CDI

Inaugural ‘Journal Roundup’ (June 2014)

Jon Otter (@jonotter) Roundup , , , , ,

JHI

I’ve been asked by the Editor of the Journal of Hospital Infection to begin writing a monthly column providing an overview of key updates in the infection prevention and control literature. I’m pleased to say that the first edition (June 2014) is now available on the Journal of Hospital Infection website, and I’m delighted that the Journal Roundup is open access.

I thought it would be useful to outline how I produced this roundup. I began by scanning the tables of contents of the following journals, pulling out articles of interest: AJIC, Ann Intern Med, BMJ, CID, ICHE, JAMA, JAMA Intern Med, JHI, JID, JIP, Lancet, Lancet ID, NEJM. This was easy for the “big five” (Lancet, BMJ, AIM, JAMA and NEJM) because only a handful of articles are directly relevant. It was more tricky for the specialist journals, since all articles are likely to be of interest. I’ve tried to avoid focusing solely on my own research interests, but these doubtless come through. One way to mitigate this in future is for others to provide a Journal Roundup now and then – or at least make some contribution. If you’re interested in this, please do let me know.

Highlights of this inaugural issue include a spike in MERS-CoV cases, coverage of the WHO report on antimicrobial resistance, more evidence that faecal microbiota transplantation works for curing recurrent CDI, the impact of nursing education on patient mortality, individualized antibiotic dosing, CA-MRSA in US Fire Stations, a successful community-based hand hygiene intervention, an outbreak of CRE in Ireland, updated SHEA guidelines for SSI and CDI, the identification of ‘optimum outlier’ (aka ‘positive deviant’) cleaners, a disturbing patient story, an update on the move towards ‘bare below the elbow’ in the US, an overview of the regulatory environment for healthcare apps, conference abstracts from APIC and ECCMID, and the use of Yelp (a customer review website) to identify cases that would otherwise have gone unreported during a foodborne outbreak.

Please feel free to share this with your colleagues, and let me know if you have any thoughts or comments.

 

Highlights from APIC 2014

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

APIC 2014I couldn’t make it to APIC this year, but I have picked out a few highlights. More than 300 abstracts were presented so I can only scratch the surface here, but the good news is that they’re all available in an AJIC supplement.

Multidrug-resistant Gram-negative rods

One of the oral presentations was on controlling CRE in Texas (Cifelli et al). The interventions comprised improvements in lab identification and patient electronic tagging, and front-line infection prevention and control practices (dedicated rooms, equipment and staff etc). It’s difficult to know which of these approaches (if any!) made the difference: we still don’t know what works to control CRE.

A group from Louisville explored transmission of CRE in an LTAC (Kelley et al). LTACs have previously been shown to be a hotbed for CRE transmission in some parts of the USA. They found that almost half of patients that acquired CRE were admitted to beds that had been previously occupied by a CRE patient, which brings a new meaning to ‘hotbed!’ This links in with previous studies showing that admission to a room previously occupied by a patient with MDROs is a risk factor for acquisition. It also shows that CRE (K. pneumoniae at least) can survive for long enough on surface to bring indirect transmission via environmental contamination into play.

Definitions and terminology surrounding CRE and MDR-GNR in general are in a state of confusion. Both require urgent clarification. A survey of 79 hospitals by Jadin et al for their definitions of MDR-GNR yielded virtually 79 different definitions! This makes it challenging for facilities to communicate clearly about MDR-GNR, since what qualifies as MDR-GNR may not make the cut in another hospital. And this is not even accounting for variations in lab diagnostics!

A small prevalence survey of CRE carriage in Michigan by Berriel-Cass et al found that 2 (3.8%) of 53 patients were colonized. Neither patient had history of CRE, but one who did have a history of CRE screened negative! It’s difficult to know who is at high risk for CRE carriage, and even more difficult to know how long they will carry it for. However, we probably know enough to conclude that “once positive always positive” is a sensible (if somewhat conservative) approach.

The rest

A fascinating study from Arizona by Sifuentes et al evaluated a hygiene intervention in a LTCF. A number of bacteriophages were used as markers for pathogenic virus transmission and inoculated onto hands and surfaces. The viruses spread rapidly throughout the faculty over a short time period (measured in hours), and a hygiene intervention significantly reduced the level of contamination of hands and surfaces. Most similar work has been performed in the acute setting, so some data from the non-acute setting is particularly welcome. This study illustrates the dynamic interplay between hand and surface contamination. In a way, hands are just another highly mobile fomite that are not disinfected frequently enough!

