Control And Prevention Of Antimicrobial Resistant Organisms in HCF Control and Prevention of Antimicrobial Resistant Organisms in HCF Introduction Antibiotics are used to prevent infection and to treat patients with proven or suspected infection. The aim is to administer a safe and cost effective dose of antibiotic that will eliminate the infecting or potentially infecting organism. Antibiotics are widely used, contributing to 35% of all prescriptions in health care facilities. Overuse of antibiotics results in bacterial resistance not only to the antibiotic prescribed, but often to other antibiotics in the same classes or groups. The abuse or misuse of antibiotics is costly because it leads to the emergence of antibiotic resistance among microorganisms in the health care facility environment as well as in the patients. Typically, there is a reservoir of patients colonized with antimicrobial resistant organisms, which can be a source of cross transmission to other susceptible patients in the facility. When infections from Antimicrobial Resistant Organisms occur, there is increased mortality, especially among those with underlying diseases or multiorgan failure. The health care facility serves to amplify these strains because of the high prevalence of use of antibiotics. The primary selective pressure for antimicrobial resistant organisms is antibiotic use both in facilities and in communities. In under-resourced countries, selection of resistance in communities is compounded by relatively easy access to antibiotics and there is little regulation of this accessibility. 4 Other factors that promote selection and transmission of these strains in all countries are failure to complete a full course of prescribed antibiotics, and lack of resources and personnel for facility infection control programs. In addition, even countries that spend considerable resources on health care do not necessarily have a lower frequency of antimicrobial resistant organisms. 62 Normal microbial flora is protective. The administration of antibiotics kills off susceptible strains of normal bacteria and these are replaced with resistant strains, which are often resistant to many different classes of antibiotics. This replacement occurs most often in the gastrointestinal tract, which carries the bulk of bacteria, and results in stool carriage of multiply antibiotic resistant bacteria. These antimicrobial resistant organisms bacteria can easily spread from patient to patient in the hospital environment via hands of staff, bedpans, and nonclinical and poorly sterilized equipment. 109 Control And Prevention Of Antimicrobial Resistant Organisms in HCF Examples of antimicrobial resistant organisms The misuse of antibiotics has led to the emergence of multiple antibiotic resistant bacteria in both gram positive and gram-negative bacteria 63. . Gram Positive Cocci Enterococci and coagulase negative staphylococci have emerged as significant pathogens in recent years, although previously considered as commensals or normal flora. Staphylococcus aureus has now acquired resistance to cloxacillin and vancomycin. 64 Methicillin (Flucloxacillin) resistant Staphylococcus aureus (MRSA) is common in most hospitals worldwide and is particularly concentrated in high risk units such as Intensive care units and Neonatal Intensive care units. Blood stream infections associated with IV sites, ventilator associated pneumonia, and infections at surgical sites and of prosthetic implants are all common infections associated with gram-positive cocci. Gram Negative Bacilli Gram-negative bacteria have become more resistant to routine antibiotics. Extended spectrum B-lactamases are now common in Klebsiella pneumoniae, particularly in high risk units such as Intensive care units and Neonatal Intensive care units. Acinetobacter spp is wide spread in most Intensive care units worldwide and is highly resistant to most antibiotics. Pseudomonas aeruginosa can be isolated from wounds and from respiratory and urinary tracts of patients in most hospitals. It is also present in the hospital environment in open containers of disinfectant, in wet or moist areas, and on equipment. Once introduced into a high risk unit, gram negative bacilli are very difficult to eliminate. Antimicrobial resistant organisms gram negative bacilli can cause any type of infection but are particularly common causes of blood stream infections, ventilator associated pneumonia, urinary tract infections, IV fluid infusion site infections, and surgery and burn site infections. 