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Antimicrobial A-gents

ELSEVIER International Journal of Antimicrobial Agents 5 (1995) 101-106

The worldwide prevalence of methicillin-resistant Staphylococcus aureus

Andreas Vossa**, Bradley N. Doebbelingb

Utziversiry Hospitul Nijnlegen, Department of Medical Microbiology, RO. Box 9101, 6500 HB Nijmegen. The Netlrrrhncis hThe University of Iowa College of Medicine, Department of Inlernul Medicine, IOWU City. IA, CSA

Accepted 16 May 1994

Abstract Literature on the occurrence of methicillin-resistant Staphylococcus aureus (MRSA) in hospitals and long-term-care facilities in

various countries of America, Africa, Asia, Australia/New Zealand, and Europe is reviewed. It is concluded that the increasing prevalence of MRSA is a worldwide problem, affecting both affluent and poor countries, and that infection control guidelines are needed in all regions affected.

Keywords: Staphylococcus uureus; Methicillin resistance; Nosocomial infections

1. Introduction

At a time when the majority of nosocomial staphylococcal isolates were already penicillin-resistant, the introduction of semi-synthetic beta-lactamase-resistant penicillins was a major therapeutical breakthrough [12]. Unfortunately the first methicillin-resistant Staphylococ- cus aureus (MRSA) was isolated just a year later in Lon- don [26]. MRSA became a clinical and therapeutical problem with the occurrence of multi-resistant strains in the late 1970s [6,7]. Today MRSA is recognized as a major nosocomial pathogen, causing nosocomial infections in community and referral hospitals, as well as long-term-care facilities throughout the world [3,27,38,44,61]. Differences in the virulence of methicillin-resistant and methicillin-susceptible strains of Staphylococcus uureus have been debated [4,23,37,46]. However, infections with MRSA continue to challenge clinicians, hospital epidemiologists and administrators, since they lead to important therapeutical and infection control problems, and significant costs [6,10].

Using phage typing in the 1960s Lidwell and colleagues demonstrated that patients admitted to the hospital gradually become colonized with staphylococci, pri- marily from other patients, although transfer of strains

*Corresponding author.

from health care workers (HCWs) was also important. Recently, higher rates of MRSA carriage have been found among patients than hospital staff [41]. Chronic colonization or infections of tracheostomies, as well as wound or decubitus ulcers are important hospital reser- voirs of MRSA [60]. Chronic nasal carriage has been convincingly demonstrated as the primary reservoir site [49]. Therefore patients or HCWs that are MRSA carriers may be the source of case clusters, leading to outbreaks of MRSA infection which are reported inter- mittently throughout the world. Furthermore, the envi- ronment may serve as the source of an MRSA epidemic, as seen among inpatients with severe psoriasis or skin ulcers who received oatmeal baths in a common bathtub [69]. Other hospitals have had recurrent outbreaks of MRSA, up to four in seven years [9]. MRSA outbreaks and the occurrence of epidemic strains have been reported in Australia [5,13,74], Argentina [29], Belgium [58], Canada [51], Denmark [25], France [29], Germany [71], Greece [29], Hong Kong [15], Italy [29], Japan [59], Malaysia [21], Netherlands [16,68], New Zealand [22], Portugal [35], Saudi Arabia [19], Spain [45,64], Sin- gapore [14], Sweden [48], Taiwan [8], United Kingdom [36,47,50] and United States of America [3,18,42].

This review will focus on the prevalence of MRSA in hospitals and long-term-care facilities. Since a number of papers do not state whether special methods necessary to reliably detect MRSA were used, the interpretation of

0924-8579/95/$29.00 0 1995 Elsevier Science Publishers B.V. All rights reserved SSDI 0924-8579(94)00036-T

102 A. Voss. B. N. Doehhelit~~llrrtrn~crtionul Jo~muI of Antimicrohiul Agents 5 (1995) 101-106

the data reviewed herein is limited to a certain degree. No attempt was undertaken to summarize data on the incidence or distribution of antibiotic resistance since these data are not reported in most published studies, and presumably vary greatly even on a national level (e.g. ciprofloxacin-resistance in various German areas: < 5% to >95%). MRSA antibiotic resistance in European countries using standardized and uniform testing methods has been recently reviewed [32,73].

2. America

colonized with methicillin-susceptible strains [37]. How- ever, severe underlying comorbidity was also strongly associated with MRSA colonization in the study; the results observed may have been due to such confounders which were not adequately controlled. Independent pre- dictors of colonization at admission include prior positive MRSA culture, male gender, urinary incontinence, and pressure sores [39]. Careful handwashing and use of gloves may limit spread within nursing homes [39]. Col- onized patients may be identified with targeted surveillance cultures of the most debilitated patients at admission, and those with a history of prior carriage [39].

