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

Abstract

To reduce drug acquisition costs, the clinical and bacteriological efficacy of low-dose ceftazidime i.v. (1 g tid) was compared with cefotaxime i.v. (2 g tid). Both regimens were combined with netilmicin i.v. (2 mg/kg bodyweight tid), in an open, randomized, multicentre trial in febrile neutropenic patients. The addition of antibiotics for gram-positive coverage was part of the protocol; alteration in the antibiotics for gram-negative cover or premature discontinuation of the study antibiotics were judged as failure. One hundred and eighty six patients were randomized by nine German centres, the patients matched for age, underlying diseases and duration of neutropenia (median duration 14 days) in both treatment arms. Infections were documented microbiologically in 29% of the patients, clinically in 16% and suspected (fever 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). The success rates with modification were 84% and 64%, respectively. The failure rate in a highly immunosuppressed subgroup of the patients (bone marrow transplant recipients) was higher for cefotaxime (53%) than for the ceftazidime arm (14%) (P < 0.001). Response rates were significantly higher in the ceftazidime group for patients with microbiologically documented and possible infections. No major bacterial superinfections occurred in the low-dose treatment arm. The tolerability was good for both regimens. Low-dose ceftazidime combined with netilmicin proved to be superior to recommended doses of cefotaxime/netilmicin in febrile neutropenic patients.

Changing pattern of bacterial susceptibility to antibiotics in hematopoietic stem cell transplant recipients

“…However, there has always been a lot of controversy about the most appropriate antibiotic regimen to use in this setting. 2,[7][8][9][10][11] On the basis that on the one hand the most frequent bacterial infectious episodes are due to Gram-positive bacteria, but that on the other hand the most severe ones are caused by Gram-negative organisms, since 1991 we elected to use a combination of a glycopeptide (vancomycin) and a third-generation cephalosporin (ceftazidime).…”

The transplant pharmacopeia

“…13 Good CNS penetration lends itself to the treatment of bacterial meningitis. 13 Good CNS penetration lends itself to the treatment of bacterial meningitis.…”