Wednesday, December 14, 2005

Is this the antimicrobial magic bullet?

Not quite, but tigecycline (Tygacil), a new tetracycline derivative (glycycycline) approved by the FDA in June 2005 and marketed by Wyeth pharmaceuticals is active against a wide spectrum of organisms and promises to be a useful addition to the antimicrobial arsenal. FDA approval processes are lengthy and drug companies, anxious to get products to the market, tend to launch antibiotics after approval of a limited number of indications that are restrictive when compared to the drug’s true range of efficacy. This invariably (and often appropriately) leads to “off label” use of antibiotics. Such may be true of tigecycline, approved only for complicated skin and soft tissue infections and complicated intra-abdominal infections. Certain pharmacokinetic advantages and a broad spectrum of activity suggest a wider range of potential use, but what other uses might be appropriate?

This review in the Journal of Antimicrobial Chemotherapy addresses the question by covering the basics of tigecycline’s antimicrobial activity and the relevant pharmacokinetics. As promising as tigecycline is, the article notes these caveats: 1) Gaps in the gram negative spectrum include Pseudomonas aeruginosa and the family Proteeae (the genera Proteus, Morganella, and Providencia). 2) Excellent tissue penetration occurs at the price of a very large volume of distribution and consequent low serum levels, raising concerns about its efficacy in bacteremic infections. 3) Predominant biliary excretion results in low urinary levels, limiting the efficacy in urinary tract infections. 4) Emergent resistance of some gram negative species was seen in phase three trials, serving to warn against indiscriminate use.

The article concludes “Whether or not significant resistance threats ultimately do emerge (and experience shows that they usually do!), it is excellent news to have a new agent with increased activity against Gram-negative as well as Gram-positive bacteria. Few others will come this decade” (Italics mine—I have previously blogged about the waning antibiotic development pipeline).

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