The end of post-op prophylactic antibiotics?

One of the best approaches we have for dealing with in-hospital antimicrobial resistance is stewardship - using antibiotics only when the patient is most likely to benefit. It's been known for a long time that there is little benefit in extending prophylactic antibiotics beyond the end of surgery, yet this practice still persists. Imamura et al. just published an RCT in Lancet ID that examined the possible benefits of extending prophylaxis in patients with gastric cancer undergoing distal gastrectomy for cure.

The trial was an open-label, stratified (by ASA score) randomized trial in seven hospitals. All patients were assigned (1:1) to receive cefazolin 1g before incision and every 3 hours. Those in the extended prophylaxis group received 1g at closure and twice daily for two  postoperative days.  Using CDC definitions, infection control staff monitored for SSI while in hospital and surgeons monitored post-discharge for 30 days.

In the intention-to-treat analysis, 176 patients received standard prophylaxis and 179 received extended prophylaxis.  Randomization appeared adequate with similar operative times and estimated blood loss in each arm; however, 4 patients in the extended prophylaxis arm received transfusions versus none in the standard arm.  I've pasted Table 2 above, so you can see the results broken down into superfical and deep SSI.  Twice as many patients in the extended arm developed an SSI (RR 0.51 95% CI 0.22-1.16), but this was not statistically significant. Caveats: open-label study and SSI not monitored by independent researchers after discharge.

The authors and the accompanying editorial (both behind a paywall) each conclude that extended prophylaxis is not recommended. Although it is likely true, as Hedrick and Sawyer state in their editorial, that "the study is unlikely to have a major impact in the USA and other countries where the maximum duration of perioperative antibiotics is limited to 24 h and is carefully monitored and regulated."

New and improved!

Eli, Dan and I thought it was time for a blog makeover. We're now in our fourth year, have posted over 1,000 pieces, and readership continues to expand. So today we've introduced a new look and some cool new features:

• At the bottom of each post, you'll note a string of colorful icons that allow you to share the post with your friends in several different ways. Clicking the first icon (the green one) enables you to share the post in multiple applications simultaneously. So next time you see a post that resonates with you, hit the button!
• In the sidebar, you'll find Featured Posts. Here each of us will choose one of our recent posts that we think you shouldn't miss.
• Also in the sidebar further down, you'll find another new feature, Presentations. Here you can view lectures that we and others have recently given that may be useful to you.

There are now several ways to follow us. If you're a regular Facebook user, by clicking "like" in the sidebar, each new post that we write will automatically show up on your wall. If you're a Twitterite, each post can be twittered to you by following eliowa. If you're averse to those, new posts can be emailed to you (see sidebar), or fed to your Google reader. So, one way or another, keep following, and send us your comments!

Graphic:  Totally Serial

Detecting antibiotic resistance is hard!

Eli linked me to this recent Nature commentary on the limitations of current screening tests for certain antibiotic resistant gram-negatives (those that carry carbapenemases). Because the resistance mechanisms for gram-negative bacteria are so complex and varied, resistance detection in the clinical microbiology laboratory has become a huge challenge. Furthermore, even if tests perform well to detect a specific single mechanism of resistance, what about bugs that use combinations of mechanisms? Consider how complicated it turned out to be to refine molecular methods for that comparatively simple organism, MRSA....emergence of empty cassette variants that result in false positives, divergent mecA genes that result in false negatives, and on and on we will go.  Multiply that complexity by a thousand fold for gram-negatives.


What this means is that every clinical microbiology laboratory needs a smart, well-trained clinical microbiologist--to optimize testing strategies, to understand the limitations of currently available methods, and to anticipate and detect problems with shiny new methods.  As the authors of the Nature commentary point out, too many hospitals are trying to cut costs in their microbiology laboratories, including being unwilling to staff them appropriately.  I was asked to talk at SHEA on molecular testing and infection prevention, and covered some of these issues (see below).
SHEA 2012 Diekema

An Iowa City Non-Virtual Chat Room

Mike dropped by Iowa City today to give a talk on C. difficile for the 14th Annual Update in Infectious Diseases at UI. Dan is the Course Director.  The talks were all excellent.  Next year, you guys have to swing by.  Next up tonight is the Great Plains Emerging Infectious Diseases Conference put on by the UI College of Public Health and directed by Tara Smith.

photo credit: Carl Lebuhn, MD

Alcohol hand rub prevents rhinovirus infection (despite the authors’ claims) and it can get you really pissed!

This morning, two kind folks independently pointed me to new reports on the efficacy of alcohol hand rub.  The first report in CID by Ronald Turner et al. describes a randomized trial of the efficacy of 62% ethanol hand rub for the prevention of rhinovirus infection.  In the study, 116 volunteers were randomized to the active hand rub group and asked to apply the hand rub after each hand washing episode and also every three hours for 9 weeks. Apparently, there is data showing ethanol hand rub prevents rhinovirus for up to 4 hours. The 96 unblinded controls were asked to practice their usual hand hygiene routine. All enrolled kept a diary of symptoms, had weekly nasal lavage for PCR and two additional nasal lavages if they developed cold symptoms.

