MDRO(multidrug resistant organisms)

MDRO(multidrug resistant MDRO(multidrug resistant organisms)organisms)

DefinitionDefinition

microorganisms, predominantly bacteria, microorganisms, predominantly bacteria, that are resistant to one or more classes of that are resistant to one or more classes of antimicrobial agents. Although the names antimicrobial agents. Although the names of certain MDROs describe resistance to of certain MDROs describe resistance to only one agent (e.g., MRSA,VRE), these only one agent (e.g., MRSA,VRE), these pathogens are frequently resistant to most pathogens are frequently resistant to most available antimicrobial agentsavailable antimicrobial agents

MDRO(multidrug resistant MDRO(multidrug resistant organismsorganisms

In addition to MRSA and VRE, certain In addition to MRSA and VRE, certain gram negative bacteria(GNB), including gram negative bacteria(GNB), including those producing extended spectrum beta-those producing extended spectrum beta-lactamases (ESBLs) and others that are lactamases (ESBLs) and others that are resistant to multiple classes of resistant to multiple classes of antimicrobial agents, are of particular antimicrobial agents, are of particular concernconcern

Drug-resistant pathogens are a growing Drug-resistant pathogens are a growing threat to all people, especially in threat to all people, especially in healthcare settings.healthcare settings.

Each year nearly Each year nearly 2 million2 million patients in the United patients in the United States get an infection in a hospital. Of those patients, States get an infection in a hospital. Of those patients, about about 90,000 die90,000 die as a result of their infection. More as a result of their infection. More than than 70%70% of the bacteria that cause hospital-acquired of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most infections are resistant to at least one of the drugs most commonly used to treat them. Persons infected with commonly used to treat them. Persons infected with drug-resistant organisms are more likely to have drug-resistant organisms are more likely to have longer longer hospital stayshospital stays and require and require treatment with treatment with second- or third-choice drugs second- or third-choice drugs that may bethat may be less effective, more toxic, and/or more less effective, more toxic, and/or more expensiveexpensive

Clinical importance of MDROsClinical importance of MDROs

- In most instances, MDRO infections have - In most instances, MDRO infections have clinical manifestations that are similar to clinical manifestations that are similar to infections caused by susceptible pathogens. infections caused by susceptible pathogens. However, options for treating patients with However, options for treating patients with these infections are often extremely limited. these infections are often extremely limited. Although antimicrobials are now available for Although antimicrobials are now available for treatment of MRSA and VRE infections, treatment of MRSA and VRE infections, resistance to each new agent has already resistance to each new agent has already emerged in clinical isolates. emerged in clinical isolates.

- Similarly, therapeutic options are limited for - Similarly, therapeutic options are limited for ESBL-producing isolates of gram-negative ESBL-producing isolates of gram-negative bacillibacilli

-These limitations may influence antibiotic usage -These limitations may influence antibiotic usage patterns in ways that suppress normal flora and patterns in ways that suppress normal flora and create a favorable environment for development create a favorable environment for development of colonization when exposed to potential MDR of colonization when exposed to potential MDR pathogens (i.e., selective advantage).pathogens (i.e., selective advantage).

-Increased lengths of stay, costs, and mortality -Increased lengths of stay, costs, and mortality also have been associated with MDROs.also have been associated with MDROs.

The type and level of care influence the The type and level of care influence the prevalence of MDROs. ICUs, especially prevalence of MDROs. ICUs, especially those at tertiary care facilities, may have a those at tertiary care facilities, may have a higher prevalence of MDRO infections higher prevalence of MDRO infections than do non-ICU settingsthan do non-ICU settings

MethicillinMethicillinResistant Staph (MRSA)Resistant Staph (MRSA)

MRSA was first isolated in the United States in MRSA was first isolated in the United States in 1968.1968.