110 Control And Prevention Of Antimicrobial Resistant Organisms in HCF Acquisition and Transmission of Antimicrobial Resistant Organisms Note: A distinction should be made between acquisition and transmission of multiple drug resistant organism pathogens. The misuse of antibiotics leads to acquisition of antibiotic resistance organisms, while poor infection control procedures lead to the transmission of antimicrobial resistant organisms. Acquisition Antimicrobial Resistant Organisms are created by selective pressure from antibiotics. Antibiotic pressure is more noticeable when certain classes of antibiotics are used. The most commonly prescribed antibiotics are betalactamases such as penicillins and cephalosporins. The latter are now recognized as having a significant role in the emergence of antibiotic resistance among bacteria, which were previously considered sensitive or commensal flora. Large amounts of antibiotics are used in the health care setting, especially in the ICU, and can lead to the emergence of resistant strains. Community factors can also cause antibiotic pressure. Wide scale usage of antibiotics for minor ailments can select for resistant pathogens which are then circulated in the community (wide scale resistance of S. pneumonia has been well described in numerous countries). Transmission Having acquired antibiotic resistance, the microbe has to have certain attributes in order that it may spread: Microbial fitness: ability to produce a clone, which can be transmitted from host to host. Virulence: ability to attach and invade tissues. Acquisition of resistance is not a normal activity for the microbe. It takes increased expenditure of energy to develop resistance. Therefore the efficiency of transmission of these antimicrobial resistant organisms may be less, compared to susceptible strains. Strategies for reducing transmission of antimicrobial resistant organsims: An infection control policy that is simple and effective, such as one that emphasizes good hygiene. Of note, this strategy not only addresses 111 Control And Prevention Of Antimicrobial Resistant Organisms in HCF antimicrobial resistant organisms but susceptible strains, which can also cause considerable morbidity and mortality. Knowledge of the infection control policy by all personnel. Repeated emphasis on hand hygiene. Appropriate use of personal protective equipment (PPE). Use of surveillance data to target specific areas at high risk for antimicrobial resistant organisms. Identify bacterial isolates per patient rather than identification of isolates per site. A well controlled testing system in place. Development of lab capacity to correctly identify antibiotic sensitivity patterns. Use of spatial separation between patients known to be infected or colonized with MRSA or VRE and patients who are not known to be infected or colonized. If resources for physical barriers are limited, establishment of a glove policy and hand hygiene policy are priorities. The goal of microbiologic screening of patients for antimicrobial resistant organisms must be identified before it is undertaken. Variables to consider are whether this is cost effective and whether appropriate laboratory support is available. Screening may be considered as part of an epidemiologic investigation of possible outbreak or cluster. Do not screen personnel unless they are epidemiologically linked to ongoing transmission. There is no evidence that antimicrobial resistant organisms are less susceptible to soap/detergent products or antiseptic agents when compared to antibiotic susceptible organisms. If only soap and water are available for hand hygiene then reinforce its use. Evidence does suggest however that removal of antimicrobial resistant organisms from hands is improved if hand antisepsis is utilized. This is especially applicable for high risk areas/populations (Intensive Care Units, Dialysis, etc.). Extraordinary environmental cleaning or disinfection is not needed for preventing transmission of antimicrobial resistant organisms. There is little evidence that use of disinfectants or antiseptics in health care facilities is selecting for antimicrobial resistant organisms. 112 Control And Prevention Of Antimicrobial Resistant Organisms in HCF Table 17: Control of antibiotic resistance Procedure Effect on acquisition + (antibiotic dependent) Lack of IC procedures none Absence of surveillance none of antibiotic resistance Absence of treatment +++ protocols or guidelines Misuse of antibiotics Effect on transmission ++ (bacteria dependent) ++ ++ ++ Antibiotic Usage Antibiotic Prophylaxis Prophylactic antibiotics are mainly used for surgery (and other invasive procedures). Maximum blood levels of antibiotic at the time of the procedure help ensure that circulating bacteria arising during the procedure can be reduced to a level that can be destroyed by the patient’s body’s natural defenses. There is no benefit in starting antibiotics too early or in continuing for longer than 24 hours after the procedure. Instead this can result in emergence of resistance. A single dose or a maximum of three doses should be administered starting with the induction of anesthesia. Prophylaxis should not continue longer than 24 hours. After 24 hours antibiotics are considered treatment and should be documented as such, for example, in cases of perforation and peritonitis. Antibiotic Therapy Antibiotics are used to treat patients with known or suspected infection: Empiric therapy is based on the ‘best-guess’ antibiotic for the suspected organism and its predicted antibiotic sensitivity patterns. Knowledge of local antibiotic sensitivity patterns is useful so that prescribing