Month: April 2014

How much Clostridium difficile infection is hospital-acquired? Part II

Jon Otter (@jonotter) C. difficile , , , , ,

I wrote a blog last year on the excellent New England Journal of Medicine Oxford CDI study, which showed that a surprisingly high proportion (45%) of new CDI cases were genetically unrelated to recent CDI cases. This is not quite the same thing as evaluating how much CDI is hospital-acquired, mainly because the test used to detect CDI in the study has been phased out due to poor sensitivity, patients and staff were not screened for asymptomatic C. difficile carriage, and the environment was not sampled, so there was a large, unrecognized, hospital-based C. difficile reservoir from which horizontal transmission almost certainly occurred. A study published at the end of 2013 provides evidence that one of these potential reservoirs for transmission – asymptomatic carriage by other patients – is substantial.

The study was performed by a team from the University of Pittsburg Medical Centre. All patients screened for VRE during 5 months in 2009 were also screened for C. difficile carriage. Stool samples from symptomatic patients were also cultured. All toxigenic C. difficile were typed by multilocus variable number of tandem repeats analysis (MLVA). A total 56 C. difficile isolates from symptomatic CDI cases defined as healthcare-associated (HA-CDI) were available for typing. In addition, toxigenic C. difficile was identified in 226 (7.5%) of 3006 patients, and these isolates were also. Of the 56 HA-CDI isolates, 30% were genetically related to isolates from symptomatic cases, 29% to isolates from asymptomatic carriers, and 30% were unrelated to other isolates (Figure).

curry CDI

Figure. Proportion of HA-CDI cases genetically related to isolates from symptomatic cases, asymptomatic carriers and unrelated to other isolates.

The study provides a somewhat skewed view of asymptomatic C. difficile carriage since only patients considered at a high risk of carrying VRE were screened (admissions from other hospitals, ICU patients and long-stay inpatients). This meant that 75% of admissions were not screened for C. difficile carriage. Symptomatic cases are often described as the “tip of the ice berg”; in this study, three quarters of the ice berg remained submerged.

The authors performed an environment survey in the rooms of six asymptomatic C. difficile carriers and found that 5/6 rooms (48% of 25 sites) were contaminated with toxigenic C. difficile. And this is in a hospital that routinely uses bleach for disinfecting patient care areas! It’s interesting to note that transmission appeared to occur from the prior room occupant in 4/56 (8%) of HA-CDI cases, two of which were from asymptomatic carriers.

Another finding was that 158 patients had CDI diagnosed during the study period but 22% of these were counter-intuitively classified as carriers. This is perhaps because the lab performed a cytotoxin cell culture assay from both formed and unformed stools. We need to apply the “no diarrhea, no diagnosis” rule!

One other consideration is the molecular typing method used: MLVA. This is less discriminatory that the whole genome sequencing (WGS) used by the Oxford team. With WGS, strain relatedness is a question of how many single nucleotide variants (SNVs). With MLVA, it’s a question of distance of separation on a phylogenic tree. But you have the same fundamental problem: how do you define genetic relatedness? In reality, strain relatedness is an arbitrary line in the sand and our understanding of molecular clock speed is a work in progress.

So, is it time to screen and isolate asymptomatic carriers of toxigenic C. difficile? One of the arguments against this is that “asymptomatic carriers don’t have diarrhea, so therefore, don’t shed much C. difficile”. However, the environmental findings of this study, and others, suggest that asymptomatic carriers shed almost as much C. difficile as do symptomatic cases. I expect to see some controlled studies in the near future that should provide outcome data to help us to decide whether to pull the trigger on screening and isolation for asymptomatic carriers of toxigenic C. difficile.

Despite sampling only 25% of the asymptomatic carriage ice berg, apparent transmission from symptomatic CDI cases and asymptomatic C. difficile carriers was approximately equal. Plus, the study did not consider staff carriers or ancient environmental reservoirs. Thus, it seems that the large majority of C. difficile is acquired in hospital, but not necessarily from symptomatic CDI cases.

Article citation: Curry SR, Muto CA, Schlackman JL et al. Use of multilocus variable number of tandem repeats analysis genotyping to determine the role of asymptomatic carriers in Clostridium difficile transmission. Clin Infect Dis 2013; 57: 1094-1102.

APIC New England 2014 Conference Report: ‘The how, when, & where of C. diff – can you “C” the difference?’

Jon Otter (@jonotter) Conferences , , ,

apic new england logo

I was privileged to be asked to speak at the APIC New England Conference today in Springfield, Massachusetts. It was a vibrant day, and congratulations to the organizing committee for putting on such an enjoyable event.