By the early 1990s, MRSA accounted for 20%-By the early 1990s, MRSA accounted for 20%-25% of 25% of Staphylococcus aureus Staphylococcus aureus isolates from isolates from hospitalized patients. In 1999, MRSA accounted hospitalized patients. In 1999, MRSA accounted for >50% of for >50% of S. aureus S. aureus isolates from patients in isolates from patients in ICUs in the National Nosocomial Infection ICUs in the National Nosocomial Infection Surveillance (NNIS) system; in 2003, 59.5% of Surveillance (NNIS) system; in 2003, 59.5% of S. aureus S. aureus isolates in NNIS ICUs were MRSA .isolates in NNIS ICUs were MRSA .

12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults

Source: National Nosocomial Infections Surveillance (NNIS) System

Methicillin-Resistant Methicillin-Resistant Staphylococcus aureusStaphylococcus aureus(MRSA) Among Intensive Care Unit Patients,(MRSA) Among Intensive Care Unit Patients,

1995-20041995-2004

Vancomycin-Resistant Vancomycin-Resistant enterococcus (VRE)enterococcus (VRE)

A similar rise in prevalence has occurred A similar rise in prevalence has occurred with VRE . From 1990 to 1997, the with VRE . From 1990 to 1997, the prevalence of VRE in enterococcal prevalence of VRE in enterococcal isolates from hospitalized patients isolates from hospitalized patients increased from <1% to approximately 15%increased from <1% to approximately 15%

VRE accounted for almost 25% of VRE accounted for almost 25% of enterococcus isolates in NNIS ICUs in enterococcus isolates in NNIS ICUs in 1999 and 28.5% in 2003 .1999 and 28.5% in 2003 .

Vancomycin-Resistant Vancomycin-Resistant EnterococciEnterococci (VRE) Among Intensive Care Unit (VRE) Among Intensive Care Unit Patients,1995-2004Patients,1995-2004

Gram-negative resistant BacteriaGram-negative resistant Bacteria

-GNB resistant to ESBLs, fluoroquinolones, -GNB resistant to ESBLs, fluoroquinolones, carbapenems, and aminoglycosides also have increased carbapenems, and aminoglycosides also have increased in prevalence. in prevalence.

*For example, in 1997, the SENTRY Antimicrobial *For example, in 1997, the SENTRY Antimicrobial Surveillance Program found that among Surveillance Program found that among K. pneumoniae K. pneumoniae strains isolated in the United States, resistance rates to strains isolated in the United States, resistance rates to ceftazidime and other third-generation cephalosporins ceftazidime and other third-generation cephalosporins were 6.6%, 9.7%, 5.4%, and 3.6% for bloodstream, were 6.6%, 9.7%, 5.4%, and 3.6% for bloodstream, pneumonia, wound, and urinary tract infections, pneumonia, wound, and urinary tract infections, respectively .respectively .

*In 2003, 20.6% of all *In 2003, 20.6% of all K. pneumoniae K. pneumoniae isolates from NNIS isolates from NNIS ICUs were resistant to these drugsICUs were resistant to these drugs

Source: National Nosocomial Infections Surveillance (NNIS) System

33rdrd Generation Cephalosporin-Resistant Generation Cephalosporin-Resistant Klebsiella pneumoniaeKlebsiella pneumoniae Among Among Intensive Care Unit Patients, 1995-2004Intensive Care Unit Patients, 1995-2004

Fluoroquinolone-Resistant Fluoroquinolone-Resistant Pseudomonas aeruginosaPseudomonas aeruginosa Among Intensive Among Intensive Care Unit Patients, 1995-2004Care Unit Patients, 1995-2004

101520

25303540

Campaign to PreventAntimicrobial Resistance

Clinicians hold the solution!

Risk factors that promote antimicrobial resistance in Risk factors that promote antimicrobial resistance in

healthcare settings includehealthcare settings include

Extensive use of antimicrobials Extensive use of antimicrobials Transmission of infection Transmission of infection

Susceptible hostsSusceptible hosts

Key Prevention Strategies

" Prevent infection " Diagnose and treat infection effectively “ Use antimicrobials wisely “ Prevent transmission

Clinicians hold the solution!

