Antibiotic Resistance - A Global Problem

Today, The Lancet Infectious Diseases Commission on Antibiotic Resistance led by Otto Cars from the Swedish Institute for Communicable Disease Control has published "Antibiotic resistance—the need for global solutions." The stated goal of this 42-page tour-de-force is to "explore why antibiotic resistance has become such a problem worldwide, and, most importantly, propose solutions to avert the impending crisis."  The Commission is broken down into nine parts with each group of authors responsible for their individual sections. I've pasted the table of contents to the right (click to enlarge). The document discusses antimicrobial use in humans and animals including stewardship, improved diagnostics (hopefully Dan will comment on part 3), novel therapeutics and antibacterial drug discovery.

The Commission is accompanied by 7 commentaries from the global community, which are each worth a read. All articles are free to access once you set up a username and password.

These documents are largely focused on antibacterial use and development, which are incredibly important global problems that will require collaborative responses at the local, national and international level.

But much like the recent Frontline documentary that, as Dan mentioned, did not have "enough discussion of the hard work of basic infection prevention," infection control is only briefly mentioned in the main document. (Section 2, page 7) You can get the sense of the Commission's approach with this quote: "From a resistance perspective, prevention reduces antibiotic use and the spread of resistant bacteria; however, prevention is not the main strategy to control resistance because antibiotic use also needs to be controlled."

Of course, "benchmarking (open comparison of health-care facilities) of frequencies of health-care-associated infections is useful." Yet public reporting is only useful as far as we have effective methods to prevent the reported infections.

Despite these minor quibbles, this is an incredibly timely and tremendously useful report. The authors and the Journal should be congratulated. Let's hope it moves the needle towards more recognition and funding for antimicrobial discovery, antibiotic stewardship, and perhaps... infection prevention?

KPC (Yeah You Know Me)

Now that I have your attention, I wanted to point out a recent review in Lancet ID by Silvia Munoz-Price and colleagues. It's behind a paywall with a $31 charge, so hopefully you have access through your institution or can email one of the authors to request a copy. The co-authors do a wonderful job highlighting the emergence of KPC containing strains in the US (1996) and subsequent spread of these β-lactamases throughout the world. Importantly, they discuss treatment options (or lack thereof) and emphasize the important role that infection prevention will play for the foreseeable future. They also suggest that stewardship might be more relevant in plasmid (non-clonal) outbreaks.

Influenza Vaccine Has Miracle Powers After All*

This blog hasn't always been kind to the humble influenza vaccine. So in fairness to our trusty old vaccine friend, I'd like to highlight a recent study published in Lancet ID by Jeffrey Kwong and colleagues in Toronto. They utilized 19 years of data (1993-2011) from the universal health care system databases in Ontario Canada to assess the risk of Guillane-Barré Syndrome (GBS) after influenza vaccination and after influenza infection. They accomplished this using a self-controlled, risk-interval design. This design compares the risk of GBS in a predefined risk interval after exposure to the vaccine or infection and compares it to the risk in the control period outside the selected exposure period. In this case, the exposure period was the first 6 weeks post exposure and the control period was weeks 9-42. Importantly, the patients were conditioned on having GBS in either the risk or control period and each patient served as their own control, which eliminates selection bias. Outcome of GBS was determined using ICD-9 or ICD-10 primary billing codes, which have reported positive predictive values in the 60% range. This is a limitation of the study.

They identified 2831 patients with GBS.  Within the 42 week period, 330 cases were preceded by influenza vaccination and 109 cases were preceded by influenza infection.  The risk of GBS was 1.5 times higher in the initial 6 weeks post vaccination compared to weeks 9-42. The risk peaked in the third week post vaccination with twice the risk. The risk was higher in patients ages 18-64 compared to older adults. Importantly, even this increased risk adds up to one GBS admission per 1 million vaccinated. I also don't think we can rule of influenza infection causing this post vaccine risk since people are more likely to receive vaccine when influenza virus is circulating in the community.

In the 6 weeks post influenza-coded healthcare encounter, the risk of GBS was 15 times higher than baseline and peaked at 61 times higher in the first week post infection. Pending a formal competing risk analysis, patients should continue to be informed of a small increased absolute risk of GBS associated with the vaccine, but also a large risk associated with the infection. Of course, there other benefits associated with influenza vaccination, which should also be discussed with patients. To be clear, influenza vaccine IS a miracle when it's compared to influenza infection.

Image source: wikipedia

*Title is just playing off the title of one of our prior posts on influenza vaccine. Nothing in medicine has miracle powers, since medicine is a science. However, if there is anything close to a miracle it would be vaccines. Antibiotics would be a close second.

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."

Learned Helplessness and Hand Hygiene

MSKCC's Kent Sepkowitz has a recent commentary in Lancet ID on hand hygiene.  He thinks that modern hospitals are too clean to benefit from hand-hygiene improvement efforts (I guess he hasn't read this paper). He concludes:

"The time has come for the infection control community to move on; please, no more cheerleading louder and harder to get thousands of people to improve their hygiene. We have to accept that our age-old dream of solving a complex problem cheaply and simply has failed. Instead, we must reacquaint ourselves with that lonely feeling familiar to clinicians when they realize a case is much more difficult than it appeared at first glance. In other words, we should embrace the intellectual audacity of our beloved Semmelweis but let go of his how-to manual. As he might tell us (loudly): an ineffective remedy is much worse than no remedy at all."

Is he right?  I don't think so.  There have been only 4 hand-hygiene intervention studies in the past few decades of high enough quality to warrant inclusion in the 2011 Cochrane Review. I say before we throw in the towel, bury our collective heads in the sand and go all Eeyore, we should probably do a few more than 4 good studies.  I also suspect that if we could really figure out why MRSA has declined in recent years, it would come down to hand hygiene improvements and not some expensive PCR.