بسم الله الرحمن الرحيم Emerging Diseases Antimicrobial Resistance Shahid Beheshti University of medical sciences 2008 2008 By: Hatami H. MD. MPH

بسم الله الرحمن الرحيمبسم الله الرحمن الرحيمEmerging DiseasesEmerging DiseasesAntimicrobial ResistanceAntimicrobial Resistance

Shahid Beheshti University of Shahid Beheshti University of medical sciencesmedical sciences

20082008

By: Hatami H. MD. MPHBy: Hatami H. MD. MPH

IntroductionIntroduction Antimicrobial resistance is not a newAntimicrobial resistance is not a new

or surprising phenomenonor surprising phenomenon

All micro-organisms have the ability All micro-organisms have the ability to evolve various ways of protecting to evolve various ways of protecting themselves from attackthemselves from attack

But over the last decadeBut over the last decade

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IntroductionIntroduction

Antimicrobial resistance has Antimicrobial resistance has increasedincreased

The pace of development for new and The pace of development for new and replacement antimicrobialsreplacement antimicrobials

have decreasedhave decreased

::But over the last decadeBut over the last decade

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The increasing threat of The increasing threat of antimicrobial resistanceantimicrobial resistance

Penicillin was once 100% successfulPenicillin was once 100% successful

for curing gonorrheafor curing gonorrhea

Now it is virtually useless againstNow it is virtually useless against

gonorrhea in all of the worldgonorrhea in all of the world

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Streptomycin was once the mostStreptomycin was once the most

effective drug we had to cure TBeffective drug we had to cure TB

It is no longer effective in manyIt is no longer effective in many

European countriesEuropean countries


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Chloroquine and sulfadoxineChloroquine and sulfadoxine

pyrimethamine could once stoppyrimethamine could once stop

malariamalaria

Now they can notNow they can not


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Lamivudine , recently developed to Lamivudine , recently developed to treat hepatitis Btreat hepatitis B

Has quickly become ineffective inHas quickly become ineffective in

percent of patientspercent of patients


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How resistance develops How resistance develops and spreads (1)and spreads (1)

* Microbiology * Microbiology (Natural selection)(Natural selection)

* The Poverty Paradigm * The Poverty Paradigm * Misdiagnosis and Resistance* Misdiagnosis and Resistance * Counterfeit Drugs* Counterfeit Drugs * Dubious Pay-offs and High-* Dubious Pay-offs and High-

priced Prescriptionspriced Prescriptions

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** Advertising for ResistanceAdvertising for Resistance * Lack of Education* Lack of Education * Resistance and Hospitals* Resistance and Hospitals * Antimicrobial Resistance and * Antimicrobial Resistance and FoodFood * Globalization and Resistance* Globalization and Resistance

How resistance developsHow resistance develops and spreads (2)0and spreads (2)0

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Misdiagnosis and ResistanceMisdiagnosis and Resistance

In Viet Nam more than 70% In Viet Nam more than 70% inadequate and 25% unnecessaryinadequate and 25% unnecessary

In China 63% the wrong choiceIn China 63% the wrong choice

In Bangladesh 50% inappropriateIn Bangladesh 50% inappropriate

In the North America 50% over In the North America 50% over prescribeprescribe

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Counterfeit DrugsCounterfeit Drugs

About 51% of counterfeiting cases About 51% of counterfeiting cases uncovered by WHO revealeduncovered by WHO revealed

that forged drugs carriedthat forged drugs carried

No active ingredientNo active ingredient

Wrong ingredient 17%Wrong ingredient 17%

Weaker concentration 11%Weaker concentration 11%

The same quality and quantity 4%The same quality and quantity 4%

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Dubious Pay-offs andDubious Pay-offs andHigh-priced prescriptionsHigh-priced prescriptions

