Tigecycline: The answer to beta-lactam and fluoroquinolone resistance?

Abstract

Patients with serious bacterial infections such as intra-abdominal infections and complicated skin and soft tissue infections are often treated empirically because a delay in appropriate initial antimicrobial therapy has been shown to significantly increase morbidity and mortality. Furthermore, pathogens that have developed resistance to mainstay therapeutic options are increasing in prevalence making these infections a challenge for physicians. Treatment guidelines for surgical and intra-abdominal infections recommend selection of an agent or a combination of agents with activity to cover both Gram-positive, Gram-negative organisms and anaerobes. Recommended agents include second-generation cephalosporins with anaerobic coverage, beta-lactam/beta-lactamase inhibitor agents, fluoroquinolone/metronidazole combinations and carbapenems. However, the effectiveness of these agents has come into question as once susceptible organisms are now showing signs of resistance to such antimicrobial therapies. Alternative agents specifically designed to overcome mechanisms of microbial resistance have been sought. The result of that search has been the development of a new class of antimicrobials termed glycylcyclines. The first of these novel antibacterials is tigecycline, with a broad spectrum of activity that includes coverage against vancomycin-resistant enterococci, methicillin-resistant S. aureus, and many species of multidrug-resistant Gram-negative bacteria. Tigecycline also has activity against most penicillin-susceptible and resistant Gram-positive organisms. Clinical trial experience with tigecycline has shown it to be at least as effective as current recommended regimens for the treatment of intra-abdominal infections and complicated skin and soft tissue infections. This new agent thus holds promise as an alternative to the beta-lactams and fluoroquinolones for the initial empiric treatment of serious bacterial infections.