CRE

Selective Digestive Decontamination (SDD) is dead; long live faecal microbiota transplantation (FMT)

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

crapsules

Ok, so the title may be a little premature, since this blog relates to a study with a sample size of exactly one. However, I do think it spells the beginning of the end for Selective Digestive Decontamination (SDD), especially when applied to suppress gut colonization with antibiotic-resistant bacteria.

A number of groups have looked at using SDD to ‘decolonise’ carriers of multidrug-resistant Gram-negative bacteria such as CRE. In one study, 20 CRE colonized patients in each arm given gentamicin + polymyxin (SDD arm) or placebo (Control arm). The results were rather modest (see chart below). Plus, SDD has substantial downsides in terms of the potential for developing further antibiotic resistance, and ‘collateral’ damage to the gut microbiota.

Figure: Modest impact of SDD to ‘decolonise’ the gastrointestinal tract of CRE carriers.

Saide-Oldes CRE decol

I’ve been waiting for some data on the effectiveness of faecal microbiota transplantation (FMT) to decolonise carriers of antibiotic resistant bacteria for some time. A case report at ID Week related how the ordeal of a 13 year old girl was ended by a faecal microbiota transplantation. After months of persistent colonization and infection, the impact of a single dose of FMT was startling: CRE carriage was eliminated and there was no further bacterial infection.

One of the push-backs against using FMT more regularly is that it’s a crude (in every sense) and labour-intensive procedure compared with an antibiotic capsule. But that was before the invention of ‘crapsules’ (aka oral FMT). Another ID Week abstract reports the successful delivery of oral FMT using crapsules. (And it’s amazing what great dinner party conversation ‘crapsules’ makes. Try it – you’ll see.)

So, I think it’s time for a cluster randomized trial to compare the impact of SDD and FMT; my money is on FMT!

Image: Barbara Krawcowicz.

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

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

apples and oranges

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

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

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

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

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

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

Q&A

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

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

Image credit: ‘Apples and oranges’.

CRE and friends: Q&A

Jon Otter (@jonotter) CRE , , , ,

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!

Q&A

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!  

Isolation: the enemy of CRE

Jon Otter (@jonotter) CRE , , , ,

isolation enemy cre

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

The webinar covered the following ground:

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

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

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

ESCMID MDR-GNR guidelines

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

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?

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.

What does lab diagnosis of MDR-GNR have to do with SURFing?

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

I met the Service Users Research Forum (SURF) yesterday, and they asked me to give a presentation on the emergence and detection of multidrug-resistant Gram-negative bacteria (you can download my slides here). I found these slides by Dr Katie Hopkins (PHE) useful in preparing mine. It was my first interaction with a patient-led research group and I enjoyed the meeting very much. I found the SURF members and their academic support team from the University of West London to be engaged, engaging, knowledgeable and thirsty for knowledge. Their questions were insightful and their suggestions were thought-provoking. Informal discussions on a current research proposal (for enhanced surveillance of carbapenem-resistant Gram-negatives) gave me some useful ideas; researchers can easily lose sight of the patient perspective. I can see why funders such as NIHR now insist on seeing patient involvement in the development of research proposals and I am sure I will be SURFing again in the near future!

I put together the flow chart below to try and summarise the diagnostic approach to the lab detection of MDR-GNR. I would appreciate any thoughts you have on this flow chart…

surf mdrgrn

Considering the burden of enhanced CRE screening

Jon Otter (@jonotter) CRE , , , ,

swabs

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

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

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

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

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

Image: ‘Swabs’ by Frank Carey.

CRE can survive on dry surfaces for longer than you may expect

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

If I was to perform a straw-poll of microbiologist on how long Enterobacteriaceae could survive on dry surfaces, I suspect that most answers would be measured in hours and days rather than weeks and months. However, a lab study that I performed in collaboration with Nancy Havill and John Boyce at Yale New Haven Hospital demonstrated that CRE are able to survive on dry surfaces for over a month.

For the study, which is published in the recent ICHE special edition on CRE and MDROs, we took two clinical isolates of CRE (Klebsiella pneumoniae and Citrobacter freundii) and dried them onto metal discs either in a water or TSB suspension. Discs were then enumerated every few days over a 19 day period. Both K. pneumoniae and C. freundii were able to survive for more than two weeks, and all but C. freundii dried in water survived to the end of the testing period (day 19) (Figure 1). In addition, K. pneumoniae and C. freundii dried in TSB survived for more than 40 days in an additional set of experiments.

CRE survival 1Figure 1. Survival of K. pneumoniae and C. freundii on dry surfaces dried on metals discs in either water or TSB; error bars represent +1 standard deviation on a mean of three replicates at each time point.

We shouldn’t be surprised by these findings. Previous drying studies of Enterobacteriaceae have demonstrated a range of survival times, from hours to months depending on the species, strain and testing conditions. Whist it is plausible that carbapenem-resistance imposes a fitness burden on Enterobacteriaceae that may curtail their survival time, the CRE that we studied seemed to exhibit survival times in the same range as carbapenem-susceptible Enterobacteriaceae. Furthermore, a previous study from my lab identified a stark difference in the survival times of three different K. pneumoniae strains (Figure 2). One of the three strains tested was dead by three weeks, whilst another survived for more than 6 weeks with a minimal log reduction.

CRE survival 2Figure 2. Survival of three different strains of K. pneumoniae dried on metal discs; error bars represent +1 standard deviation on a mean of three discs at each time point.

It seems that CRE can survive for long enough on surfaces to be potentially involved in transmission. However, recent studies by Nseir et al, and Ajao et al. have failed to identify an increased risk associated with admission to a room occupied by a patient infected or colonized with resistant Enterobacteriaceae, in contrast with other bacteria including Acinetobacter baumannii. I suspect part of this is due to the fact that the Enterobacteriaceae are such a diverse family. A number of studies have identified large differences in the rate of contamination when comparing ESBL-producing E. coli vs. K. pneumoniae. If the prior room occupancy studies had been stratified and powered according to species within the Enterobacteriaceae family, I’d expect to see the increased risk from the prior room occupant for K. pneumoniae but not for E. coli. Also, the substantial variation in survival times amongst K. pneumoniae strains has clear implications for outbreaks of K. pneumoniae: are you dealing with a strain that is a “survivor” on surfaces? If so, more attention to cleaning and disinfection may be required.

In summary, CRE are able to survive on dry surfaces for weeks to months, which is long enough to be potentially involved in transmission; this justifies the advice for enhanced cleaning and disinfection to control the spread of CRE.

Article citation: Havill NL, Boyce JM, Otter JA. Extended survival of carbapenem-resistant Enterobacteriaceae on dry surfaces. Infect Control Hosp Epidemiol 2014;35:445-447.

ICHE special edition on CRE and MDROs

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

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.