Marie-Louise Landry MD – Continuing conundrums and controversies in the laboratory diagnosis of Clostridium difficile.

Dr Landy, a virologist by trade, began by reflecting on the fact that CDI is relatively new phenomenon, discovered in the late 1970s and initially thought to be viral! Having briefly presented the clinical problem and pathogenesis of CDI, Dr Landry got to the nitty gritty of how to test for CDI. You can choose to target the toxin, bacteria or bacteria capable of producing toxin:

  • Toxin: cytotoxicity cell culture assay (complex and requires overnight incubation) or enzyme immuno assay (terrible sensitivity).
  • Bacteria: culture (slow and doesn’t tell you much) or rapid GDH antigen assay (sensitive, but requires a confirmatory test of toxigenicity).
  • Bacteria capable of producing toxin: toxigenic culture (requires incubation) or Nucleic Acid Amplification Test (NAAT) such as PCR or LAMP (rapid, expensive).

To be honest, before Dr Landry’s talk, I thought that testing for CDI was pretty much sorted: GDH as a sensitive screening test following by PCR to detect the toxin gene for GDH positives. However, Dr Landry presented a compelling case that whilst GDH makes sense as a screening test, detecting the toxin gene via PCR is only half the story: the real gold-standard test is a cytotoxicity cell culture assay to confirm that the disease-causing toxin is present. Cost & clinical association makes compelling case for cell culture cytotoxicity assays; convenience for PCR! Indeed is the initial enthusiasm for PCR CDI testing waning as reality sets in (like the famous ‘Going and Coming’ by Rockwell)?

A final point for discussion: you can have the best laboratory diagnostics in the world, but if you’re testing inappropriate specimens, you’ll end up with false positives. We need a firm “no diarrhea, no CDI diagnostics” rule!

Curtis Donskey MD – Controlling the spread of C. difficile: a multifaceted approach

Dr Donskey began by considering that no healthcare facility is an island, and that long-term care facilities are an integral part of CDI spread. Dr Donskey spent most of the talk considering the environmental considerations related to CDI. Why does cleaning fail? Due to poor implementation: a research team with a bucket of bleach can eliminate C. difficile from surfaces! Various tools are available to help us tackle C. difficile environmental contamination. However, fluorescent markers and UVC did not eliminate C. difficile contamination whereas carefully enhanced disinfection did; bleach goes round corners better than UV, apparently. A related (and under-reported) unintended consequence of introduction a “no-touch” room disinfection (NTD) system such as UVC is that cleaners stop cleaning, mistaking UVC for magical cleaning robots! Plus, you could find yourself spending more time screening than cleaning, to the extent that those tasked with monitoring the cleaning process would be better deployed by getting their hands dirty! Dr Donskey covered a number of other important environmental issues: who cleans what (“the nurses thought EVS were doing it; EVS thought the techs were doing it; nobody was doing it”), the need for daily disinfection, pre-emptive and extended isolation, the potential and under-recognized importance of proper daily bathing for CDI patients, and the potential contamination risk from asymptomatic carriers. The final word: “getting doctors to prescribe antibiotics appropriately is like getting EVS to clean properly: an ongoing challenge.” Oh, and he finished on a song.

Jon Otter PhD (who invited him?) – No-touch room disinfection (NTD) systems: when to use them and how to choose between them (Can you ‘C’ the difference?)

You can download my slides from the talk here.

The talk was loosely based around a review paper recently published in JHI. The increased risk from the prior room occupant argues for doing a better job of terminal disinfection. The goal of hospital disinfection is controversial: the ‘Pragmatist’ says a reduction in contamination is good enough, whereas the ‘Prior room occupantist’ says elimination of pathogens is required. I presented some data suggesting that transmission risk ∝ contamination level; ergo reduction in transmission ∝ decontamination level? The NTD scene is a four-horse race currently, with hydrogen peroxide vapour (HPV), aerosolized hydrogen peroxide (AHP), ultraviolet C (UVC), and the relatively new kid on the block, pulsed xenon UV (PX-UV). Each system has its pros and cons so which is best? My view is that will depend on the scenario: if you have a carbapenem-resistant Acinetobacter baumannii in your ICU, then the ‘belt and braces’ approach of HPV is warranted. However, if you have MRSA colonization on a medical ward, a ‘quick and easy’ UV treatment may the only feasible option.

