Ventilator-associated pneumonia (VAP) increases medical resource utilization (MRU), but few randomized studies have been conducted to prospectively evaluate the effect of initial antibiotic therapy. To assess MRU in patients with VAP, we conducted a pooled analysis of MRU in two prospective, randomized, open-label, multicenter, phase III studies, which showed that doripenem was clinically noninferior to comparators.
We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospital stay in patients with VAP who received doripenem or a comparator in the two phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We also assessed microbiologic outcome in the subset with Pseudomonas aeruginosa VAP.
Six hundred twenty-five patients with VAP were enrolled and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 vs 10 days; p = 0.01) and hospital stay (22 vs 26 days; p = 0.01) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (p = 0.06). All-cause, overall mortality rates were similar (51/312 [16%] vs 47/313 [15%]; p = 0.65). MIC90 values against P aeruginosa for doripenem vs comparators were 1 vs 128 mcg/mL in study 1 and 4 vs 16 mcg/mL in study 2. P aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (p = 0.15). In patients with P aeruginosa VAP, median durations of mechanical ventilation (7 vs 13 days; p = 0.03) and ICU stay (13 vs 21 days; p = 0.03) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (p = 0.13).
Doripenem was associated with lower MRU than comparators. Differences in antipseudomonal activity may have contributed to these findings.
These MRU findings, combined with previous clinical findings, suggest that doripenem may be considered an alternative for empirical treatment of VAP, especially when P aeruginosa is suspected or is prevalent.
Marin Kollef, Grant monies (from industry related sources) Kollef - Bard, Elan, Merck, Pfizer; Employee Merchant, Quintana, and Lee: J&JGast: Axio Research Corporation LLC, which received payment from J&J for its services.; Consultant fee, speaker bureau, advisory committee, etc. Kollef: Kimberly Clark, Ortho-McNeil, Pfizer; no fees for this project. Nathwani: Astellas, Wyeth, Bayer, Pfizer, and Johnson and Johnson (J&J); no fees for this project.; No Product/Research Disclosure Information