A Randomized Trial Comparing Ceftazidime Alone with Combination Antibiotic Therapy in Cancer Patients with Fever and Neutropenia

TLDR

The study evaluated whether single‑agent ceftazidime is as effective as standard combination therapy for initial management of fever and neutropenia in cancer patients. In a randomized trial of 550 fever‑neutropenia episodes, 282 were treated with ceftazidime alone and 268 with a cephalothin‑gentamicin‑carbenicillin combination, with responses assessed at 72 h and at neutropenia resolution. Survival at 72 h and at neutropenia resolution was essentially identical between groups for patients with unexplained fever, while for those with documented infection survival was similar at 72 h but slightly lower at resolution; most infection episodes required additional therapy, whereas only 22 % of unexplained fever episodes did, indicating that single‑agent therapy is a safe alternative but may need escalation in infected or prolonged cases. Published in N Engl J Med 1986; 315:552–8.

Abstract

To assess the efficacy of single-agent therapy relative to standard combination antibiotic therapy for the initial management of fever and neutropenia in cancer patients, we conducted a randomized trial comparing ceftazidime alone with a combination of cephalothin, gentamicin, and carbenicillin. Of 550 evaluable episodes of fever and neutropenia, 282 were treated with ceftazidime alone and 268 with the combination. All episodes were evaluated for responses at 72 hours after the start of treatment and at resolution of the neutropenia. Of the patients with unexplained fever who were given ceftazidime alone, 99 percent were alive at 72 hours and 98 percent were alive when the neutropenia resolved, as compared with 100 percent and 98 percent, respectively, of those given combination therapy. Of the patients with documented infection who were given ceftazidime alone, 98 percent were alive at 72 hours and 89 percent when the neutropenia resolved, as compared with 98 percent and 91 percent, respectively, of those given combination therapy. The majority of episodes of documented infection in both treatment groups necessitated additional antimicrobial treatment or other modifications of the initial regimen, as compared with only 22 percent of the episodes of unexplained fever. We conclude that initial single-agent therapy with certain β-lactam antibiotics is a safe alternative to standard combination antibiotic therapy, although patients with documented infection or protracted neutropenia are likely to require additional or modified treatment. (N Engl J Med 1986; 315:552–8.)