Medical resource utilization among patients with ventilator-associated pneumonia: pooled analysis of randomized studies of doripenem versus comparators.
BACKGROUND
Ventilator-associated pneumonia (VAP) is associated with increased medical resource utilization, but few randomized studies have been conducted to evaluate the effect of initial antibiotic therapy. To assess medical resource utilization in patients with VAP, we conducted a pooled analysis of two prospective, randomized, open-label, multicenter, phase III studies, which also showed that doripenem was clinically noninferior to comparators.


METHODS
We assessed durations of mechanical ventilation, intensive care unit (ICU) stay, and hospitalization in patients with VAP who received at least 1 dose of doripenem or a comparator in the phase III studies. Comparators were piperacillin/tazobactam (study 1) and imipenem (study 2). We analyzed between-group differences in medical resource utilization endpoints by comparison of Kaplan-Meier curves with generalized Wilcoxon test and in microbiologic eradication rates by two-sided Fisher's exact test.


RESULTS
625 patients with VAP were evaluated and received at least 1 dose of doripenem (n = 312) or a comparator (n = 313). Median durations of mechanical ventilation (7 versus 10 days; P = 0.008) and hospitalization (22 versus 26 days; P = 0.010) were shorter for doripenem than comparators; corresponding ICU stays were 12 and 13 days (P = 0.065). All-cause, overall mortality rates were similar (51/312 [16%] versus 47/313 [15%]; P = 0.648). MIC90 values against Pseudomonas aeruginosa for doripenem versus imipenem were 4 versus 16 microg/mL in study 2. P. aeruginosa was eradicated from 16/24 (67%) doripenem recipients and 10/24 (42%) comparator recipients (P = 0.147). In patients with P. aeruginosa at baseline, median durations of mechanical ventilation (7 versus 13 days; P = 0.031) and ICU stay (13 versus 21 days; P = 0.027) were shorter for doripenem; corresponding hospital stays were 24 and 35 days (P = 0.129).


CONCLUSIONS
Doripenem was associated with lower medical resource utilization than comparators. Differences in antipseudomonal activity may have contributed to these findings.


BACKGROUND
ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
Kollef
Marin H
MH
Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA. mkollef@DOM.wustl.edu
Nathwani
Dilip
D
Merchant
Sanjay
S
Gast
Christopher
C
Quintana
Alvaro
A
Ketter
Nzeera
N
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015780:Carbapenems / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic; D000077726:Doripenem; D005260:Female; D006295:Health Resources / Q000191:economics / Q000706:statistics & numerical data*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000191:economics; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D000078142:Tazobactam; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D015378:Imipenem; D010397:Penicillanic Acid; D000077726:Doripenem; D000078142:Tazobactam; D010878:Piperacillin
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