Jinadatha et al performed a very timely study exploring whether serial passage of bacteria with sub-lethal UV exposure prompts reduced susceptibility to UV. The study demonstrates that 25 serial exposures to UV did not affect bacterial UV susceptibility. However, the study did not explore whether other useful mutations may have occurred in the “survivors”; perhaps this is a job for whole genome sequencing in a follow-up study?

Faecal microbiota transplantation (FMT) is quickly becoming the standard of care for recurrent CDI. A study by Greig et al tells the story of implementing a FMT programme. The literature for FMT are impressive, but the ‘nuts and bolts’ of implementation are challenging. Where do you get the donor stool form? How do you screen the donors? Who performs the procedure? Who pays? Will it work here? Are just some of the questions that need to be negotiated for successfully implementing an FMT programme. The message from this study: it’s worth it – 83% of patients with recurrent CDI had resolved within 30 days.

Finally, I remain rather skeptical that “CA-CDI” is really on the rise. I may have to revise my opinion based on this abstract by Rogers and Rosacker, showing that a community-based educational intervention reduced the rate of CA-CDI!

Perspectives from ECCMID 2014: the box set

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

eccmid 2014

I’ve published a few ‘Perspectives from ECCMID’ on the blog over the last few days, so thought it would be useful to post a summary:

You may also be interested in some other updates from ECCMID elsewhere in the blogosphere:

Perspective from ECCMID Part III: CDI synthetic “repoopulation” (bacteriotherapy) closer than you think & “CA-CDI” still pie in the sky

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

Bacteriotheraphy for CDI is closer than you think

As our understanding of the importance of a happy, healthy microbiota develops, it seems increasingly clear to me that bacteriotherapy (administration of a controlled multi-species dose of bacteria) is a real prospect for the treatment of CDI (and most likely other conditions). This is illustrated by the dramatic effectiveness of faecal microbiota transplantation (FMT) for recurrent CDI. FMT is pretty crude, in every sense; synthetic FMT would be safer and more palatable. But I hadn’t realized how far the research towards available bacteriotherphy for CDI had advanced. Dr Trever Lawley gave an expert overview of his research programme, which is pointed in this direction.

Dr Lawley began by describing the human microbiota as a fingerprint: it’s consistent and unique. The microbiota is highly organized, to reflect its function, resulting in microenvironments. Antibiotics are like an atomoic bomb, resulting in huge perturbation of the gut microbiota. The idea of bacteriotheraphy to redress the balance is not new. Pioneers of bacteriotherapy (aka “repoopulation”) for CDI date back to at least 1989.

So, which bacteria get the nod to be included in the synthetic mix? It’s not an easy question, since examining the massively populous human microbiota is a daunting prospect and requires the application of novel tools (see Fig 1 of this excellent open-access review for a useful summary of the methods to examine the human microbiota and microbiome). Human trials and mouse model indicate that single species theraphy and probiotics are equivocal at best. These are blunt weapons to complement the nuclear fall out of the antibiotic A bombs! Dr Lawley’s reaseach has found an irreducible minimum of 6 species that are necessary for effective bacteriotherapy (in mice at least). Now all that is required is to find a common growth medium…oh, and do some humans trials!

Another speaker, Dr Cornley, mentioned another approach to preventing CDI: the prophylactic administration of metronidazole. If you’re read my Perspective from ECCMID on Selective Decontamination, you can probably guess which approach I’d choose.

“CA-CDI” still pie in the sky

A number of speakers contributed to the debate on whether “community-acquired” CDI is on the rise. Dr Scott Weese outlined the potential for foodborne risk of CDI, beginning with a ‘disclosure’ that we can all relate to: “I like to eat but I don’t like foodborne illness”! C. difficile is present in food animials (especially young ones) and strains are shared with humans. Rates of carriage are low, but Dr Weese made a good point on cumulative exposure. If 2% of burgers are C. difficile contaminated, I eat C. difficile on my 98th burger (not exactly, but you get the point). Plus, C. difficile spores can survive usual cooking times (which is not so relevant for me: I like my burger meat rare)! The carriage of C. difficile in animals combined with the high carriage of C. difficile in small human animals means that exposure to C. difficile is probably a daily event. But is this a risk? For a healthy 25 year old in the community, probably no. For a haematology inpatient, probably yes.

