Piperacillin/tazobactam monotherapy versus piperacillin/tazobactam plus amikacin as initial empirical therapy for febrile neutropenia in children with acute leukemia.

The purpose of this study is to compare the efficacy and safety of piperacillin/tazobactam (PIP/TAZO) versus PIP/TAZO plus amikacin in febrile neutropenic children with acute leukemia (AL). Children with AL who had febrile neutropenic episodes were randomized to treatment with PIP/TAZO versus PIP/TAZO plus amikacin. Modification was defined as addition of other antimicrobials and/or antifungal agents to the empirical therapy. Protocol failure was defined as withdrawal of the empirical regimen and introduction of other antimicrobials due to failure in controlling infection. Seventy-two febrile episodes of 42 patients with a median age of 4.5 years (3.5 months to 19 years) were evaluated. There were 37 and 35 episodes in PIP/TAZO and combination arms, respectively. Success without modification, with modification, protocol failure, duration of treatment were 45.9%, 35.1%, 18.9%, and 10 days in PIP/TAZO arm and 42.9%, 37.1%, 20%, and 12 days in combination arm, respectively (P > .05). There was no significant difference between the empirical therapy arms regarding median duration of neutropenia and defervescence of fever. Empirical therapy was substituted by other drugs in 6 and 5 episodes in PIP/TAZO and combination arms, respectively. There was no infection-related death. There was reversible increase in serum creatinine in 1 episode on the combination arm. Monotherapy with PIP/TAZO was effective and safe for initial empirical treatment of febrile neutropenic episodes in children with AL. However, local bacterial resistance patterns should be considered in daily practice. Combination of amikacin with PIP/TAZO did not improve treatment success, but it may increase nephrotoxicity.