Conferences

Perspective from ECCMID 2014 Part II: What to do about MDR-GNR?

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

 gram neg

I was hoping that the ECCMID 2014 session on ‘Outbreaks of MDR Gram-negative bacteria: what works and what does not work?’ would bring some answers from large, controlled studies to improve the evidence base for MDR-GNR control. I’m sorry to report that most of what was presented only served to highlight the limitations of the evidence base! There’s a bit of a Catch 22 here: in most settings, the problem lies in outbreaks, but the answers lie in large, adequately controlled cluster randomized studies in endemic settings.

  • Dr Weterings from NL provided a rather bleak start to the session, reporting an outbreak of carbapenem-resistant K. pneumoniae in a hospital and nursing home. Environmental cultures regularly grew the outbreak strain (including a shared glucose meter) and the control measures that were effective in the hospital were more challenging to implement in the nuring home.
  • Dr Gonzalez-Galan found a bundle of interventions dramatically effective to reduce the rate of endemic MDR A. baumannii. The bundle comprised surveillance, hand hygiene audit, and a checklist for environmental cleaning and contact precautions compliance. But which element of the bundle worked, and were any elements redundant?
  • Dr Cohen reported an MDR A. baumannii outbreak in Israel affecting 70% of ventilated patients at its peak, which forced colistin as the empiric VAP therapy. Proper disinfection of the ventilators brought the problem under control. Similarly, an endoscoy-associated ESBL K. pneumoniae outbreak in Norway (reminescient of the NDM outbreak in Chigago) was controlled by implementing proper endoscope disinfection.
  • Probably the most useful presentation of the session was from Dr Cataldo preseting a systematic review of interventions for MDR-GNR. Most studies (78% of the 86 included) were in outbreak settings, and plagued by low quality. Nonetheless, bundles were 2x more effective than single interventions (45% vs. 28%). The study struggled to determine convincingly which element of the bundles was most effective, but hand hygiene, contact precations and education came through as the pillars of effective bundles.
  • Dr Dettenkofer showed that an educational intervention improved compliance with standard precautions (especially hand hygiene and to a lesser extent the inappropriate use of examination gloves for some procedures). However, ‘standard precations’ are far from standard, and it seems that you need to go further than standard precautions to control MDR-GNR.
  • Dr Hussein showed that standing over healthcare workers and telling them to wash their hands improved compliance (unsurprisingly!). I venture that hospitals would only take this measure in extreme circumstances, although hand hygiene “enforcers” are not without precedent.
  • Dr Perencevich reported that the Hawthrone effect tends to strike after 15 mins of observation, so hand hygiene observations should be kept short and sweet. (Incidentally, hand hygiene compliance was higher among doctors than nurses in this study; I think it’s the first time I’ve ever seen it this way around!)
  • Dr Hansen presented data from the PROHIBIT collaborative, who found that alcohol based hand rub usage tracks the prevalence of antimicrobial resistance across Europe. However, the rate of red and yellow cards in the Euro 2008 football championships also correlates with antimicrobial resistance rates across Europe, and national consumption of chocolate correlates with the national rate of Nobel laureates: collelation doesn’t necessarily mean causation!
  • Finally, Dr Langelar reported that the Dutch national healthcare inspectorate visits were effective in raising standards. But was this papering the cracks or effecting culture change?
  • I am sure there were lots of good posters on this topic too, but I didn’t get very far with those. Perhaps somebody else did and would like to provide some additional information?

Dr Evelina Tacconnelli gave a thoughtful talk comparing the various international guidelines for MDR-GNR, reflecting on the recently published ESCMID version. The subject is broad, specifically in terms of which MDR-GNR, and in which setting. Guidelines for CRE in a general hospital population would look quite different to guidelines for CRAB in the ICU. Dr Tacconnelli focused on the areas of controvosy: isolation for ESBL carriers, how to prioritise limited side rooms (see useful ‘Lewisham’ isolation prioritization tool in Appendix 6 of these Irish guildelines), selective digestive decontamination, and the need for bundles. Finally, Dr Tacconnelli referenced a neat model for the effectiveness of various infection control interventions for controlling the spread CRKP. This is a clever study, and probably useful, but much like Berta (showing my age), incorrect inputs result in meaningless (or worse, misleading) outputs.

Dr Anna-Pelagia Magiarakos discussed some of the challenges of implementing guidelines, reminiscent of Dr Evonne Curren’s recent talk on a similar subject. One important point is to have some guidelines to implement! Countries lacking guidelines for the control of MDR-GNR tend to have higher rates (ECDC and PROHIBIT data). Once you have some guidelines, barriers to implementation need to be overcome: time, culture, resources, lack of understanding or belief that they will work, competence, habit, routines and “ivory tower” guidelines written by those detacted from the coal-face, to name but a few!

So are we any closer to knowing what works to control MDR-GNR following ECCMID 2014? Bundles are more effective than single interventions, but we still don’t know which elements of the bundle are most important, and this will vary by pathogen and setting. We need more studies like the commendable but complex MOSAR Lancet ID study.

You can view some other ‘Perspectives from ECCMID’ here.

Image credit: Iqbal Osman.

Perspective from ECCMID 2014 Part I: a voice against ‘selective’ digestive decontamination (SDD)

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

eccmid 2014

I enjoyed this year’s ECCMID in Barcelona very much, and came away feeling scientifically, culturally and culinarily enriched! Many thanks to the organizers for such a broad and interesting programme. One of the most interesting sessions was the very final session, on controlling MDROs in the ICU. The session boiled down to the pros and cons of three approaches to decolonization: selective digestive decontamination (SDD), mupirocin for MRSA nasal decolonization, and chlorhexidine gluconate (CHG) bathing. The faculty of Dr Brun-Buisson, Dr Harbarth, Dr Bonten and Dr Huang made it an engaging session.

Selective digestive decontamination (SDD)

The problem is antibiotic resistant bacteria, particularly in the ICU. Is the solution really indiscriminate use of antibiotics to temporarily suppress the load of antibiotic resistant bacteria in the gut? It doesn’t make a lot of sense to me either.

Selective oral decontamination (SOD) or selective digestive decontamination (SDD) is not a new concept, and has been around for some 45 years. Only recently have impressive studies emerged demonstrating that SDD and, to a lesser extent, SOD suppress the load of antibiotic resistant bacteria in the gut, reduce mortality and reduce transmission (de Jonge, de Smet and Daneman). But it’s not without collatoral:

  • The use of antibiotics leads to antibiotic resistance, sooner or later. A number of studies suggest that SD is not associated with an increased overall prevalence of resistant bacteria (not least the impressive Daneman review). Indeed, one study showed that rates of resistance actually decreased on units using SD. However, these studies conflate the potential for reducing transmission (and hence reducing unit-level prevalence) with the risk of selecting resistant sub-populations, which both seem likely. One particular concern is the emerging data that SDD drives colistin resistance. Are we playing with fire by overusing our drug of last resort? Furthermore, the abundance of key antibiotic resistance genes doubled on units using SDD when using a microbiotic approach in a recent study.
  • Speaking of the microbiome, another speaker described antibiotics as a ‘microbiome-busing atomic bomb’, so perhaps we should rename SDD as ‘scorched earth decontamination’ (SED)! The importance of a happy, healthy microbiota is beginning to dawn on us. We need to make friends with our microbiome, not obliterate it with unindicated antibiotics.
  • The impressive studies showing the value of SDD have been performed in the Netherlands, which has a low rate of antibiotic resistance. Will SDD be as effective elsewhere, where the background rates of antibiotic resistance are higher? Indeed, the Daneman study showed a notable (although no statistically significant) increase in the prevalence of MRSA on units using SDD. Is this a case of ‘squeezing the MDRO balloon’?
  • SDD temporarily suppresses gut colonization with multidrug-resistant Gram-negative rods but rarely decolonizes permanently. From an infection control viewpoint, it should not change the ‘once positive, always postive’ status quo for resistant Enterobacteriaceae.

