Highlights from APIC 2014

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!

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

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.

Is “community-acquired” CDI real?

A recent high profile US study delved into apparent community-associated CDI cases to evaluate healthcare exposures. The study was large, evaluating almost 1000 cases of community-associated CDI from 8 US states. Only 177 (18%) of the 984 cases had no recent healthcare exposure (Figure 1). Furthermore, healthcare exposure was only evaluated for the 12 weeks prior to the positive specimen, so I would wager that a portion of this 18% acquired their infecting C. difficile in a healthcare facility.  CA-CDIFigure 1. Data demonstrating that most MRSA and CDI presenting on admission to hospital are likely to have been acquired in a healthcare facility.  

So, it seems that the majority of these cases are more likely to be community-onset, healthcare-acquired CDI, rather than community-acquired CDI. I feel like we’ve been here before. In the 1990s before the emergence of distinct strains of CA-MRSA, MRSA presenting at hospital admission was commonly termed ‘community-associated’ or, worse, ‘community-acquired’ when really it was MRSA that had been acquired in hospital during a previous stay (Figure 1). The situation has now changed since distinct MRSA clones have emerged that have the capacity to cause infection outside the healthcare environment.

Turning our attention to the UK, the mandatory report scheme classifies cases of CDI as ‘Trust-apportioned’ if the specimens is collected from patients who have been in hospital for four or more days (Figure 2). It is tempting to speculate that the cases of CDI that are non Trust-apportioned are CA-CDI. However, the definition for ‘Trust-apportioned’ does not account for previous healthcare contact, and the rate of Trust-apportioned and non-Trust-apportioned cases tracks so closely that, once again, these are likely to be healthcare-acquired CDI presenting on admission.

Slide1Figure 2. Number of cases of CDI in England through the mandatory reporting scheme, 2004-2013.

The epidemiology of C. difficile is fundamentally different to MRSA, in that healthy neonates typically have a high rate of C. difficile colonization. Thus, there is a ready reservoir for a low rate of genuinely community-acquired CDI. However, it seems to me that most “CA-CDI” reported thus are likely to be acquired in a healthcare facility and I have not seen any data to convince me that community-acquired CDI is increasing.

Article citation: Chitnis et al. Epidemiology of Community-Associated Clostridium difficile Infection, 2009 Through 2011. JAMA Intern Med 2013;173:1359-67.