I made a flying visit to HIS today in Liverpool to have a debate with Prof Mark Wilcox on whether or not antibiotics are the most important factor in healthcare-associated C. difficile infection. Mark was arguing for the motion, and I was arguing against it. And the result…well you’ll have to read to the bottom!
- The Special Edition kicks off with a thoughtful editorial by the guest editor Dr Mark Walker, in praise of enthusiasts and in defence of conferences.
- Dr Seto’s Lowbury lecture exploring facts and myths around airborne transmission.
- My overview of trends in the infection prevention and control literature since the 2012 HIS conference (there’s been one trend that trumps all other trends: Ebola). You can download the slides and see a recording of this talk here. Also, Dr Jim Gray’s take on future trends.
- Updates on multidrug-resistant Gram-negative bacteria, including the importance of globalization, experiences of controlling CRE and Acinetobacter outbreaks, the role of antibiotic prophylaxis in driving the problem.
- Antibiotic stewardship is covered from a couple of angles, including a surgeons’ perspective and long-term care facilities in Ireland.
- Several articles address surveillance, including the role of ‘data warehousing’, integration of electronic systems, and surveillance of ventriculitis following neurosurgery.
- Not much on the role of the environment, although Dr Frederic Barbut provides an overview of methods to eradicate (or not!) C. difficile from the hospital environment.
- State-of-the-art updates on norovirus, Candida, influenza (specifically the role of point-of-care testing), P. aeruginosa, cystic fibrosis, and HCAI in neonates.
- Management and organisational factors are reviewed, and other articles address assessment and public-reporting, root-cause analysis, human factors, training, and current knowledge.
- Finally, and importantly, the impact of the recession on HCAI is reviewed. The recession has hit hard in Ireland, where this article was penned from, but the article at least offers some useful pragmatic coping strategies!
I’m all for special editions, and I think that JHI should do more of them. I know that compiling this Special Edition has been a considerable undertaking for the Journal, but well worth the effort: it’s a very useful read. Particular thanks to Dr Mark Walker who was the editor for this Special Edition, and to Dr Jenny Child who initiated it.
Welcome to Part II of my reflections from HIS. For the box-set, see the list at the beginning of Part I here.
Dr Karen Vickery – Multispecies biofilms on dry hospital surfaces – harbouring and protecting multiantibiotic resistant organisms
Probably the most important update from the entire conference was more data from the Vickery lab on biofilms on dry hospital surfaces. She excised 44 dry surface samples from the ICU, put them under the electron microscope and, lo and behold, 41 of them (93%) had fully-fledged (if somewhat unusual) EPS-producing biofilms on! The implications are huge: this could explain extended surface survival, poor success rate of surface sampling, and result in reduced biocide susceptibility up to the tune of 1000x (see my review just published in JHI with Karen as a co-author for more on biocides and biofilm susceptibility).
Dr Silvia Munoz-Price – Controlling multidrug resistant Gram-negative bacilli in your hospital: We can do it so can you!
Dr Munoz-Price described her hospital’s impressive reductions on carbapenem-resistant A. baumannii – from 12 new isolates per week to virtually none today. So what worked? It’s difficult to be sure since it was a bundled intervention. Dr Munoz-Price described the rationale behind some elements of the bundle: environmental surface and staff hand sampling to visualize the invisible, environmental cleaning and disinfection to deal with the ‘fecal [sic] patina’ [a stooly veneer emanating from the rectum] (see Dr Munoz-Price and Dr Rosa’s guest blog for more details), and chlorhexidine bathing. Perhaps the most interesting aspect was the various implementation challenges that were overcome. It was amazing how far removed practice ‘in the trenches’ was from the policy set by the epidemiologist’s office, exemplified by environmental staff buying their own UV lamps to for “spot cleaning” removal of fluorescent markers of cleaning thoroughness. Overcoming these challenges required more that the stick (citations for non-compliance, which failed); culture change takes understanding, time and a very large carrot (and some sticks too, sometimes).
