Is double coverage of gram-negative organisms necessary?

PURPOSE The appropriateness of combination therapy for infections caused by gram-negative organisms is examined. SUMMARY Mortality from Pseudomonas aeruginosa infection is particularly high; therefore, empirical regimens are often selected to ensure coverage for this organism. The initial use of combination antimicrobial therapy for gram-negative infections is usually justified by one of three reasons: the potential for synergistic activity between two classes of antimicrobial agents, the broad empirical coverage provided by two antimicrobial agents with differing spectra of activity and resistance patterns, or the prevention of resistance development during antimicrobial therapy. Disadvantages of using combination therapy are increased drug toxicity, increased costs, and increased risk of superinfection with more-resistant bacteria or fungi. There are no clinical data that suggest that the combination of a β-lactam plus a fluoroquinolone results in improved patient outcomes compared with a β-lactam alone or a β-lactam plus an aminoglycoside. Results from studies that evaluate combination therapy versus monotherapy for gram-negative bacilli conflict with the common practice of use of double coverage. Strong evidence to support the administration of antimicrobials for double coverage of gram-negative organisms is lacking. Antimicrobial overuse may lead to antibiotic resistance, unnecessary adverse effects, and increased costs. CONCLUSION The available clinical evidence does not support the routine use of combination antimicrobial therapy for treatment of gram-negative infections. Patients with shock or neutropenia may benefit from combination therapy that includes an aminoglycoside.