Review
Priorities in the prevention and control of multidrug-resistant Enterobacteriaceae in hospitals

https://doi.org/10.1016/j.jhin.2012.06.013Get rights and content

Summary

Background

Multidrug-resistant Enterobacteriaceae (MDE) are a major public health threat due to international spread and few options for treatment. Furthermore, unlike meticillin-resistant Staphylococcus aureus (MRSA), MDE encompass several genera and multiple resistance mechanisms, including extended-spectrum beta-lactamases and carbapenemases, which complicate detection in the routine diagnostic laboratory. Current measures to contain spread in many hospitals are somewhat ad hoc as there are no formal national or international guidelines.

Aim

We sought to establish what should be the priorities for the prevention and control of MDE and what is feasible for implementation. We also identify areas for further research.

Methods

We reviewed the published literature and other sources e.g. national agencies, for measures and interventions used to control MDE.

Findings

Certain categories of at risk patients should be screened, especially in critical care areas, using appropriate laboratory methods. Standard and contact precautions are essential and hand hygiene compliance requires continued emphasis and high compliance levels. As MDE may persist on environmental surfaces for weeks, environmental decontamination could also be an effective control intervention. There are limited options for decolonisation with inadequate studies to date and antibiotic stewardship within and outside the hospital remains important.

Conclusion

As there is a clear deficit in the evidence base to infor guidance on prevention and control, research in key areas, such as rapid detection, is urgently required.

Introduction

Recent years have seen greater emphasis in the UK and elsewhere on preventing and controlling healthcare-associated infection (HCAI), resulting in a decline in one of the more serious manifestations, i.e. bloodstream infection (BSI) due to meticillin-resistant Staphylococcus aureus (MRSA). Bloodstream infection due to Escherichia coli and other Enterobacteriaceae has become more prevalent, along with increasing antibiotic resistance. Traditionally, beta-lactam antibiotics have been used in the management of BSI and other infections caused by Enterobacteriaceae, but more strains currently demonstrate the presence of extended-spectrum beta-lactamases (ESBLs) which confer resistance to penicillins as well as to most cephalosporins, except the cephamycins. The genes responsible for the production of these enzymes among Enterobacteriaceae are often accompanied by resistance to other groups of antibiotics, e.g. aminoglycosides and fluoroquinolones. The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has been described in a number of countries and there are limited options for treatment of infections caused by these organisms, hence the importance of infection prevention and control measures.

The origins and subsequent dissemination of ESBLs have been highlighted.1, 2 The classification of ESBLs is complex and beyond the scope of this review. Many enzymes are responsible, the most prevalent being CTX-M. Whereas CREs are a more recent phenomenon, their evolution and spread indicate a complex and sophisticated genetic evolution involving transcontinental spread.3, 4, 5 Paterson and Doi in 2007 likened the emergence of these bacteria to Mycobacterium tuberculosis, which also demonstrates multidrug and extreme drug resistance.6 The definition of pan-resistance among Gram-negative bacilli is complicated by susceptibility testing and whether carried out according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) or Clinical and Laboratory Standards Institute (CLSI) methods.6 More recently, definitions for multi-, extensively and pandrug-resistant bacteria have been proposed, the last of these implying resistance to all antibiotic classes available for empirical treatment.7

Acquisition of drug-resistant Gram-negative bacilli is usually associated with admission to a tertiary hospital, but both ESBLs and CREs can be found outside acute hospitals such as patient carriage in long-term care facilities.8, 9, 10 Multidrug-resistant Enterobacteriaceae (MDE) can be detected in the hospital environment, including in discharge waste from hospitals and also in animal reservoirs.11, 12, 13, 14, 15 Since the road between the community and the hospital runs both ways, patients can carry these bacteria into hospital and return them to the community from the hospital.

While Acinetobacter spp. survive in surface dust for months, bacteria such as E. coli, Klebsiella spp., Enterobacter spp. and Serratia spp., have not generally demonstrated enhanced resilience to desiccation. It is generally assumed that Gram-negative micro-organisms require moist or damp sites for enhanced longevity.16 Recent reports suggest that E. coli and Klebsiella spp. may survive more than a year in dry surroundings, however, and Serratia marcescens for up to two months.16 Therefore the healthcare environment could be an important reservoir for Gram-negative bacteria during outbreaks, given their proven ability to survive on surfaces.16, 17, 18, 19

