TY - JOUR
T1 - Medical resource utilization among patients with ventilator-associated pneumonia
T2 - Pooled analysis of randomized studies of doripenem versus comparators
AU - Kollef, Marin H.
AU - Nathwani, Dilip
AU - Merchant, Sanjay
AU - Gast, Christopher
AU - Quintana, Alvaro
AU - Ketter, Nzeera
N1 - Funding Information:
Acknowledgements Funding/support. This study, including the statistical analysis and manuscript preparation, was supported by a research grant from Johnson and Johnson Pharmaceutical Services, LLC. Role of the sponsor. SM, AQ, and NK of Johnson and Johnson met authorship criteria by participating in the study design, analysis of results, interpretation of findings, and drafting of the paper. Independent statistical analysis. The accuracy of the data analysis was independently verified by William Shannon, PhD, Associate Professor of Biostatistics in Medicine, Department of Medicine, Washington University School of Medicine [email protected] . Dr Shannon received the raw database and statistical analysis plan, reviewed and replicated all analyses, and discovered no discrepancies. All reported analyses are those performed by Dr Shannon. Dr Shannon received compensation from the sponsor. Additional contributions. We thank Cindy W. Hamilton, PharmD, ELS (Hamilton House, Virginia Beach, Virginia) for assisting with manuscript preparation. Hamilton House received compensation from Johnson and Johnson Pharmaceutical Services, LLC for its contributions.
PY - 2010/5/10
Y1 - 2010/5/10
N2 - Introduction: 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 μg/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.Trial registration: ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
AB - Introduction: 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 μg/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.Trial registration: ClinicalTrials.gov number NCT00211003 (study 1) and NCT00211016 (study 2).
UR - https://www.scopus.com/pages/publications/77951963695
U2 - 10.1186/cc9012
DO - 10.1186/cc9012
M3 - Article
C2 - 20459721
AN - SCOPUS:77951963695
SN - 1364-8535
VL - 14
JO - Critical Care
JF - Critical Care
IS - 3
M1 - R84
ER -