is not based on publications from other countries. The decision should be based on: The site of infection. The probable pathogen. The known bacterial spectrum. Safety and pharmacokinetics of the chosen antibiotic. If clinical response is noted in 72 hours, then the therapy should be continued through completion. If there is no improvement or if the clinical picture changes, then alternative antibiotics must be considered. The range of antibiotics is broad 113 Control And Prevention Of Antimicrobial Resistant Organisms in HCF and a combination of two or more may be used initially. This may be reduced to one when the bacteriology results become available. Targeted therapy is instituted when microbiological results are known or when the results are pending but the clinical picture requires immediate treatment. An example would be treating meningococcal meningitis on the basis of a gram stain from the cerebrospinal fluid. Formulating an Antibiotic Policy It is difficult to formulate a general antibiotic policy because bacterial populations and antibiotic resistance patterns differ between hospitals, clinical choices vary, availability of antibiotics differs from country to country, and because route and cost of antibiotic administration varies. 9 There have been reports of successful lowering of frequency of antimicrobial resistant organisms by controlling or removing selective pressure from overuse of antibiotics.18, 66, 67 Each health care facility should have an antimicrobial management program that monitors use of antibiotics. When formulating a policy consider doing the following: List the available pharmacokinetics. List the indications for which antibiotics are required. Are they needed for prophylaxis or therapy? Determine indications for use of each antibiotic after consultation with the clinicians. When the policy has been agreed ensure that Microbiology can test for sensitivities of selected pathogens to these antibiotics. Enter the policy in the hospital formulary and display the policy on the walls of the wards. Review the policy periodically. Policies should change if there are changes in the antibiotic resistance patterns, a change in the functions of a unit, a change in staff, a price increase in a certain antibiotic, , or if there are new antibiotics on the market. antibiotics of similar spectrum, safety and Note: Antibiotic Formularies or policies should be determined by the Drugs and Therapeutics Committee and should be established after wide consultation with the clinical and hospital staff. It requires ownership by the staff and needs constant support from antibiotic surveillance (Microbiology). All policies should be reviewed after 18 months. 114 Control And Prevention Of Antimicrobial Resistant Organisms in HCF All Antibiotic policies need to consider a few basic principles: The goal is to assure treatment of confirmed infection and not to cause unnecessary colonization of resistant strains. Use different classes of antibiotics for prophylaxis and therapy. Use a high dosage for a short duration therapy. The antibiotics chosen for the policy should be rotated after a set period of time in order to reduce selective pressure. The policy should contain information on the class of antibiotic and the possible impact that this class could have on emergence of resistance. Table 18: Antibiotics against nosocomial infections Penicillins ANTIBIOTIC Penicillins Aminopen. + inhibitor (BLI) beta lactamase Acylamidopenicillins Acylamidopenicillins+ BLI Isoxazolylpenicillins EXAMPLE Benzyl penicillin ACTIVE AGAINST Meningo-, strepto-, pneumococci Amoxycillin + clavulanic acid Staphylococci Azlocillin Piperacillin Piperacillin + tazobactam Cloxacillin Flucloxacillin Enterococci P. aeruginosa P. aeruginosa EXAMPLE Cefazolin Cefaclor Cefuroxime Cefotaxime Ceftriaxone ACTIVE AGAINST S. aureus Cephalosporins ANTIBIOTIC GROUP 1st Generation 2nd Generation 3rd Generation 4th Generation Staphylococci Staph., strept,enterobacteria Gram negatives Strept., pneumococci Gram negatives, P. aeruginosa Gram negatives, anaerobes Ceftazidime Cefoxitin Carbapenems ANTIBIOTIC GROUP EXAMPLE Imipenem Meropenem ACTIVE AGAINST Gram positive Gram negative+ anaerobes ANTIBIOTIC GROUP EXAMPLE 2nd Group Ofloxacin Ciprofloxacin 3rd Group Levofloxacin ACTIVE AGAINST Enterobacteria (staphylococci, enterococci.) P. aeruginosa Gram positive + gram negative Carbapenems Quinolones 115 Control And Prevention Of Antimicrobial Resistant Organisms in HCF Aminoglycosides ANTIBIOTIC GROUP EXAMPLE Gentamicin Netilmicin Tobramicin Amikacin ACTIVE AGAINST Enterobacteria Enterobacteria Enterobacteria + P. aeruginosa Enterobacteria + P. aeruginosa ANTIBIOTIC GROUP EXAMPLE Makrolides Erythromycin Lincosamides Clindamycin ACTIVE AGAINST Gram positive cocci L. pneumophila C. jejuni Gram positive cocci Anaerobes (Bacteroides, Clostridium) Glycopeptides Vancomycin Teicoplanin Streptogramines Quinupristine / dalfopristine Rifamycins Rifampicin Aminoglycosides Other groups: Gram positive,( MRSA, enterococci) 116 GRSA , VRE Gram positive cocci Mycobacteria (not used as monotherapy)