Emerging issues in the management of infections caused by multidrug-resistant gram-negative bacteria.

Accumulating evidence indicates that treating seriously ill infected patients with active antibiotics early in the course of infection is critical to improving outcomes. The most common reason for ineffective empiric therapy is resistance to the agents used. Gram-negative bacteria are becoming increasingly resistant to many commonly used antibiotics, and some cases require older, more toxic antibiotics for adequate microbial coverage. The diversity of resistance mechanisms that underly multidrug resistance makes developing effective new antimicrobial agents very difficult, especially against problematic species such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. This growing problem requires a multipronged strategy that includes adherence to infection control principles, parsimonious and rational use of current antimicrobial agents, and development of new agents active against multidrug-resistant pathogens.