CPE

Diagnosis of CRE: time to throw away those agar plates?

Jon Otter (@jonotter) CRE , , , , ,

CRE are an emerging threat to healthcare systems worldwide. Most guidelines recommend screening and isolation of carriers. But relying on conventional agar-based culture presents a dual threat of poor sensitivity (depending on which method is used) and slow turnaround time, with a minimum overnight incubation before a presumptive positive result. PCR solves both of these problems – but at a cost. I gave a talk today at a BD seminar considering whether it’s time to switch to PCR diagnostics for the detection of CRE. You can download my slides here. (The title of the talk “Time to throw away those agar plates” was inspired by a talk by Dr Dan Diekema at a recent SHEA conference.)

There are a number of options for CRE screening, summarized in the flow chart below:

Flow chart: Overview of laboratory methods for the diagnosis of CRE. (To be precise, throughout the blog I really mean CPE most of the time, but I’m using CRE for consistency with other blogs…)CPE diagnosis

Continue reading →

Carbapenem-resistant Enterobacteriaceae (CRE): so what should an infection prevention and control team do now?

Jon Otter (@jonotter) CRE , ,

kleb pneumoGuest blogger Dr Evonne Curran (bio below) writes…

Jon asked me to write on his blog about our column (‘#15: Carbapenemase-producing Enterobacteriaceae’). As he kindly accepted my offer to co-write a column, I accept his to write this blog. I am calling this blog (which contains only my personal views): ‘Carbapenem-resistant Enterobacteriaceae (CRE): so what should an infection prevention and control team do now?’.

The problems with CRE are numerous, and the different actions needed to control or at least delay its endemnicity are likewise legion; the task can seem insurmountable. The approach being taken at national and international level covers much of what is needed. The question for individual infection prevention and control teams (IPCTs) is this: where do you begin to protect a healthcare system that has little capacity (and in some cases little will) to start to solve a problem that essentially has yet to arrive, that has at least 6 names (none of which can be spelt with confidence) and is absent from the CEO’s performance monitoring agenda? The additional challenge for IPCTs is this: it will be difficult for those working in clinical areas to believe that for all the improvement in infection prevention and control that reduced MRSA and C. difficile, still more is required for this new microbiological-kid on the block.

If I were still part of a hospital based IPCT this is where I would start…..

  1. Give it a name and stick to it in all correspondence / education / awareness sessions;
  2. Succinctly provide the reasons as to why this should be on everyone’s radar;
  3. Take a high-reliability approach to strengthening your healthcare system;
  4. Involve patient advocates.

1)      Give it a name and stick to it…

As mentioned in the column (and many times by Jon) there needs to be a name that we can a) all agree on and b) conveys to non-microbiology people the problem and its seriousness. We have to stop fighting about what it is: CPE, CRO, CPE etc, etc.  I don’t know who is on (or how you get on) the micro-organism naming committee, but I am beginning to think they need to make it more democratic and involve people who don’t understand microbiology. There is no perfect name that will keep all microbiologists happy, so let’s stop trying to find one. It’s important that IPCTs have a short name that denotes this big problem and makes this consistent in all documentation. (See this previous blog by Jon for more info on nomenclature surrounding this issue.)

2)      Succinctly provide the reasons as to why this should be on everyone’s radar

I offer the following as a succinct summary for why this should be on everyone’s radar:

  • These resistant organisms inactivate commonly used antibiotics. For any infected patient there are Few Treatment Options and there will eventually be No Treatment Options.
  • They are spread Person to Person by touch, splash or contaminated equipment / environments.
  • The resistance mechanisms are spread between different species of bacteria.
  • They are difficult to detect when people are screened.
  • They cause outbreaks, which are also difficult to detect and very costly to manage.
  • Spread across the world makes at least some transmission here inevitable.

3)      Take a ‘high-reliability’ approach to the problem in your area…

I am not going to regurgitate what is in existing guidelines but offer some high-reliability characteristics.

Sensitivity to operations: Given your patient/client population, consider how and why your healthcare system is vulnerable; share this information within your organisation.

Deference to expertise: Identify who you would go to for expert advice within and outwith your organisation should an incident arise. Keep contact details accessible.