To try to keep everybody awake after lunch, I polled the audience on a few questions (Figure). I was not surprised that most people had not used an NTD system. However, I was surprised that so few people selected UV in the scenarios!

APIC NE q1 APIC NE q2 APIC NE scenarios

Figure. Question 1: Should all acute hospitals be using a ‘no-touch’ automated room disinfection (NTD) system for terminal disinfection of some patient rooms? Question 2: Has your hospital has used the following NTD systems? Scenario 1: A patient with carbapenem-resistant A. baumannii is discharged from the ICU. Scenario 2: A patient with MRSA colonization is discharged a general medical unit. Scenario 3: A patient with recently resolved CDI is discharged from a general medical unit (‘Enhanced’ = enhanced conventional methods).

Mike McCarthy – Sustaining your gains in infection control initiatives

Mike McCarthy rounded off the day with an engaging overview of his experience from a number of industries of how to ‘sustain your gains’. There’s a temptation from administrators to dismantle the team once it has been shown to work; clearly, the results will disappear with the people! Mike gave useful advice on how to embed change in an individual and organization. Do not confuse respect for people with respect for their bad practices. We need to be good coaches of best practice – reinforce proper execution; correct improper execution. The typical number of audits is “once and done”, but this not enough to form good habits. Establishing a new habit takes 60-90 days of work to reach the happy state of ‘unconscious competence’. People like data-led feedback (we’re all nerds at heart), which results in tangible performance management and improvement.  So, implement a checklist, audit it, provide positive reinforcement and feedback and your gain will be sustained!

Points for discussion:

  • Laboratory diagnostics are only part of the story. We need to focus on making sure only appropriate specimens are tested. Dr Donskey mentioned that a shocking 12% of their stool specimens were not tested due to sample leaking or labeling errors. Unfortunately, the stools most likely to be from CDI are also most likely to be liquid! Conversely, testing formed stools doesn’t do anybody any favours.
  • Do we need to focus on asymptomatic toxigenic C. difficile carriers and, if so, how?
  • How far can conventional methods go in tacking environmental contamination with C. difficile and is it time to turn to NTD systems, at least some of the time?
  • How best to sustain our gains?

IFIC 2013 Conference Report

Jon Otter (@jonotter) Conferences , , ,

ific argentina logo

The 13th International Federation of Infection Control (IFIC) meeting took place in Buenos Aires, Argentina in October 2013. A colleague who attended sent me some notes from the meeting, which I was not able to attend. I found the notes useful, so thought I’d share them (albeit a little late)!

Pro-Con debates

The first was on government regulations in infection control. The Pro delivered by H Baguio from Uruguay and Con by M Borg from Malta. H Baguio gave examples where government regulations have had impact on infection rates, citing the case of MRSA in the UK and reductions in bacteraemia, UTI and KPC prevalence after governmental regulation and auditing introduced in Uruguay. M Borg gave examples were governmental interventions did not improve the situation:  for example, a 5x increase in the cost of medical waste disposal due to an insistence on considering it hazardous, when much could be considered non-hazardous. Also, there is a suggestion that since CLABSIs became non-refundable by the US government, many hospitals have started using peripheral lines over central lines to avoid financial loss. Another possible consequence is a less active attempt to detect infections in US hospitals, and a reticence to admit high-risk patients to avoid infection. However, in general the debate was not really pro-con as both admitted that some sort of government regulation is needed but they were not the only solution. This was reflected in the final results: 50% pro and 50% con.

The second debate was about universal vs. targeted MRSA screening. T. Boswell was arguing for universal screening, while E Lingaas of Norway was for targeted. There were good arguments from both sides but the vote suggested a swing towards targeted screening. I think the debate would have been more interesting if it as about universal screening for all pathogens of interests such as the emerging MDR Gram-negative bacteria. Whether you choose universal or targeted screening will depend on your country and healthcare setting. In countries with high carriage prevalence, universal screening will be more beneficial, especially when using quick and cheap diagnostic tests. For countries with low prevalence, targeting screening probably makes more sense. However, choose your targeted screening approach carefully: I performed a study recently where we found that reverting to our targeted screening approach would miss around 50% of carriers!

Selected talks

Stella Maimone (Buenos Aires, Argentina): “Infection control: the other side of the moon”

Stella was the first registered infection control nurse in Argentina. Most IC nurses in Argentina have been trained by her. She gave a general talk on IC in Latin America (LA) based mainly on the differences between Latin America and developed countries in IC. She noted that most LA countries ministries of health have some sort of infection surveillance systems including in Argentina. However, the data are not publicly available (at least in Argentina) which is a major difference between LA vs. USA and Europe.

