CRE

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

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

shea 2014

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

Global perspective on CRE evolution – Dr Arjun Srinivasan

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

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

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

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

Lab Identification & Surveillance for MDROs – Dr Daniel Diekema

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

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

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

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

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

Posters and oral presentations

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

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

Four impressive submitted abstracts were presented:

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

Contact Isolation Precautions: Unanswered Questions – Dr Daniel Morgan

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

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

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

Top 10 MDRO Papers – Drs Susan Huang & Ebbing Lautenbach

Dr Huang selected:

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

Dr Lautenbach chose:

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

Fecal Transplant for C. difficile Infection – Dr Michael Edmond

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

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

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

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

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

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

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

Key issues

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

References

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

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

3.       Lin MY, Lyles-Banks RD, Lolans K et al. The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae. Clin Infect Dis 2013; 57: 1246-1252.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

25.     Daneman N, Sarwar S, Fowler RA, Cuthbertson BH, Su DCSG. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infect Dis 2013; 13: 328-341.

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

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

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

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

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

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

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

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

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

Considering the burden of enhanced CRE screening

Jon Otter (@jonotter) CRE , , , ,

swabs

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

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

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

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

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

Image: ‘Swabs’ by Frank Carey.

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.

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

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

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.

What can outbreaks of Salmonella from the 1950s tell us about CRE?

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

I recently came across a fascinating review article published in 1963 mainly about outbreaks of Salmonellosis during the 1950s. The review focuses on epidemics that were traced to contaminated surfaces, including ingested, contact and inhaled transmission routes. A number of interesting epidemics stand out:

  • An outbreak linked to contaminated neonatal respirators.
  • An outbreak linked to a contaminated chopping board (see Figure). In this outbreak, one of the investigators apparently contracted Salmonellosis after touching the chopping board during sampling and then having a cigarette before washing his hands.
  • An outbreak (of microbial endotoxin syndrome) linked to a contaminated mouthpiece of SCUBA equipment. Here, the outbreak occurred in naval diving academy and the pattern of lessons and cases was so regular, that the epidemiologist could predict precisely when to visit to see the next case.

chopping board 2

Figure: A chopping board at risk of persistent microbial contamination due to surface damage. 

Although most outbreaks covered in the review relate to ancient catering-related outbreaks of Salmonella, there may be some useful learning for hospital epidemiology today, specifically CRE. It’s rare although not unheard of to find Salmonella carrying a carbapeneamase (i.e. Salmonella CRE). However, Salmonella is a member of the Enterobacteriaceae, so the involvement of contaminated surfaces during outbreaks of Salmonella suggests that contaminated surfaces may also be important during outbreaks of CRE.

It’s interesting that even back in the 1960s contaminated surfaces were recognized as potentially important in epidemics, whereas by the 1980s, the role of contaminated surfaces in endemic transmission was considered negligible. It’s difficult to know whether experts of the 1960s (perhaps there are some reading this?) would have considered contaminated surfaces important in both epidemic and endemic transmission? I suspect so, and we just lost sight of that in the 1980s and 90s.

Article citation: Sanborn WR. The relation of surface contamination to the transmission of disease. Am J Public Health Nations Health 1963;53:1278-1283.

Image: Ben Hosking.

A postcard from Latin America; carnivals, tango and carbapenem resistance

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

postcard panama

Recently, I spent some time in Latin America, first in the “Tango” country, Argentina, attending the International Federation of Infection Control (IFIC) 2013 conference and then in Panama giving a talk at a symposium. Talking to doctors and other healthcare workers from across Latin America during these two events, it was clear that multidrug resistance, especially carbapenemase and ESBL production in Enterobacteriaceae and other Gram-negative bacteria, are major problems in the region.

This prompted me to review the status of carbapenem resistance among the major nosocomial Gram-negatives in Latin America and ESBL production in E. coli and Klebsiella. Unlike the US and Europe, data on antimicrobial resistance from Latin American countries is limited. Some Latin American countries, such as Argentina, Chile and Colombia, do possess a nationwide surveillance program for monitoring antimicrobial resistance. However, the data are rarely in the public domain. Other countries such as Brazil and Mexico don’t yet have such monitoring programs. This makes it difficult to estimate the accurate prevalence and burden of diseases caused by antimicrobial-resistant bacteria in this part of the world.

