MRSA in Decline: England Edition

Don't know what I want
But I know how to get it
I wanna destroy passerby

-Sex Pistols "MRSA? in the UK"

MRSA rates have just reached their lowest levels in recorded history. Per a BBC report, there were 97 cases in the entire NHS in June, which represents the first time rates have been below 100. 25 hospitals had no MRSA cases in the month. C. difficile cases are also falling, so the decline is likely due to an overall emphasis on infection prevention including hand hygiene, which would impact both infections. Good news, overall.

BBC report
Guardian report

New C. difficile drug approved

Fidaxomicin, the new drug we discussed here, was just approved by the FDA for treatment of Clostridium difficile disease. Price is still not available, but I agree that it is likely to cost at least as much as brand-name oral vancomycin (the parenteral formulation of vancomycin can be formulated for oral use much more cheaply, a practice that is now common). If it is that expensive, fidaxomicin probably will be reserved for recurrent disease (the clinical trial demonstrated equivalence for treatment response, the benefit of fidaxomicin was in reduced recurrence rates among patients with non-NAP1/BI strains).

Photo: Dr. Sherwood Gorbach, Chief Scientific Officer at Optimer Pharmaceuticals. Sandy Huffaker/New York Times

Good news, bad news

Here’s a nice “good news, bad news” report by Becky Miller and colleagues from DICON (the Duke infection control network). First the bad news: Clostridium difficile has now replaced MRSA as the most common HAI in this 39 hospital network in the southeastern United States. The good news? This development is driven largely by a steady and substantial decline in healthcare-associated MRSA infections between 2005-2009. Check it out:

We’ve discussed this trend before, a trend documented by CDC investigators in the NHSN and EIN programs, and confirmed in the VA system as well. The challenge now is to find a way to make the C. difficile trend line resemble that for MRSA….

A more cultured approach to fecal transplant?

Mike recently blogged about the increasing interest in fecal transplant for severe and/or refractory Clostridium difficile associated disease (CDAD). The procedure remains very slow to catch on, though. Why? The lack of a controlled trial is certainly one reason, but the other is simply the “ick” factor. The ick factor, and the difficulty in controlling a trial when another person’s stool is the deliverable, is also one reason why controlled trials have been slow to come.

If only one could replicate the stool microbiome using culture techniques, this barrier would exist no longer. However, early studies of the gut microbiome revealed that the majority of species are not cultivatable in the laboratory.

So I found this report from Washington University to be very interesting—these researchers were able to preserve gut microbiome functions in germ-free mice using strict anaerobic culture techniques. If indeed a person’s “readily cultured bacterial community” could exhibit in vivo behavior that mirrors the complete microbiome, then there is the potential for complex microbial communities to be developed and passaged that could replenish the microbiome in patients with CDAD.

Kill this spore!

This month’s issue of Infection Control and Hospital Epidemiology has an interesting article from the University of Michigan group, demonstrating that having a prior room occupant with C. difficile associated disease (CDAD) is a risk factor for CDAD. Spores are hard to kill, and survive for months in the hospital environment. Meanwhile, environmental cleaning practices are highly variable….but clearly not good enough in most hospitals to eradicate C. difficile spores from the environment during terminal room cleaning. I have nothing to add to the excellent commentary on the article by David Weber and Bill Rutala. The future of environmental cleaning likely resides in touchless technologies like hydrogen peroxide vapor/mist and UV light.

Image: Transmission EM of C. difficile spore, from the Journal of Bacteriology.

Another Friday, another feces post...

Recurrent Clostridium difficile disease is a huge problem—a nightmare for patients, and a recalcitrant challenge for clinicians and infection preventionists. So this week’s New England Journal of Medicine brings good news about fidaxomicin*, a new nonabsorbable macrocyclic antibiotic active against C. difficile. In a head-to-head trial with vancomycin, cure rates were equivalent but recurrence rates were significantly lower for fidaxomicin (15% versus 25% for vancomycin, in the modified intent-to-treat groups). Unfortunately, this difference held only for non-NAP1 strains. For the nasty, hypervirulent NAP1/BI strain, recurrence rates were 24% in both groups—meaning that for the majority (64%) of patients with other strain types, the difference in recurrence rates between fidaxomicin and vancomycin was even greater (7.8% vs. 25.5%).

Why? Fidaxomicin is more active against C. difficile (bactericidal rather than bacteriostatic), has a longer post-antibiotic effect, and is slightly narrower in spectrum than vancomycin. So it probably kills C. difficile better, for longer, and without as much disruption of the rest of the colonic flora. Further studies will be needed to investigate this further, and to determine why this effect is not seen with the NAP1/BI strain.