United States South America Overall, 97% of U.S. hospitals reported having pa- Data from continent-wide or even nation-wide preva-

tients with MRSA between 1987 and 1989. The propor- lence studies were not available. However, interhospital tion of hospitals with large numbers of MRSA cases spread of MRSA - a known problem [20,28] ~ was re- (> 50 per year) increased significantly from 18% to ported by Sader et al. from Sao Paulo. Brazil [54]. The 32% during the same period [3]. Approximately 11% of authors highlighted a particularly interesting aspect of the S. aureus isolates from U.S. hospitals in the National the problem, namely the influence of the socioeconomic Nosocomial Infections Surveillance (NNIS) System situation on the prevalence of certain MRSA strains. from 1975 through 1991 tested for susceptibility to meth- Based on their molecular epidemiology study, the au- icillin, oxacillin, or nafcillin were resistant [44]. The pro- thors suggested the dissemination of a unique oxacillin-

portion of MRSA among all U.S. hospitals rose from and quinolone-resistant strain of S. aweus in several

2.4% in 1975 to 29% in 1991, although the rate of in- hospitals of Sao Paulo. They concluded that this spread

crease varied significantly among different sized hospi- is due to the disproportionate distribution of hospitals,

tals [44]. In 1991. hospitals with less than 200 beds had an extremely low health care worker-to-patient ratio,

15% of S. uUreU.s isolates that were MRSA, increasing and employment of poorly paid HCWs in two or more

with hospital size to 38% of isolates in hospitals with 500 hospitals. These observations may apply to other heavily

or more beds. MRSA has also been reported to measur- populated and poor areas of the world, thus potentially

ably add to the overall burden of nosocomial infections explaining an increased prevalence of certain MRSA

]571. strains.

MRSA colonization of patients is common in long- term-care facilities. Thurn et al. recently reported that approximately 12% of nursing homes in Minnesota had residents known to be colonized with MRSA and 69% of those facilities had sought outside help with control [62]. In contrast, 81% of facilities in western New York h?d identified patients with MRSA in the previous year [40]. Culturing of residents occurred infrequently and many facilities did not have written policies for colonized or infected residents. Policies regarding care of colonized or infected patients in nursing homes were not uniform [62]. Only bed size was an independent predictor of the number of residents with MRSA [40]. In prospective studies, the carrier state appears to be little affected by a roommates carrier status [4,24]. However, MRSA carriage in long-term-care facilities is infrequently associated with prior hospitalization.

3. Africa

Nigeria MRSA in Nigerian hospitals has been reported only

recently [1,53]. At the university hospital in Lagos, the proportion of methicillin-resistant isolates among S. au- rem rose from less than 2% in 1985 to 50% in 1987 [53,67]. Molecular typing indicated that the isolates from the two periods were unrelated and showed no similarity to epidemic MRSA strains of Australia or the UK [67].

4. Asia

Japan Although high levels of endemic MRSA colonization

were present in a Veterans Affairs facility, only 10% of newly admitted patients acquired MRSA during one year of follow-up and MRSA infections were rare [4]. In contrast, Muder and colleagues reported that MRSA- colonized patients in a similar facility had a nearly four times greater risk of staphylococcal infection than those

Among all countries of the world, Japan appears to be one of those mostly impacted with the occurrence of MRSA. The proportion of methicillin-resistant strains among S. aureus isolates from 43 university hospitals was as high as 60% in 1991 [27]. An even higher prevalence of MRSA was reported in the surgery department of another university hospital [57]. During a two-year

A. Voss, B.N. DoebbelinglInternational Journal of Antimicrobial Agents 5 (1995) 101-106 103

study period the average rate of clinical MRSA isolates was 83%. Similarly, the proportion of MRSA among all S. aureus strains causing skin infections at the Medical University of Osaka was 41.5% in 199 1, indicating a high proportion even among strains only causing infections 1391.

China No national surveys were available to determine the

prevalence of MRSA in China and data on regional occurrence varied markedly. The Tian Tan Hospital in Peking reported 15.6% of S. aureus isolates to be methicillin-resistant, a rate reportedly lower than in other districts of the area [56]. Among strains of S. aureus randomly collected from a university hospital in Wuhan, MRSA accounted for 79.6% of all isolates, responsible for over 90% of S. aureus isolates in some departments. Hands of HCWs were swabbed and 68.9% were found to be MRSA-carriers [I I].