Preoccupation with failure: Consider in which clinical areas you most likely to have an outbreak – visit these clinical areas and see if there can be changes to ways of working that would make outbreaks less likely.

Reluctance to simplify: Look for and don’t dismiss alert signals – this could be data that suggests you may have cases, cross-transmission, that you are insufficiently looking for possible cases or that your antibiotic prescribing data could make your healthcare system more vulnerable.

Commitment to resilience: Good as you and your team are – consider how you can make your systems better at preparedness, prevention and management of outbreaks.

High-reliability theory provides a framework to achieve mindfulness. Google ‘High-Reliability Theory’ and ‘Weick’ for some very useful information.

4)      Involve patient advocates

Patient advocates only really knew about MRSA and Clostridium difficile infection when the media told them. Letting patient advocates know that your team is alert to this emerging threat and that you are taking actions to prevent outbreaks may help. They can also lobby for leaders to take further action if required.

Here ends my first blog! Happy I think to receive comment, suggestions or improvements. Thanks for reading. Of note: Outbreak column 17 is on Cognitive Errors in Outbreak Prevention, Preparedness and Management.

Dr Evonne Curran bio:

curran cropped

Evonne is a practicing infection control nurse (since 1987) and a Doctor of Nursing (since 2010). She is the editor of the Outbreak column in the Journal of Infection Prevention (since 2011).

Not all resistant Gram-negative bacteria are created equal: Enterobacteriaceae vs. non-fermenters

Jon Otter (@jonotter) Acinetobacter, CRE, Epidemiology , , , , ,

apples and oranges

Apples and oranges. They’re both more or less spherical and classified as fruits, and that’s about whether the similarity ends. It’s the same for antibiotic-resistant Enterobacteriaceae (e.g. Klebsiella pneumoniae) and non-fermenters (e.g. Acinetobacter baumannii): they both share the same basic shape (more or less) and classification (Gram-negative), and that’s about where the similarity ends (see the Table below):

Table: Comparing the epidemiology of resistant Enterobacteriaceae and non-fermenters.3M webinar QA Not all created equal_table

I gave a webinar yesterday as part of a three part series on resistant Gram-negatives. You can download the slides here, and access the recording here (although you’ll have to register to do so). I am increasingly hearing people talking about ‘carbapenem-resistant organisms’ (CRO), used as a catch-all term to encompass both the Enterobacteriaceae and the non-fermenters. As you can see from the comparison table able, this doesn’t make a lot of sense given the key differences in their epidemiology. Indeed, MRSA is a CRO, so why don’t we lump that together with the Enterobacteriaceae and non-fermenters? Carbapenem-resistant Enterobacteriaceae and carbapenem-resistant non-fermenters are both emerging problems, but they are not the same problem.

I asked a few questions of the audience, which I’ve summarised below:

Figures: Questions asked of around 150 webinar participants, mainly from the USA.3M webinar QA Not all created equal Q13M webinar QA Not all created equal q23M webinar QA Not all created equal q3

I was not surprised that so few people felt comfortable explaining the difference between the Enterobacteriaceae and non-fermenters – and this rather justified the whole thrust of the webinar! I was a little surprised that the ‘prevalence’ of the two groups of resistant bacteria were so similar; I was expecting the Enterobacteriaceae to be more common (although I admit this wasn’t a brilliantly worded question). In terms of control interventions, it’s true that we still don’t really know what works to control resistant Gram-negative bacteria. But it does seem likely that the control interventions will be different for Enterobacteriaceae and non-fermenters, and this did come across in the responses. Hand hygiene was selected by most people (which makes sense), with screening & isolation, and stewardship more commonly selected for Enterobacteriaceae, and cleaning / disinfection for the non-fermenters.

