33, Japan 50, and ducks in

Malaysia 3.

Ampicillin is traditionally used as an indicator agent for the presence of β-lactamases in Enterobacteriaceae

and it is recommended to include ampicillin in the susceptibility panel rather than amoxycillin or β-lactams

combined with β-lactamase inhibitors 61. Ampicillin promotes complete cross-resistance to amoxicillin but

different potencies of the drugs exist. Therefore, resistance rates of ampicillin and amoxicillin are usually very

similar and the apparent differences are mainly a result of different collections of isolates being tested for

ampicillin or amoxicillin susceptibility. This is in agreement with the results from a number of the studies

included in this review, e.g. the poultry isolates in Nepal 188 and China 223 and cattle isolates in

Bangladesh 2. Surprisingly, resistance rates to ampicillin and amoxicillin were quite different in some studies.

A study in China found that ampicillin resistance rates of duck, pig and poultry isolates were higher than those

to amoxicillin 163. The opposite relationship, however, was observed in isolates from retail chicken in Iran, in

which resistance rates to ampicillin and amoxicillin were 10% and 70%, respectively 67. Although the reason

for these findings is unclear, they provide evidence that differences in reported susceptibility to ampicillin and

amoxicillin may occur in the same set of isolates.

Phenicols: It is interesting to observe substantial resistance to chloramphenicol in Salmonella (and other

Enterobacteriaceae) in many countries even though the drug has been banned from use in food animals for

over a decade. This phenomenon could be explained by linkage of resistance genes. Chloramphenicol-

resistance encoding genes may be located on the same elements (e.g. integrons, plasmids) with other

resistance genes and co-selected by other antibiotics. In addition, it may be a result of cross-resistance

generated by other antibiotics. The high prevalence of chloramphenicol resistance supports the observation

that removal of certain antimicrobial-selection pressures may not diminish AMR once it is established.

13

Florfenicol is a fluorinated derivative of chloramphenicol and exhibits broad-spectrum antimicrobial activity.

While the chloramphenicol-resistance gene confers resistance only to chloramphenicol, the floR gene encodes

resistance to both substances. Therefore, most isolates resistant to florfenicol are also resistant to

chloramphenicol 220. As most studies included chloramphenicol susceptibility testing, only a few studies

tested susceptibility to florfenicol. The florfenicol-resistance rate was generally low (0% to <5%), except in the

isolates from ducks, pigs and chicken from China 123, 128. In these two studies, the prevalence of resistance

to florfenicol was slightly higher than that to chloramphenicol. The reason for this observation is unclear, but

may perhaps be due to technical specificities of the laboratories.

Polymyxins: Polymyxin B and colistin are two polymyxins that are used clinically and serve as the last resort for

the treatment of infections caused by MDR Gram-negative pathogens. Of these two drugs, colistin is more

widely used in food animals 226. There is complete cross-resistance between polymyxin B and colistin.

However, cross-resistance to and co-selection with other antibiotics has never been reported.

Data on resistance to these polymyxins in East, South and Southeast Asia is limited. Based on the available

data, resistance rates to polymyxin B and colistin are still low. A study in Cambodia reported the presence

(21%) of polymyxin resistant Salmonella (isolated from chicken carcasses) 120. Low resistance rates (0% to

<10%) were also observed in isolates from poultry in Malaysia 86 and pigs in South Korea 113. Low

resistance to colistin (% to <13%) was reported in broiler isolates in Iran 170 and in isolates from cattle, pigs,

poultry in Japan 16, 17, 66. Higher rates of resistance to colistin (24%) were found in a study of isolates from

retail chicken in Iran 67 and Thailand 10.

Quinolones: Fluoroquinolones are the drugs of choice for the treatment of invasive Salmonella infections in

humans. However, decreased susceptibility to ciprofloxacin and other fluoroquinolones in Salmonella has

increased worldwide, including in the Asia-Pacific Region. Resistance rates to ciprofloxacin and nalidixic acid in

bacterial populations may be expected to be similar. Recently, nalidixic acid resistance was suggested to be an

indicator for ciprofloxacin resistance 133. Based on the data in this review, however, this is apparently not

always the case. For example, none of the isolates from raw milk in Iran was resistant to ciprofloxacin, while

the same collection of isolates was highly resistant to nalidixic acid 201. Similar results were observed in the

duck isolates from Malaysia 4. Resistance to nalidixic acid and enrofloxacin was generally high and is most

likely due to the use of these drugs in food animals for a long time. In contrast, high resistance to ciprofloxacin

was observed in isolates from chicken in China and from chicken meat in Taiwan, Province of China 37, 128.

Overall, such variations in drug resistance support that several mechanisms are responsible for

fluoroquinolone resistance, leading to different responses to the drugs. Importantly, increasing resistance to

fluoroquinolones should be taken as a warning that the choice of drugs for the treatment of salmonellosis is

being diminished.

Sulfonamides: Sulfonamides are one of the most frequently used antimicrobials in food animal production and

the prevalence of sulfonamide resistance is usually high in enteric bacteria isolated from food animals 198.

Resistance to sulfonamides is usually associated with the acquisition of resistance genes (i.e. sul1, sul2 and

sul3) 14, 222. These sulfonamide-resistance genes are commonly associated with mobile genetic elements,

particularly class 1 integrons and can be co-selected by other antibiotics. These factors facilitate the wide

dissemination of sulfonamide resistance in bacteria 15.

A high prevalence of sulfonamide resistance was observed in Salmonella isolates from food animals and animal

products in many countries covered by this study. One hundred percent sulfonamide resistance was reported

in isolates from pigs in Thailand 180, Malaysia 40 and Japan 50; from broilers in Japan 184 and Iran

170. High sulfonamide resistance rates were also reported in isolates from broilers in Japan (92.5% to 100%)

45, 183 and pigs (100%) 180 and from a combination of poultry and swine isolates (68% to 70%) in Thailand

44, 111. A study in China found that isolates from broilers, ducks, geese and pigs exhibited resistance rates of

93.8%, 20.0%, 16.7% and 52.5%, respectively 163. The lower prevalence of resistance in duck and geese

isolates could be a reflection of a more limited use of sulfonamides in these poultry species.

14

A study in Viet Nam found that sulfonamide resistance rates in different Salmonella serovars from chicken

meat and pork were quite variable (from 28% to 86%) 204. In China, isolates from meat products (i.e. pork,

chicken, beef and mutton) showed elevated resistance to sulfonamides (73.3% to 89.5%) 223. All the isolates

from pork and chicken meat in Northeastern Thailand were resistant to sulfonamides 10, while pork isolates

from Northern Thailand exhibited high resistance rates (55%) as well 219. This finding stands in contrast to a

study of AMR in serovar Welterverden from humans, animals and food products, which found a very low

prevalence of sulfonamide resistance (5.1%) 1. The authors suggested that this could be the result of

ineffective acquisition of resistance of this particular serovar or due to low exposure of the reservoirs to

antibiotics. The same study also reported very low resistance rates to ampicillin, streptomycin, tetracycline,

sulphonamides and trimethoprim (2.2% each) in the Welterverden isolates from animals, food products and

farm environment in Australia, indicating low exposure to these drugs and the effectiveness of AMR control

policy in the country 1.

Sulfonamides are usually formulated in combination with trimethoprim. Susceptibility to the

sulfonamide/trimethoprim combinations was tested with most studies originating in China. Isolates from food

animals, including broilers, ducks, geese and pigs exhibited varied degrees of resistance (16.7% to 54.1%) to

the drug combination, prevalence being highest in the pig isolates 163. In a more recent study, isolates from

chicken, ducks and pigs, collected at farms, slaughterhouses and markets in China were tested and also found

to be resistant the sulfonamide/trimethoprim combinations (20% to 95%) 123. Similarly, high resistance

rates (13% to 41%) to the drug combination were observed in the pig isolates from Thailand 180.

Resistance to sulfonamide/trimethoprim combinations was also determined in isolates from food-animal

products. The isolates from chicken meat and pork exhibited high rates of resistance to the combinations

(>50%), while resistance rates in isolates from beef and mutton were lower (26.7% and 33.3%, respectively)

223. In Lao PDR, resistance was observed in isolates from a variety of retail meats (32%) 30 and in isolates

from pigs and buffalo (12%) 29. Interestingly, the prevalence of resistance to sulfonamide/trimethoprim of

isolates from chicken, beef and veal in Iran was comparatively low (9%) 139.

Tetracyclines: Tetracyclines are used for infection treatment in humans and animals. In pig and poultry

production, tetracyclines are also often added to animal feed at sub-therapeutic levels to act as growth

promoters 43. Although the mechanism of action for the latter is still unclear, tetracyclines are commonly

used for this purpose due to their low cost. Resistance to tetracyclines is mostly associated with tet genes on

plasmids, integrons and/or transposons, and most tetracycline-resistant bacteria harbor more than one

tetracycline resistance gene simultaneously 174.

Among drugs in this class, tetracycline is the most studied. High resistance to tetracycline (>50% to 100%) was

observed in Salmonella from poultry and pigs in China 81, 128, 163 and broilers in Iran 67. Where assessed

in the same study, tetracycline resistance rates were higher in pig isolates than in those from poultry (85 and

50% vs 75.4% and 46.9%) 123, 163. Additionally, high resistance to doxycycline was reported in serovars

Indiana and Enteritidis from poultry in China 128. In Japan, a study found that none of the isolates from

cattle, pigs, broilers and layers were resistant to tetracycline but exhibited resistance to oxytetracycline (14.3%

to 83.5%) 16. This finding could be the result of differences in antibiotic use between countries and sub-

regions.

It is notable that susceptibility to oxytetracycline in Salmonella was mostly tested in Japan, which suggests that

the choice of antibiotics tested depends on the types of antibiotics commonly used in a country. Some studies

in Japan showed that all broiler and pig isolates were resistant to oxytetracycline 50, 184, while a very high

oxytetracycline resistance rate (>80%) was found in broiler isolates in another report in Japan 183.

Trimethoprim: Trimethoprim is used in combination with sulfonamides to obtain a synergistic effect and cover

a wide bacterial spectrum particularly the pathogenic bacteria in the family Enterobacteriaceae. Resistance to

15

trimethoprim is usually encoded by genes located on conjugative plasmids that play a major role in the spread

of resistance 101, 191.

In Thailand, the prevalence of trimethroprim-resistance was similar in the Salmonella isolates from poultry,

pigs and raw pork (30%) 44, 111, 219. In contrast, in a multi-country study, resistance of 197 serovar

Welterverden isolates from humans, food animals, animal products and the environment in Thailand was very

low (1%), the reason for this being unclear [1]. High resistance rates to trimethoprim (>30%) were reported in

isolates from broilers and pigs in China 81, broilers in Iran 170, and broilers in Japan 103, 184. The

Salmonella isolates from pork and chicken in Viet Nam exhibited variable resistance rates (8.7% to 62.5%)

205.

Other AB classes: Enterobacteriacae resistant to carbapenems are a growing threat in human medicine, where

imipenem is a commonly used carbapenem. However, there is currently no requirement to include imipenem

in routine AMR surveillance. Up to date, the extent of imipenem resistance in bacteria from food animals is

largely unexplored and it has been suggested that carbapenem resistance should be monitored in Salmonella

64.

No imipenem-resistant Salmonella were isolated from pigs from processing plants in Japan 50, chicken meat

in Taiwan 37, and raw milk and retail chicken in Iran 67, 200, 201. Recently, a study in Viet Nam found no

meropenam-resistant Salmonella from chicken farms as well 208. Despite these negative results, resistance

to carbapenems should be consistently monitored.

AMR by serovar and host species: One study showed that different Salmonella serovars from poultry farms

and slaughterhouses in China exhibited quite different resistance patterns and rates 128. Serovar Indiana

isolates exhibited resistance to 16 antimicrobial agents, with high rates of resistance (>60% to 99%). In

contrast, serovar Enteritidis isolates from the same sources showed resistance to only three antimicrobials at

lower rates (33% to 73%). As AMR in Salmonella is usually not serovar-specific, the reason for the observed

difference is unclear. One explanation could be that the study included clones of serovar Indiana from the

same source. It is generally assumed that Salmonella isolates of the same serovar from the same flock display a

similar resistance pattern. Therefore, it is recommended to include no more than one isolate per Salmonella

serovar from the same flock in AST 64.

The high prevalence of AMR to antimicrobials commonly used in food animal production (e.g. streptomycin,

ampicillin, nalidixic acid, tetracyclines) may reflect the (non-prudent) use of these antimicrobial agents,

exerting increased selection pressure favoring mutations and the spread of resistance genes. Resistance to

streptomycin, ampicillin nalidixic acid, and tetracycline in Salmonella spp. isolated from reptiles in the region

was 14.7%, 6.9%, 5.8%, and 9.2% respectively 33, less than one third of the respective figures in isolates from

food animals. At 6.3%, resistance to chloramphenicol was also much lower in the Salmonella spp. isolated from

reptiles than in livestock isolates.

CAMPYLOBACTER Along with Salmonella, Campylobacter are the most common bacterial causes of human gastroenteritis

worldwide, of which two most important species in food animals are C. coli and C. jejuni. This corresponds to

the present review that C. coli and C. jejuni are the main species studied in the East, South and Southeast Asia,

while other species, e.g. C. lari, C. lanienae, C. upsaliensis and C. hyointestinalis are much less prevalent among

the isolates tested. Table 7 presents the number of studies available for analysis by Campylobacter species,

host from which the isolate was obtained, and country.

16

Table 7. Number of AMR studies in Campylobacter by species and origin of isolate

Campylobacter species

Host species Studies Countries

C. coli Poultry 12 CAM (1); CHI (1); IRA (3); JAP (4); MAL (2) VIE (1)

Pigs 7 CHI(1); JAP (5); THA (1)

Ruminants 5 IRA (2); JAP (3)

C. jejuni Poultry 17 CAM (1); CHI (3); IRA (4); JAP (5); MAL (2); PHI (1); VIE (1)

Pigs 2 JAP (2)

Ruminants 7 IRA (1); JAP (6)

‘C. spp.’ Poultry 4 IRA (3); TAI (1)

Ruminants 1 IRA (1)

Mixed 2 IRA (1); THA (1)

Other species Poultry 3 CAM (1); MAL (1); VIE (1)

Pigs 1 JAP (1)

Ruminants 1 JAP (1)

Despite being a common foodborne pathogen, recent (past five years) reports on AMR in Campylobacter were

publically available from a few countries only, namely Cambodia, China, Iran, Japan, Malaysia, Philippines,

Thailand, and Viet Nam. The low number of studies is possibly due technical difficulties in the isolation and

identification of Campylobacter. Given that Campylobacter is quite difficult to grow and identify, AST of

Campylobacter may not have been possible in all countries covered by this study. Also, phenotypic

characteristics determined by biochemical tests do not give an accurate result with respect to species, and

standardization and validation of laboratory methods to ascertain genotypic properties is needed.

In contrast to Salmonella, for Campylobacter only five antibiotics are recommended to be included in AMR

monitoring, which are ciprofloxacin, erythromycin, gentamicin, streptomycin, and tetracycline 64. Different

antibiotics were examined in different studies from either the same or different countries. The available data

may not accurately reflect the AMR patterns in a certain country and comparison of resistance patterns of the

isolates from different countries may be biased.

Only the studies from Iran included amoxicillin, colistin and gentamicin in the susceptibility test panel 52, 167,

169. Cephalothin susceptibility was tested in the studies from Cambodia and Iran 120, 135. Most studies

conducted in Japan included susceptibility testing for dihydrostreptomycin 88, 102. Different choice of

antibiotics in these studies could imply current use and significance of the particular antibiotics in clinical

settings in the countries.

The number of studies, countries, number of isolates tested, etc. are detailed in Annex 3 while an overview of

the prevalence of AMR in Campylobacter spp. to selected antimicrobial compounds is presented in Table 8.

17

Table 8. Proportion (%) of C. coli and C. jejuni isolates from poultry, pigs and ruminants in East, South and

Southeast Asia resistant to selected antimicrobial compounds (≥10 isolates tested)

C. coli C. jejuni

AB

Cla

ss

Co

mp

ou

nd

Po

ult

ry

Pig

s

Ru

min

ants

Po

ult

ry

Ru

min

ants

AMI

Amikacin 71

2

Dihydrostrep. 7 62 27 2 8

Gentamicin 1 24 0 8 0

Kanamycin 75 57

6 Streptomycin 7

0 9 0

CEP Cephalothin 96

97

MAC Erythromycin 10 44 10 7 0

Tylosin

48

0 0

PEN Amoxicillin 11

12 11 0

Ampicillin 8 20 6 18 6

PHE Chloramphenicol 1 15 0 8 10

Florfenicol

0

79 POL Colistin 33

9 28

QUI

Ciprofloxacin 50 89 42 62 44

Enrofloxacin 27 49 40 30 29

Nalidixic acid 50 36 61 51 19

TET Oxytetracycline 46 88 100 37 48

Tetracycline 67 88 19 80 72

TRI Trim-Sulfa 96

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

Aminoglycosides: Campylobacter spp. are naturally susceptible to many antimicrobial agents, including

aminoglycosides. Currently, aminoglycosides are the drugs of choice for treatment of Campylobacter infection

and gentamicin is frequently used for empirical treatment. Resistance to gentamicin is usually rare. This is in

agreement with most studies in this review 52, 167, 169, 227. By contrast, most C. jejuni isolates (51.3%)

from live and retail chicken in Iran exhibited resistance to gentamicin 135. In addition, Campylobacter

isolates from broilers and ducks in China were resistant to gentamicin at the same rate (27.2%)38. This

suggests that gentamicin is extensively used in poultry production in these two countries.

