Efficacy of intravenous ciprofloxacin in patients with febrile neutropenia refractory to initial therapy

Abstract

We previously reported that monotherapy with carbapenem or cefepime exhibited efficacy equivalent to cefepime plus an aminoglycoside as initial therapy for febrile neutropenia (FN), achieving an adequate response in two-thirds of the patients. However, only one-third of the remaining poor responders to monotherapy became afebrile after an aminoglycoside was added to the initial carbapenem or cefepime. The present study was designed to evaluate the benefit of intravenous ciprofloxacin for neutropenic patients with fever who were refractory to initial therapy given for the first 3 days. Patients with FN—as defined by an axillary temperature ≥37.5°C and a neutrophil count <1,000/μL—who had no response to initial therapy with carbapenem or cefepime for 72 hours were to receive additional ciprofloxacin 600 mg/day. They were otherwise managed according to the Japanese guidelines for FN. An adequate response was defined as a decline of temperature to <37.5°C within 7 days after initiation of ciprofloxacin treatment. Thirty-one patients with FN (seventeen male and fourteen female; mean age 53.1 ± 14.8 years) were entered in the study. The initial antibiotics were cefepime (2 – 4 g/day) in twenty and carbapenem (1 – 2 g/day) in eleven. Three patients were excluded from analysis, leaving 28 patients for evaluation of efficacy. The response rate was 16/31 patients (51.6%),with four patients judged non-assessable due to adverse effects, protocol violation or early change to other agents. Adverse events occurred in seventeen patients, but all were mild and reversible. Only three patients had adverse events (skin rash, hepatic dysfunction and elevation of alkaline phosphatase in one patient, respectively) considered related to ciprofloxacin. These findings indicate that addition of intravenous ciprofloxacin is effective against FN refractory to initial antibiotic therapy and has acceptable toxicity.

Keywords:

• Febrile neutropenia
• FN
• second therapy
• ciprofloxacin