Dr Marjolein Hensgens considered whether CDI is still primarily nosocomial. The distinction of community vs. hospital onset is easy, but community vs. hospital acquisition is much more challenging and epidemiological disitinctions are approximate at best. For example, in the UK, a “Trust-apportioned” (=hospital acquired) case requires a specimen from an inpatient who has been in the same hospital for at least 4 days. Any readmission (even if they were in the hospital the previous week) is considered “non Trust-apportioned”, but it’s important to remember that this is not the same as “community-acquired”. The fact that the Trust-apportioned and non Trust-apportioned cases track each other so closely in the UK reductions suggests that almost all cases were healthcare-associated (Figure 1).

CA-CDI_2Figure 1: the number of CDI cases reported to Public Health England, defined as “Trust-apportioned” or “non Trust-apportioned” from 2007 onwards.  

An important US study suggested a stepwise increase in CA-CDI. However, this apparent increase could be explained by a number of other factors. Firstly, a high proportion of patients with apparent CA-CDI actually have had healthcare exposoure of some kind if you look hard enough (82% in this study). So this upward trend in “CA-CDI” could very well be HA-CDI with unrecognized healthcare exposures. Secondly, it is difficult to know whether there have been any changes in the number of diarrhoeal stools tested in the community. Infectious diarrohea has always been common in the community, but is rarely tested for CDI. Thirdly, comparing the epidemiology of patients who develop CDI in the community with those who develop CDI in hospitals could result in a misleading picture. A more appropriate comparator would be patients who have non-CDI diarrhea in the community. Finally, does WGS prove that hospital acquisition of CDI is now rare? No, it only proves that transmission from known symptomatic CDI cases is less frequent than you may expect. There are many other sources for hospital acquisition of CDI, not least asymptomatic carriers. We’re surrounded by C. difficile so of course a degree of CA-CDI occurs. But is it increasing? I still think no – or at least, not rapidly due to phase-shift in epideimogogy (that we saw with the emergence of CA-MRSA in the late 1990s).

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

Image: ‘C. difficile‘ by AJ Cann.

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

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

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

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

curry CDI

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

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

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

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

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

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

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

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

What does it take to prevent the transmission of C. difficile from environmental surfaces?

Jon Otter (@jonotter) C. difficile , ,

Infected patients shed pathogens into the environment, resulting in increased risk of infection for the subsequent occupant of the room by a factor or two or more.1 For example, in one study, patients admitted to rooms previously occupied by patients with C. difficile infection (CDI) were 2.8 times more likely to develop CDI than patients admitted to rooms disinfected using conventional methods. Thus, most agree that more needs to be done to reduce contamination with C. difficile spores in order to interrupt transmission. However, what level of disinfection is required to prevent the transmission of C. difficile?

A consideration of data relating to the infectious dose of C. difficile is a useful first step. In hamster studies, Larson and Borriello showed that only one or two spores of C. difficile were sufficient to initiate infection in clindamycin-treated hamsters.2  This indicates that very low levels of C. difficile spores can initiate infection.

Lawley, et al.3 developed a murine model that provides useful background data on infectious dose. A dose-response relationship was established between the concentration of contamination in the cages and the proportion of healthy mice that developed CDI. All mice became infected when exposed to 100 spores/cm2 and 50 percent of mice became infected when exposed to 5 spores/cm2.  The point at which none of the mice became infected was a concentration of less than one spore per cm2. The mice were exposed to the contaminated cages for one hour. In the healthcare environment, room exposure times are usually measured in days and so these estimates are likely to be conservative. Although translating data from animal models to meaningful clinical practice is difficult, it appears from these animal models that a low concentration of contamination is able to transmit spores to a susceptible host, as is the case with other healthcare-associated pathogens such as norovirus. 4

The low infectious dose of C. difficile is not the only challenge to disinfection. Bacterial endospores can survive on surfaces for many months5 and are resistant to several commonly used disinfectants.6 Patients with CDI result in widespread fecal contamination with C. difficile present in the feces of infected individuals at concentrations in excess of 106 spores per gram.7

Lawley, et al. examined which disinfectants were able to interrupt the transmission of C. difficile and established a relationship between the level of inactivation of C. difficile spores in vitro and the degree to which transmission was interrupted (figure).

