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

Question

• Can pediatric cancer patients with fever and neutropenia identified as low risk by clinical criteria at the time of presentation be treated safely as outpatients?

Clinical Bottom Lines

1. Patients with fever and neutropenia (F&N) can be stratified into lower and higher risk groups. However, with time and practice these criteria will likely be modified.
2. No differences were found in those treated as outpatients with oral ciprofloxacin versus IV ceftazidime.
   
3. More statistical power is needed than available in this study to fully determine if there truly is no difference in outcomes comparing oral vs. intravenous outpatient therapy.

Summary of Key Evidence

1. Seventy-three episodes of F&N in 41 pediatric patients between the ages of 3 and 20 meeting eligibility criteria were randomized after an initial single dose of IV ceftazidime to receive as outpatients a) IV ceftazidime every 8 hours or b) oral ciprofloxacin every 12 hours which were continued until the patient was afebrile and absolute phagocyte count (APC) was rising.¹
2. Patients were monitored at time of presentation for 3-16 hours, then as an outpatient by daily physical examination, CBC, and observation of antibiotic administration.
3. Outcome measures included: duration of fever, duration of neutropenia from presentation, days treated as outpatient, occurrences of bacteremia, infection, or positive blood cultures, hospitalization, days hospitalized, ICU admission, and death. No statistically significant differences were seen between the two treatment arms in any category.
4. Univariate logistic regression analysis identified duration of neutropenia (P = 0.0000485), leukemia as underlying malignancy (P = 0.0255), and temperature in the clinic (P = 0.0158) to be statistically significant factors associated with hospitalization. However, presentation APC <100 (P = 0.058), presentation ANC < 100 (P = 0.153), and antibiotic assignment (P = 0.0737) were not.
5. A stepwise multiple regression analysis of the correlation of hospitalization to duration of neutropenia, leukemia as underlying disorder, ANC and APC was conducted. Only duration of neutropenia had a statistically significant correlation to hospitalization (P = 0.00125).
6. No patient in either treatment arm suffered serious complications or death.

Additional Comments

• Eligibility criteria will likely need to be modified based on this study and a more recent study by Alexander, et al who stratified febrile, neutropenic children as high risk if neutropenia was expected to be longer than 7 days.²
• Selection of antibiotic therapy for use in outpatients should be determined by current susceptibility patterns of endemic organisms, availability of antibiotics with spectra including these organisms, and bioavailability of agent.¹
• Ciprofloxacin and ceftazidime were chosen secondary to their gram negative (including Pseudomonal) coverage and ease of administration.
• Ciprofloxacin had not been widely used in children secondary to severe joint events observed in animals. However, studies in children have shown that arthralgias occurred in less than 2% of children and resolved without interventions.³
  
  

Citation

1. Mullen CA et al. Outpatient treatment of fever and neutropenia for low risk pediatric cancer patients. Cancer 1999;86:126-34.
2. Alexander SW, Kelly CW, Hibberd PL, Parsons SK. Evaluation of risk prediction criteria for episodes of febrile neutropenia in children with cancer. J Pediatr Hematol Oncol 200;24:38-42.
3. Petrilli AS 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: Kristen M. Snyder, MD

CAT Appraisers: Jonathan Fliegel, MD

Date appraised: April 8, 2002