Journal
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
Volume 63, Issue 13, Pages 1235-1243Publisher
AMER SOC HEALTH-SYSTEM PHARMACISTS
DOI: 10.2146/ajhp050487
Keywords
antiinfective agents; dosage; drug administration; drug interactions; infections; kidney failure; liver diseases; mechanism of action; metabolism; pharmacokinetics; spectrum microbial; tigecycline; toxicity
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Purpose. The pharmacology, spectrum of activity, pharmacokinetics, clinical efficacy, adverse events, dosage and administration, drug interactions, and place in therapy of tigecycline are reviewed. Summary. Tigecycline is the first of a new class of antimicrobials, the glycylcyclines,to receive approved labeling from the Food and Drug Administration. Similar to tetracyclines, glycylcyclines contain the central four-ring carbocyclic skeleton, with a substitution at the D-9 position. This substitution confers expanded broad-spectrum activity and defense against antimicrobial efflux pumps and ribosomal protection mechanisms. Tigecycline covers a broad spectrum of gram-positive (including resistant isolates), gram-negative (including extended-spectrum beta-lactamase producing organisms), and anaerobic pathogens. It does not exhibit activity against Pseudomonas aeruginosa and Proteus species. Clinical efficacy has been demonstrated in complicated skin and skin structure infections and intraabdominal infections. Tigecycline is administered intravenously and exhibits linear pharmacokinetics. The drug does not undergo extensive metabolism and works independently of the cytochrome P-450 isoenzyme system and therefore does not affect medications metabolized by these enzymes. Tigecycline is administered as a 100-mg i.v. loading dose followed by 50 mg i.v. every 12 hours. Hepatic dosage adjustment is necessary for severe disease; however, no dosage adjustments are necessary for patients with renal impairment. Conclusion. Tigecycline is an alternative agent available for the treatment of resistant gram-negative and gram-positive infections, especially in patients with a history of a penicillin allergy or antimicrobial-related toxicities.
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