Monotherapy with a broad-spectrum beta-lactam is as effective as its combination with an aminoglycoside in treatment of severe generalized peritonitis: a multicenter randomized controlled trial

In a randomized trial conducted in 35 centers, we compared the clinical eff icacy and safety of piperacillin plus tazobactam (TAZ) alone (monotherapy [ MT]) versus those of TAZ combined with amikacin (AMK) (combined therapy [CT ]) for the treatment of severe generalized peritonitis (SGP), Primary analy sis consisted of blind assessment by an independent committee of the failur e rate 30 days after the end of treatment in the modified intent-to-treat ( ITT) analysis (mITT) population. Of the 241 patients with suspected SGP ran domized into the study, 227 were eligible for ITT analysis, including 204 ( 99 in the MT group and 105 in the CT group) with confirmed SGP (mITT popula tion). A total of 159 patients were eligible for per-protocol (PP) analysis . The clinical failure rates were equivalent in the mITT and PP populations (MT versus CT): 56 versus 52%, (odds ratio [OR] 0.87, 90% confidence inter val [CI] = 0.6 to 1.27) for mITT and i19 versus 49% (OR = 1.03, 90% CI = 0. 67 to 1.59) for PP analysis, Mortality rates (ITT population, 19%; PP popul ation, 21%) and overall adverse event rates (ITT population, 55%; PP popula tion, 54%) were also similar. Six patients (three in MT group and three in the CT group) developed acute renal failure. In conclusion, the addition of AMK to TAZ does not seem to be necessary for the treatment of SGP, even af ter adjustment for the simplified acute physiology score (SAPS II) and type of SGP.