Antibiotic Resistance Is All Around Us: IDWeek 2013

Paul G. Auwaerter, MD


October 21, 2013

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Hello. This is Paul Auwaerter with Medscape Infectious Diseases from the Johns Hopkins University Division of Infectious Diseases.

Having just returned from San Francisco and IDWeek, I thought I would take you through a very quick tour of some sessions that centered on antimicrobial resistance, a very big topic at the meeting. I wasn't able to make every session and this will do no justice to the presenters, but I thought I would pick up on a couple of comments that speakers brought up in each session that might be of interest to you.

First, gram-negative resistance is certainly the bane of many of our consultations when taking care of highly antibiotic-exposed patients. Nasia Safdar[1] from the University of Wisconsin reviewed some of the recent Centers for Disease Control and Prevention evidence suggesting that carbapenem-resistant organisms have now been described in 45 states in the United States. 4.6% of acute care hospitals in the United States have reported the organism, mostly Klebsiella species, and 92% of these people have been highly antibiotic-exposed.

Sadly, after reviewing the data, there is not much that is new to be learned about treating these highly resistant infections at this time. Still a favorite is monotherapy with an effective agent, at least for a pneumonic process, although there is perhaps some interesting evidence suggesting that colistin in combination with other drugs, such as rifampin, might be of help. Unfortunately, there is very little new information in that field.

Henry Chambers[2] focused on gram-positive organisms, as he has in many prior sessions, and gave a good overview of some of the problems right now, especially with persistent methicillin-resistant Staphylococcus aureus (MRSA) infection in the face of vancomycin. One of the basic issues is, how do we define failure or when do we consider salvage therapy? Is it at day 3 of vancomycin, day 5, day 7, or 9? Is it somewhat dependent on how well the patient is clinically doing or not?

This is all difficult, but the bit of data he did provide advocated ceftaroline (a new cephalosporin drug with MRSA activity) in combination with daptomycin as perhaps an alternative to other agents or to displace vancomycin in patients who are not thriving on that particular compound.

Michael Dudley[3] discussed some new antibacterials. The one I want to focus on is a novel beta-lactamase inhibitor called avibactam. This molecule can impair Ambler class A, C, and D carbapenemases, so some of our carbapenem-resistant Enterobacteriaceae organisms. This drug is currently in a number of phase 3 trials, combined with ceftazidime or ceftaroline. I think some of the important attributes that might be mentioned here is that although this is something that may help us combat some highly-resistant gram-negative infections, it does not appear to have activity against metalloproteinases (eg, NDM-1), and it doesn't have any anaerobic activity, unlike sulbactam and tazobactam when combined with other beta-lactams.

These drugs might make it to market soon, but they still have to go through the traditional US Food and Drug Administration process. Stay tuned, and maybe there will be some help in that venue.

Wesley Van Voorhis[4] from the University of Washington touched on the miracle of artemisinin compounds for malaria. Of historical interest, the Chinese have known about this for quite a while. It can elicit rapid killing of malaria parasites, but what I didn't know is that it has an incredibly short half-life. Also, when used as monotherapy, resistance emerges quickly. This is probably of no surprise. Artemisinin resistance has been described on a clinical basis in Southeast Asia.

Wes outlined the need to combine artemisinin with other medications to help prevent the emergence of resistance. Up until just recently, there was only the ability to detect resistance with clinical failures in patients. There is now a new laboratory-based assay that can help give better surveillance to the emergence of artemisinin resistance and make better geographic recommendations in terms of treating our patients with malaria.

Jeanne Marrazzo,[5] again from the University of Washington, touched on sexually transmitted diseases, especially gonorrhea, which has had some of the worst problems with antimicrobial resistance. She highlighted that 1% of isolates might now be resistant to ceftriaxone and 1.5% to cefixime. This is probably due to failure of eradication from mucosal surfaces in the oropharynx or perhaps the rectal area, especially in such populations as men who have sex with men.

What to do about this is difficult. There aren't many options, because many other agents have been exhausted. Exploring combination therapy, even with gentamicin, or awaiting new drug classes are in discussion.

Finally, a provocative session by Brad Spellberg[6] explored different ways -- thinking outside the box -- to tackle the problem of antibiotic resistance. We cannot outdo bacteria because they outnumber us and divide much more quickly, but some different approaches may well be entertained. There is not enough time to go into that in this brief blog, but he discussed perhaps not treating the bacteria but treating host responses, perhaps using procalcitonin or other biomarkers more aggressively, and different incentives for the pharmaceutical industry or private/public partnerships.

I have given you references for a Clinical Infectious Diseases article,[7] a Medscape Infectious Diseases article,[8] and a New England Journal of Medicine article[9] that were published by the so-called renegades John Bartlett, David Gilbert, and Brad Spellberg, who are doing great work to help stimulate thought in this important area. Thanks very much for listening.


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