Combination antibiotic therapy is appropriate for nosocomial pneumonia in the intensive care unit

Pneumonia in the intensive care unit (ICU) has been associated with highly virulent pathogens and mortality rates of 30% to 70%. Initial empirical therapy for pneumonia in the ICU remains controversial. Monotherapy with a broad-spectrum beta-lactam or fluoroquinolone may reduce toxicities associated with aminoglycosides but in nosocomial settings may fail to cover relevant pathogens and may promote antimicrobial resistance. Combining antibiotics that act by different mechanisms may achieve synergistic killing, expand the antimicrobial spectrum, and limit the emergence of antimicrobial resistance. Unfortunately, this approach may increase costs and toxicities. A plethora of studies have assessed monotherapy or combinations of antimicrobials for empirical treatment of fever in immunocompromised hosts, but these studies cannot be extrapolated to nosocomial pneumonia. Few studies have compared these disparate therapeutic strategies for nosocomial pneumonia. In this review, we emphasize the limitations of existing literature and present an approach to therapy of severe nosocomial pneumonia. Despite potential toxicities, aminoglycosides may have an important adjunctive role as empirical therapy of severe nosocomial pneumonias (pending clarification of the responsible organism) or when P aeruginosa, Acinetobacter spp, or beta-lactamase-producing aerobic gram-negative bacteria are suspected. The alarming increase in antimicrobial resistance noted in nosocomial settings in recent years, a trend that may be facilitated by extensive use of particular classes of antibiotics, provides a compelling argument in favor of combination therapy. Novel strategies employing beta-lactam and fluoroquinolone combinations also have promise.