Jim Gauthier – faeces management
A number of key pathogens are associated with faecal colonization and shedding: C. difficile, VRE, ESBL and CRE. Jim didn’t mention MRSA, but this can also cause gastrointestinal colonization and, more controversially, infection. Enterobacteriaceae can survive on dry surfaces for longer than you’d expect, too. We traditionally worry about surface contamination of high-touch sites in inpatient settings. Floor contamination isn’t important (unless you happen to be a wheel chair user, a toddler, or drop your pen). Contamination in outpatient settings isn’t a problem either (unless you happen to have a fairly short consultation for a patient with VRE). So, what to do? Jim introduced the idea of a ‘hierarchy of control’; put another way, prevention is better than cure, so do we have the right systems in place to manage faeces which is teeming with hospital pathogens? For example, should we be enforcing mandatory contact precautions for all contact with faeces (standard precautions – which aren’t very standard anyway – are probably not adequate)? Finally, Jim mentioned the growing importance of faecal microbiota transplantation (and hearing a Canadian speak about this reminded me of a hilarious spoof video).
No-touch automated room decontamination (NTD)
Paul Dickens – establishing Ebola surge isolation capacity in the UK
Paul Dickens gave a whistle-stop overview of the detailed plans for Ebola surge capacity in the UK (perish the thought). He began by describing the replacement of formaldehyde with hydrogen peroxide vapour for the decontamination of the patient isolators at the Royal Free High Level Isolation Unit (HLIU). They now have a tried and tested process and protocols in place to get the HLIU back online within days using hydrogen peroxide vapour decontamination, where the previous protocol using formaldehyde put it out of action for 6 weeks! (I was involved in writing the protocols for this tricky decontamination assignment, which were reported on a poster published at HIS.) Other challenges in establishing surge capacity include staff expertise, and PPE recommendations, supply & training. Surge capacity is now established. Let’s just hope we won’t need it!
Dr Frédéric Barbut – How to eradicate Clostridium difficile spores from the environment
There’s now plenty of evidence that contaminated surfaces contribute to the transmission of C. difficile. These environmental intervention studies show a 50-80% reduction in the rate of CDI; does this mean that 50-80% of CDI acquisition is environmentally-associated? This seems too high, but it’s difficult to think of another explanation. Furthermore, there is emerging but compelling evidence of a proportional relationship between the degree of C. difficile surface contamination and transmission risk? I really don’t think that the public have yet ‘got’ that the previous occupant can influence acquisition risk. And when they do, I think there will be increasing demand for properly decontamination rooms. So, is it time to turn to NTD systems? Sometimes, yes. And do you go for hydrogen peroxide or UV? Well, that depends on what you’re trying to achieve! If you’re trying to eliminate pathogens, which sometimes you will be, then hydrogen peroxide vapour is the best choice. But if you’re trying to reduce contamination levels without necessarily eliminating all pathogens, then UV is the best choice due to its speed and ease of use.
The debate: “Hospitals that do not use high-tech decontamination of the environment are doing their patients a disservice.”
This debate pitted Profs Hilary Humphreys and Phil Carling (pro) against Peter Hoffman and Martin Kiernan (con). It was lively, entertaining and engaging…
Prof Humphreys argued that it is not acceptable to admit patients to rooms with inherent additional risk for transmission. We can address this by ‘walking like the Egyptians’ and copperising our surfaces, for which there is now some data with a clinical outcome. Another approach is NTD systems, for which data (including some clinical outcomes) are emerging. Prof Carling’s presentation was somewhat unusual, with his arguments seemingly an appeal to common sense rather than drawn from the published literature.
Martin Kiernan began by acknowledging the role of the environment, but that hand contamination is almost always the final vector (and there’s some evidence for this). The cornerstone of Martin’s argument was that whether NTD systems work is the wrong question. We should be focusing our time, money and attention on improving conventional methods which have been shown to reduce transmission. Peter Hoffman complemented Martin’s pragmatic viewpoint with thorough, thoughtful critiques of the studies on HPV decontamination with a clinical outcome. The 2008 Boyce study has more holes than the 2013 Passaretti study, which itself is far from watertight!
The key argument for turning to NTD systems is that admission to a room previously occupied by a patient with an MDRO increases the risk of acquisition due to residual contamination, and NTD decontamination mitigates this increased risk. So, my own conclusion is that hospitals that do not use high-tech decontamination of the environment are indeed doing their patients a disservice. Sometimes!