Q&A

Following the webinar, the audience asked a few interesting questions:

  1. Can you get chlorhexidine resistant organisms? A number of studies have hinted that reduced susceptibility to chlorhexidine may be an emerging problem, (for example Batra, Otter, Lee and Suwantarat). But increases in bacterial MICs (for Gram-positive bacteria at least) appear to be a long way below the applied concentration. However, it’s worth noting that the measured CHG skin concentration in one study (15-312 mg/L before the daily bath and 78-1250 mg/L after the daily bath) was much lower than the applied CHG concentration (10,000 mg/L). This is around the CHG MIC for some Gram-negatives and potentially brings the subtly reduced susceptibility to CHG reported in MRSA into play. On balance though, the rationale and data on reduced susceptibility are cautionary but not enough to recommend against universal use in the ICU given the clinical upside.
  2. Do you think we should be doing universal chlorhexidine bathing? On our ICU in London, we have been using universal chlorhexidine decolonization for a decade combined with targeted screening and isolation, and have seen a dramatic reduction in the spread of MRSA. So yes, I think we should be doing universal chlorhexidine bathing, but the need to monitor carefully for the emergence of clinically-relevant reduced susceptibility.
  3. Can we discontinue contact precautions for CRE? The short answer is no. Quite a few studies have found that gut colonization with CRE typically lasts for at least 6 months to >1 year. And those that become spontaneously ‘decolonised’ sometimes revert to colonized, suggesting that they weren’t really decolonized at all – it’s just that their load of CRE at the time of sampling had fallen below the limit of detection. So I favour a “once positive, always positive” approach to CRE colonization.
  4. Which disinfectant would you recommend for resistant Gram–negatives? It does seem that the non-fermenters (and in particular A. baumannii) are “more environmental” than the Enterobacteriaceae. However, the Enterobacteriaceae (including CRE – especially K. pneumoniae) can survive on dry surfaces for extended periods. Therefore, I think enhanced disinfection – especially at the time of patient discharge – is prudent for both groups. Consider using bleach or hydrogen peroxide-based liquid disinfectants, and terminal disinfection may be a job for automated room disinfection systems, such as hydrogen peroxide vapour.
  5. Should we use objective tools to monitor cleaning? Effective tools are available to objectively monitor cleaning (e.g. ATP and fluorescent dyes), and these have been shown to improve surface hygiene. Therefore, we should all now be using these tools to performance manage our cleaning processes.

Image credit: ‘Apples and oranges’.

Isolation: the enemy of CRE

Jon Otter (@jonotter) CRE , , , ,

isolation enemy cre

Pat Cattini (Matron / Lead Specialist Nurse Infection Prevention and Control, Royal Brompton and Harefield NHS Foundation Trust) and I recently teamed up to present a webinar entitled: ‘Introduction to the identification and management of carbapenem-resistant Enterobacteriaceae (CRE)’. You can download our slides here, and here’s the recording:

The webinar covered the following ground:

  • Why the fuss?
  • What are CRE?
  • Who do we screen?
  • How do we screen?
  • What happens if someone is positive?
  • Key questions

CRE represent a combination of anitibiotic resistance, mortality and potential for rapid spread, so we need to be proactive in our approach to the detection and management of carriers. We simply can’t afford for CRE to become established in the same way that MRSA did, so now is the time of opportunity to develop the most effective prevention strategy. The recently published Public Health England Toolkit is useful, but it’s a set of tools to help construct a local policy, not a one-size-fits-all CRE policy. We hope that this webinar will assit you in developing your local CRE policies and plans.

Oh, and look out for the Premiere of ‘ISOLATION: THE ENEMY OF CRE’ (a Pat Cattini film)…

HIS / IPS Spring Meeting: What’s that coming over the hill? It’s a MDR-GNR monster!

Jon Otter (@jonotter) Conferences , , , , , , , , ,

HISIPS logos2

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.

References

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.

Considering the burden of enhanced CRE screening

Jon Otter (@jonotter) CRE , , , ,

swabs

The recent PHE CPE toolkit advocates implementing targeted screening and isolation of carriers. Reading the guidelines in a little more detail, the ‘triggers’ for screening a patient for CPE are, in the last 12 months: (a) an inpatient in a hospital abroad or (b) an inpatient in a UK hospital which has problems with spread of CPE (if known) or (c) a ‘previously’ positive case. Patients who screen positive should be placed in contact isolation; patients who screen negative should be placed in contact isolation until a further two consecutive negative screens have been taken. It’s important to note that the negative screens must be at least 48 hours apart. So, for patient who turns out to be negative will be in contact isolation for around 6 days (screens collection on days 0, 2 and 4, and a further day for the final negative screen result).

