Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients

Combination therapy for nosocomial pneumonia with a β-lactam and aminoglycoside is widely accepted because of synergy and reduction of resistant bacteria. This prospective study of 109 trauma patients (94 blunt, 15 penetrating) with nosocomial pneumonia was performed in consecutive phases. In phase 1, patients were randomized to an anti-pseudomonal third-generation cephalosporin—cefoperazone or ceftazidime. Gentamicin was added to each regimen in phase 2. The mean age of the patients was 37 years, the mean ISS was 31, and there were no differences among the four treatment groups relative to associated injuries. Patients receiving monotherapy had a 56% cure rate compared with 31% for combination therapy (p < 0.04). Persistence rates were similar in these two groups (15% and 20%), but superinfection was significantly higher in the combination group (49% vs. 28%; p < 0.04). The predominant superinfecting organism was methicillin-resistant Staphylococcus aureus (MRSA). Nine patients died (5% monotherapy, 10% combination), and eight had a superinfection. We conclude that monotherapy had a higher cure rate than combination therapy for empiric therapy of pneumonia in our trauma patients. Combination therapy failed because of superinfection (primarily MRSA). Emergence of MRSA may be from host overgrowth or plasmid-mediated induction of resistance, possibly caused by gentamicin.