Although LA countries are aware of the cost of HAIs, they have limited resources and it is not possible to reproduce the same IC policies that are implemented in US and UK (e.g. CDC guidelines) in LA. The reasons for that are: limited resources, different culture, LA people don’t like to be controlled (i.e. governmental regulations will have limited effect), and LA people think short term hence IC policies aimed at results in the distant future will not be adopted.

Hence for effective IC policies in LA, the limited resources of the countries/hospitals, the wider culture of society, and the ‘micro culture’ of the healthcare community must be taken into consideration.

Maria Clara Padoveze (University of Sao Paulo, Brazil): “Help! An outbreak!”

This was an interactive session with Q & A throughout. The informative talk covered outbreak definition and detection, but did not address outbreak control and infection control interventions in detail, which was a shame. Maria highlighted a useful website for performing quick literature reviews on various outbreaks from round the world: www.outbreak-database.com. This gives you an up-to-date (ish) report of outbreaks from around the world. If you register (free) you can access advance search where you can search per country for example.

Celeste Lucero (Argentina): “MDROs: a new world war”

This helpful overview began with an overview of how organisms acquire multidrug resistance. Celeste mentioned the WHONET-Argentina, which is a WHO Collaborating Centre for Surveillance of Antimicrobial Resistance in the country. Celeste offered a few examples including the CTXM-2, which is endemic in Argentina, and the emergence of CTXM-15 and OXA-163. She also mentioned that many Acinetobacter baumannii are now only treatable by Tigicycline and Colistin, and that rates of KPC have been increasing since 2010. To compound matters, Argentina had its first reported NDM-1 in 2013. I left the talk without a clear picture of prevalence of MDROs in Argentia, which may reflect the paucity of accurate epi data.

Martin Kiernan (UK): “Taking infection prevention to the next level”

Martin gave a talk on the UK experience in IC, citing examples of the impressive reductions achieved in the UK for MRSA and C. difficile, and the various interventions to achieve these reductions. He mentioned that the problem now is MDR Gram-negatives such as E. coli and Klebsiella pneumoniae. His talk focused on how to change the IC culture in a hospital, including getting everyone engaged.

Syed Sattar (University of Ottawa, Canada): “The role of high-touch environmental surfaces in the spread of HAI: strategies to minimize the risks”

The talk began by outlining the factors that determine the risk of transmission from an environmental surfaces: probability of contamination; ability of pathogen to survive on the surface; transmission potential (e.g. porous surfaces are poor at transmitting pathogens, hence focus more on hard surfaces); location and frequency of direct contact with the surface (e.g. via hands or mucous membranes). He then went to define which pathogens to focus on. He warned not to focus on the high profile pathogens or the “pathogen of the month” such as HIV or H1N1 as these are less resistant in the environment and easily killed by disinfectants. Pathogens to focus on are: C. difficile spores; norovirus and other non-enveloped viruses such as rotavirus; MRSA; Acinetobacter; VRE.

The remainder of the talk was around liquid disinfectants and wiping. He specifically highlighted the problem with disinfectants/wipes, which are effective at spreading contamination if they don’t actually kill pathogens. He outlined the results of one of his studies, where they tested a number of disinfectants with wiping action and found that all except one did not kill all pathogens and also did spread them to other surfaces.

Some key papers mentioned in the conference:

1-   Zimlichman E, et al. Health Care-Associated Infections: A Meta-analysis of Costs and Financial Impact on the US Health Care System. JAMA Intern Med. 2013. Previously reviewed on the blog here.

2-   Limb M. Variations in collecting data on central line infections make comparison of hospitals impossible, say researchers. BMJ. 2012 Sep 21;345:e6377.

3-   Sattar SA, Maillard JY. The crucial role of wiping in decontamination of high-touch environmental surfaces: review of current status and directions for the future. Am J Infect Control. 2013 May;41(5 Suppl):S97-104.

2014 Spring Update

Jon Otter (@jonotter) Updates , , , , ,

Easter Bunny

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.

Regards

Jon

Photo credit: ‘Easter Bunny’ by Jimmy Hilario.

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.

Dissecting the epidemiology of resistant Enterobacteriaceae and non-fermenters

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

chalk cheese

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
Epidemic potential High Low
Clinical UTI VAP
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.

