Acinetobacter contamination: is anywhere safe?

A study from New York City describes an environmental survey of contamination with antibiotic-resistant Gram-negative bacteria on surfaces in the community. The authors hypothesise that resistant Gram-negatives could be carried by staff, patients and visitors beyond the confines of the hospital.

Almost 500 environemntal samples were collected from surfaces in the public areas of six hospitals and surrounding communities (<1 mile from the hospital) (443 samples), with a further surfaces from communities >1.5 miles from any hospital as a control (50 samples). A total of 70 GNR were identified (Figure), mostly fairly inoccousous species from a human disease viewpoint. However, some potential human pathogens were identified (Table).

Figure: breakdown of Gram-negative rods identified from surfaces in public areas of the hospital and surrounding community.GNR contam

Table: potential human pathogens identified from surfaces in public areas of the hospital and surrounding community.

n % Species
15 3.0 Acinetobacter baumannii
3 0.6 Citrobacter freundii
2 0.4 Escherichia coli
2 0.4 Stenotrophomonas maltophilia
1 0.2 Enterobacter cloacae

Some other important findings:

  • All of the A. baumannii isolates were resistant to ceftazidime, and one was resistant to imipenem (i.e. carbapenem-resistant). Eleven of the 15 were clonally related to one another and to a patient isolate from one of the hospitals.
  • One of the S. maltophilia isolates carried an integron-encoded VIM carbapenemase, which is potentially transmissible to other Gram-negative species (including Enterobacteriaceae).  
  • Each sample was cultured in an enrichment broth, and the broth was probed for the presence of a range of beta-lactamase genes (including ESBLs and carbapenemases). No beta-lactamases were detected (other than the S. maltophilia isolate). I suspect the picture would have been rather difference in New Dehli!
  • Although the survey included both surfaces in public areas of hospitals and in the community, it seems that most of the A. baumannii were identified on surfaces in the community.

So, is it a surprise to see environmental contamination with antibiotic-resistant Gram-negatvies on touch-surfaces in the community? Not really, A. baumannii in particular can survive on surfaces for ages, and ‘mimics’ Gram-positive bacteria in terms of its environmental longevity (i.e. months / years). That said, I performed a similar study looking for MRSA on touch surfaces in the community in London, and didn’t find any. More importantly, do we need to do anything about this? As the authors state, A. baumannii can be virtually impossible to eliminate from hospital surfaces without resorting to hydrogen peroxide vapour. So is it time to roll hydrogen peroxide vapour into your local Pizza Hut? Clearly not. You’d hope that cleaning and disinfection protocols, which should deal with this sort of contamination, are already established in these public places, but it would be prudent to reinforce these basic hygienic practices. Also, I agree with the authors that these findings represent and opportunity for the promotion of hand hygiene in the community.

The authors use strong words to describe NYC as ‘plagued’ with resistant Gram-negative bacteria, and a ‘dismal failure to control A. baumannii.’ If this epidemic continues, we can expect to see the focus of the problem – and the target for our interventions – shift from the acute hospital setting to encompass the community.

CRE and friends: Q&A

the end of antibiotics_smallI gave the first in a three part webinar series for 3M last night, and you can download the slides here. Also, you can access the recording here (although you will need to register to do so).

The webinar was attended by >200 participants from across the US. I tried to outline the three pronged threat of multidrug-resistant Gram-negative rods (especially CRE) in terms of high levels of antibiotic resistance, stark mortality (for invasive disease) and the potential for rapid spread (including the prospect of establishing a community reservoir). Then, I gave an overview of the US and European picture in terms of CRE prevalence. Finally, I discussed the diagnostic challenges and options.

The most interesting part for me was the response to the questions that I threw out to the audience (see Figure below).

Figure: response to the questions from the 200 or so participants.

CRE and friends charts q1

CRE and friends charts q2

CRE and friends charts q3

I was somewhat saddened but not especially surprised that the difference between CRE and CPE was not clear in the minds of most participants. I appreciate that this may be in part due to the fact that ‘CPE’ seems to be used more commonly in Europe than in the US. But this is an international problem, so we need to get our terminology straight in our globalised world.