The accompanying editorial by Dr. Herbert DuPont is well worth reading, and raises questions about whether our initial therapy for C. difficile is too short in duration (in this study, 10 day treatment courses were used), and whether we’ll eventually be using a combination of antibiotics and immunotherapy to effectively treat and prevent C. difficile recurrences. That is, if stool transplants haven’t become the treatment of choice by then.


*This drug is made by Optimer Pharmaceuticals, and all of the authors have listed disclosures at the end of the article—three of the authors are Optimer employees

Friday feces blogging (part 2)

Since Dan had to go and bring up the subject of feces, I would like to direct our readers to a new article in Slate on fecal transplantation for C. difficile. Although Slate is written for the general public, this article does a good job explaining the procedure and the controversy that surrounds it. Of course, the issue of lack of randomized trials to support this intervention comes up in the article. I would respond by asking this question:  if you had diarrhea for 6 months unresponsive to treatment, would you try it, or would you wait for an investigator to perform a trial and publish it before you agree to giving it a try? And the other interesting question is whether randomized trials are always needed. On that one, I'll point you to an interesting paper in BMJ from a few years ago.

Fecal transplantation for C. difficile

The Washington Post had an article yesterday on fecal transplantation for C. difficile colitis. I've done a number of these procedures, including one last week, and another to be done next week. It's amazingly simple--mix donor stool with water in a blender, pour the suspension through filter paper twice, and then administer 25 mL of the suspension via an NG tube into the recipient. The patient typically experiences relief of symptoms within  24 hours. As pointed out in the article, there have not been any formal trials of this treatment. And as bad as it sounds, the patients I have treated didn't think twice when offered the treatment. Some have even sought out the treatment themselves after mulitple episodes of C. difficile. Here's an interesting paper on performing fecal transplantation at home with directions for do-it-your-selfers.

How many times must a....

....patient test negative for Clostridium difficile, before you can call him negative? The new PCR assays for toxin B detection are more sensitive, and therefore have higher negative predictive values, than the older enzyme immunoassays. And even for the EIAs, the data to support the common practice of sending “C. diff X 3” were pretty weak.

A simple retrospective study in the October Journal of Clinical Microbiology shows how low-yield a repeat C. difficile PCR is, when ordered within 7 days of a negative test. Among almost 300 patients with a negative test who were re-tested, only 10 positive results were obtained. One was a false positive (compared with gold standard cytotoxicity assay), and 7 of the remaining 9 were positive more than 7 days after the first test (and usually in the context of ongoing risk factors for C. difficile, or new onset of diarrhea).

If your lab uses PCR for C. difficile toxin detection, save money and time by abandoning the practice of sending repeated tests to "rule out C. diff".

C. difficile in the news

Tomorrow's Washington Post has an article on C. difficile, which unfortunately depicts the organism as a purely nosocomial pathogen. I recently blogged about contamination of the food supply with the organism and just last week cared for a patient with C. diff who had no exposure to hospitals or healthcare settings and had not taken antibiotics in the last year. I suspect we'll continue to see an increase of community-acquired cases. We still need to work on prevention in the hospital, but as for MRSA, VRE and many other bugs, hand hygiene should do the trick.

C. difficile in the hospital: Time to quit counting?

One of my IPs is assigned the task of looking at each inpatient with C. difficile and trying to determine whether the case should be classified as nosocomial. She says it drives her crazy. There's a new review in Clinical Infectious Diseases that looks at contamination of retail foods, primarily ground meat products, with C. difficile. The authors seem cautious in claiming that contamination of food leads to disease in humans, but given that we are increasingly seeing patients with C. difficile infection who have not had contact with healthcare facilities, it seems highly plausible. The editorial points out that new strains of C. difficile are constantly being imported into the hospital from the community. So when an inpatient who has never before been hospitalized develops C. difficile diarrhea on hospital day 12 is this from nosocomial acquisition or from the hamburger he ate a week before admission? Maybe I should quit driving my IP crazy.

PPIs: The Hospital Epidemiologist's New Challenge?

2 more studies (May 10 issue of the Archives of Internal Medicine- here and here) tie use of proton pump inhibitors (PPIs) to Clostridium difficile infection. These drugs have been linked to C. difficile in past reports, and have also been linked to hospital associated pneumonia. Although the risk is still generally small, these are among the top 3 most frequently prescribed classes of drugs in the US. I'm always amazed when I attend on Medicine how many people are on these drugs for unknown reasons. Some statistics reveal that 60-70% of people who take them don’t really need them. Maybe its time we expand our view of antibiotic stewardship in hospitals?

Holy crap!

As if hospital epidemiologists don't have enough to worry about, there's a new paper in Clinical Infectious Diseases that demonstrates that C. difficile is commonly aerosolized. It's yet another reason why hospitals should move quickly to all private rooms.