Meropenem versus ceftazidime plus amikacin in the treatment of febrile episodes in neutropenic patients: a randomized study

Abstract

Background and objective: Meropenem is the first of a new class of carbapenems which may be administered without cilastatin. This study was performed to assess the clinical efficacy and tolerability of meropenem monotherapy (1 g/8 h) compared with the standard combination of ceftazidime (2 g/8 h) plus amikacin (15 mg/kg/day) for the empirical treatment of infective febrile episodes in neutropenic cancer patients.

Methods: This was a three-center, randomized, non-blind parallel group trial. The primary objective was to compare the clinical efficacy of meropenem monotherapy with that of ceftazidime plus amikacin in the empirical treatment of febrile infective episodes in neutropenic patients. This was evaluated by the number of patients surviving on unmodified therapy at 72 h (primary end point) and by the clinical response at the end of therapy (secondary end point).

Results: A total of 93 febrile episodes (46 meropenem, 47 ceftazidime/amikacin) were evaluable. Bone marrow transplant patients accounted for 49.5% of all cases. There was a high incidence of Gram-positive infections but no pseudomonal infections. Microbiologically documented infections, clinically documented infections and unexplained fever accounted for 45%, 10% and 45% of episodes, respectively. There was a similar proportion of patients in the meropenem and ceftazidime/amikacin groups on unmodified empiric therapy at 72 h (80.4% vs 76.6%, p = 0.65,) and cured at the end of therapy (37% vs 36.2%, p = 0.9). No significant difference in tolerability was observed between the groups. Meropenem was well tolerated; of note, there were no cases of nausea/vomiting or seizure related to its use.

Interpretation and conclusions: Meropenem monotherapy was well tolerated and produced response rates similar to those obtained with ceftazidime/amikacin. The low overall success rates with both treatments concur with those of other recent studies and are probably due to a combination of several factors, including the adoption of strict assessment criteria.