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MDRO(multidrug resistant organisms). Definition
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MDRO(multidrug resistant organisms) Definition microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. Although the names of certain MDROs describe resistance to only one agent (e.g., MRSA,VRE), these pathogens are frequently resistant to most available antimicrobial agents
MDRO(multidrug resistant organisms In addition to MRSA and VRE, certain gram negative bacteria(GNB), including those producing extended spectrum beta-lactamases (ESBLs) and others that are resistant to multiple classes of antimicrobial agents, are of particular concern
MDRO(multidrug resistant organisms Drug-resistant pathogens are a growing threat to all people, especially in healthcare settings.
MDRO(multidrug resistant organisms Each year nearly 2 million patients in the United States get an infection in a hospital. Of those patients, about 90,000 die as a result of their infection. More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them. Persons infected with drug-resistant organisms are more likely to have longer hospital stays and require treatment with second- or third-choice drugs that may be less effective, more toxic, and/or more expensive
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 usage patterns in ways that suppress normal flora and create a favorable environment for development of colonization when exposed to potential MDR pathogens (i.e., selective advantage). -Increased lengths of stay, costs, and mortality also have been associated with MDROs.
Clinical importance of MDROs The type and level of care influence the prevalence of MDROs. ICUs, especially those at tertiary care facilities, may have a higher prevalence of MDRO infections than do non-ICU settings
MethicillinResistant Staph (MRSA) MRSA was first isolated in the United States in 1968. By the early 1990s, MRSA accounted for 20%-25% of Staphylococcus aureus isolates from hospitalized patients. In 1999, MRSA accounted for >50% of S. aureus isolates from patients in ICUs in the National Nosocomial Infection Surveillance (NNIS) system; in 2003, 59.5% of S. aureus isolates in NNIS ICUs were MRSA .
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Methicillin-Resistant Staphylococcus aureus(MRSA) Among Intensive Care Unit Patients,1995-2004 Source: National Nosocomial Infections Surveillance (NNIS) System
Vancomycin-Resistant enterococcus (VRE) A similar rise in prevalence has occurred with VRE . From 1990 to 1997, the prevalence of VRE in enterococcal isolates from hospitalized patients increased from <1% to approximately 15% VRE accounted for almost 25% of enterococcus isolates in NNIS ICUs in 1999 and 28.5% in 2003 .
Vancomycin-Resistant Enterococci (VRE) Among Intensive Care Unit Patients,1995-2004
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 Source: National Nosocomial Infections Surveillance (NNIS) System
Fluoroquinolone-Resistant Pseudomonas aeruginosa Among Intensive Care Unit Patients, 1995-2004
Campaign to PreventAntimicrobial Resistance Clinicians hold the solution!
Risk factors that promote antimicrobial resistance in healthcare settings include Extensive use of antimicrobials Transmission of infection Susceptible 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 Resistant StrainsRare Antimicrobial Exposure Resistant Strains Dominant x x x x x x x x x x x x Selection for antimicrobial-resistant Strains
Resistant Bacteria Mutations XX Resistance Gene Transfer New Resistant Bacteria Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Emergence of Antimicrobial Resistance Susceptible Bacteria
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!
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 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 )
ESBL? 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
ESBL? If an ESBL is detected, all penicillins, cephalosporins, and aztreonam should be reported as “resistant”, regardless of in vitro susceptibility test results
ESBL? However: ESBL producing organisms are still susceptible to: •Cephamycins: –Cefoxitin –Cefotetan •Carbapenems: –Meropenem –Imipenem Carbapenems are becoming the therapeutic option of choice
ESBL? Take home message ESBLs are harbingers of multi-drug resistance
Antimicrobial Resistance:Key Prevention Strategies Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Prevent Infection PreventTransmission Infection Antimicrobial Resistance Effective Diagnosis & Treatment Optimize Use Antimicrobial Use Pathogen Susceptiblepathogen
1. Vaccinate 2. Get the catheters out 3. Target the pathogen 4. Access the experts 5. Practice antimicrobial control 6. Use local data 7. Treat infection, not contamination 8. Treat infection, not colonization 9. Know when to say “no” to vanco 10. Stop treatment when infection is cured or unlikely 11. Isolate the pathogen 12. Break the chain of contagion 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Prevent Infection Diagnose and Treat Infection Effectively Prevent Transmission
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Prevent Infection Step 1: Vaccinate Actions: • give influenza / pneumococcalvaccine to at-risk patients before discharge • get influenza vaccine annually Fact: Pre-discharge influenza and pneumococcal vaccination of at-risk hospital patients and influenza vaccination of healthcare personnel will prevent infections.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 1: Vaccinate % Vaccinated All adults > 65 yrs. of age 63% Healthcare personnel at high risk* 38% All healthcare personnel** 34% Need for Healthcare Personnel Immunization Programs: Influenza Vaccination Rates (1996-97)
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 1: Vaccinate Need for Hospital-Based Vaccination:Post-discharge Vaccination Status of Hospitalized Adults Influenza Pneumococcal Population Vaccine Vaccine Age 18-64 years 17% vaccinated 31% vaccinated with medical risk* Age > 65 years* 45% vaccinated 68% vaccinated Hospitalized for pneumonia 35% vaccinated 20% vaccinated during influenza season**
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 • Link to:Guidelnes for the Prevention of Intravascular Catheter-related Infections
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 2: Get the catheters out Biofilm on Intravenous Catheter Connecter 24 hours after Insertion Scanning Electron Micrograph
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Diagnose & Treat Infection EffectivelyStep 3:Target the pathogen Fact: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 pathogen 17.7% mortality Relative Risk = 2.37 (95% C.I. 1.83-3.08; p < .001) No. Infected Patients 42.0% mortality # Survivors # Deaths Inappropriate Appropriate Therapy Therapy Inappropriate Antimicrobial Therapy: Impact on Mortality
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 3: Target the pathogen Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care Patients Inappropriate Antimicrobial Therapy (n = 655 ICU patients with infection 45.2% 34.3% Community-onset infection Hospital-onset infection Hospital-onset infection after initial community-onset infection % inappropriate 17.1% 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 Adults Step 4: Access the experts Infectious Diseases Specialists Healthcare Epidemiologists Infection Control Professionals Optimal Patient Care ClinicalPharmacists Clinical Pharmacologists Clinical Microbiologists Surgical Infection Experts Infectious Diseases Expert Resources
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 WiselyStep 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 WiselyStep 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 Adults Step 9: Know when to say “no” to vanco Methicillin Methicillin-resistant S. aureus (MRSA) [1970s] Vancomycin [1997] [1990s] [ 2002 ] Vancomycin Vancomycin-resistant Vancomycin- resistant S. aureus intermediate- enterococci (VRE) resistant S. aureus (VISA) Evolution of Drug Resistance in S. aureus Penicillin Penicillin-resistant S. aureus [1950s] S. aureus
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 10: Stop treatment when infection is cured or unlikely Use Antimicrobials WiselyStep 10: Stop antimicrobial treatment Fact: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 Adults Step 11: Isolate the pathogen Prevent TransmissionStep 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 Adults Step 12: Break the chain of contagion Improved Patient Outcomes associated with Proper Hand Hygiene Ignaz Philipp Semmelweis (1818-65) Chlorinated lime hand antisepsis