Meta-analysis of doripenem vs comparators in patients with pseudomonas infections enrolled in four phase III efficacy and safety clinical trials

Abstract

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.

Research design and 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.

Conclusion:

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.

Key words::

• Carbapenem
• Doripenem
• Infection
• Pseudomonas aeruginosa

Transparency

Declaration of funding

This study and resultant paper was funded by Ortho-McNeil Pharmaceuticals.

Declaration of financial/other relationships

S.G.J. has disclosed that he was sponsored by Ortho-McNeil Pharmaceuticals in the preparation of this manuscript. He has also disclosed that he has served as a consultant for Johnson & Johnson, Pfizer, Bayer/Schering Plough, Advanced Life Sciences, The Medicines Company and Forrest Labs, and serves on the Speakers’ Bureau of Ortho-McNeil, Cubist and Wyeth. A.C.F., J.H.P. and S.C.N. have disclosed they are employees of Ortho-McNeil Pharmaceuticals. K.K. has disclosed that he is an employee of Johnson & Johnson.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he or she has received grants from Cubist and is a stock holder in Myriad Genetics, Telik Inc. and Matrixx Iniatives Inc. Peer reviewer 2 has disclosed that he or she has no relevant financial relationships.

Acknowledgment

The authors acknowledge the contributions of Rebecca Redman, MD, Nzeera Ketter, MD, Michael Lee, PhD, Paul Kotey, PhD, Joel Jiang, PhD, Shin-Yir Tong, MS, Obiamiwe Umeh, MD and Ian Friedland, MD of Johnson & Johnson Pharmaceutical Research & Development, LLC who planned and conducted the individual studies that formed the basis for the current analysis. The authors also acknowledge the writing and editorial assistance of Ira Mills, PhD and Craig Ornstein, PhD of Advogent in the preparation of this manuscript.