5. Australia/New Zealand

Australiu Turnidge et al. performed a national survey involving

14 teaching hospitals in major Australian cities [66]. The study was conducted over three separate periods during 19861987. The national prevalence of MRSA was found to be 14.4%, with a wide variation among the different states: 25.2% in Queensland, 23.5% in Victoria, 12.6% in New South Wales, 11.3% in South Australia and 0.4% in Western Australia [66]. This study, as spo- radic reports of epidemic spread, e.g. among Victorian hospitals with a prevalence of 2040% [43], shows that MRSA is a major nosocomial pathogen especially in large hospitals in Eastern Australia. The increase in the isolation of MRSA in Eastern Australia was not only suspected to be associated with the spread of a particular epidemic MRSA strain, such as those seen in London hospitals, but was also shown to be indistinguishable from the London epidemic isolates by restriction endo- nuclease analysis of plasmid DNA [63]. Interestingly, the differences between Western and Eastern Australia re- semble those between Northern and Southern Europe, and furthermore led to similar prevention strategies. After an outbreak at the Royal Perth Hospital due to a patient who was transferred from outside the state, a screening of all patients and health care workers who had been in hospitals outside Western Australia was imple- mented. During the first two years of this screening pro- gram 4.3% of the patients were found to harbour MRSA, and no further serious outbreaks were observed [31].

New) Z&and According to a recent study, MRSA is isolated only

infrequently in New Zealand and has not become en-

demic in hospitals. From 1988 to 1990 only 235 patients were infected or colonized with MRSA. These were included in the three outbreaks involving more than 20 patients each that were reported to the New Zealand Communicable Disease Center. Interestingly, 30-50% of the MRSA strains originated from over- seas, mainly from Australia and the Pacific Islands [22,34].

6. Europe

Western Europe Data on the frequency of MRSA in Europe have

so far been based on the numerous reports of recent MRSA outbreaks in various European countries [2,15,17.36,45,58,68,71], and on the reports of epidemic strains that were recognized to spread in certain areas, such as the EMRSA-1 in the North Thames or EMRSA- 3 in the South-east Thames regions in England [30,33]. Only a few European countries have performed surveillance or national surveys [30,52,55,68,71]. A recently conducted systematic survey in 43 laboratories from ten European countries documented a marked difference in the prevalence of MRSA in different parts of Europe [73]. Of the more than 7000 S. uureus isolates screened by a uniform method, 12.8% were shown to be methicillin-resistant. The proportion of MRSA in the sur- veyed European countries ranged from 0.1% and 0.3% in Denmark and Sweden respectively, to > 30% in Spain, France and Italy. MRSA was most frequently isolated from patients in the surgical and internal medicine serv- ices, with a higher prevalence among patients in intensive care units. This was especially evident in Italy and Aus- tria, where more than 50% of all staphylococcal isolates from ICUs were MRSA. Approximately 87% of the MRSA strains (using the international set of phages up to 1000x RTD) could be typed, with up to 93% typed with the use of experimental phages. Strains of group III and especially those typeable with phage 77 were pre- dominant, a result observed by other investigators. Vin- de1 et al. in Spain reported that MRSA strains classified as phage group III (and a second non-typeable group) are increasingly involved in hospital infections since 1989. and are creating epidemics in different regions of Spain today [70]. For each region phage typing detected one or a few dominant (epidemic) types, although 46% of the strains were unique. The European MRSA popu- lation therefore seems to be a mixture of epidemic and non-epidemic strains.

CentraNEustern Europe Recently a prospective study on the prevalence of

MRSA in the Alpe-Adria region (including Hungary, Poland. Czech/Slovakian Republics and the former Yu- goslavia) was conducted [72]. More than 1400 S. wreus

104 A. Voss, B.N. Doebbelingllnternational Journal of Antimicrobial Agents 5 (I995) 101-106

strains were screened using standard methods and overall 218 (15.6%) MRSA strains were found. The proportion of MRSA among S, aureu~ isolates from university- affiliated hospitals was lowest in the CzechlSlovakian Republics (4.3%) and Hungary (8.6%). Similar propor- tions were reported in national surveys in the Czech Republic (7%) and Hungarian (6%) university hospitals (Urbascova P, Hatala M and Ban E, Konkoly-Thege: Abstracts, Gram-positive infection in Central Europe, Prague, 13 November 1993). In Poland and Yugoslavia, 19.7% and 30.9%, respectively, of the strains were methicillin-resistant [72]. Although the distribution of the isolates by medical specialty in these Eastern European countries was similar to those in Western Europe, East- ern European patients colonized or infected with MRSA were typically younger (mean age 35 years) and less frequently hospitalized in intensive care units (mean 28.7%). In a local survey, MRSA accounted for 13.7% of all S. aureus isolates tested at a Warsaw institute during 1992 [65]. In a national survey on the antibiotic resistance of S. aureu~ in Poland a year later, the same authors found 27% of the strains to be methicillin-resistant (Hryniewicz W. Trzcinski K: Abstract, Gram-positive infection in Central Europe, Prague, 13 November 1993). Outbreaks and endemic MRSA continue to occur as well. Currently, the proportion of MRSA in neonatal units in Warsaw is as high as 65% (personal communica- tion) .

The reports reviewed herein demonstrate that the increasing prevalence of MRSA is a worldwide problem. Despite certain national epidemiological problems, both aftluent and poor countries are affected by the occurrence of MRSA and equally in need of infection control guidelines and antibiotic restriction policies to potentially limit the spread of MRSA, locally, nationally and internationally.

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