Efficacy, nephrotoxicity, and incidence of Clostridium difficile infection with broad spectrum antibiotic regimens in elderly patients with nosocomial pneumonia

Background: Vancomycin plus piperacillin-tazobactam (V+PT) is a broad spectrum antibiotic regimen often chosen as empiric therapy for nosocomial pneumonia. Recent data suggest that this combination may increase the risk of nephrotoxicity when compared to vancomycin alone, or vancomycin plus cefepime. The purpose of this study was to evaluate the difference in nephrotoxicity, Clostridium difficile infection (CDI) and efficacy of V+PT versus vancomycin plus cefepime (V+C), or vancomycin plus cefepime plus metronidazole (V+C+M ) for aspiration, in nosocomial pneumonia.

Methods: This study was a retrospective electronic chart review of patients ≥ 18 years of age who received one of these regimens for ≥ 48 hours for nosocomial pneumonia. Patients with end stage renal disease or on dialysis were excluded. The primary outcomes were clinical efficacy, documented in progress notes, and objective efficacy, defined as improvement in 2 of the following 3 signs/symptoms at 48 hours: fever, leukocytosis/leukopenia, and purulent secretions. Secondary endpoints were nephrotoxicity and incidence of CDI within 14 days. SAS was used for statistical analysis; t-tests and contingency tables were applied.

Results: A total of 184 patients were included (mean age=73.6±11.2 years; 98% male; 75% Caucasian). Demographics were similar between groups at baseline. There was no difference in objective efficacy (26.8% for V+PT versus 21.1% for all V+C regimens) or clinical efficacy (66.1% for V+PT versus 57.9% for all V+C regimens) between groups (p>0.05 for both). Similarly, no differences were identified in the subgroups of aspiration pneumonia (V+PT versus V+C+M) and non-aspiration pneumonia (V+PT versus V+C). Finally, the incidence of nephrotoxicity (~14%) and CDI (~3%) were similar between groups (p>0.05 for both).

Conclusion: In this single-center study in an older population, it appears that these broad-spectrum regimens have similar safety and efficacy for nosocomial pneumonia. However, efficacy was generally low, especially when including symptomatic resolution (objective efficacy). This may be reflective of a complicated population with multiple co-morbidities.