It was encouraging to hear that most US hospitals have had no CRE, or only one or two cases. However, 11% of the participants see CRE regularly, with cases unconnected to outbreaks. This is a concern, and suggests that CRE has become established in these areas. Indeed, a recent study from 25 Southeastern US community hospitals reports a 5-fold increase in the prevalence of CRE since 2008, suggesting that CRE is becoming established in some parts of the US.

Most participants didn’t know which method was used by their clinical laboratory to detect CRE. I’m not sure whether or not this is a problem. You’d hope that laboratorians to know that they’re doing!


The webinar included time for a Q&A from the audience, which covered the following:

  • “How long to resistant Gram-negatives survive on surfaces?” This depends on which Gram-negative you’re talking about. Non-fermenters, especially Acinetobacter baumannnii, have remarkable survival properties measured in months and years. Enterobacteriaceae have a somewhat lower capacity to survive on dry surfaces, but it can still be measured in weeks and months, rather than hours and days.
  • How important is the environment in the transmission of resistant Gram-negatives?” Again, this depends on which Gram-negative you’re talking about. For A. baumannii the answer is probably “very important” whereas for the Enterobacteriaceae the answer is more like “quite important”.
  • “What would you recommend for terminal disinfection following a case of CRE?” I would recommend the hospitals usual “deep clean” using either a bleach or hydrogen peroxide disinfectant, and consideration of using an automated room disinfection system. I would not be happy with a detergent or QAC clean; we can’t afford to leave an environmental reservoir that could put the next patient at risk.
  • “Are antibiotic-resistant Gram-negative bacteria also likely to be resistant to disinfectants” There’s been a lot of discussion on this issue, but the short answer is no. I’d expect an antibiotic-resistant Enterobacteriaceae isolate to be as susceptible to disinfectants as a corresponding antibiotic-susceptible isolate.  
  • “Should patients with CRE be left to the end of surgical lists, and are is special instrument reprocessing required?” There is no need to implement special instrument reprocessing – follow your usual procedures here. Should CRE patients be left to the end of surgical lists? It would be prudent if possible, but don’t lose sleep over it.
  • “Are any special decontamination measures necessary for endoscopes?” A number of outbreaks of CRE have been reported associated with endoscopy. However, usual endoscope reprocessing methods should be sufficient to deal with CRE, provided they are done correctly!
  • “How do you lessen your chances of acquiring CRE?” Healthy individuals lack the risk factors for CRE infection (although CRE can occasionally cause infections in the community). Thus, the personal protective equipment (PPE) specified for contact precautions (gloves and gowns) combined with rigorous hand hygiene are sufficient to protect healthcare workers.
  • “Are toilet seats in India safe?” What a question! I guess we’re talking about an organism with gastrointestinal carriage, so it’s probably that contamination of the toilet seat will occur. It may be prudent to clean or disinfect toilet seats in India before using them. Either that, or squat!
  • “Can you expand on isolation protocols?Firstly, ensure that patients infected or colonized with CRE are assigned a single room (not so relevant in the US, but important in healthcare elsewhere). Then, make sure you have appropriate policy and supply of PPE (principally gloves and gowns). Consider implementing ‘enhanced precautions’, including a restriction of mobile devices. Finally, consider cohorting patients and staff to the extent possible. You can read more about NIH’s approach to isolation here.
  • “Can patients who are colonized with CRE be deisolated?” This is a tricky one, which is basically an evidence free zone and hence an area of controversy. Longitudinal studies show that carriage of CRE can persist for months or even years, so it makes sense to continue isolation for the duration of a hospitalization and not bother with repeated swabbing. At the time of readmission, it makes sense to take a swab to see whether colonization continues. If not, then it may be rational to deisolate them – perhaps after a confirmatory swab. I wish I could be more decisive here, but the evidence is scant.

Do please let me know if you have anything to add to this Q&A!  

Are contaminated hands more important than contaminated surfaces?

