Tigecycline is a new first-in-class
glycylcycline antimicrobial agent with expanded broad-spectrum activity against both Gram-negative and Gram-positive aerobes and anaerobes, as well as atypical bacterial species. The spectrum of activity extends to clinically relevant susceptible and multidrug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, vancomycin-resistant enterococci, and Enterobacteriaceae, including extended-spectrum
beta-lactamase-producing strains.
Tigecycline is administered as an intravenous formulation and has been studied in the treatment of serious
polymicrobial infections, including complicated skin and skin-structure
infections and
intra-abdominal infections. Pharmacokinetic analysis of data from phase 1 trials of healthy subjects indicate that
tigecycline has a large volume of distribution, signifying extensive tissue penetration, and a long terminal elimination half-life (approximately 40 h), easily allowing for twice-daily dose administration.
Tigecycline penetrates well into
blister fluid, which supports the positive findings of phase 2 and 3 studies of the efficacy of
tigecycline in the treatment of serious skin and skin-structure
infections. Metabolic studies in humans have revealed that
tigecycline undergoes very limited metabolism and the primary route of elimination of unchanged
drug is through the feces, with glucuronidation and renal elimination as secondary routes. A preliminary pharmacokinetic (PK)/pharmacodynamic analysis in experimental animal models of
infection indicates that the efficacy of
tigecycline is probably best predicted by the ratio of the area under the concentration-time curve to the minimum inhibitory concentration. The expanded in vitro activity against a broad range of bacteria, including resistant pathogens, and favorable PK profile of
tigecycline suggest that this novel
antimicrobial agent should offer clinicians an option for the treatment of patients with serious
bacterial infections.