Tigecycline: an investigational glycylcycline antimicrobial with activity against resistant gram-positive organisms

Mark W Garrison, Joshua J Neumiller, Stephen M Setter
Clinical Therapeutics 2005, 27 (1): 12-22

BACKGROUND: Bacterial resistance to currently available antimicrobials is an increasing concern, particularly among various gram-positive organisms such as drug-resistant pneumococci, methicillin-resistant staphylococci, and drug-resistant enterococci. Tigecycline is an investigational glycylcycline antibiotic that shows promising activity against these resistant gram-positive organisms.

OBJECTIVE: : This paper reviews the pharmacology, pharmacokinetic and pharmacodynamic properties, in vitro and in vivo activity, safety profile, and potential role of tigecycline in the management of gram-positive infections involving resistant microbes.

METHODS: Articles included in this review were identified through a search of MEDLINE from 1998 through 2004 using the terms tigecycline and GAR-936. Abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1998 to 2003 were searched using the same terms. The reference lists of identified articles were also reviewed for pertinent publications.

RESULTS: Whereas resistance has developed with many of the earlier tetracycline derivatives, tigecycline appears to have a reduced potential for resistance. Several reports have evaluated the in vitro activity of this agent against a number of organisms. It has exhibited pronounced activity against most gram-positive microbes, including resistant strains (eg, drug-resistant pneumococci, methicillin-resistant staphylococci, resistant enterococci). Tigecycline has also shown useful activity against many clinically important gram-negative microbes. In vivo studies of tigecycline are limited. Only 2 clinical trials have been reported to date, one in patients with complicated skin and skin-structure infections and the other in patients with complicated intra-abdominal infections. In these studies, tigecycline therapy resulted in clinical cures in more than two thirds of evaluable patients. Tigecycline was well tolerated in both studies; nausea and vomiting were the most common adverse events.

CONCLUSIONS: Although published clinical trials involving tigecycline are limited and additional trials are needed, preliminary reports on its use in the treatment of gram-positive infections are encouraging. Tigecycline has favorable pharmacokinetic properties and, apart from gastrointestinal adverse events, appears to be well tolerated.

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