Look out for the third and final installment of my reflections from HIS 2014 at some point tomorrow!
It’s been a busy quarter on the blog; please see below for the blog posts since the Christmas update (which now seems like a long time ago!).
The SHEA and HIS/IPS spring conferences provided much food for thought. Also, I was delighted to host a guest blog from Prof Sally Bloomfield on What do we mean by ‘cleaning’ and ‘disinfection’?, which prompted some fascinating discussion. If you’re interested in contributing a guest blog, these are always welcome, so please let me know.
Thanks as ever for the comments – please do keep them coming.
- HIS / IPS Spring Meeting: What’s that coming over the hill? It’s a MDR-GNR monster! (Published 9th April 2014)
- Dissecting the epidemiology of resistant Enterobacteriaceae and non-fermenters (Published 8th April 2014)
- SHEA 2014 Spring Conference: Out with contact precautions. In with faecal transplantation (Published 6th April 2014)
- Considering the burden of enhanced CRE screening (Published 1st April 2014)
- Busy hospitals, contaminated surfaces and the acquisition of Acinetobacter baumannii (Published 24th March 2014)
- CRE can survive on dry surfaces for longer than you may expect (Published 18th March 2014)
- ICHE special edition on CRE and MDROs (Published 11th March 2014)
- A postcard from São Paulo, Brazil: thank goodness for the NHS (Published 24th February 2014)
- What can outbreaks of Salmonella from the 1950s tell us about CRE? (Published 18th February 2014)
- An overview of the options for antimicrobial surfaces in hospitals (Published 12th February 2014)
- What do we mean by ‘cleaning’ and ‘disinfection’? (Published 5th February 2014)
- How much patient-to-patient spread of S. aureus occurs? Apparently, not much (Published 28th January 2014)
- The Hospital Microbiome Project (Published 17th January 2014)
- Meeting up with ‘old friends’ keeps you healthy – especially when they’re worms (Published 2nd January 2014)
Photo credit: ‘Easter Bunny’ by Jimmy Hilario.
The HIS / IPS Spring Meeting was on “What’s That Coming Over the Hill? Rising to the Challenge of Multi-Resistant Gram Negative Rods”. For those unfamiliar with the 2006 hit by the band “The Automatic”, the chorus goes: “What’s that coming over the hill? Is it a monster?”, hence the title to this post in light of the CDC-described “nightmare bacteria”! The full room (>250 delegates) illustrates how topical this issue is in the UK, and, indeed, globally. I enjoyed the day thoroughly, so thanks to all those involved in organizing the meeting.
Global Perspective – Professor Peter Hawkey
Prof Hawkey kicked off the day by considering how globalization has driven globalization in MDR-GNR, focusing mainly on ESBL-producing Enterobacteriaceae. Asia in particular is a hub of population (8/10 global ‘megacities’ are in Asia), antibiotic use (China was already the second largest consumer of imipenem back in 2002), aquaculture (Asia produces 62% of the world’s farmed fish) and travel. Prof Hawkey has been to India twice, and both times he returned colonized with an ESBL-producing Enterobacteriaceae (incidentally, we should probably start calling these ‘EPEs’.) The UK receives almost 3 million international arrivals from India and Pakistan; 80% will carry ESBL-producing bacteria.1 So, since people carry their faeces with them, the global trend of increasing rates of ESBL faecal carriage is concerning.2 Medical tourism is a related and increasingly common risk for the importation of ESBL and carbapenemase producing bacteria.3 The increasing rates of carbapenem usage is largely the consequence of the emergence of ESBL. The CPE picture in the USA is bleak, and perhaps a sign of things to come, where only two states have not yet had confirmed reports.