I appreciate that I’m presenting a polarized and rather one-side case against SDD here. But for me, whether SDD works is the wrong question: is it the right thing to do? If (perish the thought) I’m a patient in the ICU, then SDD works for me. However, if I’m working on an ICU in 2024 wondering what to do with a pan-drug resistant Gram-negative bacterium, SDD (in 2014) doesn’t work for me.

Mupirocin

Dr Huang presented the key findings from her impressive study of universal CHG combined with MUP. Mupirocin resistance in S. aureus can be low-level mutational) or high-level (acquisition of the Mup resistance genes). The use of MUP has been associated with the development of both high- and low- level resistance. Indeed, several updates from ECCMID show this. For example, Dr Sarah Deeny’s poster showed that low-level resistance appeared to develop during hospitalization. Plus, a study from our group showing that detection of phenotypic high- or low-level mupirocin resistance only represents three quarters of the picture, since carriage of mupirocin resistance determinants remains “silent” 25% of the time.

So, the key question hanging over Dr Huang’s study is the value of universal MUP over and above universal use of CHG. Dr Huang presented an excellent analysis table on this point, which I’ve reproduced below:

Table: Weighing the pros and cons of universal mupirocin use (reproduced with permission from Dr Huang).Huang ECCMID table

One of Dr Huang’s most powerful arguments was that the burden of mupirocin use is in decolonizing a large number of patients prior to elective surgery. Ergo, if you’re going to save MUP, then save it for the highest risk patients (e.g. ICU patients). However, the counter here is that local use of MUP is likely to drive local MUP resistance on the ICU. So, I still feel that we should not recommend the universal use of MUP.

Chlorhexidine

Dr Bonden, Dr Huang and Dr Harbarth reviewed the impressive studies that CHG bathing provides strong protective effects against a range of MDROs (for example Climo, Milstone and Vernon studies). These studies are not without their critics – some say that the effect on reducing relatively benign coagulase-negative staphylococci BSI amplifies the overall effect. However, both the data and rationale are stong: if you reduce the amount of MDRO on the patients’ skin (‘source control’), you reduce the chances of endogeneous infection, and transmission to others. Unlike antibiotics, CHG is a biocide with a less specific molecular target, which makes resistance more challenging from a bacterial viewpoint. However, reduced susceptibility to chlorhexidine must be monitored carefully. A number of studies have hinted that reduced susceptibility to chlorhexide may be an emerging problem, (for example Batra, Otter and Lee.) 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.

Conclusion

What shoud be the standard of care for ICU patients? My current view is: universal CHG, targeted mupirocin for MRSA decolonization and absolutely no SDD!

Headlines from ECCMID

I’ll be posting some blogs on some of these topics over the coming days. You can view some other ‘Perspectives from ECCMID’ here.

  • We are still no closer to figuring out what works to control multidrug resistant Gram-negative rods (including CRE).
  • CDI does not seem to be emerging as a community pathogen, despite apparent increases.
  • Bacteriotherpy for synthetic faecal microbiota transplant (FMT, aka transpoosion) is getting close.
  • We need to stop polluting our plant by pumping antibiotics into our environment.
  • As one tweeter (@marina_manrique) put it, whole genome sequencing (WGS) has becoming a bit like the One Ring from Tolkein’s Lord of the Rings: ‘one ring to rule them all, one ring to bind them, one ring to bring them all, and in the outbreak find them (out – the other methods that is)’.

Picture credit: ‘Antibiotics’.

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.

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.

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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.

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Key themes from ID Week 2013

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

idweek

Having somewhat dipped in towards the end of ID Week 2013 due to the overlapping Infection Prevention 2013 Conference in London, I can’t begin to provide a comprehensive overview of such a large event. Instead, I’ve tried to summarize new data on two important areas: the epidemiology and control of multidrug-resistant Gram-negative rods (MDR-GNR) and the role of the environment in transmission. You can access all of the abstracts free online here. Also, the poster abstracts that I cite below are either individually hyperlinked or can be downloaded here.

MDR-GNR

Dr Kavita Trivedi (California Department of Public Health) gave an overview of CRE in the USA, which has now been reported in virtually every state. Whilst surveillance sites, methods and definitions are problematic, CDC are coordinating some useful emerging data. For example, an NNIS prevalence survey indicates an increase in CRKP from 1% in 2001 to 10% in 2011. Also, the Multi-Site Resistant Gram-Negative Bacilli Surveillance Initiative (MuGSI) is beginning to yield some data. Early results from four states indicate that CRE is 10x less common than MRSA in the population, predominantly from urine cultures (85%) from patients with co-morbitities (93%) with a low mortality rate (4%). The CDC CRE toolkit provides a practical overview of recommended interventions. Finally, the challenges outlined by Dr Trivedi included: long-term care; variable prevalence; unknown epidemiological associations of different strains and genes; and colonization duration.

Oral presentations

A featured oral abstract by Bamburg et al. described an outbreak of NDM-producing K. pneumoniae affecting eight patients. The complex transmission map was dissected using whole genome sequencing, reminiscent of the NIH experience.

There was a useful oral session on ‘Identifying and Overcoming Challenges in Preventing Transmission of MDRO GNR’:

  • 1207, Haverkate. A Dutch group found that Klebsiella carrying OXA-48 can appear susceptible in vitro, risking ‘silent transmission’ of both the gene and the organism. The mean duration of colonization was almost one year and modeling indicated that readmission of CRE colonized patients needs to be carefully accounted for.
  • 1208, Mody. A cluster RCT in nursing home residents with urinary catheters or feeding tubes found that enhanced and preemptive isolation; ASC; and education led to a significant reduction in MDROs and CAUTI.
  • 1209, Hayden. A bundled intervention (ASC and isolation; daily CHG bathing; education; and adherence monitoring) significantly reduced CR Klebsiella in three of four LTACs included in the study. The prevalence of CR Klebsiella was remarkably high: 45% of patients at baseline. Environmental contamination was not identified, so no enhanced cleaning and disinfection was implemented, which is different to the experience of NIH.
  • 1210, Lewis. Varying the definition of ‘MDR’ made a profound impact on the proportion of patients requiring contact isolation, from 8-30%. Subsequent discussion with the authors indicated that the proposed MDR definitions developed by ECDC and CDC to be too sensitive for bacteria with less intrinsic resistance, such as E. coli. Perhaps a separate definition for the Enterobacteriaceae and non-fermenters is the way forward here?
  • 1211, Apisarnthanarak. The implementation of chlorhexidine bathing plus a switch to bleach for environmental disinfection brought an outbreak of A. bauamannii in Thailand under control. But which worked?
  • 1212, Barnes. A mathematical model indicated that hand hygiene is twice as important as environmental hygiene for interrupting A. baumannii, MRSA and VRE transmission. Whilst an awful lot of assumptions are required in this model, I can believe this 2:1 ratio in light of the following: “healthcare personnel are like small children: they touch everything and don’t always wash their hands” (Curtis Donskey) and “healthcare personnel hands are like very mobile shared surfaces” (Eric Lofgren).

