Antibiotic prophylaxis isn't needed for removal of below the knee orthopedic implants?

Wow, it has been wicked cold this week and it's only going to get colder. It's so cold that I stayed inside and read JAMA RCTs instead of racing to the mall and fighting for discounted gift wrap. Besides adding to my ID knowledge, perhaps this latest polar vortex is also behind the reduced flammability of the ID profession? One can only hope.

The folks that follow me on twitter know the real reason I'm staying current on JAMA studies is that I've recently accepted a position as an Associate Editor for a new JAMA journal called JAMA Network Open. This open-access journal will begin accepting manuscripts in early 2018. Get those fingers typing - one way to protect yourself from frostbite...

In the Boxing Day issue of JAMA there was a very nice multicenter, double-blind RCT comparing surgical site infection rates post removal of below-the-knee orthopedic implants in patients receiving 1g cefazolin vs saline placebo. The 470 randomized patients were from 19 hospitals in the Netherlands and patients were excluded if they had active infection, fistula or were receiving antibiotics. Outcomes followed CDC definitions. Implant removal is considered a clean procedure with expected SSI rates of 2 to 3.3%, so apparently antibiotic prophylaxis isn't indicated; although reported SSI rates have been higher in removal vs implantation procedures, so some recommend prophylaxis.

Spoiler alert: The study was negative. 13.2% of patients in the cefazolin arm and 14.9% in the placebo arm developed SSI, (absolute risk difference, −1.7 [95% CI, −8.0 to 4.6], P = .60). Results below in Table 2. Thus, with a negative study, I headed to the sample size calculations section where the authors stated that they powered the study with an estimated SSI rate of 3.3% in the cefazolin arm and 10% in the placebo arm based on the SSI rates in clean-contamined procedures and recent Dutch retrospective studies, respectively.

Few thoughts. First, this is an underpowered study. It's true that they hit their target sample size, but their estimates were completed using rosy expectations for the benefits of cefazolin and were not selected based on clinically meaningful reductions in SSI. Many might think a 2% absolute reduction in SSI is clinically meaningful. Second, the authors suggest that the high rates of SSI might have resulted from very low thresholds for starting antibiotics if there was "the slightest suspicion of a SSI." Since CDC definitions define SSI based on receipt of antibiotic treatment, this behavior could have biased the rates. Finally, deep SSI rates were 0.4% (1 patient) in the cefazolin group and a far higher 2.9% (7 patients) in the placebo group, (absolute risk difference, −2.5 [95% CI, −5.7 to 0.4]). Since the study was powered for the primary outcome, all SSI, not much was made of the big difference in deep SSI. 

The end result might be disappointing but this is no discredit to the authors and clinicians behind the study - RCTs are very hard to design and implement  - thumbs up for all their efforts. With that said, I would prescribe cefazolin as a peri-operative antibiotic during implant removal below the knee since a 2% absolute reduction in all SSI and a 2.5% reduction in deep SSI are both clinically meaningful benefits. I will then wait for another larger study powered using clinically meaningful SSI targets, including deep SSI.

Proton Pump Inhibitors and ESBL

We have written frequently about the many HAI and MDRO that have been linked to PPI use including VAP, CAP, HAP in non-ICU settings, SBP in patients with cirrhosis, and, of course, C. difficile. In the US, PPIs are the third most prescribed medication, they are addictive since withdrawal symptoms can develop and are now available over-the-counter.

Researchers at Amphia Hospital, an 850-bed teaching facility in the Netherlands, completed two prevalence studies (November 2014 and 2015) on all adult patients who had stayed for no more than 2 days. The cross-section study just published in CID (free full text) linked rectal carriage of ESBL-producing Enterobacteriaceae to pre-admission use of PPI and H2-antagonists among other factors.

Rectal cultures were available from 570 patients and 259 (45%) had a history of PPI use, while very few used H2-blockers or antacids. I have included the univariable and multivariable analyses below. More than concurrent antibiotic use or prior hospital admission, PPIs were associated with four times the risk of ESBL rectal carriage. (OR 3.89, 95% CI 1.65-9.19).  This is a very nicely completed study and provides more evidence supporting the inclusion of PPIs targets in our "antimicrobial" stewardship programs.

Open access: the train has left the station

More and more scientific research is freely accessible via the Internet. In this guest post, Microbiologist Willem van Schaik welcomes this change.

Earlier this month the Royal Netherlands Academy of Arts and Sciences hosted a meeting in the stately Trippenhuis building on recent developments in the field of open access publishing. In this form of publishing, scientific articles are published online, and can be read at no extra cost by anyone with an Internet connection. How much has the scientific world really been changed by open access?

Until recently, the process of publishing scientific articles followed a well-trodden path. Scientists would write a manuscript describing their finding and then would send this to a journal for publication. This journal then arranged for other scientists to complete peer review of the manuscript and if everything appeared satisfactory, the article was published in the journal. The authors then had to hand away their copyright to the publisher of the journal and finally the publisher only allowed access to the article to institutions that had paid a subscription fee.

This is a particularly successful business model for scientific publishers such as Elsevier, Springer, John Wiley & Sons, Nature Publishing Group and many others. These traditional publishers have profit margins well above 30% and earn approximately $ 2 billion per year.

