A randomized trial of empirical antibiotic therapy with one of four beta-lactam antibiotics in combination with netilmicin in febrile neutropenic patients.
Over a two year period 174 evaluable episodes of fever in neutropenic patients were treated in a randomized study comparing four beta-lactam antibiotics, each given in combination with netilmicin. Exclusions included episodes due to viral or fungal infection, and trial violations. Most patients were receiving treatment for leukaemia, including 18% undergoing bone marrow transplantation. The overall response rate (EORTC criteria) was 66%, ranging from 56% for cefoperazone to 76% for mezlocillin. Microbial documentation was obtained in 31% of episodes; Gram-positive isolates were most frequent but Pseudomonas aeruginosa was found in 18 patients. In patients with microbiologically documented infection 70% improved, overall--from 40% with cefoperazone to 80% with piperacillin (P less than 0.05). Nephrotoxicity was seen in 6.7% and was associated with severe documented sepsis. Hypokalaemia was seen in 29% and was most marked in patients receiving ticarcillin. Rashes occurred in 6.6% overall, with no difference between the groups. Ototoxicity, shown by serial audiograms, was seen in 4.7% of patients. No evidence of vestibular dysfunction was seen in 62 patients studied. Of thirteen deaths due to the primary infection, seven were caused by Ps. aeruginosa and five by fungi.
D000380:Agranulocytosis / Q000188:drug therapy*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002438:Cefoperazone / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use; D005243:Feces / Q000382:microbiology; D005334:Fever / Q000188:drug therapy*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006801:Humans; D008802:Mezlocillin / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D009428:Netilmicin / Q000009:adverse effects / Q000627:therapeutic use*; D009503:Neutropenia / Q000188:drug therapy*; D010878:Piperacillin / Q000627:therapeutic use; D011897:Random Allocation; D012137:Respiratory System / Q000382:microbiology; D015163:Superinfection / Q000188:drug therapy; D013982:Ticarcillin / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D009428:Netilmicin; D002438:Cefoperazone; D013982:Ticarcillin; D008802:Mezlocillin; D010878:Piperacillin