A study performed in 1989 found enterobacter on patient charts, and more recently, another demonstrated that 5% of about 2000 environmental sites were positive for E. coli, enterobacter, serratia and klebsiella, e.g. bedside tables, chairs, floors, door handles and infusion pumps, and as expected from bathroom sites such as urinals, shower fittings, sinks and toilet seats.20, 21, 22 These environmental coliforms were indistinguishable from those from the patient whose environment was sampled.21 Another study suggests that multidrug-resistant klebsiella is more likely to contaminate the immediate environment of colonized or infected patients than E. coli.23 Coliforms recovered from the healthcare environment display antibiotic resistance profiles that reflect local prescribing practices; indeed, wards or units that are constantly exposed to antibiotics are more likely to harbour resistant micro-organisms.22 Despite terminal cleaning, prior room occupancy has been shown to be a risk for the acquisition of some Gram-negative micro-organisms in the intensive or critical care setting.24, 25 This finding, along with similar reports for MRSA, vancomycin-resistant enterococci (VRE) and Clostridium difficile, probably offers the best available evidence for the role of the environment in HCAI.26

Traditional sites for Gram-negative microbes in hospitals have been those constantly or intermittently exposed to water. This includes hand-wash basins, sinks, sluices, showers, baths and toilets. Bacterial biofilm builds up in plumbing components, including taps, water filters and sink traps underneath water outlets. It hosts and protects a multitude of water-loving organisms and poses a threat to nearby debilitated patients.27 In addition, bacteria within biofilm may display greater capacity for antimicrobial resistance, and tolerate chlorine and other disinfectants.28 Biofilm-forming Klebsiella pneumoniae have also been shown to be more likely to produce extended-spectrum beta-lactamases.29, 30 A recent study utilizing electron microscopy of common hospital sites has reported the presence of biofilm capable of offering protection for a range of multidrug-resistant bacteria on dry surfaces.29

The risk factors associated with the acquisition of ESBLs and CREs include underlying malignancy, patients requiring multiple interventions or antibiotics, and the occurrence of more than one genotype.31, 32, 33, 34, 35, 36 The international spread of these bacteria and their presence in the food chain, as recently described in Nottingham, UK, implies that their prevention and control is a greater challenge than that presented by MRSA and C. difficile.37

This review outlines priorities for the prevention and control of MDE, in acute hospitals within the limitations of current literature. Areas requiring further evaluation and research are also highlighted.

Section snippets

Screening and laboratory detection

Unlike MRSA and VRE, there is less agreement about who and when to screen and which identification methods to use for MDE, due to the diversity of bacteria involved and their resistance mechanisms. Most of what follows is summarized from descriptive data and outbreak reports rather than from well-conducted studies although the US Centers for Disease Control and Prevention have issued a guidance document on CRE and a group of European experts has surveyed existing knowledge on therapeutic and

Conclusions and future needs

Currently the scientific literature is vague on optimal practice for many aspects of the prevention and control of MDE and official guidelines are much needed given the major public health threat that MDE represent and the many challenges that infection prevention and control practitioners and others face on a daily basis. A recent report from a 535-bed Israeli hospital with endemic carbapenem-resistant K. pneumoniae suggests that success is possible as the incidence of cases and the

Conflict of interest statement

H.H. has had recent research collaborations with Steris Corporation, Inov8 Science, Pfizer and Cepheid. He has also recently received lecture and other fees from Novartis, AstraZeneca and Astellas. S.D. has received non-recurring lectureship fees and conference support from Pfizer, Novartis and Janssen-Cilag. A.S.K. has no conflicts of interest.

Funding sources

None.

References (131)

  • D. Yang et al.

    Biofilm-forming Klebsiella pneumoniae strains have greater likelihood of producing extended-spectrum β-lactamases

    J Hosp Infect

    (2008)
  • K. Vickery et al.

    Presence of biofilm containing viable multi-resistant organisms despite terminal cleaning on clinical surfaces in an intensive care unit

    J Hosp Infect

    (2012)
  • Z.A. Qureshi et al.

    Risk factors and outcome of extended-spectrum β-lactamase-producing Enterobacter cloacae bloodstream infections

    Int J Antimicrob Agents

    (2011)
  • M. Nguyen et al.

    Carbapenem-resistant Klebsiella pneumoniae bacteremia: factors correlated with clinical and microbiologic outcomes

    Diagn Microbiol Infect Dis

    (2010)
  • Y. Carmeli et al.

    Controlling the spread of carbapenemase-producing Gram negatives: therapeutic approach and infection control

    Clin Microbiol Infect

    (2010)
  • A.D. Harris et al.

    How important is patient-to-patient transmission in extended-spectrum β-lactamase Escherichia coli acquisition?

    Am J Infect Control

    (2007)
  • M. Cotter et al.

    Dissemination of extended-spectrum β-lactamase-producing Escherichia coli at home: a potential occupational hazard for healthcare workers?

    J Hosp Infect

    (2012)
  • R.E. Warren et al.

    Control of infections due to extended-spectrum β-lactamase-producing organisms in hospitals and the community

    Clin Microbiol Infect

    (2008)
  • M.W. Casewell et al.

    Survival of multiply-resistant Klebsiella aerogenes and other gram negative bacilli on finger tips

    J Hosp Infect

    (1983)
  • H. Sax et al.

    ‘My five moments for hand hygiene’: a user-centred design approach to understand, train, monitor and report hand hygiene

    J Hosp Infect

    (2007)
  • J.R. Zahar et al.