This situation is clearly unsustainable. Because scientific research is mostly funded by governments (ergo the taxpayers), all over the world, tax revenues are funneled into the pockets of the shareholders of major publishers. To make matters worse, the same taxpayers are not given free access to the results of the research that they helped to fund. This is highly relevant in medical fields where doctors and patients are cut off from important scientific information.

In open access publishing the peer review process is the same as in traditional journals, but the authors of the article have to pay a fee for it to be published; however, upon on-line publication, the article is immediately accessible to everyone. In 2011, 12 percent of scientific articles were published under an open access license and this number continues to increase, especially as governments (in the European Union through the Horizon 2020 program, for example) make it a requirement that the scientific articles that have been funded by public money be made freely accessible to everyone.

Ultimately, almost everyone agrees with the principles of open access, but its interpretation and implementation is not always so easy. First, the cost of a publication in some open access journals can be remarkably high. This is especially true for open-access journals published by for-profit publishers. For example, the journal Cell Reports (published by Elsevier) charges $ 5,000 per published article. Particularly in the social sciences and humanities this much money can be difficult to cough up and this may be one of the reasons why in these fields the number of articles published under open access licenses remains fairly limited.

Some traditional (closed access) journals, allow the authors to pay a fee to make their individual article openly accessible, but in this type of hybrid open access, the researcher actually pays twice: once through the university library fees and once from their own research budget.

Besides commercial publishers, there are also non-profit open-access publishers. Here the publication costs can be significantly lower and can often be waived if the authors do not have sufficient funds to pay for the publication.

The best-known non-profit publisher of scientific articles, the Public Library of Science (PLOS), mainly focuses on the biological and biomedical sciences. PLOS ONE, the largest journal in the PLOS-stable, also publishes articles from other fields, but at relatively low numbers. It seems that open-access train has long since left the station in biomedicine, but in other areas the train is still waiting for passengers! Two exciting recent initiatives are the Open Library of Humanities (a non-profit open access initiative in the social sciences) and PeerJ, which has a revolutionary new publishing model.

But are there still obstacles on the open access train’s tracks? One problem is the explosive growth of so-called predatory open access journals. These journals target gullible scientists with the aim to have them pay their article processing fee with the promise of fast (read: non-existent) peer review. Researchers receive spam from these “journals” on a daily basis. Besides being annoying, the dangers of predatory open access journals should not be overestimated, even if they are almost always easy to recognize as scams. In fact, these journals are not unlike the infamous 419 email scams in which a Nigerian prince promises to park millions of dollars in your bank account. With a healthy dose of skepticism (a trait that should be natural to all scientists), predatory open access journals, just like these email scams, should not be successful.

Some claim that the quality of open access journals is lower than that of traditional journals, because the publisher has a financial interest in publishing as many articles as possible. This is not a valid argument: bona-fide journals (both open and closed access) cannot publish everything that is being sent to them, since these journals would quickly become known as a dumping ground of articles of highly dubious quality, in which no reputable scientist would want to publish. Indeed, several open access journals (eg BMJ, PLOS Biology and eLife) are already seen as ranking at or near the top of their fields.

The general expectation during the symposium of the Royal Netherlands Academy of Arts and Sciences was that in the coming years, more and more science will be available through open access, because of new regulations by governments and an increased desire of scientists to have their work read by the widest possible audience. In many cases when researchers publish their work in closed access journals, they can already post their manuscripts in freely accessible public databases, like PubMedCentral, arXiv or Figshare. In the end, the open access publishing model for the dissemination of scientific knowledge will reduce costs and be more efficient than traditional publishing models, benefiting us all, as scientists and as taxpayers.

Willem van Schaik is an Assistant Professor at the Department of Medical Microbiology of the University Medical Center Utrecht (Utrecht, The Netherlands). His research focuses on the genomics of antibiotic-resistant opportunistic bacteria and the evolution of drug resistance. Willem is an Academic Editor for PLOS ONE. His Google Scholar profile can be found here and his Twitter here.

99% of Dutch Chickens Contaminated with ESBL Strains

From De Telegraaf (De nummer 1 in nieuws), we have a report that 99% of retail chickens produced with intensive farming and sold in Dutch Supermarkets are contaminated with ESBL-containing bacteria.  Organic chicken appears to be far less contaminated, perhaps 1/8th as likely.  My Dutch is a little rusty, so I've provided the sources. Either way, fear the kipfilet!!

Sources:
1. De Telegraaf article (Dutch)
2. Radio Netherlands Worldwide (English)
3. Consumentenbond 1/31/2012 (Dutch)

UPDATE:  Overdevest et al. (EID 2011:17(7) July) reported 80% (71/89) of chicken samples from random grocery stores collected in fall 2009 in the southern part of the Netherlands contained ESBL genes. The authors noted that "ESBL-producing Enterobacteriaceae derived from meat and hospitalized patients showed a high degree of similarity of resistance genes and MLST patterns. Genotype bla_CTX-M-1 was the most frequent drug resistance gene in chicken meat and humans and the second most frequent in blood cultures."  h/t Jan Kluytmans