Meta-analysis of doripenem vs comparators in patients with pseudomonas infections enrolled in four phase III efficacy and safety clinical trials.
OBJECTIVE
Pseudomonas aeruginosa is a difficult-to-treat bacterial pathogen often isolated from patients with serious nosocomial infections. The goal of this analysis is to present the clinical and microbiologic effectiveness of doripenem in the treatment of infections due to P. aeruginosa.


METHODS
A meta-analysis was conducted on the subset of subjects enrolled in four randomized phase III clinical trials of doripenem in subjects with complicated intra-abdominal infections (cIAI) and nosocomial pneumonia/ventilator-associated pneumonia (NP/VAP) due to P. aeruginosa. Clinical and microbiologic success was determined by infection and across the two infections.


RESULTS
Clinical success rates for modified intent-to-treat (mITT) subjects with P. aeruginosa in the cIAI and NP/VAP groups were 78.7% (37/47) and 59.6% (31/52), respectively, following treatment with doripenem versus 74.3% (26/35) and 32.8% (19/58), respectively, for subjects in the comparator groups (p < 0.05 for difference in success rates across infection types). Microbiologic eradication rates also favored doripenem, although the differences did not achieve statistical significance. The weighted difference (doripenem minus comparator) for the mITT population in clinical success rates between doripenem and the comparator agents was 16.0% (95% CI: 3.1%, 29.0%) and for microbiologic eradication rates was 9.1% (95% CI: -4.2%, 22.3%). The proportion of subjects reporting one or more treatment-emergent adverse events or serious adverse events was similar for doripenem and the comparator agents. Fourteen doripenem and 14 comparator subjects died during the study. Limitations of this retrospective meta-analysis also include the qualitative heterogeneity of the data, and a selected, narrow population of moderately ill clinical trial subjects included in the analysis. Due to limitations, these data may not be generalizable to all populations and should be considered hypothesis generating.


CONCLUSIONS
The weighted difference in clinical success rates for subjects with cIAI and NP/VAP infections caused by P. aeruginosa was in favor of doripenem, with the relative benefit of doripenem compared with the comparator agents similar across the two infections.
Jenkins
Stephen G
SG
Weill Cornell Medical College, New York, NY, USA.
Fisher
Alan C
AC
Peterson
Janet A
JA
Nicholson
Susan C
SC
Kaniga
Koné
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015780:Carbapenems / Q000009:adverse effects* / Q000627:therapeutic use*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003428:Cross Infection / Q000188:drug therapy; D000077726:Doripenem; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data; D016896:Treatment Outcome; D055815:Young Adult
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem