A lovely few days in Glasgow for the IPS conference. Here’s a few reflections…
If I’m still around in 2027 (which I hope to be by the way), you have my advance express permission to throw this post back in my direction. I thought an interesting way to summarise the key themes from IP2017 would be to think about how the IPC landscape will look 10 years from now.
Another Infection Prevention Conference has been and gone; here are a few highlights. Worth noting that all of the submitted abstracts are published in an open access Journal of Infection Prevention supplement.
The now past-president Jules Storr kicked off the Conference with an inspiring talk on “real” leadership, which isn’t about CEOs and eminent professors. Real leadership inspires people to wash their hands in the dead of night when nobody’s looking. Roselinde Torres’ TED talk is worth a look (‘What it takes to be a great leader’) and ‘How to behave and why’ by the fantastically named Munro Leaf contains some leadership lessons from 1946!
Next up, IPS Patron Prof Didier Pittet challenged us to change our education methods to meet the changing (and dare I say somewhat fickle) needs of a rapidly changing world! Generation “We” (born 1980-2000, thus including me) require multimodal approaches to keep us engaged, and would probably rather watch a webinar than come to a conference! But, if you’d like to go ‘Old Skool’, there’s always Didier’s new book.
The highlight of the conference for me was Dr Jason Leitch’s address on developing a safety culture. A culture of safety has been embedded into other industries (e.g. airline, hotel and military) so why not healthcare? It’s a much quoted stat that a 747’s worth of people die from HCAI each [insert time period to suit your data]. So how many planes need to go down before we adopt a culture of safety? A culture of safety has a language to go with it – only the air traffic controller can say actually say “take-off”, and then only once. Perhaps only the IV nurse should be allowed to say “Catheter”, and only at the point of insertion!
Dr Michael Borg then took to the stage to parallel antibiotic resistance with Star Wars: a battle of intergalactic scale! Michael spent some time discussing the impressive reductions achieved in his hospital on multidrug-resistant A. baumannii, applying the principles of the ESCMID guidelines, with a particular focus on environmental issues. However, the new and more challenging threat comes from the carbapenem-resistant Enterobacteriaceae – aka the Death Star [note, pretty sure Dr Borg didn’t actually say that, but I think it’s a good fit with his analogy]. So what to do? Be an Ewok! Small and ostensibly insignificant, but surprisingly powerful as a collective force.
Cotteral Lecture – Dr Evonne Curran
Dr Evonne Curran delivered the Cotteral Lecture, entitled “The times they are a changing”. Reflecting on her thorough reviews of some older literature to write her outbreak columns on MRSA and CRE, Evonne reminded us how far we’ve come but how far we have yet to go. It wasn’t so long ago that we were questioning whether C. difficile was infectious (and now we’re asking a similar question from a different angle)! Equally, in 1990, installing one sink on a ward increased the number of sinks by 100%. Yet there can be no cause for complacency: we haven’t reached base camp for the CRE epi curve! Evonne didn’t quite finish on a song, but she did finish on a Hand Hygiene Haiku:
‘Five moments for hands
For infection prevention
Essential for all’
Universal gloves and gowns
Dr Dev Anderson (Duke) gave an engaging lecture on the impressive ‘Benefits of Universal Gloves and Gowns’ (BUGG) study. This cluster randomized controlled trial design is likely to be the gold-standard assessment of infection prevention and control interventions. The problem with this powerful design is that studies need to be large to be powered appropriately. This study involved 20 ICUs and still failed to meet the primary end point (a reduction in MRSA / VRE acquisition). So will ICUs around the world be switching to universal gloves and gowns? On the basis of this study, combined with the well-publicized downsides of “contact precautions”, no. A targeted approach to contact precautions is better…
As if to reinforce the message of judicious use of gloves, Jennie Wilson’s talk highlighted that using gloves badly is worse than not using gloves at all! Some of the staff perceptions surrounding glove use were enlightening, including the classic: “when I wear gloves, I don’t need to wash my hands as often”. Hmmm.
Or should I say CPE stream? Or perhaps CPC is more to your fancy? This excellent stream kicked off with Dr Bharat Patel assisting in us in navigating the ‘acronym minefield’ that is multidrug-resistant Gram-negative bacteria. An informal poll of the audience prior to Dr Patel’s talk suggested that only a handful would be comfortable explaining the difference between CRE and CPE to a colleague. Hopefully, this was remedied by the talk!
