Tigecycline: in-vitro performance as a predictor of clinical efficacy

Abstract

The incidence of nosocomial disease caused by Gram-negative pathogens is increasing, and infections caused by Enterobacter, Klebsiella, Acinetobacter, Escherichia coli and Pseudomonas aeruginosa are more commonly refractive to traditional antimicrobial agents, including aminoglycosides, fluoroquinolones and broad-spectrum cephalosporins. The most important mechanism of resistance to beta-lactam antibiotics among Gram-negative bacilli involves the production of beta-lactamases. Extended-spectrum beta-lactamases are particularly worrisome, since they are often associated with multidrug resistance phenotypes, which can pose a significant therapeutic challenge. Novel agents for the treatment of Gram-negative infections are uncommon, as recent emphasis has been placed on the development of agents targeting drug-resistant strains of Gram-positive bacteria, e.g., streptococci, enterococci and staphylococci. Tigecycline, a semi-synthetic derivative of minocycline, has a unique and novel mechanism of action, which not only allows this agent to overcome the well-known tet gene-encoded resistance mechanisms, but also maintains its activity against Gram-negative pathogens producing a broad array of extended-spectrum beta-lactamases. Tigecycline is the first example of a new class of glycylcyclines with activity against a wide range of clinically important Gram-negative pathogens. Tigecycline has potent antimicrobial activity, and has been associated with an excellent therapeutic response in animal infection models and recently reported clinical trials, which reflect the effectiveness of tigecycline against pathogens causing intra-abdominal, skin and soft-tissue infections, including susceptible or multidrug-resistant strains of most Enterobacteriaceae, as well as anaerobic pathogens.