Neutropenic infections: A review of the French Febrile Aplasia Study Group trials in 608 febrile neutropenic patients

Abstract

From 1986 to 1992, the Febrile Aplasia Study Group conducted a series of studies involving severely neutropenic patients. The average duration of neutropenia was 21 days, following chemotherapy for leukaemia, or chemotherapy/radiotherapy as part of a conditioning regimen for autologous or allogeneic bone marrow transplantation. A total of 591 evaluable febrile episodes were randomized to treatment with either ceftazidime 3 g daily + amikacin (the reference regimen; n = 246), ceftazidime alone (n = 98), ceftazidime + vancomycin (n = 77), ceftazidime + ciprofloxacin (n = 64) or piperacillin/tazobactam + amikacin (n = 106). Only three patients treated with the reference dose of ceftazidime died or suffered serious morbidity from infections caused by Gram-negative bacteria. Piperacillin/tazobactam + amikacin was the only antibiotic regimen to have an effect significantly different from the reference regimen. Piperacillin/tazobactam + amikacin produced a higher rate of defervescence at 72 h (P = 0.003), fewer days of fever (P < 0.001), fewer superinfections (P = 0.018), a less frequent requirement for addition of vancomycin (P = 0.01) and a higher incidence of treatment judged to be a 'complete success' (enduring defervescence without a change in antibiotics) (P = 0.04). Despite the improved control of Gram-positive microorganisms, the infection-related death rate remained unchanged from 1987 to 1992. An increase in disseminated aspergillosis compensated for the reduction in lethal Gram-positive septicaemia.