Then, Dr Tara Palmore (NIH, USA), Dr Andrew Dodgson (Manchester) and Erika Grobler & Ogra Marufu (King’s College Hospital, London) provided a series of ‘views from the trenches’ of CRE prevention and control. Dr Palmore described the fascinating utility of whole genome sequencing to dissect the outbreak more or less in real time. She also highlighted the use of ‘monitors’ whose sole job it was to ensure compliance with hand hygiene and PPE at room entry and exit! Dr Dodgson described the ongoing CRE problems in Manchester. My key message from Dr Dodgson was not to bother with contact screening when you identify a new case: just go ahead and screen the whole ward – more than once. Finally, Erika and Ogra gave their perspective on control challenges. They are now screening all paediatric admissions to their hospital for CRE carriage, which is not a popular or easy policy, but they consider it to be a cornerstone of effective control. As we all wrestle to implement the principles of the Toolkit, this session provided useful advice from those in the know.
I didn’t make it to all of the oral presentations, but I was impressed by the ones that I saw. (Remember, you can view all of the accepted abstracts from the submitted oral and poster presentation in the Journal of Infection Prevention supplement.)
- Donald Bunyan: E. coli bacteraemia in Scotland: nearly 50% classified as “community”; but how many of these were frequent fliers?
- Angela Beal: Pulsed-xenon UV (Xenex): good reduction in total aerobic count, but less effective out of line of sight & 39% of sites VRE contaminated after process. Is this satisfactory?
- John Chewins: spraying aqueous oxygen peroxide (aka ozone) onto chronic wounds less likely to withdraw from RCT due to infection and improves patient’s quality of life scores.
- Jo Keward: introduction of semi-permanent Pods reduces missed isolation days by 60% on the Alder Hey HDU.
- Andrea Whitfield: Service User Involvement in HCAI research: A necessary evil to get your grant or vital for top class research?
Use of disinfectants and HCAI – Dr David Weber
Dr Weber began by reviewing the compelling data that contaminated surfaces contribute to the transmission of some hospital pathogens. An age-old question is whether contamination of hands or surfaces is more important in transmission. A recent modeling study helps to answer this, suggesting that hands are generally more important, but that this will depend on pathogen and setting. Getting the best out of hospital cleaning and disinfection is a simple equation: ‘Product + Practice = Perfection’. The problem is the ‘practice’ part of that equation; it’s difficult to assure process repeatability. This is where new technologies such as automated room disinfection systems, and antimicrobial surfaces can come in most handy. Finally, Dr Weber pointed us towards the AJIC and ICHE recent special editions on all things environmental.
Ayliffe Lecture – Dr Stephanie Dancer
Dr Stephanie Dancer began the Ayliffe Lecture by reiterating a wish that I had earlier in the conference: for genetically modified visible microbes on surfaces! That way we’d all be able to see the long survival and low infectious dose exhibited by many hospital pathogens. As we come towards the end of antibiotics, we need to move from cure to prevention. Remember, mortality due to S. aureus bloodstream infection was once 80% and may be so again as we lose more antibiotics. We need intervention bundles (aka ‘intervention umbrellas’) but not all solutions are possible, practical, affordable or acceptable. A good dose of evidence and common sense is required to find and implement interventions that work!
The BIG debate: universal vs. targeted interventions (Dr Gould vs. Dr Otter)
I think that Dr Gould and I achieved our purpose of presenting both sides of the debate without coming to physical blows. I found myself on uncomfortable ground arguing for a “No” vote in Glasgow following the Scottish “In/Out” referendum. I think my decision to wear a bow tie (see image below) in recognition of Dr Gould’s signature neck-wear lightened the mood!
Figure: My choice of neck wear
I’ve laid my arguments for targeted interventions out in a separate blog, but in short, universal interventions are appealing but fail to demonstrate short-term, long-term and cost-effectiveness. Targeted interventions have been shown to be effective in reducing transmission, preserve the activity of our precious antimicrobial agents, require less modification of human behaviour, and are cheaper and less resource-intensive. So, on balance, I favour targeted interventions for infection prevention and control.
Rose George gave an engaging talk ‘examining the unmentionables’. It’s eye-opening to think that 40% of the world population lacks adequate sanitation; open defecation is all too common with no privacy, dignity or safety! The flushing toilet, believe it or not, was voted the biggest medical advance of the last 200 years by the BMJ. Investing in sanitation makes financial sense too, with $1 invested in sanitation yields $6. You can see Rose’s TED talk here.
IPS Patron Tricia Hart and incoming president Heather Loveday rounded off the conference, exhorting us to examine our attitude and approach to infection and control. I left the conference feeling that IPS is in good hands with Heather at the helm.
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.
32. Drawz SM, Papp-Wallace KM, Bonomo RA. New beta-Lactamase Inhibitors: a Therapeutic Renaissance in an MDR World. Antimicrob Agents Chemother 2014; 58: 1835-1846.
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.