Glycopeptide Resistant Enterococci (GRE) Policy IC/292/10

BASINGSTOKE AND NORTH HAMPSHIRE NHS FOUNDATION TRUST Glycopeptide Resistant Enterococci (GRE) Policy IC/292/10 Supersedes: IC/292/07 Owner Name Dr Nicki Hutchinson Job Title Consultant Microbiologist, DIPC Final approval Name Infection Control Committee committee Date of meeting 05/03/2010 Authoriser Name Anne Stebbing Job title Chair, ICC Signature Date of authorisation 05/03/2010 Review date (maximum 3 years from date March 2013 of authorization) Audience (tick all that apply) Trust staff NHS General public Standards Standards for Better Health & Hygiene code NHSLA Reviewed in accordance with The Health and Social Care Act 2008: Code of Practice for health and adult social care on the prevention and control of infections and related guidance as published 16 December 2009. 0

Executive Summary This is an outline of the clinical and infection control precautions necessary for the management and control of cases of GRE in BNHFT. It is based on national guidelines. Enterococci are the third most common cause of HAI being responsible for 10-12% of all HAI, 10-20 of HA-ITU and 5-10% of HA bacteraemial. 799 cases of GRE bacteraemia were reported in England from Oct 2007 to Sept2008 Enterococci are commensals of human and animal bowel. E. faecalis is the predominant commensal species of humans and causes about 90% of clinical infections; E. faecium is isolated with increasing frequency. Enterococci are relatively poor pathogens, usually causing colonization rather than infection. Most enterococcal infections are endogenous, Cross-infection between hospitalised patients can occur..acquired glycopeptide resistance has emerged in enterococci, in particular E. faecalis and E. faecium, it reduces the therapeutic options for enterococcal sepsis Risk factors for hospital infection with GRE include prior antibiotic therapy prolonged hospital stay, and admission to intensive care, renal, haematology or liver units Transmission within hospitals is mainly on hands contaminated by contact with colonised or infected patients, contaminated surfaces, or fomites. Stool carriage may persist for months or years and clearance by antibiotics is not recommended. Staff screening for stool carriage is of no value. Faeces are the most useful screening specimen for outbreak situations. Since colonization is common, patients must be reviewed before commencing antimicrobial therapy. The choice of antimicrobial therapy should be guided by susceptibility testing Management of GRE may include removal of catheters and drainage of abscesses. Hands should be decontaminated between each patient contact, including after removal of gloves. Alcohol gel is a suitable alternative if hands are socially clean. Ideally patients with GRE should be isolated in single rooms, or, if this is not possible, cohorted in bays on the open ward. Patients with GRE and diarrhoea or incontinence pose a high risk of GRE transmission to others and must be isolated. 1

Implementation Plan Summary of changes This protocol has been updated and now complies with the revised hygiene code 16 th December 2009. It complies with national guidelines. GRE have rarely been isolated from patients hospitalised at BNHFT. The precautions used are standard ones used for all hospital acquired infections and no change of practice is required. There are no significant cost implications. Action needed and owner of action This policy affects all clinical staff who might be involved in care and investigation of a patient infected or colonized with GRE The infection control team (ICT) is responsible for updating the policy regularly, monitoring compliance, investigating incidents and staff training The surveillance coordinator is responsible for monitoring and reporting all cases of blood stream infections with GRE within the trust and nationally to the Health protection agency (HPA) The ICT is responsible for monitoring infection trends and outbreak control Microbiolgists and pharmacists are responsible for updating antibiotic policies and ensuring prudent use of antibiotics to prevent GRE outbreaks. All clinical teams are responsible for adhering to this policy and the antibiotic policy to prevent and control GRE infections Audit and monitoring Monitoring through laboratory surveillance on case by case basis will be undertaken by the ICT. Audit criteria (by ICT): are staff aware of policy and able to use it are patients infected with GRE managed according to policy 2

