Monday, August 07, 2006

Pulling old antibiotics off the shelf

Gram negative infections in hospitalized patients are re-emerging, along with multiple antibiotic resistance. Options for dealing with such infections are limited because, with the exception of tygecycline the antibiotic pipeline is running dry. Tygecycline is a welcome addition to the formulary and may be an option for some, but certainly not all multiply resistant gram negative infections.

The June issue of Clinical Medicine and Research contains a review of the use of polymyxins for such multiply resistant gram negative infections. Polymyxins are polypeptide cationic antibiotics. The commercially available parenteral polymyxins, colistin (polymyxin E) and polymyxin B, were used extensively for a number of years before falling out of favor in the 1960s due to concerns about toxicity and the emergence of newer agents. The toxicity is primarily renal and neuromuscular (similar to aminoglycosides) and, the article cites more recent literature to suggest that this toxicity is less severe, or more manageable than reported decades ago.

We’ve been there before with polymyxins. This paper provides a memory jog back to my days as a Vanderbilt medical student. When I was doing my senior elective in infectious disease the VA hospital was in the throes of a severe epidemic of Serratia marcescens resistant to all commercially available antibiotics. It was 1974. Our big guns for gram negative infections were gentamicin and carbenicillin. The ID folks were able to get amikacin for some patients but it was investigational (then known as BBK8) and difficult to obtain. The polymyxins, which had already fallen into disuse by that time, were not effective against Serratia. Synergy against Serratia, however, was known to occur between the polymyxins and sulfamethoxazole/trimethoprim. The combination of sulfamethoxazole, trimethoprim and polymyxin E (STP) proved clinically effective against the infection. The Serratia epidemic and the use of STP were reported here in Antimicrob. Agents and Chemother. in 1976.

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