The high resistance rate to amikacin in C. coli isolated from broilers in China 166 is interesting. Amikacin is a

semisynthetic derivative of kanamycin. Resistance to this antibiotic is of public health concern since it is usually

reserved for treatment of aminoglycoside-resistant strains. Aminoglycosides such as neomycin, kanamycin and

amikacin are commonly used for disease treatment in conventional broiler and swine production in China

166. Therefore, the widespread resistance to amikacin and other aminoglycosides in C. coli reported from

China is likely to be the result of selection pressure created by antibiotic use.

Susceptibility to dihydrostreptomycin was tested in many studies, most likely due to its common use in food

animals. C. jejuni from poultry showed very low resistance rates to the drug (<10%) 102, 104. A study from

Japan, which assessed AMR in C. coli and C. jejuni from poultry reported similar low prevalences (<10%) in both

species 104. By contrast, a study in isolates from poultry in China found that dihydrostreptomycin resistance

18

was much higher in C. coli than in C. jejuni 166. Similar findings were obtained in C. coli and C. jejuni isolates

from broilers in Japan 90. The reason for these differences in antimicrobial susceptibility is unclear as both

Campylobacter species would have been exposed to similar antibiotic pressure. C. coli from pigs in Japan

exhibited high resistance rates (>50%) to dihydrostreptomycin 88, 102, 158. Generally, dihydrostreptomycin

resistance in C. coli isolates from pigs was higher than that of the C. jejuni isolates from poultry. The common

use of a penicillin/dihydrostreptomycin combination product in cattle and pigs could explain the high

prevalence of resistance observed.

Cephalosporins: Campylobacter spp. exhibit high intrinsic resistance to most cephalosporins due to the

synergy between low permeability of the cell membrane and overexpression the CmeABC multidrug efflux

system 85, 117. It is well known that most isolates are highly resistant to Cephalothin, a first generation

cephalosporin 8. This is consistent with the findings of high resistance to Cephalothin (>90%) in isolates from

poultry in Cambodia 120 and Philippines 25, and from retail chicken in Iran 135.

Macrolides: Macrolides, in particular erythromycin, are among the most active agents against Campylobacter

spp. The newer macrolides, including clarithromycin and zithromycin, have excellent in vitro activity against

the bacteria 203. When considering erythromycin resistance in the isolates from Cambodia, high resistance

to erythromycin was observed in C. jejuni while C. coli isolates were all susceptible to the drug 120. The

studies from Viet Nam and Iran showed that C. coli and C. jejuni from the same source and the same period

exhibited comparable erythromycin resistance rates 80, 135. In contrast, in the study from Japan, C. coli

exhibited a higher percentage of erythromycin resistance than C. jejuni when the isolates from all sources in

this study were combined 102.

Penicillins: It is well documented that C. jejuni and C. coli generally exhibit intrinsic-resistance to penicillin G

and narrow spectrum cephalosporins due to poor binding of the drugs to penicillin-binding protein in these

bacteria 117, 199. Among the drugs in the penicillin class, susceptibility to amoxicillin and ampicillin are most

commonly studied. A high prevalence of amoxicillin-resistant Campylobacter spp. (84.8%) was observed in

ducks in Taiwan Province of China 209. The studies of the isolates from poultry and chicken carcasses in Iran

showed low resistance to amoxicillin (0% to 7.9%), while that to ampicillin was slightly higher (7.4% to 25%)

168, 169, 227. None of the isolates from goats and goat meat exhibited resistance to these two drugs 167.

The latter collection of isolates was resistant to ampicillin 167. In Japan, C. jejuni from poultry varied in

ampicillin resistance rates (1.5% to 30%) 89, 104, while the same species from cattle showed low resistance

rates (7.3%)89. Interestingly, low resistance rates to ampicillin (<10%) were observed among C. coli from pigs

in Japan 88, 158.

Phenicols: Campylobacter spp. are moderately susceptible to chloramphenicol, the use of which is prohibited

in food animals due to its toxicity. However, it remains a useful alternative for treatment of human

Campylobacter infections in some countries due to its effectiveness and low cost. Florfenicol is the newly

developed fluorinated derivative of chloramphenicol and has been used as an alternative agent for the control

of Campylobacter infections.

An interesting finding is the high resistance rate to florfenicol (79.2%) in C. jejuni from broilers in China. The

authors suggested that the high resistance was likely due to the long-term use of florfenicol as a growth

promoter for broilers in this country 38. However, the C. coli isolates obtained in the same study were

susceptible to florfenicol (1.9% resistance rate) despite the fact that they must also have been exposed to the

same selection pressure. Thus, exposure to florfenicol in poultry production may not totally explain the high

resistance rate observed.

Polymyxins: Polymyxin B is a bactericidal agent for Gram-negative bacteria and is used as antibiotic

supplement in Campylobacter selective agar to eliminate competing flora, resulting in increased selectivity of

media 42. Campylobacter spp. vary in their resistance to polymyxins and C. coli can be highly susceptible

19

42. Therefore, polymixin is not used at high concentrations in selective media, particularly those containing a

combination of cefoperazone and activated charcoal (e.g. mCCDA) 42.

AMR studies to colistin and polymyxin B in Campylobacter spp are rather limited. Most studies were conducted

in Iran, where it was shown that the isolates from poultry and retail poultry meat exhibited variable levels of

resistance to colistin (9.0% to 33.3%) 52. In the Philippines, C. jejuni from poultry was shown to exhibit high

colistin-resistance of 91.7% 25. However, the number of isolates in the latter study was quite low (n=12).

Only one study from Taiwan Province of China assessed resistance to colistin (22.8%) and polymyxin B (89.1%)

in duck isolates 209.

Quinolones: Fluoroquinolones are the drug class of choice for campylobacteriosis and are frequently used in

the empirical treatment of patients with gastrointestinal symptoms. Therefore, emerging resistance to drugs in

this class is of a particular concern. The present review highlights the widespread presence of fluoroquinolone-

resistant Campylobacter in livestock and livestock products in the study region, namely Cambodia 120, China

38, Iran 227 168, Japan 102 and Viet Nam 80. It is noted that a study in China showed remarkable

resistance rates to ciprofloxacin (99%), nalidixic acid (99%) and enrofloxacin (98%) 38. This could be because

fluoroquinolones are widely used to control and prevent diseases in poultry in China 38. In poultry,

fluoroquinolone-resistance did not have an effect on the fitness or growth of fluoroquinolone-resistant

Campylobacter in the absence of antibiotics 38. This could explain the substantial resistance rates observed.

As in Salmonella, the relation between resistance rates to ciprofloxacin and nalidixic acid in Campylobacter

varied. Resistance rates to both drugs in Campylobacter were similar in some studies, e.g. in chicken from

Viet Nam 80, in swine from Thailand 65, and in chicken from Iran 202. The chicken isolates from

Cambodia exhibited much higher resistance to nalidixic acid than to ciprofloxacin and C. jejuni were more

resistant to both drugs than C. coli 120. This is similar to the report on Campylobacter isolates from chicken

and beef in Iran 52. In contrast, the recent study in the isolates from poultry and poultry products in Iran

showed the opposite relation 227.

Tetracyclines: Resistance to tetracycline and oxytetracycline was predominant in most studies. This is not

surprising since the antibiotics have a long history of being used in livestock production worldwide. Resistance

to drugs of the tetracycline class is mediated by tet genes that are commonly located on horizontally-

transferred plasmids 26. Therefore, such antibiotic use creates selective pressure for maintaining and

spreading of the resistance determinants.

Trimethoprim: Susceptibility of C. jejuni to trimethoprim and trimethoprim-sulfa was tested in two studies,

one from Malaysia (94 isolates from ducks) 4 and one from the Philippines (12 isolates from chicken) 25.

The prevalence of AMR was 96% and 100% respectively. These high resistance rates to trimethroprim are likely

to be intrinsic.

AMR by Campylobacter and host species: In general, C. coli appear to be more resistant than C. jejuni,

particularly to ciprofloxacin, erythromycin and phenicols 165. However, the comparison of resistance rates is

based on quite different numbers of Campylobacter isolates even in the same study.

ESCHERICHIA COLI The effects of antimicrobial pattern used and trends in the prevalence of resistance in an animal population

and a country can be more accurately investigated in indicator bacteria, such as E. coli, than in food-borne

pathogens 62. Therefore, it is recommended to include commensal bacteria in the active monitoring

program of AMR. Table 9 presents the number of AMR studies in E. coli available for analysis by host from

which the isolate was obtained and country.

20

Table 9. Number of AMR studies in E. coli by origin of isolate

Host species Studies Countries

Poultry 26 BGD (4); CHI (8); IND (1); IRA (1); JAP (4); NEP (1); ROK (1); SRI (1); THA (3); VIE (2)

Pigs 19 CHI (6); IND (1); JAP (5); MAL (1); ROK (3); THA (2); VIE (1)

Ruminants 20 BGD (2); CHI (3); IND (3); IRA (1); JAP (6); PAK (1); ROK (2); THA (1); VIE (1)

Mixed 6 CHI (3); JAP (1); MAL (1); ROK (1)

The number of studies, countries, number of isolates tested, etc. are detailed in Annex 4 while an overview of

the prevalence of AMR in E. coli to selected antimicrobial compounds is presented in Table 10.

Table 10. Proportion (%) of E. coli isolates from poultry, pigs and ruminants in East, South and Southeast Asia

resistant to selected antimicrobial compounds

AB Class Compound Poultry Pigs Ruminants

AMI

Amikacin 23 7 1

Dihydrostrep. 41 51 32

Gentamicin 21 24 7

Kanamycin 29 36 9

Streptomycin 34 66 27

CEP Cefazolin 11 5 2

Cephalothin 34 18 4

MAC Erythromycin 86 71 57

Tylosin 75 0

PEN Amoxicillin 59 57 81

Ampicillin 67 57 26

PHE Chloramphenicol 41 47 10

Florfenicol 27 36 17

POL Colistin 1 5 3

QUI

Ciprofloxacin 51 31 15

Enrofloxacin 37 21 2

Nalidixic acid 53 36 13

SUL Sulfamethoxazole 40 60 19

TET Oxytetracycline 61 70 36

Tetracycline 84 87 38

TRI Trimethoprim 24 26 6

Trim-Sulfa/Cotrim 75 61 3

OTH

Imipenem 0

Meropenam 0

Vancomycin 0 0 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

AMR in E. coli has been widely studied in East, South and Southeast Asia. Resistance to amoxicillin, ampicillin,

oxytetracycline, and tetracycline was predominant in the E. coli isolates in all studies included in this review.

This is most likely a result of long-term use of these antibiotics in livestock production.

21

Aminoglycosides: Amikacin is one of the most widely used antibiotics against many Gram-negative bacterial

pathogens. However, amikacin-resistant E. coli has been increasingly reported. All isolates from diseased

animals (pigs, chickens, ducks, geese, pigeons, partridges and cows) in China 54 and poultry 148 in Iran

were resistant to amikacin. Another study from China reported the presence of amikacin-resistant E. coli

(31.2%) in ducks, geese and pigeons 122. This may be due to increasing use of the drug in poultry production

in China.

Apramycin has also been used in food animal production for a long time. Apramycin resistant E. coli have been

isolated from humans even though this antibiotic has not been used in human medicine 41. Cross-resistance

between apramycin and other aminoglycosides, particularly gentamicin has been demonstrated 107.

Surprisingly, there was only one report of apramycin resistance in isolates from food animals (i.e. cattle, pigs,

chickens, ducks, geese, pigeons, and patridges) from China 54. Interestingly, the isolates also exhibited high

resistance to amikacin, gentamicin, neomycin and streptomycin. The history of drug use in the animals is

unclear, but such high level of panaminoglycoside resistance is probably due to a frequent use of these drugs

in food animal production.

Gentamicin is in principle effective against Gram-negative bacteria. However, E. coli resistant to gentamicin

has increasingly emerged. High gentamicin resistance (>50%) was observed in isolates from poultry in China

96, India 185, Viet Nam 208 and from pigs in China 108, 122. Isolates from cattle usually showed lower

levels of gentamicin resistance (0% to 26.4%) (China 95, 96, India 134, Japan 19, 112, 182, and South

Korea 211).

Tobramycin is commonly used for empirical and definitive treatment of bacterial infection, including E. coli, in

humans. Its use in food animals is not common. Most isolates from cattle, poultry and pigs showed low

resistance rates to tobramycin (0% to 15%) 108, 211. Only one study from China reported high tobramycin

resistance (47.8%) in pig isolates 108.

Observed resistance rates to other aminoglycosides, i.e. dihydrostreptomycin, kanamycin, neomycin,

streptomycin and spectinomycin were quite variable. These antibiotics have been commonly used in food

animals and the finding of variable resistance between countries should not be considered surprising.

Cephalosporins: Cephalosporins are critically important antibiotics for treatment of human bacterial

infections. In comparison to other antimicrobials, the resistance to cephalosporins reported in most studies

was low (0% to 15%). However, moderate-high resistance rates to certain cephalosporins were observed.

Isolates from ducks, geese and pigeons in China were resistant to cefazolin (38%) 122, poultry isolates from

Viet Nam were moderately resistant to cefotaxime (26%) 208 while the prevalence of resistance to the latter

in isolates from cow dung in India reached 72% 179.

All duck isolates from Nepal were resistant to cephalexin 190. High resistance rates to cephalothin were

observed in pig isolates from Japan (54%)182 and in poultry isolates from Thailand (73%) 147. Lower

resistance rates were found in poultry and pig isolates from China (32% to 48.5%) 51, 228. These differences

are most likely to be due to use of different types of cephalosporins in different countries.

Macrolides: Erythromycin is a clinically important antibiotic with only modest activity against Gram-negative

bacteria 164 but is commonly used in food animals. Erythromycin resistance rates varied from 1% to 100%.

For this review, two studies of erythromycin resistance were available from in Thailand. One found that all

tested broiler isolates were resistant to the compound 147. The other was performed in avian pathogenic

E. coli, of which 80% exhibited erythromycin resistance 34. High erythromycin resistance rates (>60%) were

reported in poultry isolates from Bangladesh 6, Iran 148 and India 185. The latter study also reported high

prevalence erythromycin resistance in E. coli isolates from pigs, goat meat and milk 185.

22

No report of azithromycin resistance in isolates from healthy animals was found. Only one study in Bangladesh

found that 9.1% of the E. coli isolates from calves with diarrhea (n=114) were resistant to azithromycin 2.

Erythromycin resistance in the same collection of isolates reached 43.2%.

Tylosin is a common antibiotic feed additive in pig and poultry production. It has a limited activity against

Gram-negative bacteria and E. coli are intrinsically tylosin-resistant due to the nature of their cell wall and

enzymatic activities 7. All broiler isolates in a study from Japan were resistant to tylosin 112. As cross-

resistance among macrolide antibiotics has been well documented, the tylosin-resistance may reflect the use

of tylosin or other macrolides (e.g. tiamulin, erythromycin) in poultry production in Japan. Concurrently, all of

the isolates from diarrheic piglets were resistant to the drug 118. Similar findings were reported for broiler

isolates in Bangladesh 6.

Penicillins: As penicillins inhibit peptidoglycan synthesis in the cell wall, most Gram-negative bacteria are

generally resistant to this class of drugs, in particular to penicillin G 178. However, some penicillins, e.g. and

ampicillin and amoxicillin with clavulanate, are active against both Gram-positive and Gram-negative bacteria

including E. coli. Resistance to penicillins is common due to the wide distribution of β-lactamase encoding

genes 140.

Among drugs in the penicillin class, amoxicillin and ampicillin are the best known in veterinary medicine.

Susceptibility to these two drugs was most commonly investigated and resistance rates varied. High

prevalences of amoxicillin resistance (>50%) were observed in poultry isolates from China 108, Thailand 34,

and Viet Nam 213, in ruminant-associated isolates from Bangladesh [2] and India 185, and in pig isolates

from China 108 and India 185.

High frequencies of ampicillin resistance (>50%) were reported in isolates from pigs in China 95, 108, 122,

228 and South Korea 211, pork in India 185, and in poultry isolates from Bangladesh [2], China 51, 95,

108, 118, Nepal 190 and Viet Nam 208. Ampicillin resistance in isolates from cattle ranged from 3% to

100%. Resistance of all isolates was found in a study from Bangladesh [2] and one from China 95. The latter

isolates were additionally resistant to amoxicillin/clavulanic acid, although at a lower rate (12.1%). The lowest

ampicillin resistance rate was observed in isolates from Japan that also exhibited very limited resistance to

amoxicillin/clavulanic acid (0.1%) 182.