Unethical pharmaceutical Unethical pharmaceutical companies pay a commission forcompanies pay a commission for

recommending more expensiverecommending more expensive

broader-spectrum medicationsbroader-spectrum medications

This troubling development This troubling development accelerates the natural processaccelerates the natural process

of resistanceof resistance

Unethical pharmaceutical Unethical pharmaceutical companies pay a commission forcompanies pay a commission for

recommending more expensiverecommending more expensive

broader-spectrum medicationsbroader-spectrum medications

This troubling development This troubling development accelerates the natural processaccelerates the natural process

of resistanceof resistance

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Advertising for ResistanceAdvertising for Resistance

Patient demand for antimicrobialsPatient demand for antimicrobials

sometimes the result ofsometimes the result of

TVTV

MagazineMagazine

InternetInternet

NewspaperNewspaper

Spouse the development ofSpouse the development of

resistanceresistance

Patient demand for antimicrobialsPatient demand for antimicrobials

sometimes the result ofsometimes the result of

TVTV

MagazineMagazine

InternetInternet

NewspaperNewspaper

Spouse the development ofSpouse the development of

resistanceresistance

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Resistance and HospitalsResistance and Hospitals

Between 40% and 91% of Between 40% and 91% of antibiotics prescribed in 10 studiesantibiotics prescribed in 10 studies

were inappropriatewere inappropriate

Health care workers of ten Health care workers of ten disregarded basic hygiene practicesdisregarded basic hygiene practices

Hand washingHand washing

Changing glovesChanging gloves

Inadequately cleaned equipmentInadequately cleaned equipment

* ** *

* ** *

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Antimicrobial Resistance and Antimicrobial Resistance and foodfood

50% 50% of antibiotics are used to :of antibiotics are used to :

1- Treat sick animals1- Treat sick animals

2- As growth promoters2- As growth promoters

3- rid cultivated3- rid cultivated

foodstuffsfoodstuffs

Development of resistance Development of resistance

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Resistance traits spreadResistance traits spread

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Animal resistance and Animal resistance and foodfood

Vancomycin-resistant Vancomycin-resistant enterococcus faecium (VRE) is enterococcus faecium (VRE) is one particularly ominous example one particularly ominous example of a resistant bacterium appearing of a resistant bacterium appearing in animals that may have jumped in animals that may have jumped into more vulnerable segments of into more vulnerable segments of the human populationthe human population

Vancomycin-resistant Vancomycin-resistant enterococcus faecium (VRE) is enterococcus faecium (VRE) is one particularly ominous example one particularly ominous example of a resistant bacterium appearing of a resistant bacterium appearing in animals that may have jumped in animals that may have jumped into more vulnerable segments of into more vulnerable segments of the human populationthe human population

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Impact of globalizationImpact of globalization

In the Middle Ages deadly plaguesIn the Middle Ages deadly plagues

were shipped from one continent towere shipped from one continent to

another ( flea - rat )another ( flea - rat )00

Today they travel by plane from oneToday they travel by plane from one

corner of the earth to another in acorner of the earth to another in a

matter of hoursmatter of hours

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* Mortality * Mortality * Morbidity * Morbidity * Cost * Cost * Limited solutions * Limited solutions

Consequences ofConsequences ofAntimicrobial ResistanceAntimicrobial Resistance

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Resistance means thatResistance means that

People can not be effectively treatedPeople can not be effectively treated

People are ill for longerPeople are ill for longer

People are at greater risk of dyingPeople are at greater risk of dying

Epidemics are prolongedEpidemics are prolonged

Others are at greater risk of infectionOthers are at greater risk of infection

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Major infectious killersMajor infectious killers

* Pneumonia* Pneumonia * Diarrhoeal Diseases* Diarrhoeal Diseases * AIDS* AIDS * Tuberculosis* Tuberculosis * Malaria* Malaria * Viral Hepatitis* Viral Hepatitis * Hospital-Acquired Infections* Hospital-Acquired Infections * Leishmaniasis* Leishmaniasis * Gonorrhoea* Gonorrhoea * Common worms* Common worms