Posters

  • 740, Jamal. CRE rate: 3% of 2000 Kuwaiti clinical isolate; 15.9% of CRE NDM-1 producers.
  • 746, Koper. A match made in hell between hypervirulent K2 Klebsiella and KPC; in vitro plasmid transfer demonstrated.
  • 1578, Madigan. No CRE detected in 69 international patients at Mayo Clinic; 22% carried ESBLs.
  • 1582, Johns. 50% of 66 MDR A. baumannii cases in Ohio in 2012 presented in first two days of admission, mostly admitted from extended care facilities, illustrating the ‘revolving door’ between acute and other healthcare facilities.
  • 1586, Carrilho. 26% of 157 Brazilian CRE polymyxin-resistant, though polymyxin resistance was not associated with increased mortality.
  • 1603, Drees. Remarkably, a survey from the SHEA Research Network indicates that 6% of hospitals do NOT isolate patients with CRE.
  • 1609. Decker. A study of CRE colonization patterns indicates median colonization of 216 days (range 134-376). One patient was colonized for >500.
  • 1611, Odom. CRE cultured from 12 (4.4%) of surfaces, predominantly sink drains.
  • 1612, Fitzpatrick. Selective broth enrichment added 10% sensitivity for detecting CRE. Is the resulting diagnostic delay worth the wait?
  • 1615, Lin. Chlorhexidine gluconate (CHG) daily bathing significantly reduces the number of body sites growing CRE, but several sites remain colonized.
  • 1618, Cheng. CRE identified in 1.2% of 6533 rectal screens and faecal specimens in Hong Kong, which is lower than I would expect.

Reflections from MDR-GNR research

  • We now have some intervention studies, but many include bundled interventions. We need more resolution on what works.
  • The duration of colonization with CRE seems to be long, probably around 1 year on average. Is this enough for a “once positive, always positive” approach?
  • Prevalence of CRE is variable around the USA, and in other parts of the world.
  • There is poor resolution between the epidemiology of Enterobacteriaceae and non-fermenters.
  • Most would agree that contaminated surface play an important role in the transmission of MDR non-fermenters such as A. baumannii. But is CRE an environmental issue? Some groups have found contamination and implemented enhanced disinfection, others have not.
  • Should chlorhexidine decolonization be part of the intervention for MDR-GNR?
  • Different research groups use different terminology and the meaning is sometimes obscured. International consensus is required.

Role of the environment in transmission

Dr Curtis Donskey (Cleveland) gave an excellent overview of ‘Environmental Controls for the Prevention of C. difficile Transmission’. Dr Donskey is one of the most active researchers anywhere in the world, focusing much of his attention on the role of the environment. Having established the importance of contaminated surfaces in the transmission of C. difficile, Dr Donskey explored emerging themes in addressing surfaces contaminated with spores covering conventional and automated terminal cleaning, and the impact of improving daily disinfection. The current challenges outlined included where to clean, how to validate “no-touch” automated room disinfection systems (NTD) to disentangle product claims from real-world performance, how best to engage environmental services and how to make disinfection easier in order to facilitate compliance.

Posters

  • 347, Livorsi. Patients with a higher nasal burden of MRSA are more likely to carry MRSA at other sites and contaminate their environment.
  • 348, Sitzlar. Useful stratification of MRSA/VRE room contamination rate by patient C. difficile status. Rooms of patients on precautions for CDI 3x more likely to be contaminated.
  • 1393, Deshpande. One hospital found more C. difficile contamination in the rooms of patients who were not on precautions for CDI than in rooms of patients on precautions for CDI!
  • 1394, Kundrapu. Suggests that the result would be better if those tasked with monitoring cleaning performance got their hands dirty and cleaned.
  • 1541, Sunkesula. Reduction in VRE in new unit; attributable to no shared rooms and bathrooms in the new unit?
  • 1685, Rose. A couple of carbapenem-resistant bacteria on public surfaces outside New York hospitals; I bet you it’d be higher in New Delhi!
  • 1685, Havill. Extended survival of CRE on dry surfaces; will surprise some.
  • 1690, Kirk. Almost no MRSA cultured from medication cabinets in isolation rooms. Direct plated swab lacks sensitivity?
  • 1691, Suwantarat. Quantitative assessment of HCP contact with equipment and fomites helps to define high touch (risk?) items; medication chart highest frequency of contact (1 per patient hour) yet possibly also the least cleaned item.
  • 1692, Hirsh. ipads (and other personal electronic devices) can become contaminated with pathogens; contact precautions should include an explicit instructions not to touch these items. (This was implemented at NIH during recent CRE outbreak there).
  • 1695, Williams. Pathogens identified on the clothing of HCP at the BEGINNING of their shift! (Reminds me of Hayden article where VRE commonly found on the hands of HCP BEFORE they entered patient rooms.)
  • 1697, Vassallo. Universal standard precautions didn’t stop impressive trend reductions. Time to abandon contact precautions?
  • 1698, Mann. Cleaning survey response rate of 100% (unprecedented). EVS staff have something to say, if only we’d listen.
  • 1700, Gerba. What’s for lunch in the hospital cafeteria? MRSA, enteric bacteria and spores, apparently.
  • 1701, Wiemken. Wipes are quicker and easier than bucket methods. Why wouldn’t you? (Perhaps only due to lack of wetting reducing efficacy.)
  • 1705, Boyce. The informal ‘standard’ for ‘clean’ is <2.5 cfu/cm2. This equates to 65 cfu/contact plate, which is almost 1/3 of the way to uncountable. Is this an acceptable standard for ‘clean’?
  • 1706, Power. Contaminated neonatal incubator? An hour of UVC should do the trick.
  • 1707, Horn. HPV for terminal room disinfection associated with significant reduction in CDI. Study design controlled for hand hygiene compliance, but time series analysis may have been more appropriate.
  • 1708, Anderson. Is variation in UVC cycle time for room disinfection explained entirely by variation in room size?
  • 1709, Uslan. Assessment of various Cu surfaces; I was unaware that you could apply Cu as a spray though have concerns over durability.

Other highlights

  • Decolonization has been a hot topic since several high-profile articles have been published recently. It’s a shame that universal chlorhexidine was conflated with universal mupirocin in the Huang study; the two should be considered separately in my view. The potential for resistance to mupirocin is extremely high, whereas the risk for ‘resistance’ or continued reduced susceptibility to chlorhexidine is lower. However, an interesting finding from poster 1615 was that the measured CHG skin concentration (20-1200 mg/L) was MUCH lower than the applied CHG concentration (10,000 mg/L). This brings the subtly reduced susceptibility to CHG reported in MRSA into play. Both Dr Aaron Milsone (Hopkins) and Prof Mary-Claire Roghmann (University of Maryland) highlighted the importance of the need to ‘tend the human microbiome’ and to consider the ‘host-microbiome-pathogen’ interaction rather than the ‘host-pathogen’ interaction, remembering that decolonization can cause considerable collateral damage to the host microbiome.  
  • Dr Denise Cardo (CDC) delivered the SHEA Lectureship on HAI Science and Policy. CDC are streets ahead of any other government health agency in leading HAI science through the development of common, simple goals; accountability; transparency; efficiency and strategy. HAI science alone is not sufficient to influence policy; this requires congressional briefings, senate hearings and the use of the scientific and lay press. The recently published CDC threat report outlines how the (somewhat bleak) future may look. Most poignantly, Dr Cardo could not attend the conference and delivered her lecture remotely due to the government shutdown, which signals leaner times ahead for CDC.  
  • BUGG. Dr Anthony Harris (University of Maryland) presented the results of the ‘Benefits of Universal Glove and Gown’ (BUGG) study. This RCT with impressive compliance to screening, gloving and gowning showed a significant 40% reduction in MRSA but no significant reduction in VRE. The a priori primary outcome (a composite measure of MRSA and VRE acquisition) was non-significant. I’m generally not a fan of universal approaches, since compliance in the real world is likely to tail off when the spotlight of a large study fades. Indeed, poster 1696 showing a ‘dismal’ 20% compliance rate with gowning in the field sheds a shadow on the BUGG study.   
  • Dr Brad Spellberg (UCLA) gave a wake-up call on the future of antibiotics and resistance. Reflecting on the three things guaranteed in life (death, taxes and resistance), Dr Spellberg outlined the unfair fight between humans and bacteria: we’re outnumbered to begin with, and multiply much more slowly! Dr Spellberg’s recent papers in CID and NEJM outline the radical approach required to curb and reverse antibiotic resistance including embracing technology, rekindling R&D, preserving effective agents and exploring novel therapies. Dr Spellberg gave a fascinating insight from the 1960s revealing that it’s not the first time the antibiotic pipeline has dried. We need to learn from history and rekindle R&D before the pipeline dries completely. More importantly though, exploring non-antibiotic therapies, or novel applications of existing agents, has a more realistic chance of brightening the future of antimicrobial therapy.   