Piperacillin is an extended spectrum β-Lactamase sensitive penicillin that is usually used in combination with a

β-lactamase inhibitor. The antibiotic is not orally absorbed. Therefore, it is given intravenously or

intramuscularly for infection treatment. Reports of piperacillin resistance are limited. A study from South

Korea found moderate (7.4% to 26.4%) piperacillin resistance rates in isolates from cattle and poultry, while

isolates from pigs exhibited higher piperacillin resistance (61%) and were additionally resistant to ampicillin

and carbenicillin 211.

Due to existing cross-resistance, resistance rates to amoxicillin and ampicillin are usually expected to be

similar. This is in agreement with the findings of a study in Viet Nam, reporting equal prevalence of amoxicillin

and ampicillin resistance in isolates from pigs, poultry and beef (the number of the isolates tested was low,

n20) 213, 214. Similar observations were obtained from Bangladesh where all cattle isolates were resistant

to amoxicillin and ampicillin [2]. By contrast, a substantial difference between amoxicillin (53.7%) and

ampicillin (99.2%) resistance was observed in a study of poultry isolates in China 108.

Phenicols: Resistance to chloramphenicol was found in most studies. However, this finding should not lead to

the conclusion that the drug is still used in food animals in these countries as it could also be the result of co-

selection of chloramphenicol resistance genes and/or cross-resistance mediated by other antibiotics. Further

studies are required to explore the reason for such high resistance in each country. A retrospective study in

China showed that florfenicol resistance in bacteria from food animals increased from 0% in 1970 to 15% in

2000 193. Even though no further data was available, the increasing level suggests an increasing use of the

drug, or one that leads to phenicol resistance through co-selection or cross-resistance, in livestock in the

23

China. The authors suggest that the increase in florfenicol resistance correlated with the use of antimicrobial

growth promoters and preventative antimicrobial usage in food animals.

Quinolones: The proportion of ciprofloxacin-resistant E. coli from pigs and poultry and derived products was

high in most countries, up to 60% to 100% in some countries, e.g. India, China, Nepal, and Iran 54, 108, 148,

185. Relatively low frequencies of ciprofloxacin resistance were observed in ruminant isolates from China,

Japan, India, South Korea and Viet Nam 95, 134, 182, 211 213. This finding probably reflects limited use of

this drug in ruminants.

The presence of plasmid-mediated transferable resistance to ciprofloxacin has been reported in clinical

isolates from hospitalized patients 216. It has recently been also shown that a multiple resistance plasmid,

conferring resistance to several antibiotics of different classes, could confer reduced susceptibility to

quinolones 216. This genetic link may become a significant cause of widespread quinolone resistance in

bacterial pathogens.

Other AB classes: Some studies included ‘rare’ antibiotics, such as bicozamycin or piperacillin/tazobactam in

their test panel. Bicozamycin or bicyclomycin is an antibacterial effective against Gram-negative bacteria,

mainly E. coli and Salmonella, which has recently been developed in Japan as feed additive for pig and chicken

feed. Low (0% to 3.1%) resistance rates to bicozamycin were observed in isolates from poultry, pigs and cattle

in Japan 19, 112, 115. Very limited resistance rates to piperacillin/tazobactam (≤1%) were found in poultry

and cattle isolates from China 95. Resistance to vancomycin was only tested in one study from Japan and all

isolates from cattle pigs and poultry were found susceptible 115.

ENTEROCOCCUS In comparison to the other three bacterial species covered by this review, the number of studies on AMR

prevalence in Enterococcus spp. is low and AST is limited to the most common antibiotics. None of the studies

assessed susceptibility to linezolid, teicoplanin, tigecycline, or daptomycin, the antibiotics additionally

suggested for AMR monitoring by EFSA 64. Tigecycline and daptomycin are not used in animals but are

considered of critical importance in human medicine. Monitoring for resistance to both antibiotics in bacteria

from animals is necessary for the assessment of possible public health risks. Due to the persistence of low

prevalence of VRE after avoparcin use was discontinued, resistance testing to teicoplanin is suggested to allow

determination of the presumptive genotype of glycopeptide resistant enterococci (van genes) which otherwise

has to be done using molecular techniques 61, 64.

The number of studies available for different Enterococcus species, broken down by host from which the

isolates were obtained and the country in which the study was carried out are presented in Table 11.

Table 11. Number of AMR studies in Enterococcus by species and origin of isolate

Enterococcus species Host species Studies Countries

E. faecalis Poultry 3 JAP (2); TAI (1)

Pigs 2 JAP (2)

Ruminants 2 JAP (2)

E. faecium Poultry 3 JAP (2); TAI (1)

Pigs 2 JAP (2)

Ruminants 2 JAP (2)

‘E. spp.’ Poultry 2 CHI (1); ROK (1)

Pigs 2 CHI (1); ROK (1)

Ruminants 1 ROK (1)

24

The number of studies, countries, number of isolates tested, etc. for different Enterococcus species are

detailed in Annex 5 while an overview of the prevalence of AMR in Enterococci to selected antimicrobial

compounds is presented in Table 12.

Table 12. Proportion (%) of E. faecalis and E. faecium isolates from poultry, pigs and ruminants in East Asia

resistant to selected antimicrobial compounds

E. faecalis E. faecium

AB

Cla

ss

Co

mp

ou

nd

Po

ult

ry

Pig

s

Ru

min

ants

Po

ult

ry

Pig

s

Ru

min

ants

AMI

Dihydrostrep. 38 50 46 25 38 11

Gentamicin 30 18 16 10 0 0

Kanamycin 27 37 27

Streptomycin 74

59

MAC Erythromycin 75 54 21 70 26 5

Tylosin 4 68 52

57 26

PEN Ampicillin 0

8 0 1

Penicillin 1

71

PHE Chloramph. 47 32 11 36

QUI Ciprofloxacin 36

54

Enrofloxacin 2 1 0

TET Oxytetracycline 73 79 45 61 64 29

Tetracycline 97

98

OTH Quinupristin

79

Vancomycin 0

0 0 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

In general, E. faecalis infection is more common in humans than infection with E. faecium, mostly due to its

ability to produce haemolysin and gelatinase 74. Resistance to antibiotics tends to be more prevalent in

E. faecium than in E. faecalis, the underlying reason still being unclear 31.

Aminoglycosides: High rates of streptomycin resistance were observed in Enterococcus isolates from China,

South Korea and Taiwan 115, 119, 125. Streptomycin is commonly used in synergistic combination with

penicillin for Enterococcus infection therapy in humans. The bacteria become resistant to streptomycin by

acquiring aminoglycoside-inactivating enzyme encoding genes or by mutations, which reduce the synergism

between aminoglycosides and cell wall active agents (i.e. penicillin). Therefore, the gentamicin-penicillin

combination has been suggested as an alternative for serious infections. However, an elevated prevalence of

gentamicin resistance is increasingly reported in isolates from pigs in China 125, broilers in Taiwan 119 and

broilers in South Korea 87. A study conducted on isolates from broilers in Taiwan found resistance rates to

gentamicin in E. faecium in the range of 6% to 20% while in E. faecalis resistance to gentamicin ranged from

32% to 55% 119. Conversely, in the same collection of isolates, resistance to penicillin ranged from 62% to

81% in E. faecium and from 0% to 1% in E. faecalis. In addition, high (>75%) amikacin resistance was observed

in chicken and pig isolates in China 126. This is not surprising because amikacin is relatively inactive against

Enterococcus due to its limited uptake through the cell membrane.

25

Macrolides: Macrolides, particularly erythromycin, are the drugs of choice for treatment of Campylobacter

infection. In Taiwan, very high resistance rates to erythromycin (>80%) were observed in E. faecalis from

broilers, assumed to be a result of continued use of the drug in food animal production 119. In a Japanese

study, both E. faecium and E. faecalis from pigs and poultry exhibited higher resistance rates to erythromycin

and tylosin than those from cattle 116. This could be due to different routes of drug application in pigs and

poultry (in feed and water) and cattle (injection) resulting in different levels of exposure of Enterococcus spp. A

high prevalence of erythromycin resistance (>70%) was also found in isolates from pigs and chicken in China

[125].

Penicillins: Enterococcus species are naturally resistant to β-lactams. This intrinsic resistance is mediated by

overproduction of low-affinity penicillin-binding proteins (PBPs) that are able to substitute the functions of

other PBPs and allow some cell-wall components to continue to be synthesized. Exposure to penicillins inhibits

growth but does not kill the bacteria. Only two studies of penicillin resistance were found and the reported

resistance rates were variable. A study in Taiwan found that resistance to penicillin was more common in

E. faecium from broilers than in E. faecalis from the same source 119. The other study, conducted in China,

reported that Enterococcus spp. from pigs exhibited higher resistance rates than those from poultry 126.

Resistance to ampicillin was low (0% to 16%) in all studies including in the isolates from poultry in Taiwan

119, pigs and poultry in China 126, and pigs, cattle and poultry in Japan 116.

Phenicols: Enterococcus isolates generally exhibit varied resistance to chloramphenicol. The resistance is most

commonly mediated by the enzyme chloramphenicol acetyltransferase, which inactivates the drug molecule

but does not confer cross-resistance to florfenicol 217. Only one study in China included susceptibility testing

for both chloramphenicol and florfenicol and found similar resistance rates to both drugs in Enterococcus spp.

from poultry (27.5% and 26.9%) and pigs (51.7% and 50.0%) 126. In Taiwan, the prevalence of

chloramphenicol resistance in E. faecalis from broilers was (63% to 77%) slightly higher than that in E. faecium

(27% to 43%) from the same source 119. In Japan, E. faecalis isolates from poultry exhibited lower resistance

rates (10%) than isolates from pigs (40%) 116.

Quinolones: Fluoroquinolones are the antimicrobial agents commonly used to treat severe

campylobacteriosis. Therefore, increasing-ciprofloxacin resistance in bacteria originating from food animals is

of particular concern. E. faecalis and E. faecium isolates from broilers in Taiwan exhibited ciprofloxacin

resistance that ranged from 28% to 68% 119. Resistance to enrofloxacin was reported in Enterococcus spp.

isolates from poultry (30.7%) and pigs (26.3%) in China 126.

Tetracyclines: Tetracyclines are extensively used in food animals and Enterococci have a remarkable capacity

to acquire resistance to tetracyclines. Therefore, tetracycline resistance is common in the bacteria 207. Very

high resistance rates to tetracyclines (>90%) were observed in isolates originating from pigs and poultry in

China 126 and Taiwan (Province of China) 119, no significant difference in tetracycline resistance rate being

found between E. faecalis and E. faecium. Susceptibility to oxytetracycline was investigated among isolates

from pigs, poultry and cattle in Japan 126. The prevalence of oxytetracycline resistance in isolates from pigs

and poultry (72.7% to 92.8%) was slightly higher than that in cattle (26.7% to 36.8%).

Other AB classes: Quinupristin-dalfopristin is used for treatment of Enterococcus infections. In Taiwan,

resistance to this drug combination was high (>60%) in E. faecium from broilers but very rare in E. faecalis

119. Such high resistance could possibly explained by the use of an analogue of quinupristin-dalfopristin,

virginiamycin, in poultry production. Assessments of vancomycin susceptibility are very limited. Only three

studies were available and no vancomycin-resistant Enterococci were found 115, 116, 125.

26

AMU IN LIVESTOCK AND NATIONAL AMR SURVEILLANCE AND CONTROL PROGRAMS

This section attempts to provide a brief overview of the national policies and regulations governing the use of

antimicrobials in food animal production, antimicrobial use in animal production, and public systems in place

for the monitoring of antimicrobial resistance in bacteria derived from food animals drawing on information

available in the public domain. Table 13 provides an overview of the availability of information on various

aspects of AMU and AMR monitoring in East, South and Southeast Asia by country. Overall, published

information is rather scant and a large proportion of the information presented in the following stems from

APHCA 2012 68 and APHCA 2013 69.

Table 13. Availability of information regarding AMU in livestock and AMR monitoring in livestock and livestock

products by country in East, South and Southeast Asia

Policy, guidelines & regulation of AMU

Extent of AMU in food animals

AMR monitoring / control program

East Asia China + + + Japan + + + Korea, DPR - - - Korea, Rep. + - - Mongolia + - +

South Asia Afghanistan + - - Bangladesh + + + Bhutan + + + India + - + Iran + - + Maldives + - + Nepal + - + Pakistan + - - Sri Lanka + + +

Southeast Asia Cambodia + - + Indonesia + - + Lao PDR + - + Malaysia + - + Myanmar + + + Philippines + + + Thailand + + + Timor-Leste - - - Viet Nam + + +

-, No published information available; +, Published data available (the symbols only represent the availability of information in public domain for this review. They DO NOT indicate absence or existence and effectiveness of national regulations or programs

EAST ASIA

CHINA, PR

Based on the published literature, there are currently no regulations, guidelines and policies on AMU in

livestock 108, 124 and a wide variety of antibiotics are used in food animal production 122, 224. There is no

established national monitoring system for the production, distribution, sale, and use of veterinary drugs and

there is little published information on the extent of antimicrobial use in livestock production. However it has

27

been stated that China is the ‘largest antibiotics producer and consumer in the world’ and for the year 2007

domestic production of antibiotics has been estimated at 210 million kg, of which 46 percent were used in the

livestock sector 9.

Currently, surveillance systems operate only for drug residues in aquatic products and for feed quality and

safety 142. In some parts of China there is a system for the “Surveillance and Epidemiology of Antimicrobial

Resistance in Bacteria of Animal Origin (ARBAO)” 186.

JAPAN

Antibiotics for therapeutic use in food animals are regulated by the Pharmaceutical Affairs Law and can be

used under veterinary prescription only. Antibiotic-growth promoters are approved as feed additives and

regulated by the Ministry of Agriculture, Forestry and Fisheries (MAFF) through the Food Safety Law (Law No.

35/1953) 131, 197.

Sale amounts and volumes of antibiotics, synthetic antibacterials and other medicines (e.g. anthelmintics and

antiprotozoals) in Japan are recorded and reported annually by the National Veterinary Assay Laboratory

Ministry of Agriculture, Forestry and Fisheries, of which the latest report covers 2011 132. However, data on

the amount of antimicrobials used in livestock production was not found.

In Japan, national AMR surveillance is carried out through the Japanese Veterinary Antimicrobial Resistance

Monitoring System (JVARM). The system was established in 1999 to evaluate isolation procedures and to

monitor AMR in bacteria isolated from food-producing animals 132. Details of the JVARM program are

included in the OIE International Standards on Antimicrobial Resistance 2003 155

KOREA, DEMOCRATIC PEOPLE’S REPUBLIC

The veterinary and anti-epizootic law, the veterinary medicinal agents management law and the animal

quarantine law provide the legal framework and arrangements on the use of antimicrobials in animal

production. Antimicrobials used in food producing animals in the country include oxytetracycline, tetracycline,

penicillin, streptomycin, tylosin, flurazolidone, norfloxacin and sulfadimedoxine, reaching a total of 16.5 MTs in

2011. Antimicrobials are used as additives in feed.

Regulatory monitoring systems and programs for antimicrobial use, antimicrobial residues and antimicrobial

resistance have not yet been implemented 83.

KOREA, REPUBLIC

Veterinarians are permitted to treat sick animals with antibiotics 76 but mixing antibiotics with animal feed

has been totally banned since July 2011. Published AMU data is very limited as is information on AMR

surveillance and AMU data collection systems 109.

MONGOLIA

The Ministry of Health regulates all drugs in Mongolia through the Drug Act, 1998 144. The purposes of the

Act are to regulate manufacturing, import, storage, retail, distribution, and utilization of drugs for humans and

livestock. The Drug Act was amended in 2002. Data on AMU is not available and there is no national AMR

surveillance program.

SOUTH ASIA

AFGHANISTAN

No published literature on policies, guidelines and regulations on AMU and AMR monitoring in livestock is

available 82 and no information on AMU and AMR in food animal production could be found.

28

BANGLADESH

Currently, no registration is required for feed additives such as antibiotics, toxin binders, vitamin-mineral

premixes, or animal protein. National regulations governing AMU and AMR do not exist 189 and antibiotics,

hormones, and sedatives are readily sold across the counter without prescription 143. The use of antibiotics

in animal feed is considered common in the country, especially in commercial poultry production.

BHUTAN

The broad legal framework on antimicrobial use and resistance is provided by the acts and regulations related

to drugs 171, 172 and food safety 22, 23. Under the broad framework of Bhutan Medicines Rules and

Regulations, the National Center for Animal Health has developed an approved list of antimicrobials for use in

food animals 149.

A high level committee meeting on Antimicrobial Resistance and Antibiotic control in Bhutan was conducted in

2013. The committee, involving all the relevant stakeholders, developed a consensus that the existing Drug

Technical Advisory Committee (DTAC), which acts as an advisory body to the Bhutan Medicine Board, will

shoulder the additional responsibilities of National Steering Committee on Antimicrobial Resistance. The DTAC

will include the role of the National steering committee on AMR as one of their mandates. The National

Steering Committee on AMR will take up the responsibilities of developing a national action plan for AMR

including public awareness and education, information material development and campaigns to improve

awareness on AMR.

