MDRO(multidrug resistant organisms) Definitionmicroorganisms, predominantly bacteria,that are resistant to one or more classesof antimicrobial agents. Although thenames of certain MDROs describeresistance to only one agent (e.g.,MRSA,VRE), these pathogens arefrequently resistant to most availableantimicrobial agents
MDRO(multidrug resistant organismsIn addition to MRSA and VRE, certaingram negative bacteria(GNB), includingthose producing extended spectrum beta-lactamases (ESBLs) and others that areresistant to multiple classes ofantimicrobial agents, are of particularconcern
MDRO(multidrug resistant organismsDrug-resistant pathogens are agrowing threat to all people, especiallyin healthcare settings.
MDRO(multidrug resistant organismsEach year nearly 2 million patients in the UnitedStates get an infection in a hospital. Of those patients,about 90,000 die as a result of their infection. Morethan 70% of the bacteria that cause hospital-acquiredinfections are resistant to at least one of the drugs mostcommonly used to treat them. Persons infected withdrug-resistant organisms are more likely to have longerhospital stays and require treatment withsecond- or third-choice drugs that may beless effective, more toxic, and/or moreexpensive
Clinical importance of MDROs - In most instances, MDRO infections have clinical manifestations that are similar to infections caused by susceptible pathogens. However, options for treating patients with these infections are often extremely limited. Although antimicrobials are now available for treatment of MRSA and VRE infections, resistance to each new agent has already emerged in clinical isolates. - Similarly, therapeutic options are limited for ESBL-producing isolates of gram-negative bacilli
Clinical importance of MDROs-These limitations may influence antibiotic usagepatterns in ways that suppress normal flora andcreate a favorable environment for developmentof colonization when exposed to potential MDRpathogens (i.e., selective advantage).-Increased lengths of stay, costs, and mortalityalso have been associated with MDROs.
Clinical importance of MDROsThe type and level of care influence theprevalence of MDROs. ICUs, especiallythose at tertiary care facilities, may have ahigher prevalence of MDRO infectionsthan do non-ICU settings
Methicillin Resistant Staph (MRSA)MRSA was first isolated in the United States in1968. By the early 1990s, MRSA accounted for20%-25% of Staphylococcus aureus isolatesfrom hospitalized patients. In 1999, MRSAaccounted for >50% of S. aureus isolates frompatients in ICUs in the National NosocomialInfection Surveillance (NNIS) system; in 2003,59.5% of S. aureus isolates in NNIS ICUs wereMRSA .
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Methicillin-Resistant Staphylococcus aureus (MRSA) Among Intensive Care Unit Patients, 1995-2004 70 60Percent Resistance 50 40 30 20 10 0 95 97 99 00 03 04 96 98 01 02 19 19 19 19 20 20 20 20 19 20 Year Source: National Nosocomial Infections Surveillance (NNIS) System
Vancomycin-Resistant enterococcus (VRE)A similar rise in prevalence has occurredwith VRE . From 1990 to 1997, theprevalence of VRE in enterococcalisolates from hospitalized patientsincreased from <1% to approximately 15%VRE accounted for almost 25% ofenterococcus isolates in NNIS ICUs in1999 and 28.5% in 2003 .
Vancomycin-Resistant Enterococci (VRE) Among Intensive Care Unit Patients,1995-2004 35 Percent Resistance 30 25 20 15 10 5 0 04 95 96 97 98 99 00 01 02 03 19 20 19 19 19 19 20 20 20 20 Year
Gram-negative resistant Bacteria-GNB resistant to ESBLs, fluoroquinolones, carbapenems, and aminoglycosides also have increased in prevalence.*For example, in 1997, the SENTRY Antimicrobial Surveillance Program found that among K. pneumoniae strains isolated in the United States, resistance rates to ceftazidime and other third-generation cephalosporins were 6.6%, 9.7%, 5.4%, and 3.6% for bloodstream, pneumonia, wound, and urinary tract infections, respectively .*In 2003, 20.6% of all K. pneumoniae isolates from NNIS ICUs were resistant to these drugs
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 3rd Generation Cephalosporin-Resistant Klebsiella pneumoniae Among Intensive Care Unit Patients, 1995-2004 30 25 Percent Resistance 20 15 10 5 0 95 97 99 00 03 04 96 98 01 02 19 19 19 19 20 20 20 20 19 20 Year Source: National Nosocomial Infections Surveillance (NNIS) System
Campaign to PreventAntimicrobial Resistance Clinicians hold the solution!