Infection Prevention 2013 Conference Report

Jon Otter (@jonotter) Conferences ,

ips-header2013

I have a long flight to San Francisco to enjoy, which provides a perfect opportunity to relax and write my report from Infection Prevention 2013 Conference (Sept 30th – Oct 2nd 2013, London). The abstracts from the excellent submitted scientific material have been published as a free supplement in the Journal of Infection Prevention.

Opening lectures – Tricia Hart, Dale Fisher, Michael Gardam, Hugo Sax and Martin Kiernan

Following a short opening address from newly appointed IPS patron Prof Tricia Hart, exhorting us to put our patients before the numbers, Prof Dale Fisher from Singapore took the stage to talk about gaining organizational buy-in. With seamless reference to ‘Pirates of the Caribbean’ throughout, most memorably “It’s not the problem that’s the problem; it’s your attitude to the problem that’s the problem” [Capt Jack Sparrow], Prof Fisher gave useful advice on gaining buy-in from all stakeholders, not just administrators. An interesting idea was to incentivize hand hygiene compliance by offering a substantial tax rebate. Another was to embrace the power of the media rather than running away scared. But, whatever you do, don’t be seen as a ‘rigid, dour zealot’.

Dr Michael Gardam from Canada was outstanding in his content (including perhaps the first ever hand gelogram) and delivery on using front line ownership to deliver patient safety. His resonating theme was ‘culture eats strategy for breakfast’. Dr Gardam drew a thoughtful parallel between healthcare and raising children: challenging, private, rewarding, unpredictable, fun. This illustrated the ‘individuality’ of healthcare; each patient is different and should be treated individually. Equally, to achieve effective culture change, you need to empower the changee.

Prof Hugo Sax from Switzerland challenged the traditional approach of: perform hand hygiene ‘education’ then if that fails, educate some more and if that fails, make education mandatory! A consideration of fundamental human limitations was helpful: our finite capacity to process information per time unit; we are more likely to behave when being observed; and physiological responses affect our behavior (e.g. olfactory cues). These so-called ‘human factors’ must be embedded in our approaches to promote hand hygiene compliance.

To round off the morning’s lectures, Martin Kiernan delivered the EM Cotteral Lecture, revealing the life and times of the urinary catheter. Typically animated and innovative (including live tweeting as he was speaking), Martin outlined the challenges surrounding urinary catheters, including non-infectious risks. There is a remarkable lack of data and heterogeneity of practice for such a high-risk healthcare intervention. Although not quite finishing on a song, Martin did finish on a poem.

Submitted oral presentations: hand hygiene compliance and MRSA control

Paul Apler (Deb Ltd) presented an electronic system for monitoring hand hygiene compliance. The numerator is accurate, with each pump of hand gel logged electronically, but the denominator is derived from an algorithm for anticipated hand hygiene opportunities. The initial data look great, but the success or failure of the system depends on the accuracy of the denominator, which may need some tweaking for new settings. It does seem that the subjectivity and Hawthorne effect of hand hygiene monitoring would be reduced or perhaps even eliminated through automating the process.

Carolyn Dawson (University of Warwick) gave an overview of her research considering triggers for hand hygiene, with overtones of Prof Sax’s opening lecture. Inherent (“urgh”) triggers are more powerful than elective (“taught”) triggers hence inherent activities result in better compliance. We need to harness these fundamental human factors to achieve the highest possible rates of compliance. Carolyn has written an engaging blog-report of Infection Prevention 2013, which includes more details on her research.

Next up, I presented some work on MRSA admission screening at St. Thomas’ in London. An informal poll of the audience revealed that, surprisingly, the majority thought that targeted screening would detect less than 50% of carriers. Our study calculated that reverting from universal MRSA admission screening to a targeted approach would result in 75% (almost 22, 000) less screens but 45% (262) undetected MRSA carriers admitted. Is this enough to reconsider scrapping universal MRSA screening and returning to a targeted approach?

Debbie Weston (Kent) experienced a sizable outbreak of mupirocin-resistant MRSA, affecting 144 patients over 10 months. Amongst other interventions, the team made a sensible switch from mupirocin to fusidic acid and octinisan for MRSA decolonization and screened staff for MRSA carriage. Five staff carriers were detected, which could have been a factor in the continuation of the outbreak. This outbreak brings into sharp focus the risk of universal application of mupiriocin to ICU patients in a recent US study.

Multidrug resistant Gram-negatives

An important forum for discussing the challenges presented by multidrug-resistant Gram-negatives began with Prof Peter Wilson (UCLH) summarizing:

  • Issues driving the “next MRSA”: antibiotic abuse in humans & animals; gastrointestinal carriage; complex, challenging sources; and rapid transmission.
  • [Scant] evidence for effective interventions: screening; isolation; staffing; enhanced disinfection (consider hydrogen peroxide vapour); antibiotic stewardship; ward closure (perhaps).
  • Research needs: gastrointestinal carriage rates; importance of imported cases; selective digestive decontamination (SDD); human vs. animal transmission; how best to improve cleaning.

Craig Bradley (Birmingham) then related his experience of controlling outbreaks of MDR A. baumannii highlighting the importance of environmental disinfection, and Alice Nutbourne (King’s, London) warned that empirical antibiotic therapy may be ineffective for an increasing proportion of Gram-negative sepsis cases.

Medical stats with Tim Boswell

Dr Tim Boswell (Nottingham) provided a useful, practical overview of how to tell whether an observed difference is due to chance. Covering theory, an overview and appraisal of available software and worked examples, this session provided a framework for understanding the difference between clinical and statistical significance.

Copper surfaces, “no-touch” automated room disinfection (NTD) and single rooms

Prof Tom Elliot (Birmingham) presented the impressive and ever-accumulating evidence for the introduction of copper surfaces in healthcare. Useful to note one cited paper from the 1980s showing that brass door handles were less likely to be contaminated than stainless steel ones, so the concept is hardly new. The data for copper surfaces are now impressive, with the Salgado study suggesting clinical impact. However, I still have questions over acceptability, durability and cost-effectiveness.

Gail Locock (Maidstone) then continued the estates theme with a view from her hospital, which is 100% single rooms. This iconic image perhaps best explains the reason why the switch to 100% single rooms was made, with the patients “so close tougher they could hold hands”. Whilst the infection prevention benefits of 100% single rooms are obvious, challenges include: patient visibility and associated safety, managing dementia, complacency, cleaning turnaround times, auditing compliance with hand hygiene and cohorting difficulties. Gail’s conclusion: pros and cons!