Cdiff_log_reduction

Figure. Correlation between in vitro log reduction and interruption of transmission of C. difficile spores in a murine model.3

The oxidizing agents sodium hypochlorite (bleach) and hydrogen peroxide vapour (HPV) were the only agents tested that achieved a 6-log reduction on C. difficile spores in vitro and completely interrupted the transmission of C. difficile. Notably, both bleach and HPV disinfection can reduce the incidence of CDI in healthcare applications.8-9  Based on these findings, the CDC recommends that surfaces potentially contaminated with C. difficile spores should be disinfected using EPA-registered sporicidal agent (such as bleach) or sterilants.

Recent data highlight the fact that agents with in vitro efficacy may not effectively eradicate hospital pathogens from surfaces due to limitations with achieving adequate distribution and contact time using conventional cleaning methods.1,10 The emergence of ‘no-touch’ automated disinfection methods provide an alternative to reliance on a manual operator for the inactivation of pathogens on surfaces.  HPV is an EPA-registered sterilant that achieves a 6-log reduction on C. difficile spores in vitro, eradicates C. difficile spores from surfaces and reduces the incidence of CDI and successfully mitigates the increased risk from the prior room occupant. 5, 9, 11-13

In summary, given the fact that a small number of C. difficile spores are sufficient to cause CDI in susceptible individuals, disinfectants with an EPA-registered sporicidal claim or sterilants should be used for disinfecting rooms used by patient with CDI. ‘No-touch’ methods, such as HPV, remove reliance on the operator to achieve adequate distribution and contact time and are appropriate for the terminal disinfection of rooms used by patients with CDI.

References:
1. Otter JA, Yezli S, French GL. The role played by contaminated surfaces in the transmission of nosocomial pathogens. Infect Control Hosp Epidem. 2011; 32:687-99.
2. Larson HE, Borriello SP. Quantitative study of antibiotic-induced susceptibility to Clostridium difficile enterocecitis in hamsters. Antimicrob Agents Chemother 1990; 34:1348-53.
3. Lawley TD, Clare S, Deakin LJ, et al. Use of purified Clostridium difficile spores to facilitate evaluation of health care disinfection regimens. Appl Environ Microbiol 2010; 76:6895-900.
4. Yezli S, Otter JA. Minimum infective dose of the major human respiratory and enteric viruses transmitted through food and the environment. Food Environ Microbiol 2011; 3:1-30.
5. Otter JA, French GL. Survival of nosocomial bacteria and spores on surfaces and inactivation by hydrogen peroxide vapor. J Clin Microbiol 2009; 47:205-7.
6. Humphreys PN. Testing standards for sporicides. J Hosp Infect 2011; 77:193-8.
7. Al-Nassir WN, Sethi AK, Nerandzic MM, Bobulsky GS, Jump RL, Donskey CJ. Comparison of clinical and microbiological response to treatment of Clostridium difficile-associated disease with metronidazole and vancomycin. Clin Infect Dis 2008; 47:56-62.
8. Mayfield JL, Leet T, Miller J, Mundy LM. Environmental control to reduce transmission of Clostridium difficile. Clin Infect Dis 2000; 31:995-1000.
9. Boyce JM, Havill NL, Otter JA, et al. Impact of hydrogen peroxide vapor room decontamination on Clostridium difficile environmental contamination and transmission in a healthcare setting. Infect Control Hosp Epidem. 2008; 29:723-9.
10. Manian FA, Griesenauer S, Senkel D, et al. Isolation of Acinetobacter baumannii complex and methicillin-resistant staphylococcus aureus from hospital rooms following terminal cleaning and disinfection: Can we do better? Infect Control Hosp Epidemiol 2011; 32:667-72.
11. Passaretti CL, Otter JA, Reich NG et al. An evaluation of environmental decontamination with hydrogen peroxide vapor for reducing the risk of patient acquisition of multidrug-resistant organisms. Clin Infect Dis 2013; 56: 27-35..
12. Manian FA, Griesnauer S, Bryant A. Implementation of hospital-wide enhanced terminal cleaning of targeted patient rooms and its impact on endemic Clostridium difficile infection rates. Am J Infect Control 2012..
13. Cooper T, O’Leary M, Yezli S, Otter JA. Impact of environmental decontamination using hydrogen peroxide vapour on the incidence of Clostridium difficile infection in one hospital trust. J Hosp Infect 2011; 78:238-40.