Prospective Randomized Trial of Cefoperazone-Sulbactam Versus Ceftazidime Plus Amikacin and Metronidazole in the Treatment of Intra-Abdominal Infections

Abstract

Purpose: Monotherapy appears to be a desirable option for treatment of intra-abdominal infections due to the simplicity of its administration, fewer side effects and wide spectrum. This prospective, randomised, open-label, parallel group, phase IV multi-centric study evaluated the efficacy and safety of cefoperazone-sulbactam compared with ceftazidime plus amikacin and metronidazole in the treatment of intra-abdominal infections in Indian patients. Methods: Subjects received study medication [cefoperazone-sulbactam (2–8 g/day) or ceftazidime (2–6 g/day) plus amikacin (15mg/kg/day) plus metronidazole (500 mg tds)] intravenously for 5–14 days. Three hundred and six subjects were clinically evaluable (cefoperazone-sulbactam, n = 154; ceftazidime/amikacin/metronidazole, n = 152). Results: Significantly more patients in the cefoperazone-sulbactam group had continued resolution of their clinical signs and symptoms at the 30-day follow-up visit (92% versus 82%; p= 0.017). The difference between treatments was 10% (95% confidence interval 2.1–18.1), which was higher than the pre-defined non-inferiority limit of >–12.5. The findings were similar even for microbiological outcomes (success or presumed success: cefoperazone-sulbactam, 93%; ceftazidime/amikacin/metronidazole, 80%) at the end of treatment. The incidence of treatment related adverse events was 6% with cefoperazone-sulbactam, vs. 16% with ceftazidime/amikacin/metronidazole. There were more discontinuations in the ceftazidime/amikacin/metronidazole group (10% vs 3%). Conclusions: Empirical cefoperazone-sulbactam monotherapy is a useful alternative to the current standard combination treatment for serious intra-abdominal infections.