Prof Dale Fisher concluded the estates theme by addressing whether it is time to turn to “no-touch” automated room disinfection (NTD). Prof Fisher outlined the rationale for considering an NTD system; principally the ‘prior room occupancy’ data combined with the fact that conventional methods do not reliably eliminate pathogens. Several different NTD systems are available (mainly hydrogen peroxide vapour or aerosol, and ultraviolet C or pulsed-xenon), each with advantages and disadvantages. Technology can help, but you need to understand the limitations. In a way, NTD systems have redefined the standard for hospital hygiene, but workflows need to be adjusted if they are to be successfully implemented.

Submitted oral presentations: ‘Get Stoolsmart’ and hub contamination

The impressive and Twitter innovating Coventry IPS team gave an entertaining overview of their ‘Get Stoolsmart’ campaign, aiming to return clinical judgment to front line clinicians (with overtones of Dr Gardam’s opening lecture).

Dr Maryanne Mariyaselvam (Kings Lynne) found that 90% of needle-free IV connectors were contaminated with bacteria whereas only 33% of open hubs remained contaminated after flushing. What’s the answer? ”Scrub the hub” or new technology (including the connector impregnated with an antimicrobial under development by Dr Mariyaselvam and colleagues)?

Infection Prevention and Control in Japan – Prof Kobayashi

Prof Kobayashi (or ‘Kobayashi-sensei’!) provided a historical perspective on the development of an IPC programme in Japan. As a cardiac surgeon turned IPC champion, Prof Kobayashi has decades of experience to relate. Ultrasonic chlorhexidine baths for hand hygiene turned out to be a bad idea due to Gram-negative contamination, but the implementation of hand gels, link nurse programmes and temporary side rooms in Japan under the expert stewardship of Prof Kobayashi were years ahead of their time.

International Forum on Infection Prevention and Control

Internationally renowned speakers representing Asia (Prof Dale Fisher), the USA (Robert Garcia), Europe (Prof Hugo Sax) and England (Carole Fry) presented their biggest IPC successes and challenges:

intl session

It was encouraging to hear the experts celebrating their success, sharing ideas and embracing the challenges. From my viewpoint, the common challenge is the threat of CPE, which have the potential to spread globally like wildfire and make antibiotics virtually redundant.

Peter Hoffman on wipes

There’s been an explosion in the use of detergent and disinfectant impregnated wipes for hospital disinfection. Parents of young children in particular will understand the convenience of wipes over “wet bucket” approaches. But how do the data look in terms of efficacy? Peter Hoffman (PHE) outlined the challenges for wipes including: variations in microbial susceptibility, dealing with soiling, achieving adequate contact time with a small amount of wetting, large / intricate areas, choosing an appropriate active chemical and the dangers of sequential wiping transferring contamination. Importantly, Peter demonstrated that adding a sporicidal chemical to a wipe does not necessarily make a sporicidal wipe. Depressingly, it seems that choosing disinfectant wipes currently relies on manufacturers’ data using non-comparable testing. Conventional suspension tests and surface tests are meaningless for wipes so an accepted standard test for wipes (like this one from the Maillard Cardiff lab) is required urgently.

Keynote addresses – Jane Cummings, Aidan Halligan

The Chief Nursing Officer, Jane Cummings, spoke on unraveling and harnessing the potential of the complex ‘new’ NHS, aided by this useful infographic. The address included discussion on a new initiative: ‘6Cs Live’, which looks like an invaluable resource. The CNO concluded with a powerful patient-centred video entitled ‘Empathy’.

The video aptly introduced the theme of Prof Aidan Halligan’s address on rediscovering lost values in the NHS. Prof Halligan was disarmingly honest and forthright with the need to put patients first, poignantly citing Martin Luther King: “Our lives begin to end the moment we become silent about things that matter”. Focusing on empathy and compassion, and having the courage to challenge poor behaviour in a ward environment that can sometimes feel like a warzone is challenging and mistakes will be made. But try we must!

Submitted oral presentations – CPE at King’s and HPV at Tommies

Anita Verma (King’s, London) discussed the challenges of managing an outbreak of VIM-producing CPE on a paediatric unit affecting 11 patients in 2012. The outbreak response included the development of a detailed care plan, enhanced cleaning and transfer guidance for other hospitals. Despite several challenges (including poor adherence to IPC standards; suboptimal cleaning and disinfection; lack of awareness by caregivers, staff and visitors; and young patients in nappies), the outbreak was successfully controlled.

David Tucker (Guy’s and St. Thomas’, London) described a comparison between the length of time and cost of disinfecting rooms and bays using conventional methods of hydrogen peroxide vapour (HPV). Surprisingly, the HPV process time (including pre-cleaning) was only marginally longer for rooms and bays, and HPV was marginally more expensive for rooms and cheaper for bays. These findings are at odds with the general perception that HPV takes considerably longer and is much more expensive than conventional methods.

Clostridium difficile – search and destroy

Search – Dr Simon Goldenberg (Guy’s and St. Thomas’, London) addressed some problematic epidemiological definitions for C. difficile, which result in confusion and make true “CA-CDI” difficult to identify. Relatively recent data on C. difficile testing suggests that ‘you’d be better off flipping a coin than using some toxin EIA tests for CDI diagnosis’. Fortunately, DH diagnosis guidelines are now clear!

Destroy – Myth-busing Dr Jimmy Walker (PHE) provided some invaluable advice on choosing a sporicide active against C. difficile. Practically speaking, Dr Walker reminded us of the need for effective cleaning prior to disinfection for both disinfectant activity and aesthetics, and to look out for material compatibility problems when using sporicides. Specifying appropriate in vitro tests for sporcidies is challenging, but a 60 minute contact time is completely unrepresentative: you’d be lucky to achieve 6 minutes in the field; 6 second is probably more realistic. Dr Walker urged us not to be passive purchasers, but to check and challenge manufacturers’ (sometimes bogus) sporicidal claims.

Closing lectures – Barry Cookson, Phil Hammond, Didier Pittet and Julie Storr

Prof Barry Cookson delivered the Ayliffe Lecture on the past, present and future of MRSA. Prof Cookson described the 1970s as the decade of complacency, the 1980s of re-emergence, the 1990s of dawning realization, the 2000s of reactivity and the 2010s of uncertainty. My alternative view is: 1970s close shave; 1980s warning signs; 1990s unchecked; 2000s action, finally; 2010s ‘post’ MRSA era. The conclusion was to learn from the past to safeguard the future, with Prof Cookson remaining fearful of future failure if effective surveillance systems are not in place and maintained.

Dr Phil Hammond lit up the room with his insightful and, at times, downright hilarious commentary on speaking the truth to power (for example, his silencing of Andrew Landsley on Question Time), on not commoditizing healthcare; on restructuring the NHS; on dark stories about gagging whistleblowers; and on transparency. His summary: the ‘top-down’ restructuring of the NHS has failed; we need to develop care partnerships with our patients.

Newly appointed patron Prof Didier Pittet inspired us to begin with the end in mind, focusing on what we want to be and do, followed by final uplifting words from the Julie Storr, the IPS President.

Overriding themes

Infection Prevention 2013 provided some useful food for thought and discussion:

  • Try new ways to achieve culture change (for example, empowering your culture changees [Gardam], embracing the media [Fischer], and ‘putting the love back into infection prevention and control’ [the irrepressible Coventry IPC team]).
  • Where and when can automation help (monitoring hand hygiene compliance, terminal disinfection)?
  • What on earth do we do about MDR Gram-negatives, specifically CPE?
  • How to do more for less, maximize the opportunities of the ‘new’ NHS, whilst retaining compassion and empathy as core values?