Resistant StrainsRare

Resistant Strains Dominant

Antimicrobial Exposure

Selection for antimicrobial-Selection for antimicrobial-resistant Strainsresistant Strains

Campaign to Prevent Antimicrobial Resistance in Healthcare Settings

New Resistant Bacteria

Mutations

Emergence of Antimicrobial Emergence of Antimicrobial ResistanceResistance

Susceptible Bacteria

Resistant Bacteria

Resistance Gene Transfer

Plasmids

•Rings of extra chromosomal DNA •Can be transferred between different

species of bacteria •Carry resistance genes •Most common and effective mechanism

of spreading resistance from bacteria to bacteria (Bacterial Conjugation)

Beta-Lactamases: What are they ?

•Enzymes produced by certain bacteria that provide resistance to certain antibiotics

•Produced by both gram positive and gram negative bacteria

•Found on both chromosomes and plasmids

Beta-lactam Antibiotics

Examples

•Penicillins: –Penicillin, amoxicillin, ampicillin •Cephalosporins: –Cephalexin,Cefuroxime,Ceftriaxone •Carbapenems: –Imipenem, meropenem

Beta-Lactamases

Mechanism of Action

•Hydrolysis of beta-lactam ring of basic penicillin structure

•Hydrolysis = adding a molecule of H2O to C-N bond with enzyme action

–This opens up the ring, thus making the drug ineffective!

•Resistance that is produced through the actions of beta lactamases.

•Extended spectrum cephalosporins, such as the third generation cephalosporins, were originally thought to be resistant to hydrolysis by beta-lactamases!

•Not so! –mid 1980's it became evident that a new type of beta-

lactamase was being produced by Klebsiella & E coli that could hydrolyze the extended spectrum cephalosporins.

–These are collectively termed the •'extended spectrum beta-lactamases '( ESBL's )

The story is more complicated….

•Multiple antimicrobial resistance is often a characteristic of ESBL producing gram-negative bacteria.

•Ceftazidime •Cefotaxime •Ceftriaxone •Aztreonam •Genes encoding for ESBLs are frequently located on plasmids that also

carry resistance genes for: •Aminoglycosides •Tetracycline •TMP-SULFA •Chloramphenicol •Fluoroquinolones

If an ESBL is detected, all penicillins, cephalosporins, and aztreonam should be reported as “resistant”, regardless of in vitro susceptibility test results

However: ESBL producing organisms are still susceptible to:

•Cephamycins: –Cefoxitin –Cefotetan •Carbapenems: –Meropenem –Imipenem

Carbapenems are becoming the therapeutic option of choice

Take home message

ESBLs are harbingers of multi-drug resistance

Antimicrobial Resistance:Antimicrobial Resistance: Key Prevention StrategiesKey Prevention Strategies

Optimize Use

PreventTransmission

PreventInfection

EffectiveDiagnosis& Treatment

Pathogen

Antimicrobial Resistance

Antimicrobial Use

Infection

Susceptible pathogen

12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults12 Steps to Prevent Antimicrobial Resistance: 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 unlikelycured or unlikely

11.11. Isolate the pathogenIsolate the pathogen12. Break the chain of12. Break the chain of

contagioncontagion

Diagnose and Treat Infection Effectively

Prevent InfectionUse Antimicrobials Wisely

Prevent Transmission

Actions:Actions:give influenza / pneumococcalgive influenza / pneumococcal vaccine to at-vaccine to at-

risk patients before dischargerisk patients before dischargeget influenza vaccine annuallyget influenza vaccine annually

Prevent InfectionStep 1: Vaccinate

Fact: Pre-discharge influenza and pneumococcal vaccination

of at-risk hospital patients and influenza vaccination of

healthcare personnel will prevent infections.