Risk factors that promote antimicrobial resistance in healthcare settings includeExtensive use of antimicrobialsTransmission of infectionSusceptible hosts
Key Prevention Strategies Clinicians hold the solution! " Prevent infection " Diagnose and treat infection effectively “ Use antimicrobials wisely “ Prevent transmission
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Selection for antimicrobial- resistant Strains xx x x Resistant Strains xx Rare x Antimicrobial xx x Exposure xx Resistant Strains Dominant
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Emergence of Antimicrobial Resistance Susceptible Bacteria Resistant Bacteria Mutations XXResistance Gene Transfer New Resistant Bacteria
Plasmids•Rings of extra chromosomal DNA•Can be transferred between differentspecies of bacteria•Carry resistance genes•Most common and effective mechanismof spreading resistance from bacteria tobacteria (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-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!
ESBL?•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 1980s 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 ( ESBLs )
ESBL? The story is more complicated….•Multiple antimicrobial resistance is often a characteristic of ESBL producinggram-negative bacteria.•Ceftazidime•Cefotaxime•Ceftriaxone•Aztreonam•Genes encoding for ESBLs are frequently located on plasmids that alsocarry resistance genes for:•Aminoglycosides•Tetracycline•TMP-SULFA•Chloramphenicol•Fluoroquinolones
ESBL?If an ESBL is detected, all penicillins,cephalosporins, and aztreonam should bereported as “resistant”, regardless of invitro susceptibility test results
ESBL?However: ESBL producing organisms arestill susceptible to:•Cephamycins: –Cefoxitin –Cefotetan•Carbapenems: –Meropenem –ImipenemCarbapenems are becoming the therapeutic option of choice
ESBL? Take home messageESBLs are harbingers of multi-drugresistance
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antimicrobial Resistance: Key Prevention Strategies Susceptible pathogen Pathogen Prevent PreventTransmission Infection Infection Antimicrobial Resistance Effective Optimize Diagnosis Use & Treatment Antimicrobial Use
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials WiselyPrevent Infection 5. Practice antimicrobial control1. Vaccinate 6. Use local data 7. Treat infection, not contamination2. Get the catheters out 8. Treat infection, not colonization 9. Know when to say “no” to vancoDiagnose and Treat 10. Stop treatment when infection isInfection cured or unlikelyEffectively Prevent Transmission3. Target the pathogen4. Access the experts 11. Isolate the pathogen 12. Break the chain of contagion
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Prevent Infection Step 1: VaccinateFact: Pre-discharge influenza and pneumococcal vaccinationof at-risk hospital patients and influenza vaccination ofhealthcare personnel will prevent infections.Actions: give influenza / pneumococcal vaccine to at- risk patients before discharge get influenza vaccine annually
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 1: VaccinateNeed for Healthcare Personnel ImmunizationPrograms: Influenza Vaccination Rates (1996-97) % VaccinatedAll adults > 65 yrs. of age 63%Healthcare personnel at high 38%risk*All healthcare personnel** 34%
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 1: Vaccinate Need for Hospital-Based Vaccination: Post-discharge Vaccination Status of Hospitalized Adults Influenza PneumococcalPopulation Vaccine VaccineAge 18-64 years 17% vaccinated 31% vaccinatedwith medical risk*Age > 65 years* 45% vaccinated 68% vaccinatedHospitalized forpneumonia 35% vaccinated 20% vaccinatedduring influenzaseason**
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Prevent Infection Step 2: Get the catheters out Fact: Catheters and other invasive devices are the # 1 exogenous cause of hospital-onset infections. Actions: use catheters only when essential use the correct catheter use proper insertion & catheter-care protocols remove catheters when not essential
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 2: Get the catheters outBiofilm on Intravenous Catheter Connecter 24 hours after Insertion Scanning Electron Micrograph
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Diagnose & Treat Infection Effectively Step 3: Target the pathogenFact: Appropriate antimicrobial therapy saves lives.Actions: culture the patient target empiric therapy to likely pathogens and local antibiogram target definitive therapy to known pathogens and antimicrobial susceptibility test results
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 3: Target the pathogenInappropriate Antimicrobial Therapy: Prevalence among Intensive Care Patients Inappropriate 50% Antimicrobial Therapy 45.2% (n = 655 ICU patients with infection % inappropriate 40% 34.3% 30% Community-onset infection 20% 17.1% Hospital-onset infection 10% Hospital-onset infection after initial community-onset infection 0% Patient Group