Cast your minds back to the 2010 HIS conference in Liverpool and Drs Stephanie Dancer and Stephan Harbarth debating the relative importance of contaminated hands vs. surfaces in the transmission of MDROs. I don’t remember the details of the debate, but I do remember the surprising lack of evidence on both sides. Back then, we had no real way to quantify the contribution of the environment to the transmission of MDROs, or to measure the relative importance of contaminated hands vs surfaces. The evidence has evolved to the extent that a group of US researchers have published a paper modeling the relative contribution of contaminated hands vs surfaces to the transmission of MDROs. I like the paper very much, and the authors should be congratulated for breaking new ground in understanding transmission routes of MDROs.

The model simulates patient-to-patient transmission in a 20-bed ICU. The values of the parameters that were used to build the model were sensible on the whole, although baseline hand hygiene compliance was set at 57-85% (depending on staff type and whether at room entry or exit), which seems rather generous when baseline environmental cleaning compliance was set at 40%. Also, the increased risk from the prior room occupant for MRSA and VRE was set at 1.4 (odds ratio) for both, whereas it probably should be higher for VRE (at least >2) based on a number of studies.

100 simulations were run for each pathogen, evaluating the impact of step-wise changes in hand hygiene or terminal cleaning compliance. The key finding is that improvements in hand hygiene compliance are more or less twice as effective in preventing the transmission of MDR A. baumannii, MRSA or VRE, i.e. a 20% improvement in terminal cleaning is required to ‘match’ a 10% improvement in hand hygiene compliance. Also, the relationship between improved terminal cleaning and transmission is more or less linear, whereas the relationship with hand hygiene shows relatively more impact from lower levels of hand hygiene compliance (see Figure, below). Thus, the line for improving hand hygiene or terminal cleaning would intercept and indeed cross over at around 40 or 50% improvement. The implication here is that hand hygiene is more important at low levels of compliance, whereas terminal cleaning is more important at high levels of compliance (although don’t forget the difference in the baseline compliance ‘setpoint’.

hand v env Figure. The impact of percentage improvement in hand hygiene or terminal cleaning on the transmission of MDROs. Dotted line represents my not-very-scientific extrapolation from eyeballing the data.

The study raises some important issues for discussion:

  • It had not struck me before that the level of compliance with hand hygiene and environmental cleaning are nearly identical, on average, with only around 40% of hand hygiene opportunities met and 40% of environmental surfaces cleaned if human beings are left to their own devices. Both of these figures can be improved considerably with concerted effort, but the sustainability of these improvements without continued effort is rather disappointing.
  • The models address MRSA, VRE and MDR A. baumannii transmission. It’s a little strange that C. difficile was not included, since most consider this to be the ‘most environmental’ hospital pathogen.
  • The study only modeled the impact of terminal cleaning, whereas daily cleaning seems likely to also be an important factor (which is acknowledged as a limitation in the discussion). This seems especially important in light of data that touching a contaminated surface carries approximately the same risk of hand contamination as touching an infected or colonized patient.
  • I am not certain that this assumption makes logical sense: ‘thoroughness of cleaning of 40% implies that, given a single cleaning opportunity, there is a 40% probability that the room will be cleaned sufficiently well to remove all additional risk for the next admitted patient’. This would be true if cleaning was performed to perfection 4 times out of 10, whereas it is actually performed with 40% efficacy 10 times out of ten! To this end, it would be interesting to insert the various automated room disinfection systems into the model to evaluate and compare their impact. Indeed, hydrogen peroxide vapour has been shown to mitigate and perhaps even reverse the increased risk from the prior room occupant (for VRE at least).
  • In the introduction, the authors comment that ‘A randomized trial comparing improvements in hand hygiene and environmental cleaning would be unethical and infeasible.’ I see what they’re saying here, in that it would be unethical by modern standards to investigate the impact of no hand hygiene or no environmental cleaning (although this has been done for hand hygiene), but it would be useful, feasible and ethical to perform a cluster RCT of improving hand hygiene and environmental cleaning. It would look something like the classic Hayden et al VRE study, but with an RCT design.
  • How useful is mathematical modeling in informing decisions about infection prevention and control practices? This is not the first mathematical model to consider the role of the environment. For example, researchers have used models to evaluate the relative importance of various transmission routes including fomites for influenza. But a model is only as good as the accuracy of its parameters.
  • Does this study help us to decide whether to invest in increasing hand hygiene or terminal cleaning? To an extent yes. If you have awful compliance with both hand hygiene and terminal cleaning at your facility, this study suggests that improving hand hygiene compliance will yield more improvement than improving terminal cleaning (for A. baumannii, MRSA and VRE at least). However, if you have high levels of compliance with hand hygiene and terminal cleaning, then improving terminal cleaning will yield more.