Step 1: Vaccinate

Need for Healthcare Personnel ImmunizationPrograms: Influenza Vaccination Rates (1996-97)

34%34%All healthcare personnel** All healthcare personnel**

38%38%Healthcare personnel at high Healthcare personnel at high risk*risk*

63%63%All adults All adults >> 65 yrs. of age 65 yrs. of age

% Vaccinated% Vaccinated

Need for Hospital-Based Vaccination:Need for Hospital-Based Vaccination:Post-discharge Vaccination Status of Hospitalized AdultsPost-discharge Vaccination Status of Hospitalized Adults

InfluenzaInfluenza Pneumococcal PneumococcalPopulationPopulation VaccineVaccine VaccineVaccineAge 18-64 yearsAge 18-64 years 17% vaccinated17% vaccinated 31% vaccinated31% vaccinatedwith medical risk*with medical risk*

Age > 65 years*Age > 65 years* 45% vaccinated45% vaccinated 68% vaccinated68% vaccinated

Hospitalized for Hospitalized for pneumoniapneumonia 35% vaccinated35% vaccinated 20% vaccinated20% vaccinatedduring influenza during influenza season**season**

Step 1: Vaccinate

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

Actions:Actions:use catheters only when essentialuse catheters only when essentialuse the correct catheteruse the correct catheteruse proper insertion & catheter-care protocolsuse proper insertion & catheter-care protocols remove catheters when not essential remove catheters when not essential

Prevent InfectionStep 2: Get the catheters out

Link to: Guidelnes for the Prevention of Intravascular Catheter-related Infections

Biofilm on Intravenous Catheter Connecter 24 hours Biofilm on Intravenous Catheter Connecter 24 hours after Insertionafter Insertion

Scanning Electron Micrograph

12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 2: Get the catheters out

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

Actions:Actions: culture the patient culture the patient target target empiric therapyempiric therapy to likely pathogens and local to likely pathogens and local

antibiogramantibiogram target target definitive therapydefinitive therapy to known pathogens and to known pathogens and

antimicrobial susceptibility test resultsantimicrobial susceptibility test results

Diagnose & Treat Infection Effectively Step 3: Target the pathogen

Inappropriate AppropriateTherapy Therapy

42.0% mortality

17.7% mortality Relative Risk = 2.37 (95% C.I. 1.83-3.08; p < .001)

# Deaths

# Survivors

Inappropriate Antimicrobial Therapy:

Impact on Mortality

12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 3: Target the pathogen

Inappropriate Antimicrobial Therapy (n = 655 ICU patients with infection

Community-onset infection

Hospital-onset infection

Hospital-onset infection after initial community-onset infection

Patient Group

opr ia

t eInappropriate Antimicrobial Therapy: Prevalence among Intensive Care Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care

PatientsPatients

Step 3: Target the pathogen

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

Diagnose & Treat Infection EffectivelyStep 4: Access the experts

Infectious Diseases Expert ResourcesInfectious Diseases Expert Resources

Infectious Diseases Specialists

Optimal Patient Care

Infection Control Professionals

Healthcare Epidemiologists

ClinicalPharmacists

Clinical Pharmacologists

Surgical InfectionExperts

ClinicalMicrobiologist

Step 4: Access the experts

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

Use Antimicrobials WiselyStep 5: Practice

antimicrobial control

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

Use Antimicrobials WiselyStep 6: Use local data

Use Antimicrobials WiselyUse Antimicrobials Wisely Step 7: Treat infection, not Step 7: Treat infection, not

contaminationcontaminationFact:Fact: A major cause of antimicrobial overuse is “treatment” of A major cause of antimicrobial overuse is “treatment” of

contaminated cultures.contaminated cultures.

Actions:Actions:use proper antisepsis for blood & other cultures use proper antisepsis for blood & other cultures culture the blood, not the skin or catheter hubculture the blood, not the skin or catheter hubuse proper methods to obtain & process all culturesuse proper methods to obtain & process all cultures

Link to: CAP standards for specimen collection and management

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

colonizationcolonizationFact:Fact: A major cause of antimicrobial overuse is A major cause of antimicrobial overuse is

treatment of colonization. treatment of colonization.

