Cefoperazone-sulbactam for treatment of intra-abdominal infections: results from a randomized, parallel group study in India

MASCOT study group, Abhijit Chandra, Puneet Dhar, Satish Dharap, Amitabh Goel, Rajesh Gupta, Jayprakash V. Hardikar, Vinay K. Kapoor, Ashok K. Mathur, Pankaj Modi, Mahendra Narwaria, Mayakonda K. Ramesh, Hariharan Ramesh, R. A. Sastry, Shashank Shah, Satpalsingh Virk, Otivilvayoth V. Sudheer, Maddibande R. Sreevathsa, Subodh Varshney, Puja Kochhar*Sanjay Somasundaram, Chetan Desai, Manjula Schou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Background: Combinations of a third-generation cephalosporin and metronidazole, with or without an aminoglycoside, often are used for the treatment of intra-abdominal infections in surgical settings. Simpler regimens that preserve an adequate spectrum of coverage, but allow easier administration and have fewer side effects, may be a more desirable option. Methods: This randomized, open-label, active comparator study evaluated the effectiveness (non-inferiority hypothesis) of the beta-lactam/beta-lactamase inhibitor combination cefoperazone-sulbactam (2-8 g/day), compared with ceftazidime (2-6 g/day)-amikacin (15 mg/kg/day)-metronidazole (500 mg three times daily) in 154 and 152 subjects, respectively, having intra-abdominal infections. The study was conducted at 17 centers in India. Results: Non-inferiority of cefoperazone-sulbactam (91.9%) compared with ceftazidime-amikacin-metronidazole (81.8%) was demonstrated for continued resolution of clinical signs and symptoms at the 30-day follow-up (primary endpoint) with a treatment difference of 10.1% (95% confidence interval 2.1%, 18.1%; pre-defined non-inferiority limit > -12.5%). Superiority of cefoperazone-sulbactam also was demonstrated for this endpoint, with significantly more subjects achieving continued resolution at the 30-day follow-up than in the comparator group (p = 0.015). On microbiologic outcomes, cefoperazone-sulbactam had higher success rates than ceftazidime-amikacin-metronidazole (92.9% vs. 80.0%). The pathogens (202 isolated) isolated most commonly were Escherichia coli (38.6%) and Klebsiella spp. (12.9%). The incidence of treatment-related adverse events was 6.5% and 16.4% in the cefoperazone-sulbactam and ceftazidime-amikacin-metronidazole groups, respectively, with more discontinuations due to treatment-related adverse events in the comparator arm (3.2% vs. 9.9%). Conclusion: Empirical cefoperazone-sulbactam monotherapy could be a useful adjunct to surgical intervention for intra-abdominal infections.

Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalSurgical Infections
Volume9
Issue number3
DOIs
Publication statusPublished - 1 Jun 2008
Externally publishedYes

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