Dusting Off the Shelf: Polymyxin B?

Paul G. Auwaerter, MD


July 20, 2012

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Hi. This is Paul Auwaerter with Medscape Infectious Diseases, speaking from the Johns Hopkins University School of Medicine.

It seems that when I am on hospital rounds, more and more frequently we are encountering gram-negative organisms that have highly resistant profiles, and we are trying to sort out whether we have any parenteral or oral drugs available to treat these ill patients with infections. For example, KPC (Klebsiella pneumoniae carbapenemase)-producing organisms are highly resistant, and Pseudomonas aeruginosa is taking up more and more of our time in thinking about drug treatment.

I thought I would speak briefly about polymyxin B, which is far less famous than polymyxin E (colistin). Polymyxin B was one of a class of drugs -- the polymyxins A-E -- first discovered in the late 1940s. Only polymyxins B and E have ever proven to be clinically useful, but they of course fell into disfavor because of their reported problems with nephrotoxicity many years ago.

With the emergence of resistant organisms, colistin has received a fair amount of attention, but polymyxin B may also have its place, even though it is not commonly used nor do most susceptibility panels include it in their analyses. For example, you would have to look hard to find a study[1] from the SENTRY database published more than 6 years ago that found, at least for Pseudomonas aeruginosa, that 98.9% of isolates from more than 3000 isolates in North America were susceptible, and for Acinetobacter, the level was more than 98% for a smaller number of isolates.

There is a growing sense that there may be bit of difference between colistin and polymyxin B, with polymyxin B being perhaps superior, at least in vitro, for some organisms, such as Stenotrophomonas. One needs to remember that some gram-negative organisms, such as Serratia or indole-positive organisms, typically are intrinsically resistant to polymyxin B, and the toxicity profiles continue to include potential nephrotoxicity, neurotoxicity, or neuromuscular blockade.[2]

To determine whether an organism has in vitro susceptibility, most of the time one would have to perform a microdilution technique, because disk diffusion of the drug through agar renders the technique hard to interpret because of its cationic properties. However, a recent study from New York University[3] examined 40 patients who received conventional dosing (typically 15,000-25,000 IU daily in 2 divided doses) vs a single loading dose of 25,000 IU, and then adjustment of the dose according to a renal dosing protocol. They found that in most respiratory infections (which comprised most of their patients), polymyxin B achieved better microbiological eradication with the loading dose protocol, although there were no significant differences in overall outcomes. Much like colistin, a loading dose might be superior for eradication and perhaps for clinical outcomes (if larger studies are performed), so this is something that you may wish to entertain.

Finally, a number of investigators and perhaps companies are looking at some derivatives of polymyxins that might have fewer toxicities and yet still maintain some of their extraordinary effects on these highly resistant organisms.[4] Clearly, we are dusting off the shelf to look at some of our older drugs, and even some that are very similar to polymyxin B. Only time will tell with additional studies whether polymyxin B holds any kind of key difference compared with colistin, which we are typically more comfortable using.

Thanks very much for listening, and have a cool summer. Thanks.


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