In general, this study adds more evidence to the status quo that hand hygiene is the single most effective intervention in preventing the transmission of HCAI. However, in a sense, the hands of healthcare workers can be seen as high mobile surfaces that are often contaminated with MDROs and rarely disinfected when they should be!

Article citation: Barnes SL, Morgan DJ, Harris AD, Carling PC, Thom KA. Preventing the transmission of multidrug-resistant organisms: modeling the relative importance of hand hygiene and environmental cleaning interventions. Infect Control Hosp Epidemiol 2014; 35: 1156-1162.

ESCMID MDR-GNR guidelines

ESCMID experts recently released comprehensive guidelines for the control of MDR-GNR. Working with a limited evidence base, the experts managed to compile a coherent set of guidelines with graded recommendations. Given the important differences in the epidemiology of the various species and resistance patterns of MDR-GNR, this is really a 6-for-the-price-of-one set of guidelines, with separate recommendations for: ESBL-producing Enterobacteriaceae, MDR K. pneumoniae, MDR A. baumannnii, MDR P. aeruginosa, Burkholderia cepacia and Stenotrophmonas maltophilia.

Five key interventions are identified: hand hygiene measures, active screening cultures, contact precautions, environmental cleaning, and antimicrobial stewardship. ‘Selective’ decontamination using antibiotics, topical ‘source control’ using chlorhexidine, and infrastructure / education are also reviewed. Which of these is most important? Most studies included multiple interventions simultaneously, so it’s difficult to tell and it will probably depend on species and setting.

MDR-GNR controlFigure: The cornerstones of MDR-GNR control (but we don’t have enough data to say which is most important, and which are redundant).

A few points for discussion:

  • We still don’t really know what works to control MDR-GNR. Reflecting on my recent blog on influenza transmission, where the relative importance of various transmission routes varies by context, this also seems likely for MDR-GNR. The relative importance of say, environment vs. hands, is likely to vary by setting for a given MDR-GNR species. This makes definitive guidelines difficult to write!
  • The guidelines begin with a useful review of the differing transmission routes for the various MDR-GNR species. This shows that person-to-person spread of Klebsiella species and some other Enterobacteriaceae (such as Enterobacter species and Serratia species) seems to be more important than for E. coli. The non-fermenters A. baumannii and P. aeruginosa have some fundamental differences with one another and with the Enterobacteriace in terms of transmission routes. If I had to rate the importance of patient-to-patient spread vs. other routes for the various MDR-GNR I would say A. baumannii > Klebsiella species > other Enterobacteriaceae > P. aeruginosa > E. coli. But don’t hold me to it!
  • It seems odd that all of the recommendations are ‘strong’ but the evidence is graded mainly as ‘moderate’, ‘low’ or ‘very low’. Perhaps more ‘conditional’ recommendations would be a better fit with the quality of the evidence?
  • The recommendations are stratified by organism-group and setting (endemic or outbreak), which is a workable approach. What you’d do in an outbreak does probably differ from what you’d do in an endemic setting.
  • There’s a useful recommendation for the identification of a new CRE case to prompt contact tracing and enhanced local surveillance, in line with PHE and CDC recommendations.
  • There’s a little fence sitting when it comes to a recommendation for active surveillance cultures in the endemic setting: ‘the implementation of ASC [active surveillance cultures] should be suggested only as an additional measure and not included in the basic measures to control the spread of MDR-GNB in the endemic setting.’ Still not clear whether this is a recommendation for or against ASC in the endemic setting!
  • I was surprised not to see a recommendation to use a disinfectant to help bring A. baumannii outbreaks under control. I appreciate that there is little evidence in endemic settings, but controlling the environmental reservoir does seem to be important in controlling A. baumannii outbreaks.
  • The remit of the guidelines is for adult patients, but what to do on neonatal units and in paediatrics?
  • The guidelines are restricted to hospitalized patients, but what about long-term acute care facilities (that are riddled with CRE in some parts of the world) and long-term care facilities (that have an unknown but probably sizable burden of resistance)?
  • The searches were restricted to MDR bacteria according to ECDC criteria, but what about all those literature on preventing the transmission of resistant (but not multiresistant) and sensitive GNR? If something works to control GNR, there’s no reason why it shouldn’t work to control MDR-GNR (except, perhaps, for antibiotic stewardship).
  • Finally, if all else fails (and only then), consider closing the ward!