SHEA 2014 Spring Conference: Out with contact precautions. In with faecal transplantation

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

shea 2014

The organizing committee of SHEA should be congratulated for putting together an interesting and engaging agenda for their Spring Meeting, based around the recent ICHE special edition. Sadly, I was only able to make it for ‘From MRSA to CRE: Controversies in MDROs’ at the tail end of the meeting.

Global perspective on CRE evolution – Dr Arjun Srinivasan

Dr Srinivasan kicked off with a frankly frightening status update on the ‘nightmare bacteria’. KPC and NDM-producing Enterobacteriaceae have spread globally and rapidly since 2006.1 The prevalence of carbapenem-resistant K. pneumoniae in the US has risen from 1% in 2001 to a whopping 10% in 2011.2 More worryingly, the prevalence of CRE colonization in long-term acute care hospitals (LTACHs) in Illinois was 30% in a recent point prevalence survey.3 Arjun gave some useful perspectives on the mortality associated with CRE. The odds ratio for mortality attributable to CRE was remarkably similar in studies from Israel and the US at around 4 (which is approximately twice that of MRSA).4-6

Arjun made the point that 10% of CRE reported to the CDC are “community-acquired”. I find this hard to believe and I suspect they’d be healthcare-associated if you searched hard enough for risk factors. The picture would be different in areas of really high prevalence like New Delhi or Greece, but I don’t think the US is quite there yet.

Arjun highlighted some practical limitations of implementing strategies to control CRE, in particular around staff cohorting. “Today you’re assigned to work on the unit dedicated to patients with the nightmare bacteria”; not a popular message to our staff.

The key questions from Arjun’s viewpoint are: the focus has been on K. pneumoniae and E. coli, but should Enterobacter be in the mix? Are we doing enough to control CRE (or possibly, too much)? What are the right policy solutions in terms of reporting and guidelines? And finally, can we control CRE? An updated national report from Israel suggests yes.7 But uncontrolled spread elsewhere (e.g. Greece and increasingly Italy) suggest no.

Lab Identification & Surveillance for MDROs – Dr Daniel Diekema

Dr Diekema gave a timely and thoughtful overview of lab diagnostics for MDROs. One problem hampering clear lab diagnosis and surveillance is how to define an MDRO, and MDR-GNR in particular. Do we go by phenotype or by genotype? Clearly, there are arguments either way; there’s a tendency for clinicians to gravitate towards phenotype and scientists towards genotype I think, so we need to look out for our own biases.

The keynote was “don’t throw away the agar plates just yet”. Molecular diagnostics has a role, but it does not replace agar plates. Molecular diagnostics are great, but do not deal with changing epidemiology; struggle with target variability; are expensive; rely on validation of carriage sites; do not tell you about phenotypic susceptibility; have a limit of detection often around a couple of logs; and need to manage shared resistance genes between species, especially for MDR-GNR. Dan concluded by questioning whether molecular diagnostics remain the realm of reference, referral and research labs!

CRE in LTCF, LTACH, Regional Control – Drs Kerri Thom & Michael Lin

Dr Thom gave a rather disturbing overview of the involvement of long-term care facilities (LTCFs) and LTACHs as reservoirs for the spread of CRE. She began by providing evidence, albeit from outbreaks, that standard hand hygiene focus and contact precautions do not control CRE spread.8,9 You need to do more: active surveillance cultures plus cohorting has worked in a number of studies.8,10,11 Several studies suggest a significant LTCF / LTACH reservoir.3,12-14 A study from 2011 carefully studying regional spread of CRE through analysis of inter-facility “social networks” suggests that a connected regional approach to control is required.12

Dr Lin, working in the “CRE battleground of Illinois”3 continued the theme for a regional approach by presenting a regional collaborative to register CRE carriers: the XDRO registry. Dr Lin referred to a successful CRE LTACH bundle, which was presented at ID Week 2013, and provides some hope that CRE can be controlled in LTACHs.

Posters and oral presentations

The SHEA Spring Meeting had some posters for the first time, which was a welcome addition. The highlights from the posters were:

  • Dr Lesho: 75 million person years of surveillance in US military yields 300 CRE cases; 1 per 100,000 person years.
  • Dr Mann: Sharklett pattern surfaces performed better than copper for reducing bacterial persistence and transfer.
  • Southard: Pulsed-xenon UV disinfection of ICU rooms following ALL discharges associated with 20 v 6 cases of unit-attributable CDI.
  • Nicole Kenny: If your microfiber is too absorbent, you can forget about a 10 minute contact time.