ICPIC 2013 Conference Report

Jon Otter (@jonotter) Conferences ,

icpic2013_banner

My head is full and my wallet is light following an enjoyable week in Geneva for the 2nd ICPIC conference (25th – 28th June 2013). I missed out on the inaugural ICPIC in 2011, so I was pleased to make the 2nd ICPIC. I was a little concerned that it would be a “hand hygiene fest”, but the programme had a good balance between hand hygiene and other areas of infection prevention and control. The conference had more than 900 delegates from 89 nations with 97 oral presentations and 427 posters. Congratulations to the organizing committee for arranging an interesting and stimulating conference. The conference abstracts are freely available in an ARIC supplement and the slides can be purchased by contacting the conference organizers.

Sadly I was unable to clone myself and attend every session, but this will give you a flavour…

TUES 25TH JUNE – OPENING SESSION

The opening session focused on viruses with pandemic potential, with an impressive introduction from some Genève luminaries and a personal video from Dr Margaret Chan (WHO Director General).

David Heymann – The legacy of SARS

Dr Heyman presented an engaging first-hand overview of the early reports of SARS, illustrating that it was predominately a healthcare-associated infection. The legacy of SARS according to David Heymann:

  1. Improved global surveillance, for example, the advent of new surveillance methods and networks such as Google outbreak software.
  2. “Research ready” capacity. The emergence of new microbial threats promotes the requirement for a research network ready and waiting to swing into action, such as the Oxford University Institute for Emerging Infections.
  3. Economic impact. SARS cost Hong Kong 4% of GDP.
  4. Understanding animal reservoirs. HIV, SARS, Avian Influenza, MERS-CoV (?) and most other pathogens with pandemic potential have emerged from animal reservoirs.

Wing Hong Seto – Infection control before and after SARS

Dr Seto’s thesis was that the spread of SARS in hospitals was due to poor basic infection control practice, evidenced by his own institution’s low rate of staff infection stemming from his enthusiastic education and awareness campaign. Put another way, sloppy infection control cost healthcare professional’s their lives. Dr Chan stated earlier that “the thermometer won the war against SARS”, which resonated with Dr Seto’s “getting the basics right” message. The experience of SARS has resulted in an increase in focus on infection control in Asia region, resulting in more investment, higher infection control staff : bed ratios and centralized expert committees. However, there has been some overreaction too, with very expensive structural changes to hospitals without proper consultation. Dr Seto’s  enthusiasm truly lit up the stage.

Laurent Kaiser – influenza, coronavirus and emerging viruses: can we predict the unexpected?

A detailed overview of the genetic basis of these pandemic viruses that are associated with respiratory disease, aerosol / droplet spread, seasonal patterns, an RNA genome and rapidly emerging strains. The most interesting part of the talk for me was a consideration of how long it takes to “humanize” an animal virus. Whilst it’s difficult to be sure, it seems that it takes decades (or perhaps even centauries) for the necessary amount of recombination and mutation to occur for a virus to jump to humans and spread efficiently. For example, the H1N1 virus seems to be a mosaic of three viruses that may trace its origins to the 1918 pandemic. In this age of almost instant phylogeny, it may not be long before we can start watching viruses evolve in real time.

Keiji Fukuda – Latest news from MERS-CoV and H7N9

Dr Fukuda (WHO) gave a brief historical view of HIV, SARS, H5N1 and H1N1 to illustrate how a pandemic response looks in relation to the two current threats: H7N9 and MERS-CoV. A relatively small number of N7N9 (132) and MERS-CoV (70) cases have been reported so far, but their high mortality rates are alarming. Interesting unanswered questions:

  1. Are we at a suitable level of readiness to respond?
  2. How should we name pandemic viruses?
  3. How do we handle intellectual property that emerges during pandemic response?

Robert Wachter – Embedding infection prevention into medical training and the patient safety agenda

Dr Wachter explained that the patient safety movement began with infection control, but is now predominant in the US. Infection control should seek to embed itself within the core values of patient safety: quality and value. Dr Wachter explained some seminal moments in the development of the patient safety movement: the realization that medical errors were killing the equivalent of a jumbo jet of Americans each day and that zero is possible. Perhaps it would be helpful to see non-compliance with hand hygiene as a medical error?

WEDS 26th JUNE

Hyde Park corner debate: decrease of MRSA in the UK successful infection control or natural decrease? Stone v Wylie

Unusually, I found myself in disagreement with both the pro and con position presented in this debate!

Dr Stone laid out the case for the pro, largely based on this study. The main conclusions from the study were that MRSA bacteraemia and C. difficile rates fell in association with increased use of alcohol based hand products and soap, respectively, but MSSA bacteraemia rates did not fall; and that the Department of Health Implementation Teams and the Healthcare Act were associated with MRSA bacteraemia. It’s odd that rates of MSSA bacteraemia did not fall in conjunction with the increased use of alcohol based hand products. Also, I wonder whether a “breakpoints” type model would have been more suitable for this dataset?

Dr Wylie tried to convince us that the national reduction in MRSA was due to natural variation. He used the wax and wane of an unusual MRSA clone in the 1970s in Denmark as evidence that clones come and go. However, this was controlled by a focused national intervention, which rather defeated Dr Wylie’s argument. He offered three alternative plausible explanations:

  1. Incompletely understood interventions. [Not an alternative explanation per se, just saying that the decline was associated with the interventions, just not in the way that Dr Stone said.]
  2. Changes in host immunity.
  3. Changes in antibiotic use.

The one alternative explanation that Dr Wylie mentioned only in passing was increased use of chlorhexidine. This seems to be a much more plausible alternative explanation, so I’m not sure why this was not explored in more detail. It would also go some way to explain the relatively rapid decline in EMRSA-16 vs. EMRSA-15.

It just seems totally implausible that a national campaign to control MRSA would happen to correspond with a natural decline in MRSA. There will always be some uncertainty in interpreting epidemiological trends. Bradford-Hills famous criteria are oft cited, but worth noting that Bradford-Hill once said “my criteria cannot provide indisputable evidence – they help us to make up our minds”.

The impact of the US Veterans Affairs initiative: too nice to be true? Samore v Bonten

Dr Samore presented a robust case that the interventions throughout the VA network in the US explained the reductions in this NEJM study by Jain et al. He included a fair overview of the study limitations (principally no control group!). Interesting to note that the admission prevalence of MRSA was around 15% in the Jain study, compared with just 2% in London. Whilst there are important differences in the patient groups admitted to VA hospitals in the USA and a London teaching hospital, the magnitude of the difference is striking and may explain in part the large reductions in transmission achieved.

Dr Bonten took the opportunity to play devil’s advocate for several recent high-profile MRSA papers. I would have preferred a more detailed critique of the Jain et al. study, which was, after all, the subject of the debate! Dr Bonten’s group have published a reanalysis of the Jain data challenging their findings. Dr Bonten concluded, rather depressingly, that we still don’t have any proven interventions to control MRSA, apart from universal mupirocin and chlorhexidine, or “selective digestive decontamination”. Neither strategy get my vote due to the obvious risk of the development of resistance; we need to work harder to evaluate the most effective ways to target our precious remaining antibiotics in order to preserve their activity.

Antoine Andremont – The gut microbioma: mother of all troubles?

This fascinating lecture outlined the challenges associated with resistant bacteria in the gut. The gut houses a phenomonial number of bacteria (up to 1014 cfu per mL), predominantly non-pathogenic anaerobes (1010), other commensals (106-109) and resident enterobacteria (106). To qualify these numbers, the population of Paris is around 106 (number of enterobacteria) whereas the number of humans that have lived on earth for the past 3 million years is 1010 (number of non-pathogenic enterobacteria).

