COMMENTARY

Six Drugs for Resistant Pathogens: Good News From IDWeek 2015

Paul G. Auwaerter, MD

Disclosures

November 02, 2015

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Hello. This is Paul Auwaerter with Medscape Infectious Diseases and the Johns Hopkins University School of Medicine. IDWeek in San Diego was a huge success, the most well-attended ever for this meeting. The meeting captured most of the important clinical and research advances in our field—it was overwhelming. I wanted to make a few comments (by no means comprehensive) on some of the sessions I attended and the highlights that impressed me.

Without a doubt, the story of Ebola captured our attention, not only because of the breadth of experience and reports from the treatment centers but because of the public health logistics and interventions that have made such huge strides over the past year. The personal story [of an Ebola patient who was an infectious diseases physician] was also well captured by Ian Crozier, who related his own experience.

The conference highlighted what has been increasingly reported in the medical literature. For survivors of Ebola, there are both infectious and postinfectious consequences. These include not only a postinfectious fatigue or arthralgia syndrome, but the virus can also persist in the body—as in Dr Crozier's case, in his eye. Excretion in semen and breast milk may provide important insights into why Ebola can crop up and continue, even after people have apparently fully recovered from the initial infection. In a year, we will learn much more.

The second presentation was given by Henry "Chip" Chambers, who was honored with a named lecture (the Maxwell Finland Lecture). In his important lecture, he related that infectious diseases clinical research for current and new anti-infectives has been woefully inadequate. Drugs are approved for conditions for which we don't commonly use those drugs. For example, ceftolozane/tazobactam, a wonderful agent for multiple drug-resistant Pseudomonas, was approved for complicated intra-abdominal infection. That isn't a condition that any of us would envision using this drug for.

Dr Chambers highlighted his paper, authored with Scott Evans and colleagues,[1] that provides a new model for assessing whether a particular anti-infective is worthy and perhaps better than existing treatments. This model uses the desirability of outcome ranking (DOOR) and response adjusted for duration of antibiotic risk (RADAR) acronyms. The concept is that for any given treatment or duration, patients may improve equally on both drugs, but one drug might have more side effects or a higher recurrence rate than the other. These may not be captured by so-called "primary endpoints" alone.

I thought it was quite a provocative talk and certainly worthy of additional discussion. Also, I found of great interest the endocarditis guideline update. Many of these questions still press us in terms of choices, without fundamentally good-quality evidence, when caring for our patients.

Lastly, compared with 2008 and 2012, when only one drug was approved by the US Food and Drug Administration (FDA), six drugs have now been approved in the past 2 years. There was great interest in the new drugs, including ceftazidime/avibactam, which I think will certainly fill a niche for carbapenemases. Ceftolozane/tazobactam is seemingly targeted well for treating highly resistant Pseudomonas aeruginosa infections, with high levels of resistance, and perhaps with fewer toxicities than alternatives such as aminoglycosides or polymyxin compounds. Isavuconazonium sulfate is active against molds and Aspergillus, maybe with a slightly cleaner side-effect profile than voriconazole. The data against Mucor species are limited, but it has received an FDA indication because of limited current drug availability, even though only 37 patients were presented to the FDA.

Peramivir is an injectable neuraminidase inhibitor approved for uncomplicated influenza, although that is probably not how it will be used. It will be used in severely ill hospitalized patients. We don't have much data other than limited evidence from the H1N1 pandemic era,[2] when the drug looked like it was tolerated, but little could be said about efficacy. In the next year or two, hopefully with some published studies, we'll get some insights about whether this drug is helpful for hospitalized patients, even several days after symptom onset.

Lastly, for many viral infections and transplant infections, such as those caused by adenovirus, there have been concerns about using drugs such as cidofovir that are toxic, with minimal improvement. Brincidofovir was reviewed. It is not yet FDA-approved but looks very exciting in being perhaps more efficacious as an antiviral agent for pathogens such as adenovirus, double-stranded DNA, and viruses, all with much less toxicity compared with cidofovir, and it is available in oral formulations.

These are just some quick points from the meeting that impressed me. I have always greatly enjoyed this meeting and learned a great deal. Thanks for listening.

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