Four impressive submitted abstracts were presented:

  • Dr Assadian performed an RCT of antimicrobial surgical gloves, demonstrating an impressive microbiological reduction – but will this translate to clinical benefit?
  • Dr Cluzet found that recurrent MRSA colonization occurred in 40% of 200 patients with uncomplicated MRSA skin and soft tissue infection in the community, and was associated with colonized household contacts and some antibiotics.
  • Dr Decker found that CRE colonization duration was a mean 241 days (range 38-649). Worrying, a few patients followed a ‘pos-neg-pos’ colonization pattern, which supports a “once colonized, always colonized” approach.
  • Dr Kwon performed a beautiful RCT of Lactobacillus probiotics, but sadly found that it did not reduce GI MDRO colonization or acquisition.

Contact Isolation Precautions: Unanswered Questions – Dr Daniel Morgan

Dr Morgan gave a very balanced and data-led overview of the pros and cons of contact isolation precautions. On the one hand, gloves and gowns are frequently contaminated with MDROs (which would be hands and clothes if no gloves and gowns).15 On the other hand, the somewhat equivocal findings of the BUGG study do not exactly provide resounding support for contact isolation precautions.16 Also, patients under contact precautions have less contact with healthcare personnel, delayed discharge, an increased risk of adverse events, potential for psychological problems, and reduced patient satisfaction. Dr Morgan’s conclusion was complex (matching the data), with a graded approach to contact isolation precautions advocated: CRE > C. difficile > MRSA > VRE.

Success Stories in MRSA Control – Drs Sarah Haessler, Michael Edmond, Steven Gordon and Jeffrey Stark.

This session was not quite what I was expecting. It turns out that all four speakers have stopped using contact precautions for MRSA colonized patients, so this became a collective justification for this practice. The arguments are compelling: none of the speakers’ MRSA rates skyrocketed when they stopped isolating MRSA patients. The alternative approach to traditional contact precautions seems to be a ‘syndromic approach’: basically, only isolate them if they’re oozing. I can see the logic here, but there may be exceptions. For example, MRSA colonized patients with respiratory viruses can enter a “super-spreader” state and would most certainly not be obviously oozing.17 Also, I wonder whether the faculty would feel differently about contact precautions if they were working outside the US in a healthcare system that is mainly composed of 4 and 6 bed bays (like most NHS hospitals)?

Top 10 MDRO Papers – Drs Susan Huang & Ebbing Lautenbach

Dr Huang selected:

  • Sivert NHSN data, demonstrating high rates of carbapenem resistance in CLABSI: 23% of Klebsiella, 26% of Pseudomonas and 65% of Acinetobacter.18
  • Rutala study showing that reflective paint results in rapidly reduced UVC cycle times and thus improves feasibility.19 (I think there’s probably two views on this study. Either the reflective paint resulted in more reflective bouncing of the UVC around the room and genuinely improved things. Alternatively, the reflective paint could have reflected the UVC directly back to the sensor more rapidly and actually reduced the dose delivered to the microbes on the surfaces.)
  • Harris BUGG study, which is testament to securing big funding for definitive studies (though with frustratingly equivocal results).16
  • Huang etc universal intervention studies.20-22 Universal chlorhexidine bathing: YES (provided resistance is monitored). Universal mupirocin decolonization: NO!

Dr Lautenbach chose:

  • van Nood faecal transplant for preventing C. difficile recurrence.23 ‘Transpoosions’ work, but we need to work on finding the right synthetic bug mix. Dr Lautenbach described the findings of the faecal transplant study as a “penicillin moment”; it’s a concept that could transform medicine.
  • Eye Oxfordshire C. difficile whole genome sequencing study: how much CDI is hospital-acquired?24 The study did not consider asymptomatic carriers or environmental contamination and 25% of patient isolates were not available for analysis. So, there was a pretty large potential burden from which hospital-acquisition could have occurred.
  • Lin LTACH CRE colonization study.3 30% of patients carried CRE; this figure was 55% in one of the facilities included in the survey.
  • Daneman selective decontamination study.25 I can’t help thinking that ‘selective decontamination’ is misnamed: it’s not very selective at all. Perhaps ‘scorched earth decontamination’ would be more accurate. My view is that, regardless of efficacy, we should be giving faecal transplantation before a cocktail of antibiotics. Let’s save the antibiotics for treating infections.
  • Gerber community-based antibiotic stewardship cluster RCT, which showed an impressive reduction in broad spectrum antibiotic prescribing.26