Contents Page 1. Introduction 4 1.1. Enterococci 4 1.2. Glycopeptide resistance 4 1.3. The epidemiology of GRE 5 2. Microbiological investigations 6 2.1. GRE identification and screening 6 2.2. Typing 6 3. Treatment and management 6 3.1. Patients infected with GRE 6 3.2. Patients and staff colonized with GRE 7 4. Infection control measures 7 4.1. Principles of outbreak management 7 4.2. Hand hygiene 7 4.3. Isolation of patients and environmental cleaning 8 4.4. Transfer of patients with GRE 8 4.5. Control of antibiotic usage 8 References 8 3

1.0 Introduction This policy is based on national guidelines developed by a joint working party of the hospital infection society (HIS), Infection Control Nurses Association (ICNA) and British Society for Antimicrobial Chemotherapy (BSAC). 1 1.1 Enterococci Enterococci colonize the bowels of most normal people in concentrations of up to 10 7 cfu/g of stool. 1 Although there are 16 recognised species of enterococci, Enterococcus faecalis predominates as a human commensal and accounts for about 90% of clinical isolates. In recent years, E. faecium has been seen with increasing frequency, probably because of its greater antibiotic resistance. Other species of enterococci are isolated infrequently from humans. Most clinical isolates represent colonization rather than infection. Infection when it occurs is usually due to endogenous strains and usually of the urinary tract, but also of the abdomen and pelvis where they may be found mixed with other bowel flora. They are relatively poor pathogens but may cause invasive disease in compromised patients, causing bacteraemia (sometimes polymicrobial), wound infection, cholangitis, endocarditis and meningitis. Nationally, Enterococci are now the third most common cause of hospital-acquired infection (HAI), being responsible for 10-12% of all HAIs, 10-20% of hospital-acquired urinary tract infections and 5-10% of hospital-acquired bacteraemias. In hospital infections the reservoir of enterococci is usually the patient s bowel. Nevertheless, crossinfection and clusters of infection occur and the emergence of resistant strains (glycopeptide-resistant or high-level aminoglycoside resistant) have informed our understanding of the dynamics of their spread via staff hands and occasionally the environment. As with outbreaks of many other antimicrobial resistant organisms, colonization is more frequent than true infection. The epidemiology is discussed below (section 1.3). At BNHFT, Enterococci are frequently isolated from urine and intra abdominal samples but GRE has rarely been detected as a cause of infection in hospitalised patients. Since 2007 GRE has not been isolated from blood cultures 1.2 Glycopeptide resistance Glycopeptide antibiotics inhibit synthesis of Gram-positive cell walls. As most clinically important Gram-positive bacteria are susceptible to glycopeptides, they have become agents of choice and the last resort for treating infections with multiply antibiotic resistant organisms. Susceptible bacteria usually have vancomycin minimal inhibitory concentrations (MICs) in the range 0.5-4.0 mg/l; teicoplanin MICs are similar or slightly lower. Acquired glycopeptide resistance can be divided into 'low-level' (vancomycin MICs: 8-32 mg/l) and 'high-level' (vancomycin MICs: 64 mg/l). However, there are several resistance phenotypes, High-level, inducible, transferable resistance to both vancomycin and teicoplanin is now called VanA, and low-level inducible resistance to vancomycin alone, VanB. VanA resistance is usually plasmid-borne but, encoded on a vana transposon, may become incorporated into the chromosome. VanB resistance is usually chromosomal but, encoded on a vanb conjugative transposon, occasionally transfers to other strains of enterococci directly or by a plasmid. Both VanA and VanB resistance are most commonly seen in E. faecium and E. faecalis. Constitutive low-level 4

