GUIDE TO INFECTION CONTROL IN THE HOSPITAL. Enterococcal Species

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GUIDE TO INFECTION CONTROL IN THE HOSPITAL CHAPTER 44 Enterococcal Species Authors Jacob Pierce, MD, Michael Edmond, MD, MPH, MPA Michael P. Stevens, MD, MPH Chapter Editor Victor D. Rosenthal, MD, CIC, MSc Cover heading - Topic Outline Topic outline - Key Issues Known Facts Controversial Issues Suggested Practice Suggested Practice in Under-Resourced Settings Summary References Chapter last updated: April, 2018

KEY ISSUE Enterococci are important nosocomial pathogens because: They are normal flora in the human gastrointestinal tract. Antimicrobial resistance allows for their survival in an environment with heavy antimicrobial usage. They contaminate the hospital environment and survive for prolonged periods of time. Contamination of the hands of healthcare workers coupled with poor handwashing compliance provides the potential for spread in the hospital. KNOWN FACTS Enterococci are common hospital-acquired pathogens, accounting for 7.4% of all healthcare-associated infections. The organism is of relatively low virulence but may be difficult to treat in the compromised host, particularly when multidrug-resistant. Resistance to nearly every known antibiotic has been described for various strains of enterococci. The vana gene, which confers high-level vancomycin resistance in enterococci, has been detected in Staphylococcus aureus strains in a small number of patients in the United States. Vancomycin resistance due to vanc is intrinsic and found in Enterococcus casseliflavus and E. gallinarum. vanc organisms do not appear to be epidemiologically important, and isolation of patients harboring these organisms is not necessary. In 2014, 44% of all enterococcal isolates in the United States involved in healthcare-associated central line-associated bloodstream infections (CLABSIs) were resistant to vancomycin. However, the two most common species display marked variability in vancomycin susceptibility, with 82.2% of E. faecium and 9.8% of E. faecalis isolates being reported as resistant to vancomycin. 1

Risk factors for acquisition of vancomycin-resistant enterococci (VRE) include prior use of antimicrobial agents (vancomycin, third generation cephalosporins, antianaerobic drugs), length of hospital stay, enteral feedings, intra-abdominal surgery, presence of a decubitus ulcer, high colonization pressure, and severity of illness. Patient populations at highest risk for VRE colonization and infection include dialysis patients, organ transplant patients, patients with hematologic malignancies, and bone marrow transplant patients. Studies have found that approximately 30% of patients following liver transplantation are colonized with VRE, of whom over 25% develop infection. Up to 40% of allogeneic hematopoietic stem cell transplant patients are colonized, of whom over 33% develop VRE bloodstream infections in the early period post-transplant. Treatment with antianaerobic drugs has been shown to promote high density colonization. Colonization of the gastrointestinal tract (GI) tract with VRE is typically of long duration, in some cases persisting for years. Rectal swab cultures for VRE have suboptimal sensitivity. Colonization of healthy healthcare workers in the United States is unusual. Risk factors for VRE bacteremia include neutropenia, gastrointestinal colonization, and hematologic malignancy. VRE colonization is highly prevalent in some long-term care facilities, which serve as reservoirs of resistant organisms for importation into acute care facilities. However, morbidity due to VRE in the nursing home population is low. SUGGESTED PRACTICE Treatment of VRE infections is problematic. Therapy should include drainage of localized infections, when possible. Daptomycin, a cyclic lipopeptide, is bactericidal against VRE. Quinupristin/dalfopristin may be 2

clinically useful for the treatment of infections due to E. faecium but is inactive against E. faecalis. Linezolid has good activity against VRE and an advantage is its 100% oral bioavailability, allowing for oral therapy. Quinupristin/dalfopristin, linezolid, and tigecycline are bacteriostatic against enterococci. Resistance has been detected for all three of these agents. A few reports have described attempts to decolonize the GI tract of VRE but results have been suboptimal. Ramoplanin has been shown to suppress carriage of VRE, but following discontinuation of the drug, the organism can again be detected in the stool. Infection control controversies include the effectiveness of active surveillance cultures and subsequent isolation of colonized patients to control nosocomial transmission, whether drugs that suppress GI colonization result in decreased nosocomial transmission and whether vancomycin restriction leads to decreased rates of VRE infection and colonization. Use of contact precautions (gloves and gowns) continues to be recommended by major organizations. However, there is some evidence (from resource-rich environments) indicating that this may not be universally necessary. This remains an area of controversy. 3

