Combination Antibiotic Treatment of Chemotherapy-Induced Neutropenia in Non-Leukemic Patients

Abstract

The use of more aggressive chemotherapies in the treatment of patients with some tumors has caused a higher frequency of neutropenia and subsequent serious infections. To verify the role in these patients of a combination therapy of amikacin (300 mg/m² i.v. every 12 hours) plus ceftazidime (2 g/m² i.v. every 8 hours) adminsitered as initial empiric treatment, followed in non-responsive cases by a second-line therapy with clindamycin (300 mg/m² i.v. every 8 hours), we conducted a prospective study in 45 febrile episodes (temperature ≥38.5 °C) in neutropenic patients (neutrophils ≤500/ml). The patients' median age was 58 (range, 19-80); 29 were women and 16 were men. The median performance status was 50 (range, 30-90), and 71 % of the patients had progressive tumoral disease. Before antibiotic therapy the median duration of fever was 12 hours (range, 4-48 hours). The median granulocyte count was 350/ml (range, 100-500 cells/ml), and the median peak temperature was 38.8 °C (range, 38.5-41 °C). The median time for neutrophils to rise towards 1000/ml was 4 days (range, 2-12), and the median duration of therapy was 8 days (range, 3-12). Documented bacterial infections were present in 28 patients whereas 17 had clinically possible infections or fever of unknown origin. The infection sites in microbiologically documented infections were: septicemia (12), multiple sites (4), tonsillitis (4), urinary tract (4), pneumonia (2) and fistula (2). Complete response to first-line therapy was obtained in 36 out of 45 episodes (80 %; 95 % confidence limits from 65 % to 90 %). Five out of 8 cases responded to second-line therapy with clindamycin for an overall recovery rate of 91 %. The amikacin-ceftazidime combination followed by clindamycin in non-responsive cases is effective, with moderate toxicity in non-leukemic febrile neutropenic patients.