Fecal Transplant for C. difficile Infection – Dr Michael Edmond

Dr Edmond gave a passionate and first-hand case for the effectiveness and value of faecal transplantation for recurrent CDI. It’s not a new concept: ‘faecal therapy’ was documented in Chinese medicine in 300AD; the first modern use was in 1957, with impressive results.27 Faecal microbiota transplantation (FMT) cures recurrent CDI by complementing reduced microbiota diversity.28 Indeed, a recent systematic review of FMT reported an overall cure rate of 91% for recurrent CDI.29 The regulatory position is in flux currently, meaning that purchasing carefully tested stool from the ‘brown cross’ (www.openbiome.org) may be more challenging in future. (Indeed, it may even come to DIY FMT, which is possible: first you collect it, then you blend it and then you stick it…) The bottom line is that fresh or frozen, yours or somebody else’s, stool bank or lab donor, NG tube or enema: FMT works for recurrent CDI. The only question is whether it could be a front-line treatment for CDI.  

The Microbiome and Its Role in Infection Prevention – Dr Clifford McDonald

Dr McDonald gave a mind-bending talk on the hugely underestimated role of the microbiome in human disease. The gut microbiome is dominated by the Bacteroidetes or Firmicutes, depending on diet; coliforms are surprisingly minor players.30 Antibiotic therapy results in profound disruption of the gut microbiome;31 thus we need to carefully tend the microbiome.32 We need to consider ways to manipulate the gut microbiome for good, using perhaps ‘advanced’ probiotics or modulating bacterial inter-cell communication. Cliff finished with a thought-proving vision of the future involving extensive testing of the patient’s microbiome, a “tending” consultation and treatment with a course of the appropriate advanced probiotic therapy.

Pro-Con: Should We Be Bare Below the Elbows? Drs Michael Edmond & Neil Fishman

The recently published SHEA guidelines on attire provide some useful background.33 Dr Edmond began with the pro position: clothing becomes contaminated with MDROs, which can be transmitted from clothing in laboratory studies; white coats are rarely washed; there is limited evidence but potential benefit. When evidence is limited, we need to avoid ‘methodolatry’, the worship of the hallowed RCT. It seems that a doctor’s appearance is the least important performance measure from a patient’s viewpoint.34 They are much more concerned with whether their doctor knows their stuff. Perhaps the most powerful argument of all for the pro is that Dr Edmond recently won an award for the best beside manner whilst dressing down.

Dr Fishman began his con in entertaining fashion: by undressing to bare below the elbow and replacing his neck tie for a fetching bow-tie. His argument was: unattractive bingo wings; bug-trapping hairy arms; may be some unintended harm; reduced patient experience; is it consistent when you consider policies for hand-held electronics; and, of course, no evidence.

The UK has been bare below the elbow for several years now. There has been some resistance: in fact, the debate reminded me of a London surgeon going apoplectic when the Prime Minister’s camera crew were not bare below the elbow during a hospital visit. So, should we be bare below the elbow? In my view, yes; it makes it easier to wash your hands. However, the manner in which you interact with you patient is far more important than what you wear.

Key issues

  • Can we control CRE and, if so, how?
  • Related to this, how to deal with the (apparently sizable) CRE reservoir in LTACHs?
  • Do molecular diagnostics remain the realm of reference, referral and research labs?
  • Has our focus on CRE taken our eye off multidrug-resistant non-fermenters (particularly A. baumannii), which are a greater ‘clear and present danger’ for many facilities?
  • Can we risk abandoning contact precautions for MRSA patients? In a US hospital with 100% single rooms, perhaps. In the NHS composed of 4 and 6 bed bays, no.
  • FMT works for recurrent CDI and regulators should not block access to it.
  • Could FMT work as a front-line treatment for CDI?
  • How can we modify the gut microbiome most effectively to confer infection prevention and control benefits?
  • Is microbiome modulation more effective than antibiotic ‘selective decontamination?

References

1.       Molton JS, Tambyah PA, Ang BS, Ling ML, Fisher DA. The global spread of healthcare-associated multidrug-resistant bacteria: a perspective from Asia. Clin Infect Dis 2013; 56: 1310-1318.

2.       Centers for Disease C, Prevention. Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep 2013; 62: 165-170.

3.       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.

4.       Cosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y. Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 2003; 36: 53-59.

5.       Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol 2008; 29: 1099-1106.

6.       Borer A, Saidel-Odes L, Riesenberg K et al. Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia. Infect Control Hosp Epidemiol 2009; 30: 972-976.

7.       Schwaber MJ, Carmeli Y. An ongoing national intervention to contain the spread of carbapenem-resistant enterobacteriaceae. Clin Infect Dis 2014; 58: 697-703.