SUGGESTED PRACTICE IN UNDER-RESOURCED SETTINGS In resource-limited settings compliance with guidelines can be inconsistent; low nurse-to-patient staffing ratios, insufficient infection prevention training of healthcare workers, poor access to medical supplies, and hospital overcrowding can all contribute. Infection prevention training for healthcare workers is critical; strict compliance with hand washing should be emphasized as outlined above. 1-6 Limiting unnecessary antimicrobial exposure should be emphasized, especially to drugs that can promote the development of VRE. More data on the burden of enterococcal infections in low- and middleincome countries are needed. SUMMARY Enterococci are ubiquitous Gram-positive cocci that are part of the normal flora of humans and other animals. Infections caused by enterococci include urinary tract infections, abdominal-pelvic infections, wound (especially decubitus ulcers and diabetic foot) infections, and endocarditis. Strains of enterococci have acquired resistance to virtually all available antimicrobial agents. In general, antimicrobial resistance has been more problematic for E. faecium than E. faecalis. The prevalence of vancomycin resistance among the enterococci has reached high levels. In 1989, less than 0.5% of enterococcal isolates from ICU and non-icu settings were vancomycin resistant. Currently, 44% of all enterococcal isolates involved in healthcare-associated CLABSIs in the United States are vancomycin resistant. However, when stratified by species, E. faecium isolates demonstrate a markedly higher proportion of vancomycin resistance than E. faecalis isolate 4

Numerous case-control studies have evaluated risk factors for the development of colonization and/or infection with VRE. A variety of antimicrobial agents have been implicated and include vancomycin, ceftazidime, aminoglycosides, ciprofloxacin, aztreonam, and antianaerobic drugs. Other risk factors have included severity of illness, length of hospital stay, hematologic malignancy or bone marrow transplantation, and mucositis. Colonization of the GI tract has been shown to be a risk factor for the development of VRE bacteremia. Environmental contamination with VRE is common, especially when the patient has diarrhea. To control VRE in the hospital setting, we recommend placing colonized/infected patients in a private room. Gloves and gowns should be worn on entering the patient s room, and strict attention paid to hand hygiene. 6 In addition, there should be no sharing of noncritical items (i.e., BP cuffs, stethoscopes, etc., should remain in the patient s room). Housekeeping staff should wipe down all horizontal surfaces in VRE patient rooms daily. In addition to infection control measures, controlling VRE requires prudent use of antibiotics. Vancomycin should be avoided for routine surgical prophylaxis unless high rates of methicillin-resistant Streptococcus aureus (MRSA) exist or the patient is known to be MRSA colonized. Vancomycin should also be avoided for the treatment of a single positive blood culture growing coagulase-negative staphylococci if contamination is likely. Vancomycin should not be used for selective gut decontamination or for routine prophylaxis of low birth weight infants, continuous ambulatory peritoneal dialysis patients, or intravascular catheters. REFERENCES 1. de Bruin MA, Riley LW. Does Vancomycin Prescribing Intervention Affect Vancomycin-Resistant Enterococcus Infection and 5

