An open, randomized, multicentre study comparing the use of low-dose ceftazidime or cefotaxime, both in combination with netilmicin, in febrile neutropenic patients

To reduce drug acquisition costs, the clinical and bacteriological efficacy of low-dose ceftazidime iv (1 g tid) was compared with cefotaxime iv (2 g tid). Both regimens were combined with netilmicin iv (2 mg/kg bodyweight ti d), in an open, randomized, multicentre trial in febrile neutropenic patien ts. The addition of antibiotics for Gram-positive coverage was part of the protocol; alteration in the antibiotics for Gram-negative cover or prematur e discontinuation of the study antibiotics were judged as failure. One hund red and eighty six patients were randomized by nine German centres, the pat ients matched for age, underlying diseases and duration of neutropenia (med ian duration 14 days) in both treatment arms. Infections were documented mi crobiologically in 29% of the patients, clinically in 16% and suspected (fe ver of unknown origin) In 102/186 patients (55%). The 82 pathogens isolated were predominantly Gram-positive bacteria. In an intent-to-treat analysis, the overall response rate without modification at the final evaluation was 58% in the ceftazidime group and 34% in the cefotaxime group (P < 0.01). T he success rates with modification were 84% and 64%, respectively. The fail ure rate in a highly immunosuppressed subgroup of the patients (bone marrow transplant recipients) was higher for cefotaxime (53%) than for the ceftaz idime arm (14%) (P < 0.001). Response rates were significantly higher in th e ceftazidime group for patients with microbiologically documented and poss ible infections. No major bacterial superinfections occurred in the low-dos e treatment arm. The tolerability was good for both regimens. Low-dose ceft azidime combined with netilmicin proved to be superior to recommended doses of cefotaxime/netilmicin in febrile neutropenic patients.