The Drugs, Vaccines and Equipment Unit of the National Centre for Animal Health have revised the essential

veterinary drugs for use in the country and have produced a National Drug Formulary 2013. This formulary

includes necessary guidelines for the users. The unit is also responsible to monitor and evaluate the usage of

veterinary drugs in the country including quality control and adverse drug reactions. Further, the unit is

drafting standard treatment guidelines for the users 49.

INDIA

There are currently no national guidelines for AMU in food animals nor government regulations to control

AMR 79. The Export Inspection Council of India prohibits the use of certain antibiotics in the feed and

medication of poultry. However, the regulation is applied to export eggs only. Common antibiotics e.g.

tetracycline, oxytetracycline, trimethoprim and oxolinic acid may be used in feed but with the specification

that they “shall not exceed the prescribed tolerance limit”.

Up to date, little has been published about the use of antibiotics in animal production in India. Many drugs

commonly used in human medicine are also used in farm animals 78. There is currently no national program

to monitor AMR in bacteria from food animals in India.

The Directorate General of Health Services, Ministry of Health & Family Welfare has announced a national

policy for containment of antimicrobial resistance 146 that outlines approaches for both human and animal

AMU, infection control and prevention strategies, education and training on administration of antimicrobials,

national AMR surveillance systems, and enforcement of regulations. Rational use of antibiotics in food animals

and banning non-therapeutic usage in animals and farms are also included in the Terms of Reference of the

task force committee for national antimicrobial resistance monitoring 127, 146.

IRAN, ISLAMIC REPUBLIC

The legal framework and associated institutional arrangements regulating antimicrobial usage are based on

governmental guidelines. Every approved drug has a Master File (DMF), which contains all important

information about safety, efficacy and potency, residue limits in milk and meat as well as about limitations of

use and particularly withdrawal times for the respective pharmaceutical. Important information such as

dosage, route of administration, period of use, contraindications has to be notified on the labels.

29

Antimicrobials used in Iran are mainly produced by domestic manufacturers while only a minor percentage is

imported. Close to 1 000 000 kg of active ingredient were used in food animals in 2011.

As rising levels of AMR are of concern, a national study on antimicrobial resistance patterns was carried out by

the animal health authorities in Iran in 2011, covering all provinces of the country and performing nearly 6 000

antimicrobial sensitivity tests. Based on the alarming results, a national monitoring plan for AMR is envisioned

21.

MALDIVES

No national policy nor guidelines on AMU and AMR monitoring have been issued. Since livestock is of little

significance and as a commercial livestock sector does not exist, AMU and AMR in livestock are not considered

a serious problem. No national focal point, no national surveillance system and no laboratory network on AMR

are available. However, regulations for rational use of antimicrobials in human medicine are now under

development 189.

NEPAL

The government of Nepal has promulgated the Drug Act 1978 to prohibit misuse or abuse of drugs and allied

pharmaceutical materials as well as false or misleading information relating to efficacy and use of drugs and to

regulate and control the production, marketing, distribution, export-import, storage and utilization of drugs.

To implement and fulfill the aim of Drug Act 1978 and various regulations under it, the government of Nepal

established the Department of Drug Administration (DDA) in 1979. The DDA is the sole authority responsible

for regulating drug use in Nepal and is responsible for regulating all types of medicines including veterinary,

allopathic, ayurvedic and homeopathic drugs in the country. There is no separate organization for regulating

veterinary medicines in Nepal. The Veterinary Standards and Drug Administration Office (VSDAO) has been

established under the Directorate of Animal Health in Nepal to regulate drug use in food animals. However,

due to the absence of a Veterinary Drug Act, VSDAO is not functioning as envisaged and has only been

involved in regulating veterinary vaccines imported in the country.

In Nepal, AMR has been studied in Vibrio, Shigella, Streptococcus, Haemophilus, E. coli, Neisseria, and

Salmonella, but these studies have been mostly carried out on isolates from humans. AMR studies on animal

pathogens have started in 2011 and the National Public Health Laboratory is coordinating national AMR

monitoring whereby the veterinary laboratories are working in coordination with the NPHL on AMR

surveillance.

PAKISTAN

Import and registration of antimicrobials are controlled by the Drug Regulatory Agency of Pakistan (DRAB),

Ministry of National Regulation and Services 58, 59. The most commonly sold antimicrobials in Pakistan are:

oxytetracycline, gentamicin, amoxicilin, enrofloxacin, flumequine, norfloxacin, tylosin, ampicillin, procaine

penicillin, and sulphonamides 106.

Precise information on policies and regulation of AMU could not be found. It has been stated that Pakistan

government has banned the use of antibiotics in poultry feed and that the Drug Act is under modification to

control the irrational use of antibiotics 225.

SRI LANKA

The Department of Animal Health and Production (DAPH) is in the process of updating the regulations

pertaining to antimicrobials in the Animal Diseases and Animal Feed Acts. DAPH has prohibited the use of

therapeutic antibiotics in feed, is screening selected poultry pathogens (E. coli, Campylobacter spp. and

C. perfringens) for AMR and has strengthened the control of illegal antibiotic sales 53.

30

SOUTHEAST ASIA

CAMBODIA

No national policy exists on antimicrobial use in livestock 221, published data on AMU is not available and

there is no national AMR surveillance program in place. Farmers have easy access to antimicrobials via

pharmacies selling drugs for use in humans, VAHWs, and village markets, where they can also purchase

medicated feed. Furthermore, itinerant drug sellers from Viet Nam and China travel through villages selling

antimicrobials to farmers, with accompanying documentation in foreign language (Tornimbene, pers. comm.).

INDONESIA

Veterinary drugs are regulated under the Animal Health and Animal Husbandry Law No. 18/2009, article 22

68 and the Government Regulation no. 78/1992. Veterinary drug Inspection and the operational procedure

for the control of veterinary drugs were established under Government Regulation no. 15, 1994. While

veterinary drugs can be used as feed additives, chloramphenicol and hormones are prohibited for growth

promotion in food producing animals by Government Regulation no. 806, 1994 68.

A code of practice for the use of veterinary drugs was prepared to be harmonized with the Codex Code of

Practice for Control of the Use of Veterinary Drugs (CAC/RCP 38-1993). The code were assigned to cover

regulations on the use of veterinary drugs in feed, and the use of veterinary drugs by an authorized company,

institution or personnel and to promote prudent use of veterinary drugs 70.

No published AMU data is available and a national AMR monitoring program has not been established. An

initial pilot AMR monitoring program was carried out in 2012 and 2013, but is still not recognized as a national

program to monitor antimicrobial resistance in indicator bacteria (E. coli and Salmonella spp.) 196.

LAO PDR

Most aspects of animal raising and management, including importation of veterinary drugs, are governed by

Livestock Product Management Regulations No. 0313/MAF or 0036/DLF 195 130, 206. However, AMR is not

mentioned in this regulation.

Many antimicrobials are approved for treatment or growth promotion in Lao PDR. Antimicrobials may be used

as prophylactic agents in the drinking water of healthy birds and as growth promoters at sub-therapeutic

concentrations in feed. Bacitracin, bio-tetra, bio-tylo, chlortetracycline, tylosin, neomycin, oxytetracycline, and

others are used for these purposes. The antimicrobials used most frequently in swine are tetracyclines,

gentamicin, tylosin, and sulfamethazine or other sulfas. Available data suggest that antimicrobials are used in

most phases of swine and poultry production and that usage has been increasing, most frequently through in-

feed additives 206.

No published data on regulations, guidelines and policies on AMR monitoring in livestock and livestock

products could be found nor is published data on AMU available.

MALAYSIA

The National Pharmaceutical Control Bureau Ministry of Health, Malaysia (NPCB, MOH) regulates most aspects

of veterinary drugs through the Registration Guideline of Veterinary Products (REGOVP); Version 2, March

2009 145. Ninety-seven different antimicrobials are registered with the NPCB, MOH. Most of the registered

drugs are used in poultry and pigs and less in cattle and goats. The guideline includes a list of drugs that are

not allowed to be registered for use in food animal production, e.g. chloramphenicol or vancomycin.

All drugs used in humans or animals are required to be registered with the Drug Control Authority (DCA).

Animal feed containing drug(s) is exempted from the registration requirements until a separate regulatory

control is established 145. It is reported that the sale or use of drugs in animals and animal feed in Malaysia is

hardly restricted or controlled 11.

31

Malaysia has formulated an AMR Action Plan comprising seven major lines of activity: (i) awareness

campaigns, (ii) establishment of MIC testing capacity for AMR assessments, (iii) AMR information

dissemination, (iv) promotion of collaborative AMR research, (v) capacity building and harmonization of

laboratory methods / protocols, (vi) development of a national AMR surveillance program for poultry at farm

and processing plant level and (vii) establishment of a joint AMR working group comprising representatives of

the Department of Veterinary Services and the Ministry of Health.

MYANMAR

Although a Food and Drug Authority (FDA) has been established, Myanmar does not have a national policy on

use of antimicrobials and a national co-ordination mechanism on AMR does not exist. Review and

development of practical legislation and regulatory framework for AMU and AMR management are in process

138.

Most antimicrobials used in livestock production are imported. The main sources of antimicrobials are

Bangladesh, Belgium (VMD), China, Germany (Bremer Pharma, Bayer), India (Cipla, Agio Pharmaceuticals),

Korea (Choong Ang Biotech, Samyang Anipharm), Spain (Invesa, Dex Iberica), and Thailand 192.

The main antibiotics used in poultry production are oxytetracycline, doxycycline, chlortetracycline,

enrofloxacin, amoxicillin, colistin, erythromycin, sulphadiazine, trimethoprim and neomycin. While

enrofloxacin is particularly used for prevention and treatment of bacterial diseases of the respiratory tract,

amoxicillin and colistin are mainly used for prevention and treatment of bacterial diseases of the gastro-

intestinal tract. Most of antimicrobials are given in drinking water.

Antimicrobials are freely available in Myanmar. The major problem, leading to inappropriate use of

antimicrobials, is that most poultry farmers use antimicrobials without any consultation with veterinarians.

Most poultry producers use antimicrobials as preventive measures for bacterial diseases. Chlortetracycline is

used as feed additive for growth promotion by some poultry feed producers.

The patterns of antimicrobial use in cattle and pig production are quite similar. In cattle and pig production,

penicillin, streptomycin, lincomycin, enrofloxacin, gentamicin and kanamycin are the main antibiotics used for

parenteral administration. Some in-feed antibiotics are used as growth promoter in pig fattening enterprises.

PHILIPPINES

In the Philippines two agencies are involved in the regulation of AMU: the Department of Agriculture (DA)

through the Bureau of Animal Industry (BAI) and the Department of Health through its Food and Drug

Administration (DOH-FDA). Both agencies work in cooperation based on their respective regulatory functions.

FDA regulates all veterinary drugs for injection and individual administration for animals. The BAI regulates

veterinary drugs and products that are used or mixed or incorporated in feeds and drinking water. RA No. 9711

of the Food and Drug Administrative Act of 2009 is the most current legislation for regulating and monitoring

of establishments and products including veterinary drugs and other health products 73.

Most veterinary drugs are imported and are usually mixed in feed and water for controlling diseases and

infections in pigs and poultry. Of the products registered at the Department of Agriculture's Bureau of Animal

Industry (BAI), in 2011 the most commonly sold antimicrobials were chlortetracycline and tiamulin hydrogen

fumarate 48. No publications on AMU in livestock could be found.

Information on national AMR surveillance in livestock and livestock products could not be found.

32

THAILAND

Veterinary drugs are regulated by Drug Act B.E. 2510 (1967) 57. Feed and feed additives are regulated by

Feed Act B.E. 2542 (1999) 56. Introduction and spread of animal diseases are controlled by the Animal

Epidemics Act B.E.2542 (1999) 55.

The Department of Livestock Development (DLD) closely cooperates with the Food and Drug Administration

(FDA), Ministry of Public Health, in the regulation of veterinary drugs. FDA is responsible for licensing and

registration of veterinary medicinal products and authorizes the relevant officials of DLD to enforce the Drug

Act with respect to the post-marketing use of veterinary drugs/biologics. DLD is responsible for the control and

surveillance of the usage of veterinary medicinal products. DLD also lists drugs and chemicals that are not

allowed to be used in food animals 145. Currently, FDA has banned all antibiotics from use for growth

promotion in food animals.

There is no national surveillance and data collection system for AMR in livestock and livestock products. The

institute that is mainly involved in national AMR monitoring is the National Institute of Health, DLD. AMR in

livestock and livestock products are routinely but not systematically monitored. Therefore, DLD is now working

on a project to harmonize AMR monitoring across the country.

AMR is now included in the strategic plan to prevent and resolve National Emerging Infectious Disease

Problems (AD 2556-2559) by the Thai government. In May 2013, the National Committee on Preparedness,

Prevention and Resolution of Emerging Infectious Diseases established the Sub-Committee on Prevention,

Control and Resolution of Antimicrobial-Resistant Pathogens.

TIMOR-LESTE

No data on AMU regulation or AMR monitoring could be found.

VIET NAM

Veterinary drugs are regulated by the Ministry of Agriculture and Rural Development through “Regulations on

registration procedures of production, import and circulation of veterinary drugs, raw materials for veterinary

drugs, biological products, microorganisms, chemicals used in veterinary medicine”, No:

10/2006/QĐ‐BNN/2006 13 and by the Ordinance on Veterinary medicine No: 18/2004/PL-UBTVQH11 137,

which covers animal disease prevention and treatment, control of epidemics, quarantine of animals and animal

products, slaughter control, veterinary hygiene inspection, management of veterinary drugs, bio-products,

microorganisms and chemicals for veterinary-use; veterinary practice. Currently, there are no guidelines for

rational use of antimicrobials in food animals.

Antibiotics are widely used in Viet Nam and about 50 percent of the total drug sale is for veterinary use. In

food animals antibiotics are used for both treatment and as feed additives for prophylaxis and growth

promotion 155, 156. A recent survey on AMU in pig and poultry production in the Red River delta region

found that at least 45 different antibiotics (including chloramphenicol) of more than ten classes were used by

farmers and veterinarians for treatment, prevention and growth promotion. Fifteen antibiotics were used in

feed 114.

A national AMR monitoring program is not in place.

33

DISCUSSION This review is the first attempt to systematically assess the available literature on AMR in selected zoonotic

pathogens and indicator bacteria in East, South and Southeast Asia with the aim to obtain a broad initial

overview of the situation.

The method of testing for antimicrobial susceptibility and the selection of the isolates to be tested varied

markedly between the countries. Monitoring and surveillance schemes for antimicrobial resistance in food

borne pathogens and commensal bacteria covered in this report are not harmonised among the countries

reported. The data presented may not have necessarily been derived from sampling plans that were

statistically designed, and, thus, findings may not accurately represent the national situation regarding

antimicrobial resistance in food borne pathogens and commensal bacteria. Additionally, there may not be

harmonization in the interpretive criteria (clinical breakpoints) used between, or even within, the countries

covered in this report. The findings presented in this report must, therefore, be interpreted with great care

and no direct comparison between countries should be made.

In order to mitigate some of the shortcomings in the available data, apparent proportions of resistant isolates

were grouped into resistance categories, namely ‘low’ (AMR ≤10%); ‘moderate’ (>10% to 20%); ‘high’ (>20% to

50%); ‘very high’ (>50% to 70%); and ‘extremely high’ (>70%), largely following the nomenclature provided in

EFSA 2013 63. Some misclassification will still occur and the approach masks differences that may well exist

between countries, but the initial picture that emerges is probably quite robust and, particularly when

compared with findings from countries with tighter regulation of AMU in food animals and systematic AMR

monitoring, provides ample justification for concern about the extent of AMR and its likely impact in the

region.

AMR IN EAST, SOUTH AND SOUTHEAST ASIA AND IN OTHER COUNTRIES

The following provides a brief overview of the main results of this review and attempts to put these into

perspective by comparison with AMR levels reported from countries that have dedicated monitoring programs

for AMR in livestock associated zoonotic pathogens and commensals. Again it should be noted, that

differences exist between the studies whose results are reported and that caution needs to be exercised when

interpreting the presented findings.

SALMONELLA For Salmonella isolates from poultry, the estimates of resistance to the antimicrobial compounds listed in

Table 15 are derived from a minimum of 213 isolates in the case of sulfonamide to a maximum of 3 871

isolates in the case of tetracycline. For most listed compounds, estimates are derived from five studies or more

usually including more than 500 isolates. Estimates of AMR in Salmonella isolates from pigs are based on a

smaller number of studies and fewer isolates but still in most cases more than 100 isolates, in the case of

ampicillin and tetracycline more than 1 000 isolates tested in more than 10 studies. With regards to Salmonella

isolates from ruminants, the estimates of AMR are based on testing 500 or more isolates for all compounds in

Table 15 with the exception of ceftriaxone, amoxicillin and trimethoprim. However, the number of studies of

ruminant isolates is considerably lower than that for pigs and poultry, limiting ‘regional representativeness’ of

the results for ruminants.