The number of patients who will meet the trigger for screening is currently unknown, but I have heard whispers of 25-50% of all admissions. This will place a considerable burden on already over-stretched isolation facilities, and bear substantial cost implications.

Single rooms in the NHS are already in very short supply. Indeed, recent press and commentary highlights the implications of running out of single rooms: patients shunted around “like parcels” in the middle of the night to relieve bed pressures.

Now, you could argue that patients who screen negative for CPE but are awaiting their confirmatory negative screens do not need to be isolated in a single room; they can be isolated in a bay. But if 25-50% of patients suddenly begin contact precautions, you’d quickly run into problems. Patients on contact precautions take longer to care for, and tend to get less attention than other patients resulting in more adverse events, as illustrated by a couple of recent Controversies blogs. Also, I fear you may begin to see ‘isolation fatigue’, where the procedure loses its impact if it has to be applied so broadly. And then there’s the cost. A recent US study calculated that contact precautions cost around £23 ($35) per patient day (not including the cost of disposal for all that additional waste!). If 25% of the 100,000 patients admitted to a London hospital Trust met the trigger for CPE screening and turned out to be negative, the price tag for isolation alone would be pushing £3.5m.

I support the PHE guidelines and agree that we need to “search and destroy” CPE above all else before it becomes endemic. However, are they feasible to implement in their current form?

Image: ‘Swabs’ by Frank Carey.

Prevalence survey illustrates the difference between CRE and CPE

Jon Otter (@jonotter) Antibiotic resistance, CRE , , ,

I recently posted an article on the difference between CPE and CRE, which is neatly illustrated by a prevalence survey from Alder Hey Children’s Hospital in Liverpool. In case you didn’t read my CPE/CRE blog (shame on you), here’s a reminder of the difference between the two:

Carbapenem-resistant Enterobacteriaceae (CRE) – Enterobacteriaceae that are resistant to carbapenems by any mechanism, including the production of an acquired carbapenemase or the production of an ESBL or AmpC combined with porin loss.

Carbapenemase-producing Enterobacteriaceae (CPE) – Enterobacteriaceae that are resistant to carbapenems by means of an acquired carbapenemase.

At Alder Hey, a large children’s hospital in Liverpool, a prevalence survey was performed between September 2011 and August 2012. All clinical and screening specimens were included; rectal screens were collected on admission and weekly from all patients in the ICU and HDU. 24 patients with CRE were identified, five (21%) from clinical specimens and 19 (79%) from rectal screens. The prevalence of CRE in rectal screens was 4.5% (19/421). Four of the 19 patients identified by screening specimens only went on to develop an infection, so 9 (38%) of patients ended up with a CRE cultured from a clinical specimen.

The majority (71%) of the 24 isolates were resistant to carbapenems by AmpC or ESBL combined with impermeability; seven (29%) were CPE, 4 with NDM and three with KPC (Figure). Typing indicated that the 3/4 NDM producing Klebsiella pneumoniae isolates were clonal, and they were clustered in space and time, which may indicate a small outbreak.

CRE alder hey Figure. Composition of CRE at Alder Hey Children’s Hospital. 

Carbapenem-resistance due to the production of an ESBL or AmpC combined with porin loss may lead to treatment failure, but it is often unstable and may impose a fitness cost, meaning that these strains rarely spread. Hence, carbapenem resistance conferred by an acquired carbapenemases is the key problem. This study helps to define the prevalence of CRE (and, more importantly CPE) in the population. We are not given a denominator for the clinical specimens, so the prevalence of CRE amongst clinical specimens cannot be calculated. However, the fact that around 5% of patients admitted to ICU / HDU were carrying CRE is a concern, although the prevalence of CPE on the rectal screens was lower at 1.7% (7/421).

Currently, the prevalence and epidemiology of CRE and CPE is poorly defined in the UK so this useful prevalence survey from Alder Hey is welcome. However, we urgently need more research from other hospitals to scale the CRE problem.

Article citation: Drew et al. Emergence of carbapenem-resistant Enterobacteriaceae in a UK paediatric hospital. J Hosp Infect 2013;84:300-304.