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WHO's RecommendationsWHO's Recommendations11. . Adopt WHO Strategies and PoliciesAdopt WHO Strategies and Policies22. Educate Health Workers and the Public on . Educate Health Workers and the Public on

the Use of Medicinesthe Use of Medicines33. Contain Resistance in the Hospital. Contain Resistance in the Hospital44. Reduce the Use of Antimicrobials in . Reduce the Use of Antimicrobials in

LivestockLivestock55. Increase Research for new Drugs and . Increase Research for new Drugs and

VaccinesVaccines66. Build Alliances and Partnerships to . Build Alliances and Partnerships to

Increase Access to AntimicrobialsIncrease Access to Antimicrobials77. Increase Availability of Essential Drugs. Increase Availability of Essential Drugs88. Make Effective Medicines Available to Poor . Make Effective Medicines Available to Poor

PeoplePeople4242

CDC: CDC: 12 Steps to Prevent 12 Steps to Prevent Antimicrobial Resistance Antimicrobial Resistance

Among Hospitalized Adults to Among Hospitalized Adults to Prevent InfectionPrevent Infection

(A campaign to educate (A campaign to educate Doctors)Doctors)

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12 Steps to Prevent Antimicrobial 12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsResistance: Hospitalized Adults

1.1. VaccinateVaccinate

2.2. Get the catheters outGet the catheters out

3.3. Target the pathogenTarget the pathogen

4.4. Access the expertsAccess the experts

5.5. Practice antimicrobial controlPractice antimicrobial control6.6. Use local dataUse local data7.7. Treat infection, not contaminationTreat infection, not contamination8.8. Treat infection, not colonization Treat infection, not colonization 9.9. Know when to say “no” to vancoKnow when to say “no” to vanco10.10. Stop treatment when infection is Stop treatment when infection is

cured or unlikely cured or unlikely

11.11. Isolate the pathogenIsolate the pathogen12. Contain the contagion12. Contain the contagion

Diagnose and Treat Diagnose and Treat Infection Infection EffectivelyEffectively

Prevent InfectionPrevent InfectionUse Antimicrobials Use Antimicrobials WiselyWisely

Prevent TransmissionPrevent Transmission

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Fact:Fact:Predischarge influenza and Predischarge influenza and pneumococcal vaccination of at-pneumococcal vaccination of at-risk risk hospital patientshospital patients AND AND influenza vaccination of influenza vaccination of healthcare personnelhealthcare personnel will prevent will prevent infections. infections.

Prevent InfectionPrevent Infection

Step 1: VaccinateStep 1: Vaccinate

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ActionsActions::give influenza/give influenza/S. pneumoniaS. pneumonia vaccine to vaccine to

at-risk patients before discharge at-risk patients before dischargeget influenza vaccine annuallyget influenza vaccine annually

Prevent InfectionPrevent InfectionStep 1: VaccinateStep 1: Vaccinate

FactFact: : Predischarge influenza and pneumococcal Predischarge influenza and pneumococcal vaccinationvaccination

of at-risk hospital patients and influenza of at-risk hospital patients and influenza vaccination of vaccination of

healthcare personnel will prevent infections.healthcare personnel will prevent infections.

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FactFact: :

Catheters and other invasive devices are Catheters and other invasive devices are the #1 exogenous cause of hospital-the #1 exogenous cause of hospital-acquired infections.acquired infections.


Step 2: Get the catheters outStep 2: Get the catheters out

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FactFact:: Catheters and other invasive devices are the #1 Catheters and other invasive devices are the #1 exogenous cause of hospital-acquired infections. exogenous cause of hospital-acquired infections.

ActionsActions::use catheters only when essentialuse catheters only when essentialuse the correct catheteruse the correct catheteruse proper insertion and catheter-careuse proper insertion and catheter-care

protocols protocolsremove catheters when not essential remove catheters when not essential

Prevent InfectionPrevent InfectionStep 2: Get the catheters outStep 2: Get the catheters out

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FactFact::Appropriate antimicrobial therapy Appropriate antimicrobial therapy (correct regimen, timing, dosage, route, (correct regimen, timing, dosage, route, and duration) saves lives. and duration) saves lives.