For Salmonella isolates from poultry, the pooled estimate of AMR across the study region fell into the

categories of ‘high’ to ‘extremely high’ for 10 of the 15 compounds listed in Table 15 for comparison across

species and with findings from other AMR assessments. ‘Low’ levels of AMR were only found for the two

cephalosporins cefotaxime and ceftriaxone and for ciprofloxacin while overall AMR to gentamicin was

34

‘moderate’. A very similar pattern of AMR was found for Salmonella isolates from pigs, with overall ‘high’ to

‘extremely high’ AMR levels to 11 of the 15 compounds in Table 14. As for isolates from poultry, ‘low’ levels of

AMR were only found for the two cephalosporins cefotaxime and ceftriaxone while ‘moderate’ AMR levels

were displayed for florfenicol and ciprofloxacin. The pooled estimate of AMR across studies for Salmonella

isolates from poultry vis-à-vis pigs fell into the same category for eight of the 15 compounds, fell into adjacent

categories for six compounds, and differed by two classes for one compound only, namely tetracycline.

Table 14. AMR (%) to selected antimicrobial compounds in Salmonella isolates from poultry, pigs and

ruminants in East, South and Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound Poultry Pigs Ruminants

AS US1 NL

2 AS NZ

3 US

1 DK

4 NL

2 AS NZ

3 US

1 NL

2

AMI

Gentamicin 17 5 0 24 0 3 3 1 3 0 5 0

Kanamycin 28 4 0 24 11 35 13 4

Streptomycin 62 36 0 58 0 32 37 50 65 11 27 68

CEP Cefotaxime 2 0 0 0 0 0 0 0

Ceftriaxone 4 12 1 0 2 0 0 22

PEN Amoxicillin 36 12 22 0 4 80 0 22

Ampicillin 25 14 3 60 17 31 81 77 26 44

PHE Chloramph. 23 3 0 47 0 8 5 21 56 0 25 12

Florfenicol 26 0 12 3 20 12

QUI Ciprofloxacin 10 0 8 11 0 0 0 3 3 0 0 0

Nalidixic acid 44 0 8 36 0 0 0 2 5 0 3 0

SUL Sulfameth. 77 0 85 33 0 92

TET Tetracycline 48 42 0 82 0 51 41 70 76 0 34 80

TRI Trimethoprim 59 0 38 17 9 34 0 0 28

Trim-Sulfa 39 0 44 2 7 5

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 US: NARMS 2010; 2 NL: MARAN 2013 (S. Typhimurium); 3 NZ: MAF 2011; 4 DK: DANMAP 2012

The pattern of AMR in Salmonella isolates from ruminants showed some differences to those observed in

poultry and pigs. ‘High’, ‘very high’ and ‘extremely high’ levels of resistance were only found for six of the

compounds in Table 14, while for the remaining seven compounds for which data was available only ‘low’

levels of resistance were recorded. Relatively large differences in AMR between Salmonella isolates from

ruminants and those from poultry and pigs appear to exist for amoxicillin, where AMR estimates are

substantially higher in ruminant isolates and for trimethoprim and trimethoprim-sulfa, where the estimates

are substantially lower in ruminant isolates. However, as stated before, the number of studies on Salmonella

isolates from ruminants was considerably lower compared to the other two species and the results are

therefore less robust. Nevertheless, these differences in AMR probably do reflect differences in AMU between

poultry and pigs on the one hand and ruminants on the other.

Comparison of the pooled AMR estimates for East, South and Southeast Asia with those from systematic AMR

monitoring efforts in high income countries with regulated AMU revealed that, with very few exceptions, the

highest estimates of AMR were reported in this study for all compounds and livestock species included in Table

14. In only four cases (out of 99 comparisons) was the AMR category of the Asian group of countries lower

than that of one of the countries used for comparison, namely for ceftriaxone in Salmonella isolates from

poultry (‘low’ vs. ‘moderate’ in the USA) and ruminants (‘low’ vs. ‘high’ in the USA), for ampicillin in isolates

from pigs (‘very high’ vs. ‘extremely high’ in the Netherlands), and for trimethoprim in Salmonella isolates from

ruminants (‘low’ vs. ‘high’ in the Netherlands).

35

CAMPYLOBACTER Compared with the available literature for Salmonella, only few studies of AMR in C. coli could be retrieved

and, for the results presented in Table 15, the number of poultry isolates tested rarely reached 200 while for

pig isolates the number subjected to AST mostly fell between 200 and 400. All AMR studies in C. coli isolates

from pigs were either from Japan or China.

Considerably more reports were available on AMR in C. jejuni isolates from poultry with all pooled estimates

displayed in Table 16 derived from AST of more than 800 isolates across at least seven studies. Similar to the

situation with C. coli isolates from pig, estimates of AMR rates in C. jejuni isolates from ruminants are based on

a limited number of studies from two countries only, Iran and Japan.

Table 15. AMR (%) to selected antimicrobial compounds in C. coli isolates from poultry and pigs in East, South

and Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound Poultry Pigs

AS US1 NL

2 AS NL

2 FI

3 SW

4

AMI Gentamicin 1 5 4 24 0 0 0

MAC Erythromycin 10 4 22 44 11 0 0

PEN Ampicillin 8 13 20 17

PHE Chloramphenicol 1 0b 0 15 0

QUI Ciprofloxacin 50 22 83 89 13 8 37

Nalidixic acid 50 22 83 36 13 8 37

TET Tetracycline 67 56 70 88 88 0 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 US: NARMS 2010 (b florfenicol); 2 NL: MARAN 2013; 3 FI: FINRES-VET 2007-2009; 4 SW: SVARM 2011

As should be expected, AMR patterns in C. coli and C. jejuni isolates from poultry were very similar and for six

of the eight compounds listed in Tables 15 and 16 the pooled estimates fell into the same resistance category.

For the remaining two compounds, ampicillin and tetracycline, the prevalence of AMR was estimated as ‘low’

vs. ‘moderate’ and as ‘very high’ vs. ‘extremely high’ respectively, the higher estimate applying to poultry

isolates. Overall, it appears that in the Asian countries from which studies were available Campylobacter

populations harbored by poultry have developed ‘high’, ‘very high’ or ‘extremely high’ levels of resistance to

ciprofloxacin, nalidixic acid, and tetracycline while, in contrast to Salmonella and E. coli populations circulating

in poultry, they still showed ‘low’ levels of resistance to gentamicin, erythromycin, and chloramphenicol. ‘High’

and ‘extremely high’ levels of resistance to ciprofloxacin, nalidixid acid, and tetracycline have also been found

in C. coli and C. jejuni isolates from poultry in the USA and the Netherlands. Levels of resistance to these three

compounds was substantially lower in C. jejuni from poultry in Australia, New Zealand and Finland, possibly

indicating more limited use of these compounds in poultry production in these countries.

36

Table 16. AMR (%) to selected antimicrobial compounds in C. jejuni isolates from poultry and ruminants in

East, South and Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound Poultry Ruminants

AS AU1 NZ

2 US

3 DK

4 NL

5 FI

6 AS NZ

2 DK

4 NL

5 FI

6

AMI Gentamicin 8 0 0 1 0 0 1 0 0 0 1 0

MAC Erythromycin 7 11 0 0 0 0 0 0 0 1 0 0

PEN Ampicillin 18 62 6 25

PHE Chloramph. 8 0 0b 0 1 10 0 0 1

QUI Ciprofloxacin 62 0 3 23 15 62 1 44 0 16 47 2

Nalidixic acid 51 0 3 23 15 62 1 19 0 16 47 2

TET Tetracycline 80 21 0 48 15 60 3 72 0 1 84 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2010 (b florfenicol); 4 DK: DANMAP 2012; 5 NL: MARAN 2013; 6 FI: FINRES-VET 2007-

2009

Although for C. jejuni the number of ruminant isolates tested was comparatively low, the observed pattern of

AMR was similar to that of C. jejuni isolates from poultry, the exception being nalidixic acid, where only

‘moderate’ vs. ‘very high’ resistance levels were found. As in isolates from poultry, the prevalence of resistance

against tetracycline was classified as ‘extremely high’. The apparently ‘extremely high’ prevalence of AMR

rates to tetracycline in Asian C. jejuni isolates from ruminants stands in stark contrast to the ‘low’ AMR levels

reported in ruminant C. jejuni isolates from New Zealand, Denmark and Finland but is similar to findings

reported from the Netherlands.

In contrast to C. jejuni isolates from poultry and ruminants and to C. coli isolates from poultry, C. coli isolates

from pigs in China displayed high rates of resistance to gentamicin (and kanamycin) and to erythromycin. High

levels of resistance to erythromycin in C. coli isolates from pigs were also found in Japan, where isolates were

also highly resistant to tylosin and chloramphenicol. Tylosin resistance may be due to use of this antibiotic or

cross-resistance caused by exposure to other macrolides. Chloramphenicol has been withdrawn from use in

food animals since 1999. Such persistence of chloramphenicol resistance may be a result of co-selection or

cross-resistance by other antimicrobial agents. C. coli isolates from pigs in China and Japan also displayed ‘high’

to ‘extremely high’ AMR rates to quinolones and tetracyclines.

Compared with reports from non-Asian countries, resistance rates observed in this review were mostly higher.

In a study in Italy, all C. jejuni and C. coli isolates from farms and abattoirs were susceptible to ciprofloxacin,

gentamicin, erythromycin and tylosin 150. The isolates in the latter study however exhibited high levels of

resistance to ampicillin, tetracycline and lincomycin. A study in Australia reported that all C. jejuni and C. coli

isolates from broiler farms were susceptible to ciprofloxacin 141. Similarly, none of the chicken isolates in a

study in Sweden were resistant to chloramphenicol, gentamicn and erythromycin and the prevalence of

quinolone resistance was very low 175.

E. COLI A substantial number of AMR studies was available for E. coli and the pooled estimates of AMR rates reported

in Tables 17 to 19 are based on AST of more than 500 isolates with the exception of AMR to sulfamethoxazole

in isolates from poultry and ruminants and to florfenicol in isolates from ruminants. The latter was derived

from testing of 60 isolates in one study only. For most compounds listed in Tables 17 to 19, the estimates of

AMR rates were derived from pools of a thousand or more E. coli isolates from a broad range of countries and

are therefore thought to be fairly indicative of the overall situation.

37

The extent and pattern of AMR resistance seen in E. coli was very similar to that in Salmonella isolates: ‘high’

to ‘extremely high’ resistance rates to most compounds listed in Tables 17 to 19 were recorded for isolates

from poultry and pigs while isolates from ruminants exhibited lower levels of AMR. For E. coli isolates from

poultry, the pooled estimate of AMR across the study region fell into the categories of ‘high’ to ‘extremely

high’ for 15 of the 17 compounds listed in Table 17. ‘Low’ levels of AMR were only found for the 3rd

generation

cephalosporin ceftiofur and for colistin, representative of the polymyxin class.

As with Salmonella, the pattern of AMR in E. coli isolates from pigs was very similar to that in poultry isolates

and ‘high’ to ‘extremely high’ rates of AMR were found for 14 of the 17 compounds used for comparison

(Table 18). As seen in the isolates from poultry, AMR in E. coli isolates from pigs was low for ceftiofur and

colistin. Overall, the pooled estimate of AMR rates in E. coli isolated from poultry and from pigs fell into the

same category for 13 of the 17 compounds used for comparison and into adjacent classes for the remaining

four compounds. Resistance to chloramphenicol was estimated as ‘high’ and resistance to trimethoprim-sulfa

as ‘extremely high’ both in isolates from poultry and from pigs.

Table 17. AMR (%) to selected antimicrobial compounds in E. coli isolates from poultry in East, South and

Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound AS AU1 NZ

2 US

3 DK

4 NL

5 FI

6

AMI

Gentamicin 21 0 0 43 0 9 0

Kanamycin 29 6 9 3

Streptomycin 34 10 49 11 58 14

CEP Ceftiofur 8 0 0 10 2 1

Cephalothin 34 2

PEN Amoxicillin 59 5 12

Ampicillin 67 33 22 20 70 6

PHE Chloramph. 41 2 1 1 0 16 0

Florfenicol 27 3 0 1 0

POL Colistin 1 0

QUI Ciprofloxacin 51 0 <0.5 8 50 2

Nalidixic acid 53 2 6 3 8 50 2

SUL Sulfamethox. 40 31 61 8

TET Oxytetracycline 70 44

Tetracycline 61 12 43 8 51 7

TRI Trimethoprim 24 7 10 51 2

Trim-Sulfa 75 27 6

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2010; 4 DK: DANMAP 2012; 5 NL: MARAN 2013; 6 FI: FINRES-VET 2007-2009

38

Table 18. AMR (%) to selected antimicrobial compounds in E. coli isolates from pigs in East, South and

Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound AS AU1 NZ

2 US

3 DK

4 NL

5 FI

6 SW

7

AMI

Gentamicin 24 3 0 1 1 2 0 1

Kanamycin 36 1 1 0 1

Streptomycin 66 32 15 42 60 15 16

CEP Ceftiofur <1 0 0 1 0

Cephalothin 18 2

PEN Amoxicillin 57 9 0

Ampicillin 57 35 13 29 25 7 13

PHE Chloramph. 47 44 10 3 3 12 0 4

Florfenicol 36 34 1 1 1 0

POL Colistin 5 0 0

QUI Ciprofloxacin 31 0 0 1 1 1 2

Nalidixic acid 36 5 1 0 1 1 1 2

SUL Sulfamethox. 60 33 45 12

TET Oxytetracycline 70 76

Tetracycline 87 49 47 36 56 18 8

TRI Trimethoprim 26 8 22 37 12 11

Trim-Sulfa 76 33

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2011 (pork); 4 DK: DANMAP 2012; 5 NL: MARAN 2013; 6 FI: FINRES-VET 2007-2009; 7 SW: SVARM 2011

AMR rates in E. coli isolates from ruminants were considerably lower than those found in poultry and pig

isolates and the pooled estimate of AMR prevalence only fell in to the ‘high’ category for four out of the 15

compounds listed in Table 19. As in isolates from poultry and pigs, AMR rates for ruminant isolates were

estimated to be ‘low’ for ceftiofur and colistin, but in contrast to isolates from poultry and pigs, AMR in

isolates from ruminants was also rated as low for trimethoprim and for trimethoprim-sulfa, the latter in stark

contrast to the ‘extremely high’ level of AMR found in poultry and pig isolates.

Table 19. AMR (%) to selected antimicrobial compounds in E. coli isolates from ruminants in East, South and

Southeast Asia (AS) and in countries with national AMR monitoring programs

Class Compound AS AU1 NZ

2 US

3 DK

4 NL

5a NL

5b FI

6

AMI

Gentamicin 7 0 0 1 0 0 3 1

Kanamycin 9 1 0 11 2

Streptomycin 27 44 7 6 1 45 2

CEP Ceftiofur 8 0 0 0 0

PEN Ampicillin 26 0 4 5 1 38 0

PHE Chloramph. 11 0 3 2 2 1 23 1

Florfenicol 17 1 2 1 10 1

POL Colistin 3

QUI Ciprofloxacin 15 0 0 0 <0.5 10 1

Nalidixic acid 13 0 <0.5 0 0 <0.5 9 <0.5

SUL Sulfamethox. 19 45 1 48 1

TET Oxytetracycline 36 3

Tetracycline 38 41 18 7 2 74 1

TRI Trimethoprim 6 13 2 <0.5 40 <0.5

Trim-Sulfa 3 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2011 (pork); 4 DK: DANMAP 2012; 5a NL: MARAN 2013, dairy cows; 5b NL: MARAN 2013,

calves, white; 6 FI: FINRES-VET 2007-2009

39

Comparison of the pooled AMR estimates in E. coli isolates from poultry and pigs in East, South and Southeast

Asia with those from systematic AMR monitoring efforts in high income countries with regulated AMU

revealed that for most compounds used for comparison they fell into the highest observed category. Only in

three of 64 comparisons was the AMR category for isolates from poultry higher in one of the countries used

for comparison, namely for streptomycin, sulfamethoxazole and trimethoprim in the Netherlands. In E. coli

isolates from pigs this was only the case for one compound (out of 73 comparisons), namely oxytetracycline in

Australia (‘extremely high’ vs. ‘very high’). For isolates from poultry and pigs, differences in AMR rates to

gentamicin and kanamycin and to ciprofloxacin and nalidixic acid appear most marked between the Asian

group of countries and those used for comparison, AMR being classified as ‘high’ in the former and mostly as

‘low’ in the latter.

For isolates from ruminants, the assigned resistance category was higher for sulfamethoxazole and

trimethoprim in New Zealand (‘high’ vs. ‘moderate’ and ‘moderate’ vs. ‘low’ respectively) and for kanamycin

(‘moderate’ vs. ‘low’), chloramphenicol (‘high’ vs. ‘moderate’), sulfamethoxazole (‘high’ vs. ‘moderate’),

tetracycline (‘extremely high’ vs. ‘high’), and trimethoprim (‘high’ vs. ‘low’) in the Netherlands. The results

from the Netherlands however refer to AMR in isolates obtained from calves, which appear to be much higher

than those obtained for isolates from adult cows. Age of the animal from which an isolate is obtained thus

appears to introduce another confounding element into cross-study comparisons.

In the Netherlands, AMR rates in E. coli isolates obtained from vegetables were below five percent to all

compounds against which isolates from livestock were tested (except sulfamethoxazole with 10% resistance)

136. Similar results were obtained in New Zealand with E. coli isolates from fresh produce, where resistance

rates were below three percent for all antimicrobial compounds used to test for resistance in isolates from

livestock (except tetracycline with 7%) 132.