Actions:Actions: treat bacteremia, not the catheter tip or hubtreat bacteremia, not the catheter tip or hub treat pneumonia, not the tracheal aspiratetreat pneumonia, not the tracheal aspirate treat urinary tract infection, not the indwelling treat urinary tract infection, not the indwelling

catheter catheter

Link to: IDSA guideline for evaluating fever in critically ill adults

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

Use Antimicrobials WiselyStep 9: Know when to say “no” to vanco

S. aureus

Penicillin

[1950s]

Penicillin-resistant

S. aureus

Evolution of Drug Resistance in Evolution of Drug Resistance in S. aureusS. aureusMethicillin

[1970s]

Methicillin-resistant S. aureus (MRSA)

Vancomycin-resistant

enterococci (VRE)

Vancomycin

[1990s]

[1997]

Vancomycin

intermediate-resistantS. aureus (VISA)

[ 2002 ]Vancomycin

resistantS. aureus

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

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

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

is unlikelyis unlikelywhen infection is not diagnosedwhen infection is not diagnosed

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

Step 10: Stop treatment when infection is cured or unlikely

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

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

Actions:Actions: use standard infection control precautions use standard infection control precautions contain infectious body fluidscontain infectious body fluids

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

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

Step 11: Isolate the pathogen

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

Prevent TransmissionStep 12: Break the chain

of contagion

Improved Patient Outcomes associated with Improved Patient Outcomes associated with Proper Hand HygieneProper Hand Hygiene

Ignaz Philipp Semmelweis

(1818-65)Chlorinated lime hand antisepsis

Step 12: Break the chain of contagion

Prevention and Control of MDRO Prevention and Control of MDRO transmissiontransmission

Successful control of MDROs has been documented Successful control of MDROs has been documented using a variety of combined interventions.using a variety of combined interventions.

These include:These include: - Improvements in hand hygiene,- Improvements in hand hygiene, - Use of Contact Precautions until patients are culture-- Use of Contact Precautions until patients are culture-

negative for a target MDRO,negative for a target MDRO, - Active surveillance cultures (ASC), - Active surveillance cultures (ASC), - Education,- Education, - Enhanced environmental cleaning, and improvements in - Enhanced environmental cleaning, and improvements in

communication about patients with MDROs within and communication about patients with MDROs within and between healthcare facilities.between healthcare facilities.

Infection control practices and the campaign Infection control practices and the campaign to prevent multi-drug resistance in to prevent multi-drug resistance in

PaPaleleststineine Problem!Problem!

Unrestricted use of antibiotics in the community:Unrestricted use of antibiotics in the community:- Role of physicians-evidence based guidelines Role of physicians-evidence based guidelines

and protocols and protocols - Role of pharmacists-policies (Role of pharmacists-policies (antibiotics should antibiotics should

not be over the counter drugs!not be over the counter drugs!))- Role of public-educationRole of public-education- Role of the ministry of health-rules and Role of the ministry of health-rules and

regulationsregulations

Infection control practices and the campaign Infection control practices and the campaign to prevent multi-drug resistance in to prevent multi-drug resistance in

PaPaleleststineineProblem!Problem!

Lack of National Nosocomial Infection Surveillance (NNIS) Lack of National Nosocomial Infection Surveillance (NNIS) system (governmental and non-governmental)system (governmental and non-governmental)

Problem!Problem!

Do we have adequate Infectious Diseases Expert Do we have adequate Infectious Diseases Expert Resources ? Resources ?

- Infectious Diseases Specialists

- Infection Control Professionals

- Clinical Pharmacologists

- Clinical Microbiologists

- Health care Epidemiologists

Protect patients…protect healthcare personnel…promote quality healthcare!

PreventionIS PRIMARY!

The End!

•Bacteria have evolved numerous mechanisms to evade antimicrobial drugs. •Chromosomal mutations are an important source of resistance to some antimicrobials. •Acquisition of resistance genes or gene clusters, via conjugation, transposition, or transformation, accounts for most antimicrobial resistance among bacterial pathogens. •These mechanisms also enhance the possibility of multi-drug resistance.

MDRO(multidrug resistant organisms)

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