Colonization in Hospitals? A Systematic Review. BMC Infect Dis. 2007; 7:24. 2. DeLisle S, Perl TM. Vancomycin-Resistant Enterococci: A Road Map on How to Prevent the Emergence and Transmission of Antimicrobial Resistance. Chest. 2003; 123:504S 518S. 3. Hayden MK. Insights into the Epidemiology and Control of Infection with Vancomycin-Resistant Enterococci. Clin Infect Dis 2000; 31(4):1058 1065. 4. McNeil SA, Malani PN, Chenoweth CE, et al. Vancomycin-Resistant Enterococcal Colonization and Infection in Liver Transplant Candidates and Recipients: A Prospective Surveillance Study. Clin Infect Dis 2006; 42(2):195 203. 5. Rice LB. Emergence of Vancomycin-Resistant Enterococci. Emerg Infect Dis. 2001; 7(2):183 187. 6. Weinstock DM, Conlon M, Iovino C, et al. Colonization, Bloodstream Infection, and Mortality Caused by Vancomycin-Resistant Enterococcus Early After Allogeneic Hematopoietic Stem Cell Transplant. Biol Blood Marrow Transplant. 2007; 13(5):615 21. 7. Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial Bloodstream Infections in US Hospitals: Analysis of 24,179 Cases from a Prospective Nationwide Surveillance Study. Clin Infect Dis 2004; 39(3):309 317. 8. Weiner LM, Webb AK, Limbago B, et al. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infect Control Hosp Epidemiol 2016; 37(11):1288 301. 9. CDC. Antibiotic Resistance Threats in the United States, 2013; available at http://www.cdc.gov/drugresistance/threat-report-2013. Accessed 17 November 2017. 10. Edmond MB, Masroor N, Stevens MP, et al. The Impact of Discontinuing Contact Precautions for VRE and MRSA on Device- 6

Associated Infections. Infect Control Hosp Epidemiol 2015; 36(8):978 980. 11. Rosenthal VD, Al-Abdely HM, El-Kholy AA, et al. International Nosocomial Infection Control Consortium Report, Data Summary of 50 Countries for 2010-2015: Device-associated Module. Am J Infect Control. 2016; 44(12):1495 504. doi: 10.1016/j.ajic.2016.08.007. 12. Chakravarthy M, Myatra SN, Rosenthal VD, et al. The Impact of the International Nosocomial Infection Control Consortium (INICC) Multicenter, Multidimensional Hand Hygiene Approach in Two Cities of India. J Infect Public Health 2015; 8(2):177 86. doi: 10.1016/j.jiph.2014.08.004. 13. Rosenthal VD, Pawar M, Leblebicioglu H, et al. Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach over 13 Years in 51 Cities of 19 Limited-Resource Countries from Latin America, Asia, the Middle East, and Europe. Infect Control Hosp Epidemiol 2014; 34(4):415 23. doi: 10.1086/669860. 14. Kanj SS, Zahreddine N, Rosenthal VD, et al. Impact of a Multidimensional Infection Control Approach on Catheter-Associated Urinary Tract Infection Rates in an Adult Intensive Care Unit in Lebanon: International Nosocomial Infection Control Consortium (INICC) Findings. Int J Infect Dis 2013; 17(9):e686 90. doi: 10.1016/j.ijid.2013.01.020. 15. Barahona-Guzmán N, Rodríguez-Calderón ME, et al. Impact of the International Nosocomial Infection Control Consortium (INICC) Multidimensional Hand Hygiene Approach in Three Cities of Colombia. Int J Infect Dis 2014; 19:67 73. doi: 10.1016/j.ijid.2013.10.021. 16. Rosenthal VD, Todi SK, Álvarez-Moreno C, et al. Impact of a Multidimensional Infection Control Strategy on Catheter-Associated Urinary Tract Infection Rates in the Adult Intensive Care Units of 15 Developing Countries: Findings of the International Nosocomial 7

Infection Control Consortium (INICC). Infection 2012; 40(5):517 26. doi: 10.1007/s15010-012-0278-x. 17. Rosenthal VD, Guzman S, Safdar N. Reduction in Nosocomial Infection with Improved Hand Hygiene in Intensive Care Units of a Tertiary Care Hospital in Argentina. Am J Infect Control 2005; 33(7):392 7. 8