A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy

N Engl J Med. 1999 Jul 29;341(5):305-11. doi: 10.1056/NEJM199907293410501.


Background: Among patients with fever and neutropenia during chemotherapy for cancer who have a low risk of complications, oral administration of empirical broad-spectrum antibiotics may be an acceptable alternative to intravenous treatment.

Methods: We conducted a randomized, double-blind, placebo-controlled study of patients (age, 5 to 74 years) who had fever and neutropenia during chemotherapy for cancer. Neutropenia was expected to be present for no more than 10 days in these patients, and they had to have no other underlying conditions. Patients were assigned to receive either oral ciprofloxacin plus amoxicillin-clavulanate or intravenous ceftazidime. They were hospitalized until fever and neutropenia resolved.

Results: A total of 116 episodes were included in each group (84 patients in the oral-therapy group and 79 patients in the intravenous-therapy group). The mean neutrophil counts at admission were 81 per cubic millimeter and 84 per cubic millimeter, respectively; the mean duration of neutropenia was 3.4 and 3.8 days, respectively. Treatment was successful without the need for modifications in 71 percent of episodes in the oral-therapy group and 67 percent of episodes in the intravenous-therapy group (difference between groups, 3 percent; 95 percent confidence interval, -8 percent to 15 percent; P=0.48). Treatment was considered to have failed because of the need for modifications in the regimen in 13 percent and 32 percent of episodes, respectively (P<0.001) and because of the patient's inability to tolerate the regimen in 16 percent and 1 percent of episodes, respectively (P<0.001). There were no deaths. The incidence of intolerance of the oral antibiotics was 16 percent, as compared with 8 percent for placebo (P=0.07).

Conclusions: In hospitalized low-risk patients who have fever and neutropenia during cancer chemotherapy, empirical therapy with oral ciprofloxacin and amoxicillin-clavulanate is safe and effective.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Amoxicillin / administration & dosage
  • Amoxicillin / adverse effects
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Antineoplastic Agents / adverse effects*
  • Bacterial Infections / drug therapy
  • Ceftazidime / administration & dosage
  • Ceftazidime / adverse effects
  • Child
  • Child, Preschool
  • Ciprofloxacin / administration & dosage
  • Ciprofloxacin / adverse effects
  • Clavulanic Acid / administration & dosage
  • Clavulanic Acid / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination / administration & dosage
  • Drug Therapy, Combination / adverse effects
  • Female
  • Fever / drug therapy*
  • Fever / etiology
  • Fever of Unknown Origin / drug therapy
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Neutropenia / drug therapy*
  • Neutropenia / etiology


  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Clavulanic Acid
  • Ciprofloxacin
  • Amoxicillin
  • Ceftazidime