Controlling a national outbreak of CRE in Israel – Dr Mitchell Schwaber
Dr Schwaber described the impressive and successful national intervention to control CRE in Israel.4 Dr Schwaber began in the beginning (Genesis 1) where the infection control landscape was ‘without form and void’ in Israel; the emergence of CRE changed that. The problems began in 2007 after which CRE spread like wild-fire. Local interventions failed and 22% of K. pneumoniae were carbapenem-resistant at the peak of the epidemic. Long-term and long-term acute care facilities were identified as particular issues, as has been recently reported in the USA.5 CRE carriage was found to be 17% at the height of the epidemic in long-term acute care facilities.6 In these “black-hole” CRE reservoirs, there is little focus on infection prevention and control, and social contact is a necessary part of the rehabilitation process, so complete segregation is unhelpful. Active detection, isolation of carriers, and staff cohorting were cornerstones of the effective intervention, but implementation was challenging and required a “top down” approach. Directives and feedback were administered through hospital chief executives. In Dr Schwaber’s view, Israel began their national programme too late and succeeded by the skin of their teeth. Israel is a small country with a well-funded and connected healthcare system. Will the national programme succeed elsewhere, even if implemented earlier?
Dissecting the Epidemiology of the Enterobacteriaceae and Non-Fermenters – Dr Jon Otter (who he?)
My exploration of the differences in the epidemiology of resistant Enterobacteriaceae and non-fermenters (mainly A. baumannii) was designed to prompt anybody tempted to conflate these two related problems to think twice; not all monsters are created equal. Resistant Enterobacteriaceae and non-fermenters do share the same response to the Gram-stain (more or less) and can be resistant to key antibiotics occasionally through shared mechanisms (principally the carbapenemases). But that’s about it. Otherwise they’re like chalk and cheese. (A. baumannii = chalk, which turns to dust; Enterobacteriaeae = a good cheese, which ultimately ends up in the gut.) You can read more about my talk and download my slides in yesterday’s post.
Infection prevention and control in the acute setting – Sheila Donlon
Sheila Donlon began by describing the low prevalence of MDR-GNR in Ireland. Around 2% of Enterobacteriaceae are carbapenem resistant, according to a recent point prevalence survey. Sheila’s comment that you need to go above and beyond standard precautions to control MDR-GNR resonated with Dr Schwaber’s talk, and with Dr Thom’s assessment from the SHEA meeting last week. Sheila spent the remainder of the talk discussing some of the approaches outlined in the Irish MDRO screening and control guidelines. Is hand hygiene for patients a black spot?7 How do we isolate patients effectively when we only have 20% single rooms? How and when should we cohort staff? What is the appropriate PPE? When should we consider ward closure, environmental screening or hydrogen peroxide vapour disinfection? Can we or should we discontinue contact precautions for CRE carriers?
Getting the message over: strategies for ensuring new guidance is put into practice – Dr Evonne Curran
Dr Curran outlined a frequent gap between theory and practice; guidance written in an ‘ivory tower’ without the correct stakeholders around the table will fail to influence practice. Even if the guidance is carefully crafted with implementation in mind, what happens on the wards will never perfectly reflect the guidance; we need a healthy dose of pragmatism. The addition of ‘adjectives’ don’t add clarity: ‘aggressive’, ‘robust’, ‘effective’, ‘strict’, ‘excellent’ are all vague; guidelines need to be specific.8 Dr Curran’s analysis of the differing definitions of ‘standard precautions’ was outstanding, and illustrates the challenges of local interpretation of international guidelines. We need to speak to front-line staff in a language they understand to implement guidance into practice.9
Dealing with Multidrug-Resistant Acinetobacter and Stenotrophomonas – Dr Beryl Oppenheim
Dr Beryl Oppenheim considered MDR Acinetobacter and Stenotrophomonas. These environmental non-fermenters are more of a niche problem than the resistant Enterobacteriaceae, but tend to be more resistant. Dr Oppenheim spent most of the time considering A. baumannii, which can be considered an “honorary Staphylococcus”; it’s more than a little Gram-positive!10 MDR A. baumannii combine inherent and acquired resistant mechanisms, survive for prolonged periods on dry surfaces and have the ability to produce biofilms.10-12 This makes them ideally suited for survival in the antibiotic-rich ICU environment, where they are most commonly problematic. MDR A. baumannii are also associated with infection following trauma in military hospitals.13 MDR A. baumannii is a problematic pathogen for a number of reasons. The epidemiology of hospital outbreaks can be difficult to dissect, with whole genome sequencing now the gold standard typing method.14 Contact isolation, perhaps even pre-emptive, is a must. Cleaning is critical, but the best approach is not obvious; ‘no-touch’ automated disinfection systems may be warranted sometimes.15 Active screening is rational but practically challenging: which sites to screen (a rectal swab alone is not sufficient) and which methods to use? Dr Oppenheim concluded by reflecting on the patchy prevalence of MDR A. baumannii (and Stenotrophomonas); it’s not a problem everywhere, but it’s a major problem where it rears its monstrous head.