vancomycin resistance, encoded by the vanc genes, is found in strains of E. gallinarum and related resistance genes have been reported in E. casseliflavus and E. flavescens. There are many variants of these basic phenotypic patterns. VanA resistance has been transferred in the laboratory and on animal skin to other Gram-positive bacteria, including Staphylococcus aureus. This potential for gene transfer has now been realised with reports of outbreaks of vancomycin resistant S. aureus in 2002 in UK hospitals The emergence of enterococci with acquired glycopeptide resistance is mainl y the result of the appearance and spread of transposons encoding VanA and VanB genes. This usually occurs within environments where there is heavy usage of glycopeptides or cefalosporins, for example in renal, liver, haematology, oncology, transplant and intensive care units. The emergence of GRE in the mid 1980s coincided with an increase in the global usage of glycopeptides for the treatment of methicillin resistant S. aureus and coagulase-negative staphylococci and Clostridium difficile diarrhoea. 1.3 The epidemiology of GRE The risk factors for hospital infection with GRE include prior antibiotics therapy, prolonged hospital stay and admission to intensive care, renal, haematology or liver units. Cefalosporin and vancomycin therapy are the most cited antimicrobial risk factors for GRE colonization or infection. Preceding therapy with agents active against anaerobes have also been implicated, especially in the context of C. difficile associated diarrhoea. Patients are more likely to acquire GRE if their length of hospital stay is prolonged. GRE are encountered more frequently in teaching hospitals and in hospitals with a higher complement of beds possibly due to their more complex case-mix. In Europe, GRE are found in the bowels of normal people in the community, in frozen meats and animal carcasses, and in the bowels of animals fed the glycopeptide avoparcin as a food supplement. Although there is considerable debate, and the scientific evidence is incomplete, it is generally accepted that the use of avoparcin as an ergotropic agent in animal husbandry is associated with the emergence of GRE in animal faeces. At least some of these strains then enter the food chain and colonize humans. Administration of glycopeptides may result in the subsequent emergence of GRE following hospital admission. GRE may also spread by cross-infection between hospital patients. The main routes of transmission between patients and health care workers are probably via hands, fomites and/or environmental contamination. Enterococci may contaminate the environment around a patient and survive there for several days and environmental contamination is increased when patients have diarrhoea. Surfaces or fomites (including medical instruments and equipment) that come into contact with staff hands may also become contaminated. These environmental sites are potentially secondary sources for crossinfection. Alert organism surveillance from routine clinical specimens, is the usual method of GRE surveillance in the United Kingdom. 5

2.0 Microbiological investigations 2.1 GRE identification and screening During suspected outbreaks (two new cases of GRE detected in clinical specimens related in time and place) and in response to important incidents (defined on the basis of risk assessment by the ICT), patient screening will be undertaken to identify colonization, elucidate the epidemiology and permit introduction of appropriate preventative measures, including isolation. It can be assumed that patients who are clinically infected with GRE are already colonized in the gastrointestinal tract. The screening specimen with the greatest yield is the stool. GRE may not be detected in rectal swabs from some patients and it is important to include other clinically relevant sites when screening patients for GRE carriage. Colonized sites other than faeces include the throat, skin, vagina, perineum, wounds, urine and vascular catheter sites. The laboratory at BNHFT has a separate standard operating procedure for processing specimens ; the use of a selective medium is recommended. 2.2 Typing Preliminary checks will be undertaken by the microbiology laboratory, to monitor isolates for characteristic or unusual biotypes or antibiograms. However these markers are not discriminatory and, because of the complex epidemiology, further typing at the reference laboratory is required 3.0 Treatment and management 3.1 Patients infected with GRE Enterococci are poorly pathogenic and frequently cause colonization rather than invasive infection. The clinical team should assess each patient to distinguish between colonization and infection and then decide whether antimicrobial therapy and / or other interventions are necessary. GRE infection of the blood or urinary tract may be associated with intravenous and urinary catheters respectively. Such catheters should be removed. Wounds should be debrided and abscesses drained. GRE are often associated with gastrointestinal tract pathology and hence polymicrobial bacteraemia, in which case the underlying condition must be addressed with antimicrobial therapy also directed against the other pathogens. If after clinical assessment and primary management, antimicrobial treatment of GRE is considered necessary, a Microbiologist should be contacted to discuss treatment options. The antibiotic treatment will be selected according to the susceptibility testing result of the organism involved. If prophylaxis is required for surgical or other invasive procedures then this should be discussed with a Microbiologist Nearly all strains of E. faecalis, including glycopeptide-resistant ones, are susceptible to ampicillin. GRE often remain susceptible to tetracycline, chloramphenicol or rifampicin and there have been anecdotal reports of successful treatment with these agents. In addition, a number of new agents with potential use for GRE infections are available, including the streptogramin combination, quinupristin/dalfopristin (which, however, is not active against E. faecalis), and the oxazolidinone, linezolid and Daptomycin. 6