The results of the study were somewhat surprising, especially if you just read the abstract and focus on the highlighted p-values.  The authors conclude that "hand disinfection did not reduce rhinovirus infection or rhinovirus-related common cold illnesses."  When you look more closely, only 39% of treated subject developed a confirmed infection versus 49% of untreated. Sure, the p=0.3, but this is just because the study is underpowered. Oh, and reported common cold illnesses were lower in the hand disinfection arm (56% vs 72%, p=0.01). And then read their conclusion - a bit of an over-reach: "the results of our study call into question commonly held assumptions about the route of spread of rhinovirus infection..."  Wow. Do one underpowered study - not blinded, cherry pick the results and then claim rhinovirus might not be spread via hands?

h/t Charlesnika Evans 

The second report highlights the efficacy of hand rub in getting kids wasted.  The MSNBC.com report by Jane Weaver (with Today Show video) describes how 16 LA teens have been treated for intoxication after guzzling 120-proof alcohol hand rub.  Some might even be distilling it first.  Very ingenious.

h/t Mark Vander Weg

If you're criticizing methods, your methods better be strong

This morning I innocently set out to review a new study in ARIC that looks at methodological issues in C. difficile outcomes studies assessing the association between infection and excess hospital stay.  The authors make a very important point in the paper: "The studies did not collect data concerning the time of onset of CDI; therefore, it is not possible to exclude the possibility of reverse causality, in which longer lengths of hospitalisation may have increased the risk of CDI." They then go on to discuss time-dependent bias and recommend the use of multi-state models...we've made this point before.

What caused me the emotional anguish was their Table 1 that lists the 16 studies included in the review. In column two, three of the studies are listed as retrospective case-control studies...what??!!  How can you do a case-control study with an outcome being hospital length of stay?  I'm pretty sure you can't, at least not easily.

You see, a case-control study requires identifying an outcome and looking back for risk-factors associated with the outcome. For example, you could look at 50 people that died (and 100 that didn't die) and see how many had CDI, to determine if CDI was a risk-factor for death.  For length of stay, I can't even make up a good way to do a case-control study.  Would you find patients who stay >14 days and compare them to patients that stay <14 days? The three studies listed MUST have been cohort studies, so why did the authors of the ARIC paper seeking to teach us about proper methods for outcomes studies list them as case-control studies? Perhaps they pasted them from the individual studies' methods sections?

Just to confirm this, I looked at all three papers: (Ananthakrishnan (2008), Bajaj (2010), Pepin 2005).

Pepin: from the Methods  - "We compared mortality and total length of hospital stay among inpatients in whom nosocomial CDAD developed and among control subjects without CDAD."  This is a cohort study - exposed and unexposed to CDAD, looking forward to outcomes.  Just because they incorrectly use the word control, doesn't make this a case-control study. (Strike 1)

Ananthakrishnan: "Our primary case group (C difficile–IBD group) included patients who had a primary diagnosis of C difficile colitis and a secondary diagnosis of either Chrohn's Disease (CD) or Ulcerative Colitis (UC). Patients admitted to hospital with a primary diagnosis of CD or UC without a diagnosis of C. difficile colitis formed one of our comparison groups (IBD group)." Another cohort study - defined by the exposure to C. difficile and not by the outcome. (Strike 2)

Bajaj: "Among the cohort of hospitalized patients with any diagnosis of cirrhosis, co-existing diagnosis of C. difficile was associated with significantly greater in-hospital mortality."(Strike 3)

The error of incorrectly describing cohort studies as case-control studies is very common - enough to be a pandemic.  The journal CID is one of the worst offenders. One of my favorite examples is this recent VAP treatment cohort study described as a case-control study in the title!  When I've mentioned the problem to CID editors, they suggest I write a letter.  You can't write letters for each issue.

OK: Cohort - exposed/unexposed look forward in time to the outcome. Case-control - find outcomes and look back for exposures. Got it?  EOR

CDC "shameful and unethical"???

I'm heading to Delaware in a few weeks to speak at an Infectious Diseases symposium. My assignment is to talk about myths and controversies in infection prevention. It's a juicy topic, and one that I find fascinating. So once again I'll be speaking on "Getting to Zero," a myth so big it rivals the Tooth Fairy. We've blogged about it many times, with Eli recently attributing the death of Facts to be partly due to this big lie.

There are a couple of interesting recent developments on the GTZ front. First, one of the biggest promoters of the concept, APIC, appears to have expunged it from its website. Good thing I made screenshots of the old website for posterity's sake! Secondly, Paul Levy, a former hospital administrator, who writes the blog Not Running a Hospital, devoted a posting to GTZ yesterday. The title of the post is "Unethical and Shameful Behavior at the CDC." He blasts CDC and its director, Tom Frieden, for the use of the standardized infection ratio (a "meaningless methodology"), risk adjustment (he questions why medical school affiliation should impact infection rates), and the use of benchmarks (since zero is the goal). Unethical and shameful? Really?

The concept of Getting to Zero HAIs is at least 5 years old, and I find it amazing that I have yet to meet an infectious diseases physician (you know, those people that every day actually take care of patients with infections) who believes that HAI rates can be reduced to zero. Those of us in the reality-based community understand that when you immunosuppress patients as profoundly as we do, and use ever more invasive devices for ever longer durations of time, believing in Getting to Zero requires ingesting an awful lot of kool-aid. We certainly have to keep trying our best to reduce infections, but we also have to recognize that the advances in medicine are double-edged swords, and honesty requires that we acknowledge that infections will continue to occur despite our best efforts.

So kudos to APIC for moving on, and to CDC for the great work it does with not nearly enough resources. 


Graphic: Jeffrey Sumber