Principles of antibiotic therapy.

The primary development in the area of antibiotic treatment for surgical infections in the last 5 years has been the expanded clinical importance of beta-lactamases in the protection of Gram-negative organisms from previously active drugs. To counter this problem, a series of new antibiotic agents has been developed, including new cephalosporins, carbapenems, quinolones, and beta-lactamase inhibitors. This article describes the various beta-lactamases and their mechanisms of action, and details the activity of new antibiotic agents against resistant Gram-negative organisms. Recent information on the importance of combination therapy for patients with severe Gram-negative infections is reviewed. The use of optimized aminoglycoside dosing regimens, including once-a-day dosing, provides an additional strategy for treating serious Gram-negative infections.