Emerging Issues in the Management of Infections Caused by Multi-Drug-Resistant, Gram-Negative Bacilli

Abstract

The past decade has witnessed the continued emergence and spread of multidrug resistance in gram-negative bacilli. Infections caused by multi-drug-resistant, gram-negative bacilli lead, in many instances, to increased morbidity and mortality, prolonged hospital stays, and the use of broad-spectrum antibiotics. Recent literature from 1990 to the present is reviewed in order to put into perspective the effects of increasing incidences of multi-drug-resistant gram-negative bacilli on patient care. Factors important in the emergence and spread of multi-drug-resistant gram-negative bacilli include increasing severity of illness in hospitalized patients, poor attention to infection control practices by healthcare personnel, and the large, often indiscriminate use of broad-spectrum antimicrobial agents. Unlike earlier iterations, there is no steady stream of newer antimicrobial agents in development to address the problem. The only broad-spectrum antimicrobial agent with activity against multi-resistant, gram-negative bacilli and with potential to be licensed in the foreseeable future is tigecycline. Tigecycline, the first member of a novel class of antimicrobials, the glycylcyclines, is a structural derivative of minocycline, with potent activity against most gram-positive, gram-negative (excepting Pseudomonas aeruginosa and Proteus spp.) and anaerobic species. Phase 3 trials indicate that tigecycline is effective for treating both complicated skin and skin structure infections, and intra-abdominal infections in hospitalized patients. Tigecycline promises to be an important addition to our monotherapy armamentarium, complementing essential efforts to promote compliance with good infection control measures and rational use of currently available antimicrobial agents.