Antibiotic resistant enterobacteria can be found in the gut, comprising somewhere between 0 to 100% of all enterobacteria, which varies over time with diet and antibiotic usage. The presence of resistant enterbacteria is likely to result in widespread shedding into the environment based on VRE data.

The carriage of resistant bacteria in the gut is probably impossible to eliminate, but could be addressed by the following:

  1. Reduce the use of antibiotics.
  2. Increase hygiene and sanitation.
  3. Decolonization (although attempts to decolonize using antibiotics and probiotics have failed thus far).
  4. Moderate counts of resistant bacteria in the gut. There are several approaches here, for example the co-administration of a recombinant enzyme to inactivate antibiotics in the gut or the use of an “antibiotic sponge”.

George Daikos – The how’s and where’s of colistin resistance

Dr Daikos explained how polymyxins have been ‘reinvented’ to tackle multidrug-resistant Gram-negative rods, citing data from this Medscape report:

Colistin interest

The antibiotic works through electrostatic interaction with the cell membrane predominately via lipopolysaccharides which facilitates the update of colistin and subsequent cell death. Resistance can be intrinsic, adaptive or acquired, and heteroresistance has been reported. Heteroresistance could be greatly underreported: a recent SENTRY study found that 23% of multidrug resistant Acinetobacter were heteroresistant to colistin.

Colistin resistance is emerging fast in certain areas; 23% of K. pneumoniae are now resistant to colistin in Greece. The fact is, we still have a lot to learn about how to use colistin most effectively, it’s mode of action, resistance mechanisms and how to detect reduced susceptibility in the clinical lab.

Matthew Samore – C. difficile in the community: community-onset or silent reservoir?

Dr Samore began with some entertaining analogies to illustrate the various ways to understand the interchange between hospital and community C. difficile: Gwyneth Paltrow in Contaigon, an Iceberg, a Straw Man and a Bathtub! Several studies identify apparently rising rates of CDI in the community yet carriage by healthy community members remains rare (2-3%). Combined with the finding that C. difficile colonization increases with length of stay make me think that CDI remains a predominantly hospital problem with some community-onset cases. Indeed, the recent JAMA Intern Med study of apparent CA-CDI only evaluated healthcare-exposure for three months prior to the CDI episode, and most patients had some healthcare exposure. I was surprised that Dr Samore did not mention high rates of carriage in neonates, which seems to be a genuine community-based reservoir doubtless resulting in a background of community acquisition of C. difficile.

There’s perhaps a parallel with MRSA here. For a long time, people talked about “community-acquired” MRSA, when it was really MRSA transmitted in the hospital manifesting in the community. However, there did come a phase shift in the epidemiology of MRSA with the emergence of distinct CA-MRSA strains that began to transmit outside of hospitals. So, we shouldn’t rule out CA-CDI as a possibility, but I don’t think we’re there yet.

Walter Zingg – C. difficile control in the hospital

Dr Zingg considered the various factors in the transmission of C. difficile: contamination of patients’ skin, hands, air and surfaces; proximity to other patients and colonization pressure. The control interventions highlighted were isolation, hand washing, single use thermometers, environmental disinfection using a sporicide (including adjunctive hydrogen peroxide vapour where feasible) and antibiotic restriction. I was surprised not to hear of the role of molecular diagnostics in C. difficile control. The switch to more accurate molecular diagnostics has facilitated improved identification of infected patients, and hence more successful isolation.

Innovation Academy

Or should I say, the ‘Infection Control Dragon’s Den’. Just like the TV show, 15 innovations were granted a 3 minute pitch followed by two minutes of quick-fire questioning from the expert panel and audience. Prof Pittet ensured that each presenter stuck to their 3 minutes, which was entertaining in itself. Five finalists were selected for an extended pitch the following day and a winner selected by the expert panel. A classic quote from Einstein set us off: “If at first the idea is not absurd, it is not good”! I’ve listed the finalists below along with some details of all 15 pitches:

  1. The winner: ‘A novel immediate pre-operative decolonization strategy reduces surgical site infections.’ Pre-operative decolonization using photodisinfection combined with chlorhexidine bathing. High compliance, well tolerated and saved money. My only problem is that it was difficult to delineate the relative impact of photodisinfection (novel innovation) from chlorhexidine (already well established). Nonetheless, a worthy winner!
  2. Second place: ‘A novel antiviral technology for air filtration.’ An external antiviral layer for masks. The agent is only effective against enveloped viruses and the need was not well defined. Is this to prevent penetration of infected viruses through the mask or to reduce the risk of hand contamination when removing the mask?
  3. Third place: ‘A novel antibacterial material for transparent dressings.’ A small trial (n=10) of a polyurethane dressing with antimicrobial properties.
  4. Fourth place: ‘Can Dav132, a medical device targeting an adsorbent to the late ileum, decrease significantly the impact of antibiotics on the fecal microbiota?’ A medical device to “mop-up” antibiotics in the gut with huge potential to suppress resistant gut flora.
  5. Fifth place: ‘Infection Control Enclosure (ICE) pod: meeting the need for more single rooms’. [COI – I am listed as a co-author on this one!] A way to increase single room capacity in a multi-occupany bay setting.

The other pitches:

  • ‘Reduction of resistance by sublingual administration of antimicrobials.’ A gutsy musical presentation of an old paper from the 1970s. The only problem was, not a shred of data to support the innovation!
  • ‘A new generation of hybrid biomaterials for antimicrobial medical devices.’ Impregnated silicon for medical devices to reduce bacterial adhesion.
  • ‘Electronic hand hygiene monitoring for the WHO 5-moments method.’ An automated way to monitor hand hygiene compliance by placing a chip in each dispenser to measure usage in real-time and compare with expected usage patterns generated by an algorithm.
  • ‘Evaluation of the efficacy of a novel hydrogen peroxide cleaner disinfectant concentrate.’ ‘Accelerated’ hydrogen peroxide is an impressive product, but it’s been around for a long time so has no place in the innovation academy!
  • ‘A new genre of surface disinfectant with long residual bactericidal activity.’ A polymer antimicrobial surface film that can be impregnated with various antimicrobials (I think – wasn’t particularly clear on this point)!
  • ‘Development of an electronic dashboard to assist surveillance’. The e-dashboard ticks some important boxes for me, not least because it’s free! However, how does it compare with proprietary systems in terms of functionality?
  • ‘Combining electronic contacts data and virological data for studying the transmission of infections at hospital.’ Tagging patients and staff with RFID badges to track movements and then trace proximity (though not contact per se). Useful Harry Potter “Marauders’ Map” style technology.
  • ‘New holistic approach to determine the infection risk profile of a hospital; visualized in an easy-to-read plot’. A way to produce a visual, fairly intuitive ward-level report to easily identify areas for improvement. A useful tool, but lacks the novelty of other contenders.
  • ‘Organisational transformation – the application of novel change techniques & social media understanding to motivate infection-prevention activists.’ A pitch from the Infection Prevention Society using collaboration focused on social media to effect organizational change following a “pre-mortem” self-assessment.

I particularly enjoyed the Innovation Academy. The Dav132 antibiotic gut “sponge” got my vote as the most important innovation.

THURS 27th JUNE

Meet the experts (Boyce and Dettenkofer): Controversial issues about environmental cleaning and disinfection

Dr Dettenkofer began with a framework for understanding hospital cleaning and disinfection needs. His position is that low-level disinfection is the main requirement. However, the presence of C. difficile spores means that a sporicide (i.e. high-level disinfectant) is necessary on occasion. So, is the requirement for hospital disinfection high or low level disinfection? Dr Dettenkofer talked briefly about the debate over whether surface disinfection is required at all in hospitals, when cleaning (without the use of a chemical disinfectant) is often sufficient. Interesting to hear that Dr Dettenkofer has begun to use a liquid hydrogen peroxide disinfectant in his hospital. Finally, the question of whether a two-step process (cleaning followed by disinfection) is necessary. It’s difficult enough to get good compliance with one round of cleaning or disinfection, let alone assuring adequate coverage of first a cleaning agent, then a disinfectant. Effective combination products are required urgently.