In summary, these guidelines are very well written and will provide useful guidance for those on the front line try to deal with endemic and epidemic MDR-GNR. However, above all else, they highlight the need for high-quality studies telling us what works to control MDR-GNR.

Article citation: 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.

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

 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.

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

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.


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

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.

Busy hospitals, contaminated surfaces and the acquisition of Acinetobacter baumannii

acinetobacterPhoto: Acinetobacter on MacConkey by Iqbal Osman.

Guest bloggers Dr. Rossana Rosa and Dr Silvia Munoz-Price write: The relationship between patients and their hospital environment is obvious yet intangible. What do we mean by environment? We are talking about the room, and objects within the room such as bedside tables, bedrails and IV pumps. In our study, which was published in the recent ICHE special edition, we found when patients are exposed to rooms contaminated with Acinetobacter baumannii they have an increased risk of acquiring this organism during their index admission. This association remained strong even after controlling for other variables.

In a previous study1, we addressed the other side of the equation, and reported the high degree of contamination detected in the rooms of A. baumannii positive patients. We found that the paired isolates had similarity by PFGE of at least 94.8% with each other, thus suggesting a direct contamination of the environment from the A. baumannii positive patient occupying the room. Put in perspective, the results of these two studies highlight how close, dynamic and interactive is the association between patients and the hospital environment.

Interestingly, we found two variables to be ‘effect modifiers’. An effect modifier is a variable that differentially modifies the observed association between an exposure and an outcome. Despite finding a very strong association between exposure to a contaminated environment and acquisition of A. baumannii in the whole cohort, this association was rendered non-significant when evaluated in sub-groups admitted either to a unit with high colonization pressure or admitted to the trauma intensive care unit. This is relevant because colonization pressure has been shown to play a role in the horizontal transmission of CRE2, as well as VRE3, MRSA4 and C. difficile5. This poses the question of whether contamination of the environment could be primarily a result of the colonization pressure within a unit, to the extent of reaching a threshold after which most of the surfaces in a unit will be contaminated.

The good news is that the exposure to a contaminated environment should be a modifiable risk factor for the acquisition of CRE and MDRO. Active surveillance cultures can be performed to screen for carriers, colonization pressures can then be estimated for each unit, and high touch surfaces can be determined and targeted for cleaning.


1. Munoz-Price LS, Namias N, Cleary T, et al. Acinetobacter baumannii: association between environmental contamination of patient rooms and occupant status. Infect Control Hosp Epidemiol 2013;34:517-520.

2. Swaminathan M, Sharma S, Poliansky Blash S, et al. Prevalence and risk factors for acquisition of carbapenem-resistant Enterobacteriaceae in the setting of endemicity. Infect Control Hosp Epidemiol. 2013;34:809-817.

3. Bonten MJ, Slaughter S, Ambergen AW, et al. The role of “colonization pressure” in the spread of vancomycin-resistant enterococci: an important infection control variable. Arch Internal Med 1998;158:1127-1132.

4. Merrer J, Santoli F, Appere de Vecchi C, Tran B, De Jonghe B, Outin H. “Colonization pressure” and risk of acquisition of methicillin-resistant Staphylococcus aureus in a medical intensive care unit. Infect Control Hosp Epidemiol 2000;21:718-723.

5. Lawrence SJ, Puzniak LA, Shadel BN, Gillespie KN, Kollef MH, Mundy LM. Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure. Infect Control Hosp Epidemiol 2007;28:123-130.


TICU_photo1_031914Photo key: from left to right: Dr. Nicholas Namias, Dr. Silvia Munoz-Price, Dr. Rossana Rosa and Dr. Daniel Kett. Location: Trauma Intensive Care Unit.