ENTEROCOCCUS Only three studies on AMR were available for E. faecalis and E. faecium isolates, two of which were from Japan

and the remaining one from Taiwan Province of China. Despite the low number of studies, with the exception

of vancomycin, the AMR rates reported for E. faecalis and E. faecium isolates from poultry in Tables 20 and 21

are based on AST of more than 450 isolates, in most cases even close to 1 000 or even more isolates. Given the

large number of isolates tested, it is felt that the results are likely to reflect the situation in Japan and Taiwan

Province of China and can be used in cross-country comparison as done for the other microorganisms included

in this review.

40

Table 20. AMR (%) to selected antimicrobial compounds in E. faecalis isolates from poultry in Japan and

Taiwan Province of China (AS) and in countries with national AMR monitoring programs

Class Compound AS AU1 NZ

2 US

3 DK

4 NL

5 FI

6 SW

7

AMI Gentamicin 30 0 0 0 3 0 0

Streptomycin 74 4 3 46 3 0

MAC Erythromycin 86 77 34 36 20 66 26 31

PEN Ampicillin 1 0 0 0 0 0 0

PHE Chloramph. 47 0 0 1 5 0 0

QUI Ciprofloxacin 36 1 0 0 4

TET Tetracycline 97 78 63 43 732 30 31

OTH Vancomycin 0 0 0 0 0 0 0 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70%

1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2011 (pork); 4 DK: DANMAP 2012; 5 NL: MARAN 2013; 6 FI: FINRES-VET 2007-2009; 7 SW: SVARM 2011

Similar to the findings in other microorganisms included in this review, AMR rates found in E. faecalis isolated

from poultry in Japan and Taiwan Province of China always fell into the highest category seen for all eight

compounds used for the cross-country comparison. AMR was found to be ‘high’ or ‘extremely high’ for six of

the eight compounds listed in Table 20, resistance being ‘low’ to ampicillin, while not a single isolate was

found to be resistant to vancomycin.

As with E. faecalis, AMR rates in E. faecium isolates from poultry in Japan and Taiwan Province of China fell

into the highest category observed for the compounds listed in Table 21, the only exception being ampicillin,

where isolates from the Netherlands exhibited a ‘high’ level of resistance while the corresponding estimate for

the isolates from the two Asian countries was ‘low’. Overall, ‘high’ to ‘extremely high’ levels of resistance were

found for six of the nine compounds included in the comparison, resistance being rated as ‘low’ for gentamicin

and ampicillin, while no isolate was found to be resistant to vancomycin.

Table 21. AMR (%) to selected antimicrobial compounds in E. faecium isolates from poultry in Japan and

Taiwan Province of China (AS) and in countries with national AMR monitoring programs

Class Compound AS AU1 NZ

2 US

3 DK

4 NL

5 FI

6 SW

7

AMI Gentamicin 10 0 0 0 3 0 0

Streptomycin 59 3 4 43 1 0

MAC Erythromycin 70 46 25 22 14 64 14 13

PEN Ampicillin 8 5 0 1 27 1 2

PHE Chloramph. 36 1 0 0 0 1 0

QUI Ciprofloxacin 54 46 34 0 16

TET Tetracycline 98 35 43 7 583 15 12

OTH Quinupristin 79 32 1 82

Vancomycin 0 0 0 0 0 0 5 0

Low: ≤10% Mod.: >10% to 20% High: >20% to 50% V. High: >50% to 70% Ex. high: >70% 1 AU: DAFF 2007; 2 NZ: MAF 2011; 3 US: NARMS 2011 (pork); 4 DK: DANMAP 2012; 5 NL: MARAN 2013; 6 FI: FINRES-VET 2007-2009; 7 SW: SVARM 2011

2 In contrast to the ‘extremely high’ (73%) level of tetracycline resistance in E. faecalis isolates from poultry, tetracycline resistance in

E. faecalis isolates from vegetables was ‘low’ (3%).

3 In the Netherlands, E. faecium isolates from vegetables were included in the AST and again displayed ‘low’ (9%) levels of resistance to

tetracycline as opposed to the ‘very high’ level found in isolates from poultry.

41

Quinupristin is usually used in combination with dalfopristin for the treatment of life-threatening infections

associated with vancomycin-resistant E. faecium bacteraemia. However, clinical E. faecium isolates resistant

quinupristin-dalfopristin have been reported 152. High resistance to quinupristin has been suggested to be

associated with the use of virginiamicin as a feed additive in food animal production 94. The observation of

an ‘extremely high’ prevalence of resistance to quinupristin in E. faecium isolates from poultry in Taiwan

Province of China is of concern and warrants further studies across the region.

Given the clinical importance of erythromycin-resistant enterococci, continuous surveillance and geographical

expansion of erythromycin resistance in these bacteria in the region is strongly recommended, particularly in

view of erythromycin being the drug of choice.

AMU AND AMR MANAGEMENT IN EAST, SOUTH AND SOUTHEAST ASIAN COUNTRIES AND IN

THE USA AND THE EU

The main findings on AMU and AMR management in livestock production in the countries in the study region

are summarized states below. Policies and regulations of AMU exist in some countries but systematically

recorded information on actual AMU (either type or extent) in the livestock sector is absent. AMU has to be

deduced from AB sales data, which however is also difficult to obtain.

EAST ASIA Regulation of AMU in livestock and national responses to AMR in the East Asian countries are quite varied.

Some information in English language was available from China, Japan and Republic of Korea while this was

not the case for the Peoples Democratic Republic of Korea and Mongolia.

China plays an important role both as importing and exporting country of livestock products. Large amounts of

livestock are being produced to satisfy the high and growing domestic demand. Many antibiotics are

domestically manufactured and there is evidence that various antibiotics are being been imprudently used in

food animal production. Development of policies, guidelines and regulations on AMU and AMR in livestock

production is rather slow and relevant data is limited 108, 124. It is clear that national surveillance of AMR,

national reference laboratory and a network database for AMR are urgently needed 186. In China and its

province Taiwan, AMR in food animals has been widely studied, resulting in a substantial number of

publications in many high-ranking scientific journals and clearly suggest that AMR has reached significant

levels.

Japan is a country with prominent national policy for control and surveillance of AMR in livestock production.

Its policies have been publicly available and used as models for development of relevant programs in many

countries. Japan has established guidelines for rational use of antibiotics in food animals and antimicrobial risk

assessment. The outstanding development is the annual report of AMU in livestock and fisheries. All these

movements have placed Japan in the leading position in terms of AMU and AMR management. However, even

though veterinary drugs can be used only under veterinary prescription, restriction on AMU in veterinary

sector may still need to be increased.

The Peoples Democratic Republic of Korea and Mongolia are among the countries with limited headway in

the development of a national policy for AMU and AMR in livestock production. There is not much data

available on the websites and if there is any, it is usually in native languages. Consequently, it is difficult to

assess if restrictions on veterinary drugs, if they exist, are actually being implemented and to what extent.

Mongolian livestock (mostly herbivores) are mainly reared by grazing on extensive grasslands and antibiotic

use may not be common in these animals.

42

The Republic of Korea is among the more advanced countries with respect to the regulation of AMU in food

animals. The use of antimcirobial agents in food animals for sub-therapeutic or non-therapeutic purposes has

been restricted. In 2011, the Ministry for Food, Agriculture, Forestry and Fisheries (MIFF) banned the addition

of antibitics to animal feed. The ban covers use of the antimcirobial agents apramycin, avilamycin, bacitracin

methylene disalicylate, bambermycin, sulfathiazone, teramycin, tiamulin, tylosine and virginiamycin as feed

additives 109. However, information on AMU and data collection systems is limited 109

SOUTH ASIA Data on AMU and AMR in livestock and livestock products in most South Asian countries is limited. Responses

to the AMR threat in each country are different.

Large and small ruminants, i.e. cattle, sheep and goats, are the main livestock species in Afghanistan and are

usually reared by grazing in sedentary or nomadic production systems. Therefore, these animals may not be

normally exposed to antimicrobial agents and AMR in microorganisms associated with livestock is not a major

concern. In contrast, AMR in Afghanistan hospitals is a major concern because irrational use of antibiotics is

very common in human medicine. A survey reported that up to 100 percent of the patients in a private

hospital received third-generation cephalosporins, indicating the overuse of antibiotics in Afghanistan

hospitals. Together with lack of prophylaxis guidelines and standardized surgical protocols, such overuse and

misuse of the antibiotics results in substantial long-term effects, including increased medical costs, more

adverse drug reactions (ADRs) and increasing development of AMR 82.

In Bangladesh, antimicrobials are widely used in both humans and animals 189. Several scientific papers

regarding AMR in livestock, particularly in cattle, calves, chicken, and ducks, have been published and

highlighted the problem of AMR in the country 91, 92, 105. In addition, AMR is a topic of extensive research

in bacteria from shrimp, aquaculture being an important contributor to Bangladesh’s economy. Despite AMR

being considered a national priority, Bangladesh still has no national regulation and surveillance for AMU and

AMR, especially in food producing animals 189. However, a bill on antibiotic use in livestock and fish feed has

been proposed by the Bangladesh government in 2010. The bill prohibits the use of antibiotics, growth

hormones, steroids and harmful pesticides in animal and fish feeds. Once it becomes law, it will improve the

safety standards for fish and animal feeds in the country 12.

Livestock are an important contributor to Bhutan’s economy and are commonly used for draught 218.

Chicken meat needs to be imported to meet domestic requirements. It seems that antibiotics are not

extensively used in livestock and that AMR is not a main concern in Bhutan. This is likely a major reason for the

very limited study of AMR in domestic livestock and their products.

In India, antibiotics have been used widely in food animals and AMR is considered a serious public health

problem. Currently, India does not have national regulatory provision and active national surveillance

regarding AMU and AMR in livestock. The Government has recently urged all the relevant agencies to act on

antibiotic resistance. The outstanding progress in control and prevention strategy is the announcement of a

new national antimicrobial policy in 2011 by Ministry of Health and Family Welfare task force 146. This could

be partly a result from the previous identification of New Delhi Metallo-beta-lactamase-1 (NDM-1) in the

country. This new national policy regulates antibiotic use in both humans and food animals and is the first

regulation in India that states specifications of AMU and how much antibiotics can be mixed into animal feed.

One of the outstanding observations in Iran is the extensive research publications on AMR bacteria associated

with livestock. This reflects that AMR is a current issue of particular concern in the country. However, data on

AMU, surveillance and national control program could not be obtained.

In the Maldives, aquaculture makes a significant contribution to its economy while the contribution of

livestock and livestock products is marginal. This could explain the absence of scientific papers and national

43

policy of AMU and AMR in food animal production. The Maldives lack well-trained staff, laboratory capacity

and reagent supplies, and national laboratory-based AMR surveillance has not been established 221.

AMR is a major public health concern in Nepal, Pakistan and Sri Lanka. Among the three countries, Nepal has

several regulations and policies that aim to control AMU but most focus on human medicine. It was reported

that AMU for veterinary practice in Sri Lanka and Pakistan is legally restricted 189, 225 but further

information could not be retrieved. Some publications on AMR have originated from these countries in the

past five years. It can be noted that almost all studies focused on bacterial isolates from chicken and chicken

meat, suggesting the increasing importance of the poultry industry. Then again, there is still no national

surveillance and control program that is directly applied for AMU and AMR in food animals in these countries.

SOUTHEAST ASIA Among the Southeast Asian countries, most information is available from Thailand, Malaysia and the

Philippines and these countries seem to have progressed furthest with regards to managing AMU and AMR

risk in food animal production. In contrast, information from Cambodia, Lao PDR, Myanmar and Timor-Leste

was limited and AMU and AMR seem to receive little attention.

In Indonesia, animal and human health authorities appear to be concerned about the risk of AMR but all

legislation and regulations regarding veterinary drugs and their use were only available in the native language

making them difficult to evaluate. Indonesia is also one of the countries that has banned the use of antibiotics

for growth promotion since 1994. However, it appears that the competent authorities are encountering major

challenges in the establishment of national AMR surveillance comprising lack of facilities, data management

system and human resources 70.

Most antimicrobials registered in Malaysia are used in poultry and pig production while regulations on the sale

or use of drugs in animals and animal feed are not well established. Veterinary drug residues have been

regularly monitored in food of animal origin and AMR monitoring in the human medical sector has been well

organized. However, there is little information about national surveillance and control of AMR in livestock

production. Harmonization of AMR management, standardization of detection methods and limited well-

trained personnel seem to be some of the problems.

Regulation of veterinary drugs in Philippines is rather comprehensive by many authorities. Rational use of

antimicrobials and other veterinary drugs in animal production is now governed by national policy on drug

residue control. However, AMR surveillance in the country is underfunded, lacks adequate laboratory staff,

does not have the capacity to link data from laboratory surveillance with epidemiologic data, and lacks a

master plan for laboratory surveillance.

Thailand is an important exporter of agriculture products, of which one of its major export goods are chicken

products. Thailand’s poultry industry has been well developed to meet international standards and the

importing country requirements. Thailand has become increasingly concerned about AMR and increased

restrictions and policies on AMU in livestock. The use of antibiotic growth promoters in food animals has been

prohibited, probably in response to the antibiotic ban in the EU, its major trade partner. One example of

progress made in AMR policy is the draft guideline for judicious use of antimicrobials in broiler farms with a

good response from poultry producers. This is the first development of policy for rational use of antimicrobials

in food animals and similar guidelines specific for other livestock species are in preparation. Despite the

extensive studies of AMR in the country, Thailand does not have reliable national surveillance of AMR.

Relevant information is scattered and not systematically recorded. It is clear that a regional and national

mechanism for regularly sharing of AMR data of public health importance is needed. Importantly,

collaboration between regulators, public health officials, academic institutes and industrial partners needs to

be established. The major challenges of the country include lack of standardized and harmonized methods for

44

AST, inadequate regulation on AMU, unclear picture of antimicrobials in animal farms and limited trained

personnel.

Viet Nam is one of the fastest-growing economies in the world. Rational use of veterinary drugs is becoming of

increasing concern due to the very rapid growth of the livestock sector. Particular interest has been paid to

drug registration, reduced use of antibiotics, increasing use of alternatives for growth-promotion (i.e.

probiotics, premix, vitamins, minerals and herbs) and use of environmentally friendly chemicals. Viet Nam is

facing a major problem of counterfeit and low quality drugs, implying the ineffectiveness of drug regulation.

Additional problems in AMR management include a dis-connect between veterinary practice and drug sales,

the lack of regulations of prescription and retail sales, and no regulation of withdrawal periods 156.

USA Antimicrobial use in livestock sectors particularly in industrial poultry and swine production is common in the

USA 212 and has been increasing 71. AMU is regulated by the US Food and Drug Administration (FDA). The

USA has developed policies for judicious AMU in various types of animals 72, 162. The country has a well-

established AMU recording and reporting system managed by the FDA. However, it has been lamented that

reliable data on total antibiotic use in livestock in the USA is not publicly available 27.

The USA has also established national policies for the control and surveillance of AMR associated with food

animals. AMR monitoring has been standardized and harmonized and has been used (partly) as model of AMR

monitoring programs in other countries (e.g. Thailand, South Korea). AMR (either phenotypic and genotypic

properties) in bacteria derived from livestock and livestock products has been extensively reported.

EUROPEAN UNION AMR in bacteria associated with food animals is a common concern across EU member states and AMR control

is a high priority of the community. The EU is taking a leading position in almost all aspects associated with

AMU and AMR management in food animal production. As of 2006, the EU has disallowed the use of

antimicrobials for the purpose of growth promotion in food animal production 20, 46.

Two agencies deal with the control of infectious diseases and AMR: the European Centre for Disease

Prevention and Control (ECDC) and the European Food Safety Authority (EFSA). ECDC is focusing on the

epidemiology, surveillance, prevention and control of infectious diseases while EFSA has the responsibility of

collecting and analyzing data on AMR in microorganisms from food-producing animals to be used for risk

assessments. EFSA has developed detailed rules for AMR monitoring to ensure comparability of data on AMR

occurrence among the Member States 61, 64. The technical specifications of the AMR monitoring program

are publicly available and are updated upon the review of suggestions made by other relevant agencies. EFSA

regularly issues European Union Summary Reports (EUSRs) on AMR 64.

The most up-dated EU action plan for AMU and AMR management has been (partly) used as model for the

formulation relevant policy and programs in other countries, such as Thailand.

45

CONCLUSIONS AND RECOMMENDATIONS Both AMR and food-borne diseases are a public health threat and a vital challenge in human medicine in East,

South and Southeast Asia. The high prevalence of AMR observed in zoonotic bacteria from food animals and

their products suggests an important role of the livestock sector in the emergence, dissemination, and

maintenance of AMR in human pathogens. In most of East, South and Southeast Asia AMU in food animal

production is not well regulated and existing regulations are often poorly enforced. The levels of AMR found in

the four livestock-associated micro-organisms covered by this review are in many cases at least as high if not

higher than those observed in other countries where food animal production is dominated by intensive

production methods. As in the human medical sector, high levels of AMR provide strong evidence for the

widespread and ‘non-responsible’ use of antimicrobials.