Diagnose and Treat Infection Effectively Diagnose and Treat Infection Effectively

Step 3: Target the pathogenStep 3: Target the pathogen

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Fact: Fact: Appropriate antimicrobial therapy saves lives.Appropriate antimicrobial therapy saves lives.

ActionsActions:: culture the patient culture the patient target target empiric therapyempiric therapy to likely to likely

pathogens and local antibiogrampathogens and local antibiogram target target definitive therapydefinitive therapy to known to known

pathogens and antimicrobial pathogens and antimicrobial susceptibility test resultssusceptibility test results

Diagnose and Treat Infection EffectivelyDiagnose and Treat Infection Effectively Step 3: Target the pathogenStep 3: Target the pathogen

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FactFact::

Infectious diseases expert input Infectious diseases expert input improves the outcome of serious improves the outcome of serious infections.infections.

Diagnose and Treat Infection EffectivelyDiagnose and Treat Infection Effectively

Step 4: Access the expertsStep 4: Access the experts

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Infectious Diseases Expert Infectious Diseases Expert ResourcesResources

Infectious Diseases Infectious Diseases SpecialistsSpecialists

Optimal Optimal Patient CarePatient Care

Optimal Optimal Patient CarePatient Care

Infection Control Infection Control ProfessionalsProfessionals

Healthcare Healthcare EpidemiologistsEpidemiologists

ClinicalClinicalPharmacistsPharmacists

Clinical Clinical PharmacologistsPharmacologists

Surgical InfectionSurgical InfectionExpertsExperts

ClinicalClinicalMicrobiologisMicrobiologis

tsts

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FactFact:: Infectious diseases expert input improves theInfectious diseases expert input improves the

outcome of serious infections.outcome of serious infections.

ActionAction:: consult infectious diseases experts consult infectious diseases experts

about patients with serious about patients with serious infectionsinfections

Diagnose and Treat Infection Diagnose and Treat Infection EffectivelyEffectively

Step 4: Access the expertsStep 4: Access the experts

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Fact:Fact: Programs to improve Programs to improve antimicrobial use are effective.antimicrobial use are effective.

Use Antimicrobials WiselyUse Antimicrobials Wisely

Step 5: Practice Step 5: Practice antimicrobial controlantimicrobial control

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Methods to Improve Methods to Improve Antimicrobial UseAntimicrobial Use

Passive prescriber education Passive prescriber education Standardized antimicrobial order formsStandardized antimicrobial order forms Formulary restrictionsFormulary restrictions Prior approval to start/continuePrior approval to start/continue Pharmacy substitution or switch Pharmacy substitution or switch Multidisciplinary drug utilization evaluation Multidisciplinary drug utilization evaluation

(DUE)(DUE) Interactive prescriber educationInteractive prescriber education Provider/unit performance feedbackProvider/unit performance feedback Computerized decision support/online Computerized decision support/online

orderingordering55555555

Use Antimicrobials WiselyUse Antimicrobials WiselyStep 5: Practice Step 5: Practice antimicrobial controlantimicrobial control

FactFact::Programs to improve antimicrobial Programs to improve antimicrobial use are effective.use are effective.

ActionAction::engage in local antimicrobial engage in local antimicrobial

use quality improvement use quality improvement efforts efforts

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FactFact::The prevalence of resistance can The prevalence of resistance can vary by time, locale, patient vary by time, locale, patient population, hospital unit, and length population, hospital unit, and length of stay.of stay.


Step 6: Use local dataStep 6: Use local data

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Use Antimicrobials WiselyUse Antimicrobials Wisely Step 6: Use local dataStep 6: Use local data

FactFact::The prevalence of resistance can vary by The prevalence of resistance can vary by locale, patient population, hospital unit, locale, patient population, hospital unit, and length of stay.and length of stay.