Dr. Silvia Munoz-Price is an Associate Professor of Clinical Medicine at the University of Miami. Dr. Rossana Rosa is currently an Internal Medicine Resident at Miami Miller School of Medicine and an incoming fellow of Infectious Diseases at the same institution. She hopes to continue developing her career in Hospital Epidemiology and Infection Control.

ICHE special edition on CRE and MDROs

CRE medium

Infection Control and Hospital Epidemiology have once again excelled themselves in putting together a fine special edition on CRE and MDROs. Around this time last year I posted an article on the ICHE special edition on the role of the environment, and this special edition is equally important. I strongly recommend that you read the special edition from cover to cover, but I’ve picked out a few of my personal highlights below:

  • A thoughtful editorial by Drs Lautenbach and Perencevich sets the scene. They reflect on our ‘woeful unpreparedness’ to address both current and future MDROs.
  • A number of articles provide updates on surveillance and prevalence. Brennan et al. report findings from a 6-month CRE point-prevalence survey based on voluntary reporting in the state of Michigan, finding a crude rate of 1.07 cases per 10,000 patient days. Interestingly, this rate was almost 3 cases per 10,000 patient days in long-term acute care facilities. Isolates were not collected and analyzed, so carbapenemase genes were not confirmed; the fact that close to 10% of isolates were susceptible to meropenem suggests that a good number of the CRE were not carbapenemase producers. Indeed, another state-level point-prevalence survey (Pfeiffer et al., from Oregon) found that only 3 of the 60 CRE isolates reported were carbapenemase producers. Another state-level survey of CRE (Johnson et al., from Michigan) identified regional clustering of CRE colonization of mechanically ventilated patients in the central region of the state.
  • Analysis through the SHEA Research Network found that contact isolation policies for multidrug-resistant Gram-negative rods (MDR-GNR) are surprisingly variable. Worryingly, almost 20% of facilities surveyed did not isolate patients infected or colonized with MDR Pseudomonas or Acinetobacter, and 6% do not isolate patients with CRE. Policies for de-escalation of contact precautions were equally variable. Contact isolation policies seem to be even more lax in long-term care facilities based on data from Pfeiffer et al., reporting that only half of patients colonized with MDROs are placed on contact precautions.
  • A number of studies evaluated risk factors for CRE. For example, Bhargava et al. identified high acute morbidity score, immunosuppression, presence of indwelling medical devices and prior antimicrobial exposures to be consistent risk factors for CRE in the various patient populations they evaluated.
  • A survey of the kitchen in a Swiss hospital identified ESBL-producing Enterobacteriaceae in 92% of raw chicken and 6% of rectal samples from food handlers.
  • The efficacy of chlorhexidine bathing for MDR-GNR has been questioned, so data from Lin et al. on this issue are particularly welcomed. In a study of 62 patients in a long-term acute care facility, daily chlorhexidine gluconate (CHG) bathing halved the chances of culturing CRE from the body sites analyzed. However, it’s worth noting that the measured CHG skin concentration (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 potentially brings the subtly reduced susceptibility to CHG reported in MRSA into play.
  • Several studies evaluated the potential for environmental contamination with MDR-GNR. Rosa et al. found that exposure to surfaces contaminated with MDR A. baumannii increased the risk of acquisition by almost 3-fold. Although the design of the study was fundamentally different, it is interesting to note that the increased risk from admission to a room previously occupied by a patient with MDR A. baumannii was also around 3-fold in a previous study. Havill et al. reported that the survival time for CRE (including K. pneumoniae) on dry surfaces is measured in weeks not days. Rock et al. carefully observed 220 unique interactions between healthcare workers (HCW) and patients with KPC or non-KPC producing K. pneumoniae, finding that HCW gloves or gowns became contaminated during 14% of the 220 interactions, and 26% of 43 environmental samples were positive. There was no significant difference between HCW or environmental contamination rates for KPC vs. non-KPC producing K. pneumoniae.
  • There was not much on therapy for CRE – perhaps because there is little to say for pan-drug resistant CRE! An article discussing the challenges of managing CRE infections by Drekonja et al. through surveying the CDC funded Emerging Infections Network highlighted the common problems due to toxicity from using “last-line” antimicrobials colistin and tigecycline.

