The proportion of hospital-onset infections that are due to a resistant organism has increased at an alarming rate. The next four slides show trends in antimicrobial resistance among pathogens causing infections in ICU patients. These trends are based on data from the CDC’s National Nosocomial Infections Surveillance (NNIS) system. Shown on this slide are trends in the proportion of Staphylococcus aureus infections caused by methicillin-resistant strains. From 1995 through 2004, the percent of S. aureus infections caused by methicillin-resistant strains increased from approximately 40% to 60%.
During the same time period, there also was a significant increase in the proportion of gram-negative pathogens (e.g., Klebsiella spp. and Enterobacteriaceae) that had acquired extended-spectrum beta-lactamases (ESBLs). Shown above are trends in 3 rd generation cephalosporin resistance among Klebsiella pneumoniae . As of 2004, approximately 25% of K. pneumoniae isolates causing infections in ICUs were resistant to 3 rd generation cephalosporins.
Once resistant strains of bacteria are present in a population, exposure to antimicrobial drugs favors their survival. Reducing antimicrobial selection pressure is one key to preventing antimicrobial resistance and preserving the utility of available drugs for as long as possible.
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.
Once a pathogen produces infection, antimicrobial treatment may be essential. However, antimicrobial use promotes selection of antimicrobial-resistant strains of pathogens. As the prevalence of resistant strains increases in a population, subsequent infections are increasingly likely to be caused by these resistant strains. Fortunately, this cycle of emerging antimicrobial resistance / multi-drug resistance can be interrupted. Preventing infections in the first place will certainly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains. Effective diagnosis and treatment will benefit the patient and decrease the opportunity for development and selection of resistant microbes; this requires rapid accurate diagnosis, identification of the causative pathogen, and determination of its antimicrobial susceptibility. Optimizing antimicrobial use is another key strategy; optimal use will ensure proper patient care and at the same time avoid overuse of broad-spectrum antimicrobials and unnecessary treatment. Finally, preventing transmission of resistant organisms from one person to another is critical to successful prevention efforts.
These 12 steps to Prevent Antimicrobial Resistance among hospitalized adults are action steps that clinicians can and should take now. They are designed to optimize patient safety and the outcome of infectious disease management. Together, these steps can prevent the emergence and spread of antimicrobial-resistant pathogens.
The Advisory Committee on Immunization Practices (ACIP) recommends standing orders for influenza and pneumococcal vaccinations to improve vaccination of hospitalized patients before discharge. In addition, ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that healthcare personnel should receive an annual influenza vaccine to protect patients and other healthcare personnel.
Outbreaks of influenza in hospitals have been linked to transmission from otherwise healthy healthcare personnel and are a major patient safety issue. The Advisory Committee on Immunization Practices (ACIP) recommends that healthcare personnel with patient care duties receive an annual influenza vaccine. However, vaccination rates among healthcare personnel are extremely poor; less than 40% of personnel are immunized in most facilities. * One or more high-risk medical conditions including diabetes, current cancer treatment, or chronic heart, lung, or kidney disease. ** Healthcare workers included persons currently employed in healthcare occupations, regardless of setting, and persons currently employed in healthcare settings without a healthcare occupation.
Hospitalization represents a “missed opportunity” for vaccination. Discharged patients are unlikely to have received pneumococcal vaccine even when they are at high risk. Older hospital patients are more likely to have received influenza vaccine than younger patients, but a significant proportion in both groups was not vaccinated in either group.
The most effective way to decrease device-associated infections is to decrease device utilization. In other words, get the catheters out ! Catheters should only be used when essential to patient care, not for convenience or as a “routine” practice. In some cases, antimicrobial-impregnated catheters may be warranted to prevent infections. Proper insertion and catheter care may decrease contamination and infection risk. The need for a catheter should be assessed on a daily basis so that unnecessary catheters will be recognized and removed.
