Beta-lactam antibiotic therapy in febrile granulocytopenic patients: a randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone

Granulocytopenia, the depletion of granulocyte white blood cells, places patients at grave risk from infection. Nowadays, this condition occurs quite frequently, often as a side effect of chemotherapy or other immunosuppressive therapies. Aggressive antibiotic treatment is necessary to prevent any bacterial infection from attaining life-threatening magnitude, and therefore indications of infection such as fever are treated without necessarily waiting for laboratory confirmation of the type of bacteria and the antibiotic sensitivity of the bacteria. Many of the patients experiencing granulocytopenia are already receiving drugs which are toxic to the kidneys. Therefore, the use of additional drugs which are also toxic to the kidneys is probably unwise; unfortunately, this rules out the aminoglycosides, an important group of antibiotics. (Streptomycin and gentamicin are examples of aminoglycosides.) To make matters worse, chemotherapy seems to increase the toxicity of aminoglycosides. A study was conducted to evaluate three antibiotic regimens for the treatment of granulocytopenic patients with fever; 429 patients were entered into the study, but 26 were excluded from analysis for a variety of reasons, including infections which turned out to be viral rather than bacterial. The patients were randomly assigned to receive cefoperazone with piperacillin, ceftazidime with piperacillin, or imipenem alone. Complications were not common, but included seizures in six patients and diarrhea in 83. The lower dose of imipenem tested, 2 g per day, was found to be just as effective as the regimens containing two antibiotics. Imipenem is less costly than the other antibiotic treatments, and the results of this study provide no reason for using the more expensive combination therapy in the treatment of granulocytopenic patients with fever. (Consumer Summary produced by Reliance Medical Information, Inc.)