Dr Boyce discussed:

  • What is the ‘best’ surface disinfectant? He considered aldehydes, QACs, phenolics, chlorine releasing agents, hydrogen peroxide and peracetic acid. The conclusion: all have pros and cons!
  • So, how to assess cleaning performance? Visual assessment, microbiological cultures, ATP or fluorescent markers. These are not mutually exclusive and, again, all have pros and cons.
  • Finally, which “no-touch” room disinfection system to use? Hydrogen peroxide vapour, aerosolized hydrogen peroxide, UVC, pulsed-xenon UV and other systems are available. You guessed it, all have pros and cons!

Control of hyperendemic Carbapenem-resistant Enterobacteriacae

Abdul Ghafur – The Indian perspective

A passionate presentation by Dr Ghafur beginning with 50% attributable mortality in his neutropaenic patients due to CRE resulting from carbapenem and colistin abuse; mortality for pan resistant CRE approached 100%. Dr Ghafur discussed some of the underlying problems in India: poor sanitation, high rates of carriage of resistant bacteria (80% CR Acinetobacter and 40% CR Klebsiella), reflecting on the fact that tight local antimicrobial prescription will not save you if everyone else is sloppy. How to treat pan-drug resistant CRE? “Pentatherapy” using a 5 drug cocktail and a prayer. (Actually, there is probably some synergy between colistin and other antibiotics so pentatherapy isn’t as daft as it sounds.)

Yehuda Carmeli – An Israeli perspective

Israel experienced a dramatic initially clonal national outbreak of CRE (KPC CC258) in 2006. Analysis of data from the outbreak indicated that compliance with cohorting correlated tightly with CRE transmission; more data that getting the basics right works. The risk-based screening that was implemented detected a low prevalence of carriage (5% from long-term care facilities, 0.5% from other high risk groups) but was considered worthwhile to prevent outbreaks. Dr Carmelli raised several points for discussion:

  • Media interest. It seems to me that the media can be a friend or foe in dealing with outbreaks and wider healthcare issues. If left unbriefed, they will be a foe. But if properly briefed, they can be a powerful ally.
  • Emergence of different CRE genes (OXA-48 and NDM-1) in Israel with different epidemiological associations than KPC.
  • Dealing with the long-term care facility reservoir.
  • Non-compliance with basic infection control.
  • “Eye off the ball” syndrome, where hospital administrators only respond to current threats.

The national successful response in Israel is an encouraging success story. However, Israel has a population of 8 million, with only 31 hospitals. Can successful national control strategies be implemented in larger countries with an inferior healthcare infrastructure and national debt problems such as Greece and Italy?

Achilles Gikas – The Greek perspective on CRE: from surveillance to control

Dr Gikas described the development of the CRE epidemic in Greece with overlapping outbreaks of VIM and KPC carriers, and how CRE is now a “frequent flyer” travelling around the world. Reassuringly, there are some local success stories in Greece where focused interventions have reduced rates of CRE, but, mindful of Dr Kulakkattil’s comment that “no hospital is an island”, concerted national efforts are required to grasp this rampaging Hellenic bull by the horns.

Environmental decontamination with hydrogen peroxide vapor – does the effect evaporate over the Atlantic? Perl v Huttner

Having spent some 10 years researching this particular topic, needless to say I was looking forward to this debate. The debate was not particularly well framed. Was this about most of the studies of HPV (and all of the controlled studies with a clinical outcome) coming from US hospitals? Or that many European countries have a lower proportion of single rooms, which makes the application of HPV more challenging? Or a wider debate about whether to consider “no-touch” disinfection (NTD) systems at all? I felt that Dr Perl addressed the more general questions while Dr Huttner focused on HPV studies, which rather took the wind out of the sails of the debate.

Dr Perl summarized data that pathogens are shed into the environment, they survive for extended periods, persist despite conventional cleaning and disinfection and improving conventional methods helps, but transmission continues. Hence, NTD systems and specifically HPV are warranted in some circumstance. Dr Perl acknowledged the lack of RCTs but showed convincing data that HPV eliminates pathogens from surfaces and reduces transmission, and fulfils Bradford-Hill’s criteria of causation.

Dr Huttner began like Dr Perl by considering some things that evaporate over the Atlantic: big cars, big guns and flavoured coffee to name but a few! His American wife gives him an unusually sharp perspective on trans-Atlantic issues. Dr Huttner had clearly done his homework and read the various HPV studies in detail. He presented a series of good points, although I didn’t feel that he constructed a particularly coherent argument. To address some specific points:

The short debate (30 mins) did not allow time for the authors to present a rebuttal, which was a shame, but it was a stimulating session.

FRI 28th JUNE

Controlling ESBLs – a global perspective

Jean-Christophe Lucet – Europe

Dr Lucet began by demonstrating a startling increase in the proportion of invasive isolates that carry ESBLs in Europe comparing 2005 with 2011. He reviewed data that ESBL-producing K. pneumoniae is much more likely to be transmitted in hospitals than ESBL-producing E. coli, perhaps due to an increased capacity for environmental survival. Effective interventions are difficult to recommend due to lack of RCTs, outbreak settings (and regression to the mean), publication bias and control bundles. However, Dr Lucet concluded:

  • Hand hygiene: yes.
  • Active surveillance cultures and contact precautions: equivocal.
  • Cohorting: yes during outbreaks.
  • Environmental control: less important than for other pathogens.
  • Selective digestive decontamination (SDD) / universal use of chlorhexidine: equivocal. My view is that SDD should not be used – the indiscriminate use of antibiotics will drive further resistance.

Wing-Hong Seto – Far East / Asia

Carriage rates of ESBLs in E. coli and K. pneumoniae are alarmingly high in parts of Asia, reaching >50% in India and Vietnam. Dr Seto suggested that single room isolation is more important for Gram-positive vs. Gram-negative bacterial pathogens based on relatively higher recovery of Gram-positive bacteria from the hospital environment. However, lactose non-fermenting Gram-negatives such as Acinetobacter seem to ‘mimic’ Gram-positive bacteria in terms of their environmental survival, and even the Enterobacteriaceae can survive for days to weeks to months on surfaces. So, I would argue that priority for single room isolation should be dictated by an assessment of local epidemiology and risk, not the survival properties of various bacteria.

Andrew Stewardson – Australia

Carriage rates of ESBL-producing bacteria are lower in Australia than in nearby Asian countries (<10% in the hospital population and <5% in the community). Dr Stewardson presented some interesting Australian data showing that rigorous implementation of standard precautions and antibiotic restriction programmes can result in impressive reductions of ESBL producing K. pneumoniae in hospitals.

Final reflections

My first ICPIC was an enjoyable experience. Highlights included the opening session learning lessons from SARS, the entertaining innovation academy and some grim updates on the ‘rampaging Hellenic bull’ that is CRE. Regretfully, I didn’t get to see a single poster and missed few concurrent sessions (including the review of best papers by Eli Perencevich and Andreas Widmer – they’ve published their slides here). Of all the analogies presented at the conference, I think the most useful was the ‘Infection Control Football Club’ by Dr Sheldon Stone. Hand hygiene is the goal keeper (i.e. last line of defence). But you won’t have a winning football team with just a goal keeper. No matter how good they are, they will never stop every shot.