8.       Palmore TN, Henderson DK. Managing Transmission of Carbapenem-Resistant Enterobacteriaceae in Healthcare Settings: A View From the Trenches. Clin Infect Dis 2013; 57: 1593-1599.

9.       Kochar S, Sheard T, Sharma R et al. Success of an infection control program to reduce the spread of carbapenem-resistant Klebsiella pneumoniae. Infect Control Hosp Epidemiol 2009; 30: 447-452.

10.     Agodi A, Voulgari E, Barchitta M et al. Containment of an outbreak of KPC-3-producing Klebsiella pneumoniae in Italy. J Clin Microbiol 2011; 49: 3986-3989.

11.     Ben-David D, Maor Y, Keller N et al. Potential role of active surveillance in the control of a hospital-wide outbreak of carbapenem-resistant Klebsiella pneumoniae infection. Infect Control Hosp Epidemiol 2010; 31: 620-626.

12.     Won SY, Munoz-Price LS, Lolans K et al. Emergence and rapid regional spread of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis 2011; 53: 532-540.

13.     Marquez P, Terashita D. Editorial commentary: long-term acute care hospitals and carbapenem-resistant Enterobacteriaceae: a reservoir for transmission. Clin Infect Dis 2013; 57: 1253-1255.

14.     Marchaim D, Perez F, Lee J et al. “Swimming in resistance”: Co-colonization with carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii or Pseudomonas aeruginosa. Am J Infect Control 2012; 40: 830-835.

15.     Morgan DJ, Liang SY, Smith CL et al. Frequent multidrug-resistant Acinetobacter baumannii contamination of gloves, gowns, and hands of healthcare workers. Infect Control Hosp Epidemiol 2010; 31: 716-721.

16.     Harris AD, Pineles L, Belton B et al. Universal glove and gown use and acquisition of antibiotic-resistant bacteria in the ICU: a randomized trial. JAMA 2013; 310: 1571-1580.

17.     Sheretz RJ, Reagan DR, Hampton KD et al. A cloud adult: the Staphylococcus aureus-virus interaction revisited. Ann Intern Med 1996; 124: 539-547.

18.     Sievert DM, Ricks P, Edwards JR et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol 2013; 34: 1-14.

19.     Rutala WA, Gergen MF, Tande BM, Weber DJ. Rapid hospital room decontamination using ultraviolet (UV) light with a nanostructured UV-reflective wall coating. Infect Control Hosp Epidemiol 2013; 34: 527-529.

20.     Climo MW, Yokoe DS, Warren DK et al. Effect of daily chlorhexidine bathing on hospital-acquired infection. N Engl J Med 2013; 368: 533-542.

21.     Milstone AM, Elward A, Song X et al. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet 2013; 381: 1099-1106.

22.     Huang SS, Septimus E, Kleinman K et al. Targeted versus Universal Decolonization to Prevent ICU Infection. N Engl J Med 2013; 368: 2255-2265.

23.     van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med 2013; 368: 2145.

24.     Eyre DW, Cule ML, Wilson DJ et al. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 2013; 369: 1195-1205.

25.     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.

26.     Gerber JS, Prasad PA, Fiks AG et al. Effect of an outpatient antimicrobial stewardship intervention on broad-spectrum antibiotic prescribing by primary care pediatricians: a randomized trial. JAMA 2013; 309: 2345-2352.

27.     Eiseman B, Silen W, Bascom GS, Kauvar AJ. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery 1958; 44: 854-859.

28.     Chang JY, Antonopoulos DA, Kalra A et al. Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis 2008; 197: 435-438.

29.     Sha S, Liang J, Chen M et al. Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children. Aliment Pharmacol Ther 2014; in press.

30.     De Filippo C, Cavalieri D, Di Paola M et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010; 107: 14691-14696.

31.     Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci U S A 2011; 108 Suppl 1: 4554-4561.

32.     Tosh PK, McDonald LC. Infection control in the multidrug-resistant era: tending the human microbiome. Clin Infect Dis 2012; 54: 707-713.

33.     Bearman G, Bryant K, Leekha S et al. Healthcare personnel attire in non-operating-room settings. Infect Control Hosp Epidemiol 2014; 35: 107-121.

34.     Aitken SA, Tinning CG, Gupta S, Medlock G, Wood AM, Aitken MA. The importance of the orthopaedic doctors’ appearance: a cross-regional questionnaire based study. Surgeon 2014; 12: 40-46.

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.