Decontamination of instruments, equipment and the environment – Peter Hoffman
Peter Hoffman in his inimitable style reviewed the risks and environmental interventions specific to MDR-GNR. Contrary to the view of some, you can’t take a “leave them and they’ll die off approach” for Gram-negative rods; they will survive on dry surfaces.16 The issues covered by Peter included:
- Outbreaks linked to endoscopes (like the recent outbreak of CRE in Illinous).17
- The problems associated with designating equipment as single-use. Oftentimes only part can feasibly be single-use, meaning that there is a body of the equipment that needs to be decontaminated (and often isn’t). Portable ultrasound machines are a particular challenge. Safe working methods (one hand for the patient, one for the machine) are sound in theory, but challenging in practice (requiring considerable manual dexterity)! Ultrasound gel must be single-use sachets, regardless of cost implications.
- Don’t rely on privacy curtains with antimicrobial claims; they should be changed between MDR-GNR patients. (I wonder whether disinfection using advanced formulations of liquid hydrogen peroxide may be another option.18)
- Don’t rely on wipes for disinfecting mattress covers, especially ‘dynamic’ mattresses, which are full of bug-trapping folds. They probably don’t provide enough wetting (amongst other things).
- Should we invest in single-use pillows?19
- Water systems require careful management, particularly for P. aeruginosa.20
- Bed-pan washers represent a real risk for faecally-associated MDR-GNR. Why are they not more often foot pedal operated?
- Physiotherapy equipment on rehabilitation units is made for physiotherapy, not for effective decontamination. Careful design, with a dose of compromise, is required.
- Peter rarely believes negative results from environmental sampling due to a high risk of spot contamination.21
Peter’s somewhat provocative conclusion was that “there are no special decontamination requirements to control MDR-GNR.” I think the point here was that the issues outlined above are generic, such that addressing them would improve the safety of all patients, not just those with MDR-GNR. However, I fear that the conclusion could be misinterpreted to mean that increased focus on the potential environmental reservoir is not warranted when dealing with MDR-GNR. This does not concur with Peter’s citation of the surprising survival capacity of MDR-GNR, and Dr Oppenheim’s discussion of the ‘critical’ environmental reservoir for MDR A. baumannii.
Controversy: Decolonization and Staff Screening – Prof Peter Wilson
Prof Wilson began by challenging the feasibility of the recommended PHE screening approach. It would result in a lot of patients being identified for screening, and a high proportion of those held preemptively in contact isolation until confirmed negative. Prof Wilson suggesting prioritizing NDM and KPC producers over OXA-48 producers. Whilst I like this idea in principle, I am not sure that we have enough epidemiological data to support this distinction. The recent ESCMID guidelines are a useful resource on screening approaches, if a little wordy.22 Staff screening should be avoided, unless a member of staff is clearly implicated in transmission; what would you do with a carrier? Peter’s view is that clearance swabs are a waste of time, and advocated a “once positive, always positive” approach to CRE. “Once positive, always positive” works in a low prevalence setting, but comes increasingly unstuck as prevalence increases. Is selective decontamination the answer?23,24 Not really; whilst individual patient mortality is decreased, neither selective oral decontamination (SOD) nor selective digestive decontamination (SDD) decolonize carriers. The potential collateral damage of SOD and SDD when applied to MDR-GNR is clear: hastening the arrival of pan-drug resistance.
