Tigecycline: a novel glycylcycline.
Antibacterials have been in clinical use for almost 60 years; however, the effectiveness of these valuable agents has been diminished by widespread emergence of bacterial resistance. Tigecycline is the first in a new class of glycylcyclines with activity against a wide range of clinically important pathogens. Tigecycline has demonstrated potent microbiological activity and excellent therapeutic response in animal infection models and in recently reported phase III human clinical trials. It is effective against intra-abdominal and skin and soft tissue infections caused by susceptible or multidrug-resistant staphylococci, enterococci or streptococci as well as most Enterobacteriaceae and anaerobic pathogens. In clinical trials nausea and vomiting were the most common adverse events and were of a magnitude typical of those observed with tetracyclines in general. Additionally, tigecycline has proven to be efficacious in animal models of infection, including pneumonia, endocarditis and peritonitis. Tigecycline is only available as an intravenous agent and distributes extensively in tissues. Administration of a 100mg loading dose of tigecycline followed by twice-daily doses of 50mg yielded an apparent volume of distribution of 7-10 L/kg. Systemic clearance ranged from 0.2 to 0.3 L/h/kg and its half-life varied from 37 to 67 hours. The pharmacokinetics of tigecycline appear unaffected by sex, age, renal disease or the presence of food. Data from animal studies would suggest that time above the minimum inhibitory concentration is the pharmacodynamic factor that best correlates with bacterial eradication. The efficacy, safety profile and pharmacodynamic attributes of tigecycline support its continuing clinical development as empirical parenteral treatment of challenging nosocomial and community-acquired infections, including those caused by proven or suspected resistant pathogens.
Section of Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada. erubins@yahoo.com
Ethan
E
Rubinstein
David
D
Vaughan
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D002986:Clinical Trials as Topic; D006801:Humans; D008911:Minocycline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013754:Tetracyclines / Q000737:chemistry* / Q000494:pharmacology; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D013754:Tetracyclines; C087533:CL 331002; D000078304:Tigecycline; D008911:Minocycline