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Diagnose & Treat Infection Effectively Step 4: Access the experts Fact: Infectious diseases expert input improves the outcome of serious infections.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 4: Access the experts Infectious Diseases Expert Resources Infectious Diseases Specialists Healthcare Infection Control Epidemiologists Professionals Clinical OptimalPharmacists Patient Care Clinical Clinical Pharmacologists Microbiologist s Surgical Infection Experts
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 5: Practice antimicrobial control Fact: Programs to improve antimicrobial use are effective.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 6: Use local data Fact: The prevalence of resistance can vary by time, locale, patient population, hospital unit, and length of stay.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 7: Treat infection, not contamination Fact: A major cause of antimicrobial overuse is “treatment” of contaminated cultures. Actions: use proper antisepsis for blood & other cultures culture the blood, not the skin or catheter hub use proper methods to obtain & process all cultures Link to: CAP standards for specimen collection and management
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 8: Treat infection, not colonization Fact: A major cause of antimicrobial overuse is treatment of colonization. Actions: treat bacteremia, not the catheter tip or hub treat pneumonia, not the tracheal aspirate treat urinary tract infection, not the indwelling catheter Link to: IDSA guideline for evaluating fever in critically ill adults
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 9: Know when to say “no” to vanco Fact: Vancomycin overuse promotes emergence, selection,and spread of resistant pathogens.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 9: Know when to say “no” to vanco Evolution of Drug Resistance in S. aureus Penicillin Methicillin Penicillin-resistant Methicillin-S. aureus resistant [1950s] S. aureus [1970s] S. aureus (MRSA) Vancomycin  [1990s] Vancomycin Vancomycin Vancomycin-resistant - [ 2002 ] intermediate- enterococci (VRE) resistant resistant S. aureus S. aureus (VISA)
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 10: Stop treatment when infection is cured or unlikely Use Antimicrobials Wisely Step 10: Stop antimicrobial treatmentFact: Failure to stop unnecessary antimicrobial treatment contributes to overuse and resistance.Actions: when infection is cured when cultures are negative and infection is unlikely when infection is not diagnosed
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 11: Isolate the pathogen Prevent Transmission Step 11: Isolate the pathogen Fact: Patient-to-patient spread of pathogens can be prevented. Actions: use standard infection control precautions contain infectious body fluids (use approved airborne/droplet/contact isolation precautions) when in doubt, consult infection control experts
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Prevent Transmission Step 12: Break the chain of contagion Fact: Healthcare personnel can spread antimicrobial-resistant pathogens from patient-to- patient.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized AdultsStep 12: Break the chain of contagion Improved Patient Outcomes associated with Proper Hand Hygiene Ignaz Philipp Semmelweis (1818-65) Chlorinated lime hand antisepsis
Prevention and Control of MDRO transmissionSuccessful control of MDROs has been documented using a variety of combined interventions.These include:- Improvements in hand hygiene,- Use of Contact Precautions until patients are culture- negative for a target MDRO,- Active surveillance cultures (ASC),- Education,- Enhanced environmental cleaning, and improvements in communication about patients with MDROs within and between healthcare facilities.
Infection control practices and the campaign to prevent multi-drug resistance in Palestine Problem! Unrestricted use of antibiotics in the community: Role of physicians-evidence based guidelines and protocols Role of pharmacists-policies (antibiotics should not be over the counter drugs!) Role of public-education Role of the ministry of health-rules and regulations
Infection control practices and the campaign to prevent multi-drug resistance inProblem! Palestine Lack of National Nosocomial Infection Surveillance (NNIS) system (governmental and non-governmental)Problem! Do we have adequate Infectious Diseases Expert Resources ? - Infectious Diseases Specialists - Infection Control Professionals - Clinical Pharmacologists - Clinical Microbiologists - Health care Epidemiologists
Campaign to Prevent Antimicrobial Resistance in Healthcare SettingsPreventionIS PRIMARY! Protect patients…protect healthcare personnel… promote quality healthcare!
•Bacteria have evolved numerous mechanisms to evade antimicrobial drugs.•Chromosomal mutations are an important source of resistance to someantimicrobials. •Acquisition of resistance genes or gene clusters, via conjugation,transposition, or transformation, accounts for most antimicrobial resistance amongbacterial pathogens. •These mechanisms also enhance the possibility of multi-drugresistance.