    Is hand-rub consumption correlated with hand hygiene and rate of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL)-acquired infections?

    J Hosp Infect

    (2012)
  • S. Goddard et al.

    The efficacy of infection control interventions in reducing the incidence of extended-spectrum β-lactamase-producing Enterobacteriaceae in the non-outbreak setting: a systematic review

    Am J Infect Control

    (2011)
  • F. Randrianirina et al.

    Role of contaminated aspiration tubes in nosocomial outbreak of Klebsiella pneumoniae producing SHV-2 and CTX-M-15 extended-spectrum β-lactamases

    J Hosp Infect

    (2009)
  • N. Virgincar et al.

    Klebsiella pneumoniae producing KPC carbapenemase in a district general hospital in the UK

    J Hosp Infect

    (2011)
  • K. Thom et al.

    Environmental decontamination because of multidrug-resistant Acinetobacter baumanii surrounding colonized or infected patients

    Am J Infect Control

    (2011)
  • E. Creamer et al.

    The contribution of beds to healthcare-associated infection: the importance of adequate decontamination

    J Hosp Infect

    (2008)
  • K. Ragan et al.

    Use of audit and feedback with fluorescent targeting to achieve rapid improvements in room cleaning in the intensive care unit and ward settings

    Am J Infect Control

    (2012)
  • C. Werry et al.

    Contamination of detergent cleaning solutions during hospital cleaning

    J Hosp Infect

    (1988)
  • J.W. Medcraft et al.

    Potential hazard from spray cleaning of floors in hospital wards

    J Hosp Infect

    (1987)
  • S. Dharan et al.

    Routine disinfection of patients' environmental surfaces: myth or reality?

    J Hosp Infect

    (1999)
  • G. Moore et al.

    A laboratory evaluation of the decontamination properties of microfibre cloths

    J Hosp Infect

    (2006)
  • L.K. Bergen et al.

    Spread of bacteria on surfaces when cleaning with microfibre cloths

    J Hosp Infect

    (2009)
  • S.J. Dancer

    Mopping up hospital infection

    J Hosp Infect

    (1999)
  • S. Engelhart et al.

    Pseudomonas aeruginosa outbreak in a haematology–oncology unit associated with contaminated surface cleaning equipment

    J Hosp Infect

    (2002)
  • A.A. Forder

    Buckets and mops in operating theatres

    Lancet

    (1973)
  • L. Naparstek et al.

    Reduced susceptibility to chlorhexidine among extremely-drug-resistant strains of Klebsiella pneumoniae

    J Hosp Infect

    (2012)
  • C. Pena et al.

    Risk factors for faecal carriage of Klebsiella pneumoniae producing extended spectrum β-lactamase (ESBL-KP) in the intensive care unit

    J Hosp Infect

    (1997)
  • W.A. Rutala et al.

    Serratia marcescens nosocomial infections of the urinary tract associated with urine measuring containers and urinometers

    Am J Med

    (1981)
  • D.J. Weber et al.

    Faucet aerators: a source of patient colonization with Stenotrophomonas maltophilia

    Am J Infect Control

    (1999)
  • C.A. Lucero et al.

    Outbreak of Burkholderia cepacia complex among ventilated pediatric patients linked to hospital sinks

    Am J Infect Control

    (2011)
  • S. Malnick et al.

    Pyjamas and sheets as a potential source of nosocomial pathogens

    J Hosp Infect

    (2008)
  • N.S. Meakin et al.

    Comparison of cleaning efficacy between in-use disinfectant and electrolysed water in an English residential care home

    J Hosp Infect

    (2012)
  • A. Davies et al.

    Gaseous and air decontamination technologies for Clostridium difficile in the healthcare environment

    J Hosp Infect

    (2011)
  • J. Mandal et al.

    Microbicidal effect of electrolysed water

    J Hosp Infect

    (2010)
  • M.A. Boyle et al.

    Control of bacterial contamination of washbasin taps and output water using Ecasol: a one-year study

    J Hosp Infect

    (2012)
  • J.A. Otter et al.

    Hydrogen peroxide vapour decontamination of an intensive care unit to remove environmental reservoirs of multidrug-resistant Gram-negative rods during an outbreak

    Am J Infect Control

    (2010)
  • P. Nordmann et al.

    Does broad-spectrum β-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria?

    J Antimicrob Chemother

    (2011)
  • D.L. Paterson et al.

    A step closer to extreme drug resistance (XDR) in Gram-negative bacilli

    Clin Infect Dis

    (2007)
  • A.-P. Magiorkos et al.

    Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

    Clin Microbiol Infect

    (2012)
  • I. Willemsen et al.

    Highly resistant Gram-negative microorganisms: incidence density and occurrence of nosocomial transmission (Triangle Study)

    Infect Control Hosp Epidemiol

    (2011)
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