Thankfully, some data are flittering through from several national and international reports, including the SENTRY antimicrobial surveillance program (Table). SENTRY has been monitoring the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a broad network of sentinel hospitals since 1997 using validated, reference-quality identification and susceptibility testing methods performed in a central laboratory. Data from the SENTRY reports identify the five most frequently isolated Gram-negatives in Latin America as the Enterobacteriaceae (E. coli, Klebsiella and Enterobacter), P. aeruginosa and Acinetobacter.3

Table. Percentage of carbapenem resistance among the main nosocomial Gram-negatives in Latin America.CRE latinIMP; imipenem, MER; meropenem

Resistance of these organisms to carbapenems has been increasing over the years, especially among Klebsiella, P. aeruginosa and Acinetobacter. The 1997-2001 SENTRY program reported on the antimicrobial resistance of 8,297 isolates of the 5 above organisms for 7 Latin American countries (Brazil, Argentina, Chile, Colombia, Mexico, Uruguay and Venezuela).1 The data found carbapenems to be effective against Enterobacteriaceae (<1% resistance level). Resistance among Acinetobacter and P. aeruginosa was around 13% and 26% respectively. In 2001, carbapenem resistance among the Enterobacteriaceae remained <1%, while resistance for Acinetobacter and P. aeruginosa rose to around 17% and 36% respectively.

The Tigecycline Evaluation and Surveillance Trial (TEST)2 reported  the antimicrobial resistance of bacteria from 33 centres in Latin America (Argentina, Brazil, Chile, Colombia, Guatemala, Honduras, Jamaica, Mexico, Panama, Puerto Rico and Venezuela) between 2004 and 2007, finding that imipenem-resistance among Enterobacteriaceae remained stable at <1%. However, resistance of Acinetobacter to imipenem increased to 33.2%.

The 2008-2010 SENTRY report from 10 Latin American medical centres located in Argentina, Brazil, Chile and Mexico, found a marked increase in imipenem and meropenem resistance among Klebsiella (7.7% and 7.8% respectively) and Enterobacter (8% and 1.8% respectively).3 KPC-2 was prevalent in Klebsiella but OXA-163, IMP and VIM were also detected. There was an important increase in KPC-2 producing K. pneumonia noted in Argentina and Brazil. Colistin resistance was highest among Klebsiella and Enterobacter with resistance rates of 3.1% and 17.6%, respectively. Nearly 70% of Acinetobacter were resistant to carbapenems and 1.2% were resistant to colistin. There was a marked increase in resistance in this organism particularly in Argentina and Brazil. OXA-23 and OXA-24were the most frequent OXA-carbapenemase genes detected. In P. aeruginosa, 42% of the isolates were resistant to carbapenems and 0.3% were resistant to colistin.

A recent article reported the antimicrobial resistance among 3,040 Gram negatives collected in 2011 from 11 countries in Latin America (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Panama, Peru and Venezuela).4 With the exception of Mexico (1.1%), all other countries had high rates of Carbapenem-Resistant Enterobacteriaceae (CRE) (10-20%). Panama, Colombia and Brazil had particularly high rates of 20%, 18.2% and 17.3% respectively. Resistance in Enterobacter was 2.9% with the highest rates in Colombia and Venezuela (10-12.5%). KPC-2 was identified in Brazil, Ecuador and Venezuela, KPC-3 in Colombia and Panama while NDM-1 was also found in Colombia.

ESBL production by E. coli and Klebsiella isolated from Latin America is a well-recognized problem. The prevalence of ESBL-producers in Latin America has progressively increased over the years (Figure). The rates of these isolates in the region are now in excess of 50% in some regions.4 Peru, Guatemala and Chile have the highest ESBL-producing Klebsiella rates (70%, 69% and 59% respectively), while Mexico, Guatemala and Peru have the highest rates of ESBL-producing E. coli (71%, 59% and 54% respectively).

Latin americaFigure. Inexorable rise in rate of of ESBL-producing E. coli and Klebsiella in Latin America. 

It is clear that increasing antimicrobial resistance among Gram-negatives is a major problem in Latin America. The spread of carbapenem resistance is particularly troubling with increase prevalence of KPC and NDM carriage. Steps to reduce the transmission of these pathogens in Latin America require strategies at the institutional, community, national and international levels. For a start, it is important that true the prevalence rate of antimicrobial resistance among Gram-negatives in Latin America is determined at national levels with robust surveillance systems. Effective antibiotic stewardship and the control of inappropriate antibiotic use are important to slow the proliferation of resistant strains and should be targeted at both hospital and community levels. Strict infection control measures and targeted screening and isolation of patients with problematic strains should also help to slow the spread of resistant Gram-negatives in Latin America.