Therapeutic Options and Looking to the Future – Prof David Livermore
The resistance profile of MDR-GNR leaves few antibiotic classes left; sometimes only colistin, and colistin-resistance is emerging in both Enterobacteriaceae25 and non-fermenters26. Indeed, a national Italian survey found that 22% of KPC-producing K. pneumoniae were resistant to colistin.27 Leaving aside the risk of nephrotoxicity,28 colistin monotherapy results in the development of colistin resistance.29 Another issue relates to challenges in laboratory testing. Apparent MDR-GNR susceptibility depends on the testing methods used, and may not match clinical outcome:30 the mice who died despite antibiotic treatment in one study would surely query the EUCAST and CLSI breakpoints that defined their K. pneumoniae isolates as susceptible.31 The use of existing and more creative combinations of existing antibiotics can help. Also, a small number of new antibiotics are in development (although we have run out of truly novel targets, meaning that they are modifications of existing classes). A more promising approach is the use of antibiotics combined with β-lactamase inbibitors, but these are currently at a fairly early stage of clinical trial.32
Summary and points for discussion:
- People carry their faeces with them, so the global trend of increasing rates of carriage of resistant Enterobacteriaceae is concerning.
- Will the successful national CRE control programme in Israel (a small country with a well-funded, connected healthcare system) be feasible elsewhere?
- Can we safely ‘de-isolate’ CRE carriers? Israel has managed to do it, but I suspect the answer will depend on your level of prevalence and pragmatism.
- Do not conflate the epidemiology of resistant non-fermenters and Enterobacteriaceae; they’re like chalk and cheese!
- Do we have the right stakeholders around the table to write national guidance, and is it written with implementation in mind?
- How best to address the environmental reservoir for A. baumannii and, to a lesser extent, CRE?
- We need to carefully consider the likely collateral damage before applying SOD / SDD when applied to MDR-GNR: pan-drug resistance!
- How far can combinations of existing antibiotics, novel combination and new treatment options go in treating MDR-GNR? Probably not that far; prevention is better than cure.
1. Tham J, Odenholt I, Walder M, Brolund A, Ahl J, Melander E. Extended-spectrum beta-lactamase-producing Escherichia coli in patients with travellers’ diarrhoea. Scand J Infect Dis 2010; 42: 275-280.
2. Woerther PL, Burdet C, Chachaty E, Andremont A. Trends in human fecal carriage of extended-spectrum beta-lactamases in the community: toward the globalization of CTX-M. Clin Microbiol Rev 2013; 26: 744-758.
3. Hanefeld J, Horsfall D, Lunt N, Smith R. Medical tourism: a cost or benefit to the NHS? PLoS ONE 2013; 8: e70406.
4. Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant Enterobacteriaceae. Clin Infect Dis 2014; 58: 697-703.
5. Lin MY, Lyles-Banks RD, Lolans K et al. The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis 2013; 57: 1246-1252.
6. Ben-David D, Masarwa S, Navon-Venezia S et al. Carbapenem-resistant Klebsiella pneumoniae in post-acute-care facilities in Israel. Infect Control Hosp Epidemiol 2011; 32: 845-853.
7. Landers T, Abusalem S, Coty MB, Bingham J. Patient-centered hand hygiene: the next step in infection prevention. Am J Infect Control 2012; 40: S11-17.
8. Rouse W, Fuzzy Models of Human Problem Solving, in Advances in Fuzzy Sets, Possibility Theory, and Applications, Wang P., Editor. 1983, Springer US. p. 377-386.
9. Pronovost PJ, Berenholtz SM, Needham DM. Translating evidence into practice: a model for large scale knowledge translation. BMJ 2008; 337: a1714.
10. Wagenvoort JH, Joosten EJ. An outbreak Acinetobacter baumannii that mimics MRSA in its environmental longevity. J Hosp.Infect 2002; 52: 226-227.
11. Strassle P, Thom KA, Johnson JK et al. The effect of terminal cleaning on environmental contamination rates of multidrug-resistant Acinetobacter baumannii. Am J Infect Control 2012; 40: 1005-1007.
12. Espinal P, Marti S, Vila J. Effect of biofilm formation on the survival of Acinetobacter baumannii on dry surfaces. J Hosp Infect 2012; 80: 56-60.
13. Scott P, Deye G, Srinivasan A et al. An outbreak of multidrug-resistant Acinetobacter baumannii-calcoaceticus complex infection in the US military health care system associated with military operations in Iraq. Clin Infect Dis 2007; 44: 1577-1584.