ActionsActions::know your local antibiogramknow your local antibiogram

know your patient populationknow your patient population

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Interpreting a “Positive” Blood Interpreting a “Positive” Blood CultureCulture

True BacteremiaTrue Bacteremia:: UnlikelyUnlikely UncertainUncertain LikelyLikely

• S. aureusS. aureus• S. pneumoniaeS. pneumoniae• EnterobacteriaceaeEnterobacteriaceae• P. aeruginosaP. aeruginosa• Candida albicansCandida albicans

• Corynebacterium Corynebacterium sppspp..• Non-anthracis Non-anthracis Bacillus Bacillus sppspp..• Propionibacterium acnesPropionibacterium acnes

• Coagulase-negative Coagulase-negative staphylococcistaphylococci

Pre-test Pre-test probabilityprobabilitypatient risk factorspatient risk factorsprosthetic devicesprosthetic devicesclinical evidenceclinical evidence

Post-test probabilityPost-test probability# positive/# cultures # positive/# cultures compare compare antibiograms antibiograms compare genotypescompare genotypes

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FactFact::

A major cause of antimicrobial A major cause of antimicrobial overuse is “treatment” of overuse is “treatment” of contaminated cultures. contaminated cultures.


Step 7: Treat infection,Step 7: Treat infection,not contaminationnot contamination

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FactFact:: A major cause of antimicrobial A major cause of antimicrobial overuse is “treatment” of overuse is “treatment” of colonization. colonization.


Step 8: Treat infection, Step 8: Treat infection, not colonizationnot colonization

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Use Antimicrobials WiselyUse Antimicrobials WiselyStep 8: Treat infection, not Step 8: Treat infection, not

colonizationcolonization

FactFact:: A major cause of antimicrobial overuse is treatment A major cause of antimicrobial overuse is treatment of colonization. of colonization.

ActionsActions::treat pneumonia, not the tracheal treat pneumonia, not the tracheal

aspirateaspiratetreat bacteremia, not the catheter tip or treat bacteremia, not the catheter tip or

hubhubtreat urinary tract infection, not the treat urinary tract infection, not the

indwelling catheter indwelling catheter 62626262

FactFact:: Vancomycin overuse promotes Vancomycin overuse promotes emergence, selection, and spread emergence, selection, and spread of resistant pathogens.of resistant pathogens.


Step 9: Know when to say Step 9: Know when to say “no” to vanco“no” to vanco

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S. aureusS. aureus

PenicillinPenicillin

[1950s][1950s]

Penicillin-resistantPenicillin-resistant

S. aureusS. aureus

Evolution of Drug ResistanceEvolution of Drug Resistance in in S. aureusS. aureus

MethicillinMethicillin

[1970s][1970s]

Methicillin-Methicillin-resistantresistant S. aureus S. aureus (MRSA)(MRSA)

Vancomycin-resistantVancomycin-resistant

enterococci (VRE)enterococci (VRE)

VancomycinVancomycin

[1990s][1990s]

[1997][1997]

VancomycinVancomycin

intermediate-intermediate-resistantresistantS. aureusS. aureus (VISA)(VISA)

VancomycinVancomycin--

resistantresistantS. aureusS. aureus

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Use Antimicrobials WiselyUse Antimicrobials WiselyStep 9: Know when to sayStep 9: Know when to say

“ “no” to vancono” to vanco

FactFact:: Vancomycin overuse promotes emergence, selection, Vancomycin overuse promotes emergence, selection, and spread of resistant pathogens.and spread of resistant pathogens.

ActionsActions::treat infection, not contaminants or treat infection, not contaminants or

colonization colonization fever in a patient with an intravenous fever in a patient with an intravenous

catheter is not a routine indication for catheter is not a routine indication for vancomycinvancomycin

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FactFact::Failure to stop unnecessary Failure to stop unnecessary antimicrobial treatment antimicrobial treatment contributes contributes to overuse and resistance. to overuse and resistance.