Lack of awareness of the extent and consequences of AMR and the contribution of uncontrolled AMU in food

animal production by policy makers appears to be at the root of the rather low level of policy concern and

relative regulatory inertia seen in many of the countries in the region. The immediate consequences of the low

level of policy engagement in AMR risk management are:

inadequate regulation and coordination between relevant actors, e.g.

- lack of national policy, guidelines and regulation of AMU and AMR (and poor application of

existing regulations);

- absence of a national program on AMU and AMR;

- lack of standardized and harmonized AST (data from different laboratories cannot be compared);

- no linkage of data from laboratory surveillance with epidemiologic data from the field;

- easy access to antibiotics (antibiotics may be obtained over counter without veterinary

prescription);

- limited participation of stakeholders in AMR awareness programs;

and

inadequate human and financial resources, e.g.

- scarcity of quality assured laboratories for antimicrobial susceptibility testing;

- limited qualified manpower within each competent laboratory;

- difficulty to assign laboratory personnel to AMR surveillance;

- limited availability of commercial laboratory supplies such as culture media, antibiotics,

antibiotics discs, other chemicals;

- poor access to (electronic) information.

The combination of the above limitations results in insufficient antimicrobial susceptibility data analysis and

dissemination and a lack of AMR surveillance data, which perpetuates the status quo and limits much needed

research on AMR and on alternatives to antimicrobials.

An interdisciplinary approach involving a wide range of partners is needed to manage AMR. The following

recommendations are suggested for different actors.

For governmental agencies and regulatory authorities

Governmental agencies and regulatory authorities should:

1. Acknowledge AMR management as a national priority;

2. Develop national lists of critically important antimicrobials specifically ranked for each country;

3. Develop guidelines for judicious AMU in food animals;

4. Establish mechanisms to reliably monitor AMU in prevailing food animal production systems;

5. Develop strategies and action plans for national control and prevention programs for AMR in food

animals;

46

6. Formulate and pass transparent and systematic regulations for AMU and AMR in food animal

production based on scientific evidence, risk assessment and appropriate precaution;

7. Build and strengthen laboratory and epidemiological capacities to provide reliable AMR data for

utilization at local level and for national guidelines;

a. Establish and / or strengthen a national reference laboratory for AMR;

b. Establish and / or strengthen national laboratory-based surveillance of AMR;

c. Establish and / or strengthen capacity to design sampling strategies that ensure the

collection of representative samples of field isolates;

d. Establish and / or strengthen capacity to interpret the results of national AMR surveillance.

8. Initiate and support research and development to enhance application of various measures to combat

AMR including better diagnostics, new antimicrobials, alternatives to antibiotics;

9. Support a collaborative relationship between regulators, public health officials, academic institutions

and industrial partners (pharmaceutical and livestock production);

10. Provide proper education on AMU and AMR and promote awareness of rational drug use to farmers,

animal producers, drug manufacturers, drug distributors and veterinarians to maximize the benefits

of therapeutic antibiotic use, while minimizing the development of resistance;

11. Encourage herd health programs including herd immunization, infection control, good agricultural

practice and enhanced biosecurity to reduce the burden of disease and need for AMU.

For AMR laboratories

AMR laboratories should:

1. Develop antimicrobial susceptibility test guidelines, standard operating procedures and standardized

and harmonized protocols for AMR monitoring and encourage their use;

2. Improve and strengthen diagnostic facilities for AST and microbial diseases to support antimicrobial

prescription and AMR monitoring;

3. Encourage the production and use of quantitative data (i.e. MICs) in the monitoring of AMR;

4. Establish a national system of AMR surveillance using internationally-recognized software e.g.

WHONET for data analyses;

5. Establish a national system to monitor the emergence and spread of AMR and assess its impact on

public health;

6. Improve and increase number of laboratory facilities, manpower and training;

7. Improve and strengthen the laboratory quality-assurance system;

8. Establish regional and national mechanisms for regularly sharing of AMR data of public health

importance, practices of laboratory-based surveillance of AMR, practices to promote rational AMU

and other relevant information;

9. Participate in the Asia-Pacific Network for Surveillance of AMR.

For research and academic institutions

Research and academic institutions should:

1. Perform basic and clinical research to monitor and prevent / reduce emergence and spread of AMR

and ensure that findings (e.g. new rapid diagnostics, new therapeutics, alternatives to antibiotics,

monitoring and strategic monitoring and control models for countries with low resources) are taken

into account in the formulation of future policies and actions;

2. Perform research using the “farm-to-fork” approach to assess the actual impact, to understand the

transmission, and to identify potential areas for management of AMR throughout the food chain;

3. Enhance collaboration with academic partners and the private sector to monitor and curb the

emergence and spread of AMR;

4. Improve the knowledge base and information flow to health providers, veterinarians, drug suppliers,

food animal producers and consumers;

47

5. Describe the value chains associated with antimicrobial usage, determine the economic and social

drivers of associated behaviours and develop interventions for appropriate behaviour change.

For the private sector

The private sector should:

1. Adopt the principle of rational use of antimicrobials to maximize the benefits of the therapeutic

antibiotic use and minimize the development of resistance;

2. Encourage rational usage of AM through appropriate incentives for producers;

3. Collaborate with governmental agencies, local partners and other private sector partners in AMU and

AMR monitoring programs.

For international organizations

International organizations should continue to:

1. Develop and publicize international guidelines for establishing national surveillance of AMR;

2. Provide technical assistance to national authorities for establishing national laboratory-based

surveillance and control/prevention programs of AMR;

3. Advocate and support the establishment of regional reference laboratories and/or laboratory

networks;

4. Provide information and updates on international standards and trade requirements;

5. Support a network of experts and officials in the region to share knowledge and data about AMU and

AMR.

This review has provided a first insight into the possible extent of AMR in selected pathogens and commensals

associated with food animal production in East, South and Southeast Asia and although it appears that the

levels of AMR are high in comparison to a number of countries with systematic AMR monitoring programs, the

true extent and impact of AMR in the region remain largely unknown. There is an urgent necessity to produce

comparable data from national monitoring and surveillance programs in different countries in the region and

to combine the results at the regional level to support the formulation of rational and cost-effective AMR

programs across the region. Better communication and collaboration and among Asian countries (e.g. at

ASEAN and SAARC level) is a prerequisite for the development of harmonized and standardized schemes for

AMR monitoring and regional approaches to conserve antibiotic effectiveness for human and animal health

protection.

48

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60

ANNEXES

ANNEX 1: STUDY INCLUSION AND EXCLUSION CRITERIA

Criteria Inclusion Exclusion

Antimicrobials - Antibiotics - Antibacterials

- Antifungals - Antiseptics - Disinfectants

Animal species - Poultry (i.e. broilers, layers, ducks, geese, partridges and quail)

- Pigs - Horses - Large ruminants (i.e. cattle, cow and

buffalo) - Small ruminants (i.e. sheep and

goats)

- Aquatic animals - Wild birds - All other animals beyond list

Animal food products - Chicken meat - Pork - Beef - Veal - Lamb - Goat meat - Raw milk

- Eggs - All other products beyond

list

Bacteria - S. enterica - Campylobacter spp. - E. coli - Enterococcus spp.

- S. bongori - All other bacteria beyond list

Countries - 40 countries listed in Table 2 - All other countries

61

ANNEX 2: AMR STUDIES AND SUMMARY STATISTICS FOR SALMONELLA SPP.

Table A2-1. Results of AMR studies in Salmonella from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Gentamicin 18

CAM (1); CHI (6); IRA (2); JAP (1); MAL (2); NEP (1); PAK (1); TAI (2); THA (1); VIE (1)

2,082 17 0.0 92.5

Kanamycin 11 CHI (3); IND (1); JAP (4); PAK (2); TAI (1)

1,630 28 0.0 92.9

Streptomycin 16 CAM (1); CHI (3); IRA (2); JAP (2); MAL (3); NEP (1); PAK (2); TAI (1); THA (1)

1,844 62 0.0 100

CEP

Cefotaxime 8 CAM (1); CHI (2); IRA (2); JAP (1); MAL (1); PAK (1)

1,050 2 0.0 9.1

Ceftiofur 5 CHI (2); IRA (1); JAP (1); THA (1)

515 23 0.0 85.7

Ceftriaxone 7 CHI (3); MAL (2); TAI (1); VIE (1)

638 4 0.0 61.0

Cephalothin 8 CAM (1); CHI (3); JAP (1); MAL (1); NEP (1); TAI (1)

1,094 29 0.0 94.9

MAC Erythromycin 5 BGD (1); IND (1); MAL (2); PAK (1)

289 86 5.4 100

PEN

Amoxicillin 8 CAM (1); CHI (2); IND (1); IRA (1); NEP (1); TAI (1); THA (1)

682 36 0.0 97.4

Ampicillin 24

CHI (7); IND (1); IRA (2); JAP (4); MAL (3); NEP (1); PAK (2); TAI (1); THA (2); VIE (1)

3,827 25 0.0 100

PHE

Chloramphenicol 20

CAM (1); CHI (4); IRA (2); JAP (4); MAL (3); NEP (1); PAK (2); TAI (1); THA (1); VIE (1)

2,450 23 0.0 100

Florfenicol 5 CHI (2); IRA (1); TAI (1); THA (1)

495 26 0.0 90.9

POL Colistin 5 IRA (2); JAP (1); TAI (1); THA (1)

426 12 0.0 24.0

QUI

Ciprofloxacin 17

CAM (1); CHI (6); IRA (2); MAL (2); NEP (1); PAK (1); TAI (2); THA (1); VIE (1)

1,899 10 0.0 100

Nalidixic acid 19

CAM (1); CHI (4); IND (1); IRA (2); JAP (2); MAL (3); NEP (1); PAK (1); TAI (2); THA (2)

3,359 44 0.0 100

Norfloxacin 6 CHI (2); MAL (1); NEP (1); TAI (1); THA (1)

693 18 0.0 78.9

SUL Sulfamethoxazole 6

CHI (2); IRA (1); JAP (2); THA (1)

824 77 0.0 100

Sulfonamide 2 CAM (1); CHI (1) 213 16 0.0 75.0

TET

Oxytetracycline 5 JAP (5) 1,105 82 14.3 100

Tetracycline 25 CAM (1); CHI (7); IND (1); IRA (2); JAP (2); MAL (3); NEP (1); PAK (2); TAI (2);

3,871 48 0.0 100

62

Class Compound Studies Countries N % Res. Min Max

THA (3); VIE (1)

TRI

Trimethoprim 9 CHI (2); IRA (2); JAP (2); MAL (1); PAK (2)

907 59 2.7 82.8

Trim-Sulfa 12 CAM (1); CHI (4); MAL (2); TAI (2); THA (2); VIE (1)

2,950 39 0 100

OTH Imipenem 1 TAI (1) 328 0

Meropenam 1 VIE (1) 86 0

Table A2-2. Results of AMR studies in Salmonella from pigs by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Gentamicin 10 CHI (3); JAP (2); TAI (1); THA (3); VIE (1)

955 24 0.0 48.0

Kanamycin 7 CHI (1); JAP (3); ROK (1); THA (1); VIE (1)

494 24 0.0 33.3

Streptomycin 10 CHI (3); JAP (1); TAI (1); THA (4); VIE (1)

850 58 0.0 100

CEP

Cefotaxime 2 CHI (1); JAP (1) 105 0

Ceftiofur 4 CHI (1); JAP (1); THA (2) 405 <1 0.0 4.0

Ceftriaxone 4 CHI (2); THA (2) 434 <1 0.0 3.3

Cephalothin 6 CHI (1); JAP (1); MAL (1); ROK (1); TAI (1); THA (1)

496 7 0.0 43.8

PEN

Amoxicillin 4 CHI (2); MAL (1); THA (1) 185 22 15.4 31.1

Ampicillin 13 CHI (4); JAP (3); MAL (1); THA (4); VIE (1)

1,016 60 10.0 96.0

PHE Chloramphenicol 14

CHI (3); JAP (3); MAL (1); ROK (1); TAI (1); THA (4); VIE (1)

952 47 15.4 99.0

Florfenicol 2 CHI (1); THA (1) 165 12 5.0 33.3

POL Colistin 2 JAP (1); MAL (1) 71 6 0.0 12.5

QUI

Ciprofloxacin 10 CHI (3); TAI (2); THA (4); VIE (1)

932 11 0.0 47.0

Nalidixic acid 11 CHI (3); JAP (2); TAI (1); THA (4); VIE (1)

939 40 0.0 100

Norfloxacin 5 CHI (1); JAP (1); TAI (1); THA (2)

338 9 0.0 19.0

SUL Sulfamethoxazole 4

JAP (1); MAL (1); THA (1); VIE (1)

245 85 57.3 100

Sulfonamide 2 CHI (1)*; THA (1) 132 55 55.0 100

TET

Oxytetracycline 4 JAP (3); MAL (1) 125 83 60.0 100

Tetracycline 14 CHI (4); JAP (1); MAL (1); ROK (1); TAI (1); THA (5); VIE (1)

1,063 83 0.0 100

TRI

Trimethoprim 4 CHI (1); JAP (1); THA (1); VIE (1)

291 38 10.0 56.7

Trim-Sulfa 8 CHI (3); ROK (1); TAI (1); THA (3)

718 44 15.4 95.0

OTH Imipenem 1 JAP (1) 44 0

*Only 1 isolate

63

Table A2-3. Results of AMR studies in Salmonella from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Gentamicin 5 BGD (1); CHI (1); IRA (1); JAP (2)

728 3 0.0 20.0

Kanamycin 3 IRA (1); JAP (2) 584 35 0.0 36.0

Streptomycin 4 CHI (2); IRA (1); JAP (1) 710 65 0.0 83.0

CEP

Cefotaxime 1 JAP (1) 545 0

Ceftriaxone 1 CHI (1) 30 0

Cephalothin 2 CHI (1); IRA (1) 44 7 0.0 21.4

MAC Erythromycin 1 BGD (1) 114 28

PEN

Amoxicillin 2 BGD (1); CHI (1) 144 80 0.0 100

Ampicillin 6 BGD (1); CHI (2); IRA (1); JAP (2)

735 77 0.0 100

PHE Chloramphenicol 6 BGD (1); CHI (2); IRA (1); JAP (2)

735 56 0.0 76.0

POL Colistin 1 JAP (1) 25 0

QUI

Ciprofloxacin 4 BGD (1); CHI (1); IRA (1); JAP (1)

703 3 0.0 20.0

Nalidixic acid 5 CHI (1); IRA (1); JAP (2) 728 5 0.0 78.6

Norfloxacin 1 CHI (1) 30 0

SUL Sulfonamide 2 CHI (1); JAP (1) 552 90 71.4 90.0

TET Oxytetracycline 1 JAP (1) 25 72

Tetracycline 5 CHI (2); IRA (1); JAP (2) 621 76 0.0 84.0

TRI Trimethoprim 2 JAP (2) 15 0

Trim-Sulfa 2 CHI (1); JAP (1) 575 7 5.5 33.3

OTH Imipenem 1 IRA (1) 14 0

64

ANNEX 3: AMR STUDIES AND SUMMARY STATISTICS FOR CAMPYLOBACTER SPP.