14. Lewis T, Loman NJ, Bingle L et al. High-throughput whole-genome sequencing to dissect the epidemiology of Acinetobacter baumannii isolates from a hospital outbreak. J Hosp Infect 2010; 75: 37-41.
15. Otter JA, Yezli S, Perl TM, Barbut F, French GL. Is there a role for “no-touch” automated room disinfection systems in infection prevention and control? J Hosp Infect 2013; 83: 1-13.
16. Kramer A, Schwebke I, Kampf G. How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Infect Dis 2006; 6: 130.
17. Centers for Disease C, Prevention. Notes from the Field: New Delhi metallo-beta-lactamase-producing Escherichia coli associated with endoscopic retrograde cholangiopancreatography – Illinois, 2013. MMWR Morb Mortal Wkly Rep 2014; 62: 1051.
18. Rutala WA, Gergen MF, Sickbert-Bennett EE, Williams DA, Weber DJ. Effectiveness of improved hydrogen peroxide in decontaminating privacy curtains contaminated with multidrug-resistant pathogens. Am J Infect Control 2014; 42: 426-428.
19. Reiss-Levy E, McAllister E. Pillows spread methicillin-resistant staphylococci. Med J Aust 1979; 1: 92.
20. Loveday HP, Wilson J, Kerr K, Pitchers R, Walker JT, Browne J. Pseudomonas infection and healthcare water systems – a rapid systematic review. J Hosp Infect 2014; 86: 7-15.
21. Lerner A, Adler A, Abu-Hanna J, Meitus I, Navon-Venezia S, Carmeli Y. Environmental contamination by carbapenem-resistant Enterobacteriaceae. J Clin Microbiol 2013; 51: 177-181.
22. Tacconelli E, Cataldo MA, Dancer SJ et al. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients. Clin Microbiol Infect 2014; 20 Suppl 1: 1-55.
23. Price R, MacLennan G, Glen J. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 2014; 348:
24. Daneman N, Sarwar S, Fowler RA, Cuthbertson BH, Su DCSG. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13: 328-341.
25. Bogdanovich T, Adams-Haduch JM, Tian GB et al. Colistin-Resistant, Klebsiella pneumoniae Carbapenemase (KPC)-Producing Klebsiella pneumoniae Belonging to the International Epidemic Clone ST258. Clin Infect Dis 2011; 53: 373-376.
26. Agodi A, Voulgari E, Barchitta M et al. Spread of a carbapenem- and colistin-resistant Acinetobacter baumannii ST2 clonal strain causing outbreaks in two Sicilian hospitals. J Hosp Infect 2014; 86: 260-266.
27. Giani T, Pini B, Arena F et al. Epidemic diffusion of KPC carbapenemase-producing Klebsiella pneumoniae in Italy: results of the first countrywide survey, 15 May to 30 June 2011. Euro Surveill 2013; 18:
28. Drekonja DM, Beekmann SE, Elliott S et al. Challenges in the Management of Infections due to Carbapenem-Resistant Enterobacteriaceae. Infect Control Hosp Epidemiol 2014; 35: 437-439.
29. Lee GC, Burgess DS. Treatment of Klebsiella pneumoniae carbapenemase (KPC) infections: a review of published case series and case reports. Ann Clin Microbiol Antimicrob 2012; 11: 32.
30. Weisenberg SA, Morgan DJ, Espinal-Witter R, Larone DH. Clinical outcomes of patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae after treatment with imipenem or meropenem. Diagn Microbiol Infect Dis 2009; 64: 233-235.
31. Mimoz O, Gregoire N, Poirel L, Marliat M, Couet W, Nordmann P. Broad-spectrum beta-lactam antibiotics for treating experimental peritonitis in mice due to Klebsiella pneumoniae producing the carbapenemase OXA-48. Antimicrob Agents Chemother 2012; 56: 2759-2760.
