University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Among neutropenic children with fever, is treatment with outpatient oral antibiotics as effective as IV antibiotics?

Clinical Bottom Lines

1. "Features that help to define patients at lower risk of bacteremia during hospitalization include the presence of some sign of bone marrow recovery, short duration of fever, absence of severe comorbidity factors (i.e., incoercible bleeding, hypotension, metabolic disorders, altered mental status, and respiratory failure), the control of local infection, type and status of the underlying malignancy, and the absence of bacteremia."¹
2. It is unclear from this study whether episodes of fever and neutropenia can be successfully treated as outpatient with oral antibiotics with no difference in treatment failure between IV therapy group versus oral therapy group.

Summary of Key Evidence

1. Study was based on single-center, randomized, prospective, clinical trial.¹
2. 177 episodes of fever and neutropenia in 136 children were randomized and analyzed for treatment failure, defined as persistent fever or neutropenia in one week, or hospitalization or new febrile episode during initial neutropenic period.
3. All subjects were treated as outpatients and they were initially evaluated and given ceftriaxone IV plus amikacin for one dose. They were then randomized to receive either oral ciprofloxacin or IV ceftriaxone
4. The patients were followed every 24 hours for clinical exam, blood count every 48hrs, and blood culture every 24hrs (if persistent fever).
5. Antibiotics were stopped in both groups once the child was afebrile for >24hrs and ANC >100mm³
6. Treatment success occurred in 85 patients (95%) in group A vs. 82 (93%) in group B. (p=NS).

Additional Comments

• The goal of this study was to assess efficacy of the oral ciprofloxacin as a way to treat fever and neutropenia episodes for those undergoing chemotherapy with low risk for serious bacterial infection.
• The study cites prior studies for carefully selecting a lower risk group and showing that they can be safely, and efficaciously be treated as outpatient with oral antibiotic.
• The study design did not provide for double-blinding, which could introduce bias in both parents and clinicians.
• The study also did not provide power of the study.
• There was one design flaw where patients were excluded from the study after being randomized if they had developed bacteremia.
• Other studies confirm the findings in this study; however, inclusion criteria and the population studied were slightly different. For example, one study by Petrilli excluded those children with leukemia as their underlying diagnosis.²
• The study also uses ceftriaxone IV as the standard IV therapy for comparison, which differs from our institution's standard for treatment of fever and neutropenia, which is Zosyn and gentamicin. This may affect the outcome if the study were to be done at our institution since microorganism resistance pattern maybe different from the center in Argentina where this study was conducted.
  

Citation

1. Paganini H, Gomez S, Ruvinsky S, et al.Outpatient, Sequential, Parenteral-Oral Antibiotic Therapy for Lower Risk Febrile Neutropenia in Children with Malignant Disease. Cancer 2003;97:1775-80.
2. Petrilli AS, Dantas LS, Campos MC, et al. Oral Ciprofloxacin vs. Intravenous Ceftriaxone Administered in an Outpatient Setting for Fever and Neutropenia in Low-Risk Pediatric Oncology Patients: Randomized Prospective Trial. Med Pediatr Oncol. 2000;34:87-91.

CAT Author: Jin Chang, MD

CAT Appraisers: Stephen Park, MD

Date appraised: October 18, 2005