Table A3-1. Results of AMR studies in C. coli from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Amikacin 1 CHI (1) 48 71

Dihydrostrep. 4 JAP (4) 158 7 0.0 13.0

Gentamicin 5 IRA (3); JAP (2) 140 1 0.0 3.2

Kanamycin 1 CHI (1) 48 75

Streptomycin 1 IRA (1) 27 7

CEP Cephalothin 2 CAM (1); MAL (1) 71 96 93.5 97.5

MAC Erythromycin 8

CAM (1); IRA (3); JAP (2); MAL (1); VIE (1)

418 10 0.0 58.1

Tylosin 1 JAP (1) 9 33

PEN Amoxicillin 5 CAM (1); IRA (3); VIE (1) 332 11 0.0 16.2

Ampicillin 5 IRA (3); JAP (2) 166 8 1.5 19.0

PHE Chloramph. 5 IRA (3); JAP (1); MAL (1) 140 1 0.0 3.7

POL Colistin 1 IRA (1) 27 33

QUI

Ciprofloxacin 5 CAM (1); IRA (3); VIE (1) 332 50 7.5 71.0

Enrofloxacin 9 CAM (1); IRA (3); JAP (4); MAL (1)

252 27 12.9 50.0

Nalidixic acid 10 CAM (1); IRA (3); JAP (5); VIE (1)

509 50 15.0 100

TET Oxytetracycline 4 JAP (4) 158 46 27.3 60.0

Tetracycline 5 IRA (3); MAL (2) 113 67 46.7 100

Table A3-2. Results of AMR studies in C. coli from pigs by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 4 JAP (4) 440 62 54.2 68.3

Gentamicin 1 CHI (1) 190 24

Kanamycin 1 CHI (1) 190 57

MAC Erythromycin 6 CHI (1); JAP (5) 747 44 15.1 55.0

Tylosin 1 JAP (1) 145 48

PEN Ampicillin 4 CHI (1); JAP (3) 485 20 1.5 43.2

PHE Chloramphenicol 2 CHI (1); JAP (1) 345 15 0.0 32.9

Florfenicol 1 CHI (1) 190 0

QUI

Ciprofloxacin 2 CHI (1); JAP (1) 273 89 71.0 97.4

Enrofloxacin 6 CHI (1); JAP (5) 736 49 23.4 94.2

Nalidixic acid 4 JAP (4) 368 36 23.4 70.0

TET Oxytetracycline 4 JAP (4) 440 88 82.4 91.7

Tetracycline 2 CHI (1); JAP (1) 273 88 67.0 97.4

65

Table A3-3. Results of AMR studies in C. coli from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 2 JAP (2) 11 27 0.0 100

Gentamicin 2 IRA (2) 26 0

Streptomycin 2 IRA (2) 26 0

MAC Erythromycin 3 IRA (2); JAP (1) 29 10 0.0 100

Tylosin 1 JAP (1) 3 100

PEN Amoxicillin 2 IRA (2) 26 12 0.0 13.6

Ampicillin 3 IRA (2); JAP (1) 34 6 0.0 25.0

PHE Chloramphenicol 2 IRA (2) 26 0

POL Colistin 1 IRA (1) 26 9

QUI

Ciprofloxacin 2 IRA (2) 26 42 41.0 50.0

Enrofloxacin 4 IRA (1); JAP (3) 24 40 0.0 66.7

Nalidixic acid 4 IRA (2); JAP (2) 37 61 25.0 82.0

TET Oxytetracycline 2 JAP (2) 11 100

Tetracycline 2 IRA (2) 26 19 18.2 25.0

Table A3-4. Results of AMR studies in C. jejuni from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Amikacin 1 CHI (1) 80 2

Dihydrostrep. 5 JAP (5) 729 2 0.0 5.2

Gentamicin 7 CHI (1); IRA (4); JAP (1); MAL (1)

902 8 0.0 51.3

Kanamycin 1 CHI (1) 90 6

Streptomycin 3 IRA (2); PHI (1) 204 9 2.8 91.7

CEP Cephalothin 3 CAM (1); MAL (1); PHI (1)

118 97 91.7 97.3

MAC Erythromycin 12

CAM (1); CHI (1); IRA (4); JAP (2); MAL (2); PHI (1); VIE (1)

1,569 7 0.0 45.9

Tylosin 1 JAP (1) 202 0

PEN Amoxicillin 6 CAM (1); IRA (4); VIE (1) 900 11 1.7 25.7

Ampicillin 8 IRA (4); JAP (3); PHI (1) 947 18 7.2 83.3

PHE Chloramphenicol 10

CHI (1); IRA (4); JAP (2); MAL (2); PHI (1)

1,219 8 0.0 75.0

Florfenicol 1 CHI (1) 202 79

POL Colistin 3 IRA (2); PHI (1) 204 28 20.5 91.7

QUI

Ciprofloxacin 8 CAM (1); CHI (1); IRA (4); PHI (1); VIE (1)

1,114 62 20.3 99.5

Enrofloxacin 10 CHI (1); IRA (3); JAP (5); MAL (1)

1,439 30 2.6 98.0

Nalidixic acid 13 CAM (1); CHI (2); IRA (4); JAP (4); PHI (1); VIE (1)

1,646 51 2.6 99.0

TET Oxytetracycline 5 JAP (5) 729 37 27.0 50.4

Tetracycline 8 CHI (1); IRA (4); MAL (2); PHI (1)

886 80 31.5 100

TRI Trim.-Sulfa 1 MAL (1) 94 96

66

Table A3-5. Results of AMR studies in C. jejuni from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 4 JAP (4) 213 8 2.9 10.9

Gentamicin 1 IRA (1) 18 0

Streptomycin 1 IRA (1) 18 0

MAC Erythromycin 2 IRA (1); JAP (1) 95 0

Tylosin 1 IRA (1) 77 0

PEN Amoxicillin 1 IRA (1) 18 0

Ampicillin 4 IRA (1); JAP (3) 145 6 0.0 11.1

PHE Chloramphenicol 2 IRA (1); JAP (1) 82 10 0.0 12.5

QUI

Ciprofloxacin 1 IRA (1) 18 44

Enrofloxacin 6 IRA (1); JAP (5) 321 29 13.0 100

Nalidixic acid 4 IRA (1); JAP (3) 167 19 13.0 33.3

TET Oxytetracycline 4 JAP (4) 213 48 34.3 51.4

Tetracycline 1 IRA (1) 18 72

67

ANNEX 4: AMR STUDIES AND SUMMARY STATISTICS FOR E. COLI

Table A4-1. Results of AMR studies in E. coli from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Amikacin 9 CHI (6); IRA (2); VIE (1) 3,200 23 1.0 99.5

Dihydrostrep. 4 CHI (1); JAP (3); 1,511 41 25.8 61.9

Gentamicin 20 BGD (3); CHI (6); IND (1); IRA (1); JAP (4); THA (3); VIE (2)

4,636 21 0.0 84.0

Kanamycin 13 CHI (2); IND (1); JAP (6); NEP (1); ROK (1); THA (1); VIE (1)

2,796 29 5.1 50.0

Streptomycin 6 BGD (3); IND (1); ROK (1); VIE (1)

584 34 3.0 70.0

CEP

Cefazolin 9 CHI (5); JAP (3); ROK (1) 4,016 11 0.0 92.0

Ceftiofur 6 CHI (3); JAP (2); THA (1) 2,165 8 0.0 89.0

Cephalothin 2 CHI (1); THA (1) 863 34 32.8 73.3

MAC Erythromycin 8

BGD (3); IND (1); IRA (1); NEP (1); THA (2)

763 86 25.0 100

Tylosin 3 BGD (2); JAP (1) 455 75 13.3 100

PEN

Amoxicillin 4 CHI (1); IND (1); THA (1); VIE (1)

513 59 53.7 86.0

Ampicillin 24

BGD (4); CHI (6); IND (1); IRA (1); JAP (4); NEP (1); ROK (1); SRI (1); THA (3); VIE (2)

5,672 67 12.3 100

PHE Chloramphenicol 17

BGD (4); CHI (4); IND (1); IRA (1); JAP (2); NEP (1); ROK (1); THA (1); VIE (2)

4,297 41 0.0 100

Florfenicol 5 CHI (3); JAP (1); THA (1) 740 27 6.0 77.0

POL Colistin 4 CHI (1); JAP (3); 1,503 1 0.0 12.9

QUI

Ciprofloxacin 16 BGD (4); CHI (5); IND (1); IRA (1); NEP (1); ROK (1); THA (1); VIE (2)

3,160 51 0.0 100

Enrofloxacin 12 CHI (5); JAP (4); THA (2); VIE (1)

3,495 37 2.6 100

Nalidixic acid 11 BGD (2); CHI (2); IRA (1); JAP (3); NEP (1); THA (1); VIE (1)

3,249 53 6.0 98.4

SUL Sulfamethoxazole 1 ROK (1) 307 40

TET

Oxytetracycline 7 CHI (1); JAP (4); THA (1); VIE (1)

1,683 61 39.7 100

Tetracycline 14 BGD (4); CHI (3); IND (1); ROK (1); SRI (1); THA (3); VIE (1)

2,559 84 24.0 100

TRI Trimethoprim 7

IND (1); JAP (4); ROK (1); VIE (1)

1,905 24 8.2 90.0

Trim-Sulfa/Cotrim 11 BGD (2); CHI (4); IRA (1); SRI (1); THA (2); VIE (1)

2,613 75 17.0 100

OTH Imipenem 1 CHI (1) 592 0

Vancomycin 1 JAP (1) 1,001 0

68

Table A4-2. Results of AMR studies in E. coli from pigs by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Amikacin 5 CHI (4); ROK (1) 1,257 7 0.0 14.8

Dihydrostrep. 4 JAP (4) 1,116 51 43.0 66.9

Gentamicin 17 CHI (6); IND (1); JAP (5); MAL (1); ROK (2); THA (1); VIE (1)

3,497 24 0.8 80.4

Kanamycin 16 CHI (3); IND (1); JAP (5); MAL (1); ROK (3); THA (2); VIE (1)

3,269 36 0.0 81.0

Streptomycin 6 CHI (1); IND (1); MAL (1); ROK (2); VIE (1)

1,248 66 48.8 92.2

CEP

Cefazolin 9 CHI (3); JAP (4); ROK (2) 2,193 5 0.0 22.0

Ceftiofur 5 CHI (1); JAP (3); THA (1) 1,225 0 0.0 1.8

Cephalothin 4 CHI (1); JAP (1); ROK (2) 1,656 18 7.3 54.0

MAC Erythromycin 1 IND (1) 41 71

Tylosin 1 THA (1) 120 0

PEN

Amoxicillin 4 CHI (2); IND (1); VIE (1) 664 57 30.0 80.4

Ampicillin 15 CHI (5); IND (1); JAP (5); MAL (1); ROK (2); THA (1); VIE (1)

3,460 57 22.6 100

PHE Chloramphenicol 14

CHI (4); IND (1); JAP (4); MAL (1); ROK (3); VIE (1)

3,915 47 5.7 90.3

Florfenicol 4 CHI (3); THA (1) 842 36 3.0 64.5

POL Colistin 6 CHI (1); JAP (4); THA (1) 1,296 5 0.0 35.6

QUI

Ciprofloxacin 11 CHI (5); IND (1); JAP (1); ROK (2); THA (1); VIE (1)

2,155 31 1.6 100

Enrofloxacin 11 CHI (3); JAP (4); ROK (1); THA (2); VIE (1)

2,204 21 0.0 88.0

Nalidixic acid 10 CHI (3); JAP (5); THA (1); VIE (1)

2,369 36 0.8 94.9

SUL Sulfamethoxazole 3 CHI (1); JAP (1); ROK (1) 658 60 42.0 74.0

TET

Oxytetracycline 4 JAP (4) 1,116 70 66.8 80.5

Tetracycline 12 CHI (4); IND (1); JAP (1); MAL (1); ROK (3); THA (1); VIE (1)

3,060 87 52.0 100

TRI Trimethoprim 8

IND (1); JAP (4); MAL (1); ROK (1); VIE (1)

1,554 26 12.2 66.0

Trim-sulfa/Cotrim 7 CHI (3); JAP (1); MAL (1); ROK (2

2,232 61 7.1 91.0

OTH Vancomycin 1 JAP (1) 558 0

69

Table A4-3. Results of AMR studies in E. coli from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Amikacin 3 CHI (2); ROK (1) 585 1 0.0 1.7

Dihydrostrep. 5 JAP (5) 2,544 32 18.2 75.8

Gentamicin 14 BAN (1); CHI (3); IND (2); IRA (1); JAP (4); ROK (2); VIE (1))

2,314 7 0.0 81.6

Kanamycin 8 IND (1); IRA (1); JAP (4); ROK (1); VIE (1)

1,372 9 0.0 70.6

Streptomycin 6 BGD (1); IND (1); IRA (1); ROK (2); VIE (1)

606 27 7.1 88.2

CEP

Cefazolin 7 CHI (1); JAP (4); ROK (2) 1,700 2 0.0 27.0

Ceftiofur 4 CHI (1); JAP (3); 1,195 1 0.0 23.0

Cephalothin 3 IND (1); JAP (1); ROK (1) 481 4 2.3 7.1

MAC Erythromycin 3 BGD (1); IND (1); IRA (1) 180 57 43.2 88.2

PEN

Amoxicillin 3 BGD (1); IND (1); VIE (1) 183 81 20.0 100

Ampicillin 15 BGD (2); CHI (2); IND (2); JAP (6); ROK (2); VIE (1)

2,416 26 3.0 100

PHE Chloramphenicol 11

BGD (1); CHI (1); IND (1); IRA (1); JAP (4); ROK (2); VIE (1)

2,076 10 0.0 65.3

Florfenicol 1 CHI (1) 60 17

POL Colistin 6 CHI (1); IRA (1); JAP (4) 1,224 3 0.0 70.9

QUI

Ciprofloxacin 10 BGD (1); CHI (2); IND (3); JAP (1); ROK (2); VIE (1)

1,242 15 0.0 100

Enrofloxacin 8 CHI (1); IRA (1); JAP (4); ROK (1); VIE (1)

1,558 2 0.0 22.0

Nalidixic acid 8 CHI (1); IND (1); JAP (5); VIE (1)

1,659 13 0.0 75.0

SUL Sulfamethoxazole 2 JAP (1); ROK (1) 292 19 13.0 28.6

TET Oxytetracycline 7 IRA (1); JAP (5); VIE (1) 2,581 36 25.3 88.2

Tetracycline 8 BGD (1); CHI (1); IND (3); JAP (1); ROK (2)

1,075 38 7.1 68.4

TRI

Trimethoprim 8 IND (2); JAP (4); ROK (1); VIE (1)

1,389 6 0.0 42.8

Trim-sulfa/Cotrim 4 CHI (1); BGD (1); JAP (1); ROK (1)

1,949 3 0.0 50.0

OTH Vancomycin 1 JAP (1) 646 0

70

ANNEX 5: AMR STUDIES AND SUMMARY STATISTICS FOR ENTEROCOCCUS SPP.

Table A5-1. Results of AMR studies in E. faecalis from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 1 JAP (1) 419 38

Gentamicin 2 JAP (1); TAI (1) 1,440 30 3.0 55.0

Kanamycin 1 JAP (1) 419 27

Streptomycin 1 TAI (1) 860 74

MAC Erythromycin 3 JAP (2); TAI (1) 1,620 75 36.7 93.0

Tylosin 1 JAP (1) 180 4

PEN Ampicillin 1 TAI (1) 1,021 0

Penicillin 1 TAI (1) 1,021 1

PHE Chloramphenicol 3 JAP (2); TAI (1) 1,620 47 3.6 77.0

QUI Ciprofloxacin 1 TAI (1) 1,021 36

Enrofloxacin 1 JAP (1) 419 2

TET Oxytetracyclin 2 JAP (2) 599 73 59.0 92.8

Tetracycline 1 TAI (1) 1,021 97

OTH Vancomycin 1 JAP (1) 251 0

Table A5-2. Results of AMR studies in E. faecalis from pigs by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 1 JAP (1) 154 50

Gentamicin 1 JAP (1) 154 18

Kanamycin 1 JAP (1) 154 37

MAC Erythromycin 2 JAP (2) 275 54 53.2 54.5

Tylosin 1 JAP (1) 121 68

PHE Chloramphenicol 2 JAP (2) 275 32 26.0 40.5

QUI Enrofloxacin 1 JAP (1) 154 1

TET Oxytetracycline 2 JAP (2) 275 79 74.7 84.3

Table A5-3. Results of AMR studies in E. faecalis from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 1 JAP (1) 37 46

Gentamicin 1 JAP (1) 37 16

Kanamycin 1 JAP (1) 37 27

MAC Erythromycin 2 JAP (2) 56 21 15.8 24.3

Tylosin 1 JAP (1) 19 52

PHE Chloramphenicol 2 JAP (2) 56 11 8.1 15.8

QUI Enrofloxacin 1 JAP (1) 37 0

TET Oxytetracycline 2 JAP (2) 56 45 36.8 48.6

71

Table A5-4. Results of AMR studies in E. faecium from poultry by compound

Class Compound Studies Countries N % Res. Min Max

AMI

Dihydrostrep. 1 JAP (1) 337 25

Gentamicin 2 JAP (1); TAI (1) 1,304 10 0.6 20.0

Streptomycin 1 TAI (1) 848 59

MAC Erythromycin 4 JAP (2); TAI (2) 1,415 70 10.7 94.0

PEN Ampicillin 2 JAP (1); TAI (1) 1,078 8 0.0 16.0

Penicillin 1 TAI (1) 967 71 30.8 88.3

PHE Chloramphenicol 1 TAI (1) 967 36

QUI Ciprofloxacin 1 TAI (1) 967 54

TET Oxytetracycline 2 JAP (2) 448 61

Tetracycline 1 TAI (1) 967 98

OTH Quinupristin 1 TAI (1) 848 79

Vancomycin 2 JAP (2) 289 0

Table A5-5. Results of AMR studies in E. faecium from pigs by compound

Class Compound Studies Countries N % Res. Min Max

AMI Dihydrostrep. 1 JAP (1) 128 38

Gentamicin 1 JAP (1) 128 0

MAC Erythromycin 2 JAP (2) 238 26 23.6 28.1

Tylosin 1 JAP (1) 110 57

PEN Ampicillin 1 JAP (1) 110 0

TET Oxytetracycline 2 JAP (2) 238 64 57.0 72.7

OTH Vancomycin 1 JAP (1) 128 0

Table A5-6. Results of AMR studies in E. faecium from ruminants by compound

Class Compound Studies Countries N % Res. Min Max

AMI Dihydrostrep. 1 JAP (1) 106 11

Gentamicin 1 JAP (1) 106 0

MAC Erythromycin 2 JAP (2) 251 5 4.1 5.7

Tylosin 1 JAP (1) 145 26

PEN Ampicillin 1 JAP (1) 145 1

TET Oxytetracycline 2 JAP (2) 251 29 26.7 33.0

OTH Vancomycin 1 JAP (1) 106 0