References

  1. Sader HS, Jones RN, Gales AC et al. SENTRY antimicrobial surveillance program report: Latin American and Brazilian results for 1997 through 200. Braz J Infect Dis 2004;8:25-79.
  2. Rossi F, García P, Ronzon B et al. Rates of antimicrobial resistance in Latin America (2004-2007) and in vitro activity of the glycylcycline tigecycline and of other antibiotics. Braz J Infect Dis 2008;12:405-15.
  3. Gales AC, Castanheira M, Jones RN, Sader HS. Antimicrobial resistance among Gram-negative bacilli isolated from Latin America: results from SENTRY Antimicrobial Surveillance Program (Latin America, 2008-2010). Diagn Microbiol Infect Dis 2012;73:354-60.
  4. Jones RN, Guzman-Blanco M, Gales AC et al. Susceptibility rates in Latin American nations: report from a regional resistance surveillance program (2011). Braz J Infect Dis 2013 Oct 10.
  5. Paterson DL, Rossi F, Baquero F et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother 2005;55:965-73.
  6. Rossi F, Baquero F, Hsueh PR et al. In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). J Antimicrob Chemother 2006;58:205-10.

Key themes from ID Week 2013

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

idweek

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

MDR-GNR

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

Oral presentations

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

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

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

Posters

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

Reflections from MDR-GNR research

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

Role of the environment in transmission

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

Posters

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

Other highlights

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

CRE outbreak control: a view from the trenches

Jon Otter (@jonotter) CRE , , ,

Drs Tara Palmore and David Henderson have written an engaging ‘view from the trenches’ in CID reflecting on their efforts to control an ongoing outbreak of CRE at the NIH Clinical Center, beginning in 2011.

The review outlines their interventions, including:

  • aggressive active surveillance (including regular house-wide surveys);
  • rapid identification and characterization of resistant organisms and resistance mechanisms (a mixture of conventional culture-based microbiology, mass-spec and mass spec);
  • whole-genome sequencing of outbreak isolates (which allowed the identified of counterintuitive transmission patterns);
  • enhanced contact precautions for all infected or colonized patients (patients only to leave room for medical reasons, visitors to wear gloves and gowns, staff not to touch personal electronic devices, preferable use of single-use equipment and enhanced terminal disinfection);
  • geographic and personnel cohorting;
  • daily chlorhexidine gluconate baths;
  • dedicating equipment for cohorted patients and aggressive decontamination of equipment that had to be reused on uncohorted patients;
  • monitoring adherence to infection control precautions, including unwavering attention to adherence to appropriate hand hygiene procedures (included the use of observing ‘enforcers’ to make sure staff complied with the basics);
  • enhanced environmental decontamination (including double bleach wipe daily disinfection, hydrogen peroxide vapor for terminal disinfection and careful management of drains);
  • engagement of all stakeholders involved in care of at-risk patients;
  • and detailed, frequent communication with hospital staff about issues relating to the outbreak.

The authors discuss the problem of determining which of these interventions worked, since they were implemented more or less simultaneously; the so-called “kitchen sink” approach (Figure). A recent systematic review performed by ECDC identified this problem in virtually all studies evaluating control interventions for CRE.

NIH CRE control measuresFigure. Perceived relative importance of outbreak control interventions at NIH.

There’s an interesting section on the ‘unintended consequences’ of publishing in report, including the inevitable scaremongering in some parts of the lay-press. It wasn’t all bad though; this is an unusually detailed article based on the original NIH outbreak report in the Washingtonian.

Some reflections from me:

  • This all started with the transfer of a colonized patient from New York. Recognizing and containing colonized patients that are transferred from other hospitals is going one of the most important fronts in the battle against CRE. Worth noting that ECDC are recommending a rectal screen of all cross-border transfers of hospital patients in Europe.
  • Mortality was especially high in the NIH outbreak (albeit in patients with serious underlying illness), illustrating the clinical ‘teeth’ that this issue bares.
  • The outbreak reignited from an unidentified reservoir after apparently being brought under control; we have a limited understanding of the challenging epidemiology of these organisms.
  • It’s sad, though not surprising, that the high hand hygiene compliance achieved during the outbreak could not be sustained following the outbreak.
  • As you would expect, relying on clinical cultures only is looking at the tip of the iceberg. Active surveillance is a must.
  • One unique aspect of their enhanced contact precautions was an instruction for staff to avoid touching personal electronic items. This makes a lot of sense, and should be considered for inclusion in regular contact precautions.
  • There are some telling insights on the practical challenges of cohorting staff, not least the fact that there were not enough physicians to feasibly cohort!
  • The initial isolation measures failed, and NIH (commendably) went to extraordinary lengths to bring the outbreak under control. ‘Aggressive’ is used to describe several aspect of their strategy, which seems apt. Israel is another success story of extraordinary CRE control measures. Greece and Italy are examples of where extraordinary measures have not been undertaken and CRE have quickly become endemic.

Article citation: Palmore TN, Henderson DK. Managing Transmission of Carbapenem-Resistant Enterobacteriaceae in Healthcare Settings: A View From the Trenches. Clin Infect Dis 2013 in press.

Prevalence survey illustrates the difference between CRE and CPE

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

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

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

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

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

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

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

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

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

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