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It was a great privilege to speak at the HIS / IPS Spring Meeting today. You can download my slides here. The meeting was entitled: “What’s that coming over the hill? Rising to the challenge of multi-resistant Gram-negative rods”. This, I think, is an (oblique) reference to the signature hit of a Welsh band ‘The Automatic’: “What’s that coming over the hill? Is it a monster?”. So, are multi-resistant Gram-negative rods monsters lurking underneath the bed? Dr Tom Frieden, CDC Director, has described CRE as “nightmare bacteria” and Dr Sally Davies, CMO, has painted a bleak post-antibiotic era picture in reference to the emergence of these bacteria. So, is it a monster? Yes, I think it probably is. But all monsters are not created equal…
My exploration of the differences in the epidemiology of resistant Enterobacteriaceae and non-fermenters (mainly A. baumannii) was designed to prompt anybody tempted to conflate these two related problems to think twice. Resistant Enterobacteriaceae and non-fermenters do share the same response to the Gram-stain and can be resistant to key antibiotics occasionally through shared mechanisms (principally the carbapenemases). But that’s about it. Otherwise they’re like chalk and cheese. (A. baumannii = chalk, which turns to dust; Enterobacteriaeae = a good cheese, which ultimately ends up in the gut.) (Table).
Table: Comparing the epidemiology of resistant Enterobacteriaceae and non-fermenters.
|Enterobacteriaceae (K. pneumoniae)||Non-fermenters (A. baumannii)|
|At-risk population||Primarily acute pts||ICU, burns|
|Risk factors||Travel||Trauma, ICU stay|
|Mortality||Stark increase (CPE)||Minimal increase|
|Prevalence||Emerging (rapidly)||Patchy but stable|
|Sites of colonisation||GI tract||Skin, resp & GI|
|Colonization duration||Months to >1 year||Days to weeks|
|Transmission routes||Hands ++, Env +/-||Hands +, Env ++|
|Resistance||Mainly acquired||Intrinsic & acquired|
|Common clones||KPC-producing ST258||Intl clones I-III|
Probably the most important difference between the Enterobacteriaceae and the non-fermenters is their at-risk populations. A. baumannii is restricted mainly to high-risk patients in intensive care units. This is not so for the resistant Enterobacteriaceae, which have the potential to cause infection and colonization in a wide group of hospitalized patients and, perish the thought, the community. Related to this is their epidemic potential: resistant Enterobacteriaceae, including CRE, have already demonstrated the capacity to spread rapidly and broadly in hospital and to a lesser extent community populations. Rates of antibiotic resistance in A. baumannii can be high, but it does not possess the tools to spread outside of high-risk hospitalized patients.
Other differences between these two groups of resistant Gram-negative bacteria include the types of infection they cause and associated attributable mortality, their prevalence, their sites and duration of colonization, their transmission routes, their resistance mechanisms and their population structure and clonal dissemination patterns (Table).
One of the many acronyms in current circulation to describe resistant Gram-negatives is CRO (carbapenem-resistant organisms), which is used as a catch-all term to encompass both Enterobacteriaceae and non-fermenters. Given the fundamental differences in epidemiology, I don’t think it’s very helpful. After all, MRSA is a ‘CRO’ but we wouldn’t dream of lumping it together with K. pneumoniae or A. baumannii! So, we should expunge ’CRO’ from our collective vernacular and stick to CRE and CRAB.
I accept that there are limitations with my presentation. You could (and probably should) further dissect the epidemiology of K. pneumoniae vs. E. coli, A. baumannii vs. P. aeruginosa, and ESBL vs. carbapenemase producers. I suspect we will eventually have data to demonstrate different clinical manifestations associated with the various common carbapenemase genes.
That said, I think a separation of the resistant Enterobacteriaceae and non-fermenters is a useful distinction in terms of at-risk populations, epidemic potential, and effective control measures.
Finally, my preparation for the talk raised several challenging questions:
- Which interventions work?
- Are they different for Enterobacteriaceae and non-fermenters? (Probably, given their epidemiology.)
- Has our focus on CPE taken our eye off CPNF, which are the ‘clear and present danger’ for many of us?
- What is the prevalence of CPE in the UK?
- How much do we believe a single negative screen?
- Do we need rapid molecular diagnostics?
- What is the duration of colonisation?
- Are there decolonisation strategies other than “selective” decontamination using antibiotics?
Image credit: ‘Chalk and Cheese’ by Jackson Boyle.