Step 10: Stop treatmentStep 10: Stop treatmentwhen infection is cured when infection is cured

or unlikely or unlikely

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FactFact:: Failure to stop unnecessary antimicrobial Failure to stop unnecessary antimicrobial treatmenttreatment contributes to overuse and resistance. contributes to overuse and resistance.

ActionsActions::when infection is curedwhen infection is curedwhen cultures are negative and when cultures are negative and

infectioninfection is unlikely is unlikely

when infection is not diagnosedwhen infection is not diagnosed

Use Antimicrobials WiselyUse Antimicrobials Wisely Step 10: Stop antimicrobial Step 10: Stop antimicrobial

treatmenttreatment

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FactFact::

Patient-to-patient spread of Patient-to-patient spread of pathogens can be prevented.pathogens can be prevented.

Prevent TransmissionPrevent TransmissionStep 11: Isolate the pathogenStep 11: Isolate the pathogen

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Prevent TransmissionPrevent Transmission Step 11: Isolate the pathogenStep 11: Isolate the pathogen

FactFact:: Patient-to-patient spread of pathogens can be Patient-to-patient spread of pathogens can be prevented.prevented.

ActionsActions::use standard infection control use standard infection control

precautions precautions contain infectious body fluids (use contain infectious body fluids (use

approved airborne/droplet/contact approved airborne/droplet/contact isolation precautions)isolation precautions)

when in doubt, consult infection control when in doubt, consult infection control expertsexperts

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FactFact::

Healthcare personnel can spread Healthcare personnel can spread antimicrobial-resistant pathogens antimicrobial-resistant pathogens from patient to patient.from patient to patient.

Prevent TransmissionPrevent TransmissionStep 12: Step 12:

Contain your contagionContain your contagion

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Prevent TransmissionPrevent Transmission Step 12: Break the chain Step 12: Break the chain of contagionof contagion

FactFact:: Healthcare personnel can spread antimicrobial-Healthcare personnel can spread antimicrobial-resistant pathogens from patient to patient.resistant pathogens from patient to patient.

ActionsActions::stay home when you are sick stay home when you are sick contain your contagioncontain your contagionkeep your hands cleankeep your hands cleanset an example!set an example!

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12 Steps to Prevent 12 Steps to Prevent Antimicrobial Resistance: Antimicrobial Resistance:

Hospitalized AdultsHospitalized Adults

12 Contain your contagion12 Contain your contagion 11 Isolate the pathogen11 Isolate the pathogen

10 Stop treatment when cured10 Stop treatment when cured 9 Know when to say “no” to vanco9 Know when to say “no” to vanco 8 Treat infection, not colonization8 Treat infection, not colonization 7 Treat infection, not contamination7 Treat infection, not contamination

6 Use local data6 Use local data 5 Practice antimicrobial control5 Practice antimicrobial control

4 Access the experts4 Access the experts3 Target the pathogen3 Target the pathogen

2 Get the catheters out2 Get the catheters out 1 Vaccinate1 Vaccinate

Prevent TransmissionPrevent Transmission


Diagnose and Treat EffectivelyDiagnose and Treat Effectively


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Antimicrobial Resistance:Antimicrobial Resistance: Key Prevention StrategiesKey Prevention Strategies

Optimize Optimize UseUse

PreventPreventTransmissionTransmission

PreventPreventInfectionInfection

EffectiveEffectiveDiagnosisDiagnosisand Treatmentand Treatment

PathogenPathogenAntimicrobial-ResistantAntimicrobial-Resistant PathogenPathogen

Antimicrobial Antimicrobial ResistanceResistance

Antimicrobial UseAntimicrobial Use

InfectionInfection

Susceptible PathogenSusceptible Pathogen

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Hand washingHand washing7474

Source :Source :

• CDC, Internet citeCDC, Internet cite• WHO, Internet citeWHO, Internet cite

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Documents

بسم الله الرحمن الرحيم Emerging Diseases Antimicrobial Resistance Shahid Beheshti University of medical sciences 2008 2008 By: Hatami H. MD. MPH