3.2 Patients and staff colonized with GRE Faecal carriage of GRE may persist for months or years. Chronic carriers and those subject to frequent hospital admissions are a continuing potential source of crossinfection. A number of attempts have been made to clear stool carriage of GRE using a variety of oral agents. Thus far, none of these attempts have been clearly successful and no single regimen can be recommended. Distinguishing failure of eradication from recolonization may be even more problematical in view of the possibility of continual GRE re-colonization from food sources. There have been no published reports implicating staff gut carriage as a source of patient colonization or infection. Screening of staff for stool carriage of GRE during outbreaks is thus unhelpful and may cause considerable stress. 4.0 Infection control measures 4.1 Principles of outbreak management It is important to control the emergence and spread of GRE for the reasons stated previously: the limited therapeutic alternatives, the increasingly compromised in-patient population, and the potential for transfer of glycopeptide resistance to more pathogenic bacteria such as S. aureus (including MRSA). The epidemiology is complex: hospitals may be affected by sporadic cases of GRE, epidemics or endemic colonization and infection. Each of these situations will need to be managed in different ways, depending on the risk to the patients involved. 1 Since enterococci are of low virulence and usually cause serious infection only in more compromised patients, the cost and risks of control procedures should be weighed against risks and benefits to the patient group concerned. One study has shown the cost of bacteraemia due to GRE to be $27.000 higher than that due to glycopeptide-sensitive enterococci. 1 As with all other infection control interventions, the quality of clinical care must not suffer as a result of the precautions implemented. Because of the uncertainty surrounding the management of GRE, discussion between the infection control team and the clinical staff is essential. Control measures must be informed by a risk assessment. This should be discussed with the ICT and based on: the extent of patient GRE colonization (including wounds, intravenous and urinary catheters) whether the patient is incontinent of faeces or not whether they have diarrhea whether the GRE are also resistant to other antimicrobials and which, the prevalence (and severity) of GRE colonization and infection, and the susceptibility to infection of patients on the affected wards. 4.2 Hand hygiene Effective hand hygiene is the most important measure to prevent and control the spread of antimicrobial resistant organisms. Hands should be decontaminated between each patient contact, whether or not the patient is known to be colonized with GRE. Either soap or water or alcohol gel should be used. Alcohol hand gel is effective and convenient but should only be used on socially clean hands. 7

4.3 Isolation of patients and environmental cleaning The decision to isolate individual patients affected by GRE should be based on the clinical needs and risk assessment described above, by the clinical team caring for the patient in conjunction with the ICT. Ideally, patients colonized or infected with GRE should be source isolated in single rooms. However, where there are larger patient numbers and insufficient isolation rooms, patients should be cohorted in bays on the open ward. Patients with GRE and diarrhoea or incontinence are at a higher risk of spreading GRE and must be given priority for single rooms. During GRE outbreaks, the ward environment may become heavily contaminated and will need further thorough cleaning following the discharge of the patients. There is no evidence that one cleaning regimen is better than another for eliminating GRE. The sideroom in which a patient with GRE has been cared for should be cleaned after the patient s discharge with a chlorine-releasing agent (500 ppm available chlorine) such as hypochlorite or 1-2% phenolic disinfectants with special attention to horizontal surfaces and dust-collecting areas. Bedding and curtains should be sent to the laundry for standard processing. 4.4 Transfer of patients with GRE When a patient with GRE is transferred to another hospital, the clinical team and/or infection control team responsible for the patient must inform the receiving clinical and infection control staff of the patient's GRE carriage status. In general, GRE neither present a risk to normal people in the community, nor to patients in residential or nursing homes who do not have catheters, wounds or other lesions. 4.5 Control of antibiotic usage The emergence and spread of GRE is encouraged by the use of certain antimicrobials.. In hospital practice, the acquisition of GRE has been associated with antimicrobial administration, especially cephalosporins and glycopeptides. 1 It is good clinical practice not to use any antimicrobial unnecessarily and clinical units should adhere to the trust wide antibiotic policy. References 1. Guidelines for the control of glycopeptide-resistant enterococci in hospitals. A report of a combined working party of the Hospital Infection Society, Infection Control Nurses Association and British Society for Antimicrobial Chemotherapy. 2004 8