All invasive medical devices support the development of biofilms. Biofilm is a complex three-dimensional structure that consists of cells, bacteria, and extracellular matrix materials. In this scanning electron micrograph, many bacteria are seen in a matrix of material that also contains a red blood cell. This biofilm developed within 24 hours of catheter insertion. Biofilms may promote development of antimicrobial-resistant infections in several ways: Serving as a nidus for deposition and growth of resistant strains that then are released to cause infection; Creating a permeability barrier to antimicrobial diffusion, so that bacteria imbedded in the biofilm may be exposed to sub-inhibitory concentrations of drug that promotes emergence of resistance; Providing a matrix in which bacteria can exchange resistance factors. Biofilms cannot be prevented but some strategies may decrease the rate at which biofilms are formed and decrease bacterial colonization of biofilms.
Correct diagnosis of the causative pathogen is necessary to ensure appropriate antimicrobial therapy. Hence, cultures are almost always indicated when managing hospitalized adults with known or suspected infection. Empiric antimicrobial therapy should be selected to target likely pathogens and be consistent with local antimicrobial susceptibility data. Definitive therapy should target known pathogens once they are identified and their antimicrobial susceptibility test results are known.
Several studies suggest that input from professionals with infectious diseases expertise can improve patient outcomes, improve antimicrobial use, decrease treatment costs, and decrease the length of hospital stay.
Infectious diseases specialists are one important resource for providing input, but many other professionals also contribute to optimal care for patients with infections. Like all patient safety endeavors, multidisciplinary collaboration is key!
The importance of wise use of antimicrobials has been emphasized for many years. Many hospital-based programs to improve antimicrobial utilization have been implemented.
Antimicrobial susceptibility data are often aggregated into “antibiograms”, which provide a summary picture of common organisms and their susceptibility to many antimicrobial drugs. Antibiograms provide a starting point for making decisions about empiric antimicrobial treatment, but do not necessarily reliably predict susceptibility of pathogens from a given patient because the data are not stratified by relevant characteristics that may affect the prevalence of resistance.
Optimizing skin antisepsis is the first critical step in obtaining blood samples for culture. Proper specimen collection and management is key to preventing contaminated cultures.
Clinical criteria and additional laboratory data can help distinguish infection from colonization. Improving the specificity of diagnostic criteria for infection can help reduce unnecessary antimicrobial use.
Emergence of vancomycin resistance among gram-positive organisms is a major threat to patient safety in hospitals. Overuse of vancomycin promotes selection and spread of these resistant organisms.
Introduction of every new class of antimicrobial drug is followed by emergence of resistance. By the 1950s, penicillin-resistant S. aureus were a major threat in hospitals and nurseries. By the 1970s, methicillin-resistant S. aureus had emerged and spread, a phenomenon that encouraged widespread use of vancomycin. In the 1990s, vancomycin-resistant enterococci emerged and rapidly spread; most of these organisms are resistant to other traditional first-line antimicrobial drugs. At the end of the century, the first S. aureus strains with reduced susceptibility to vancomycin were documented, prompting concerns that S. aureus fully resistant to vancomycin may be on the horizon. In June 2002 the first case of vancomycin-resistant S. aureus was detected.
Stopping treatment when infection is unlikely or not diagnosed does not lead to harm and in fact, might benefit patients.
Adherence to common-sense measures to isolate antimicrobial-resistant organisms before they are transferred to other patients or become endemic in a facility is essential. When in doubt about appropriate isolation procedures, consultation with an infection control professional is indicated.
Healthcare personnel are important components of the chain of transmission in hospitals. Antimicrobial-resistant pathogens from one patient are transmitted to another when lapses in proper hand hygiene and other infection control practices occur. Healthcare personnel can also transmit their own flora and infectious pathogens to patients.
Ignaz Philipp Semmelweis (1818-65), a Hungarian obstetrician, introduced antiseptic hand hygiene techniques. Semmelweis noted that post-partum women examined by medical students who did not wash their hands after performing autopsies had high mortality rates. He required students to clean their hands with chlorinated lime before examining patients Maternal mortality declined from 12% to less than 1% after this hand hygiene intervention was implemented.
Prevention is Primary!
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.