It seems that the prevalence of CRE is patchy in the USA at present, and that long-term care, and long-term acute facilities are an integral part of the story. Given the limited evidence base, interventions need to cover all bases: active surveillance, rapid and accurate diagnostics, environmental (and perhaps food) hygiene, contact isolation and perhaps antiseptic decolonization, all combined with facility-wide education and communication initiatives. The most effective – and cost-effective – interventions to prevent and control the spread of CRE and other MDR-GNR are controversial so to this end I am looking forward to the SHEA ‘From MRSA to CRE: Controversies in MDROs’ and joint HIS / IPS ‘What’s that coming over the hill: rising to the challenge of resistant Gram-negative rods’ Spring meetings next month!

Photo credit: Enterobacter cloacae NDM-1 growing on Oxoid Brilliance CRE Agar by Nathan Reading.

A postcard from São Paulo, Brazil: thank goodness for the NHS

sao paulo traffic mediumI recently had the opportunity to spend a week in São Paulo, Brazil, to meet with some infection control and infectious diseases folks. I came away feeling pretty disturbed and very grateful for the NHS.

Brazil is a massive country, with almost 200m inhabitants. São Paulo is Brazil’s largest city, with more than 20m inhabitants making it the 7th largest city in the world. I have lived in London and close to New York, and spent quite some time in Tokyo but nothing comes close to the traffic in São Paulo. It took me 3 hours to travel the 30km from the airport to the hotel, not because it was the middle of the rush hour or because there was a problem, just because the volume of traffic is too big for the infrastructure to handle.

Brazil has around 7000 hospitals; 70% are private with a healthcare insurance system for those who can afford it. The public hospitals are the only option for those who cannot afford healthcare insurance. I visited a number of public and private hospitals and was struck by the following:

  • Rates of antibiotic resistance are eye-wateringly high. Around 40% of healthcare-associated Klebsiella pneuomoniae are carbapenem-resistant and of these, around 20% are colistin-resistant. More than 50% of K. pneumoniae produce ESBLs. The situation with Acinetobacter baumannii is even worse, with >80% resistant to carbapenems. Whilst there is usually some treatment option left, pan-drug resistant Gram-negative bacteria are a daily reality on the ICUs. To top it off, around 60% of S. aureus are MRSA, 80% of E. faecium are VRE and C. difficile is chronically under-reported due to lack of testing infrastructure and limited awareness about sending specimens. There’s an excellent 2011 review on antibiotic resistance in Brazil here, although a lot has happened since 2011.
  • The public hospitals are chronically overcrowded. This is best illustrated by a quick visit to the Emergency Department, where patients on stretchers line the corridors as far as the eye can see. These patients usually stay for days, not hours. The problem is so endemic that ICUs have been established in the ED. The wards are crowded too, with very small distances between beds. Plus, there are not enough staff to cover their beds, especially during nights and weekends. Following one meeting at a very large public hospital (2000 beds), we literally could not leave the building due to the sheer volume of patients trying to get in. Just like the roads, the volume of patients is too high for the infrastructure to handle.
  • The contrast between public and private hospitals is stark. Instead of being met by patients on stretchers when you arrive at public hospitals, you’re met by glass fronted healthcare insurance offices.

So, what can be done? The various strategies to curb the growing threat of antibiotic resistance are as relevant in Brazil as elsewhere: prevention is better than cure; reduce antibiotic use; improve accurate and timely diagnosis; perform surveillance for action; embrace novel solutions; highlight the financial burden; and develop new antibiotics. Some progress has been made, for example, antibiotics are no longer available without prescription over-the-counter. The commitment and enthusiasm of the infection control and infectious diseases folks that I have met here is inspiring. However, they are limited by poor healthcare infrastructure, virtually no investment in microbiology laboratory facilities, lack of national reporting, the widespread availability of poor-quality antibiotics and extensive use of antibiotics in the veterinary sector, which makes progress difficult.

Next time you have the misfortune of visiting an Accident & Emergency Department in an NHS hospital, rather than moan if you have to wait a few hours to access world-leading healthcare free at the point of care, instead be thankful for the NHS.

Photo credit: Fred Inklaar.