Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting

The purpose of this study is to determine whether, in children with cancer presenting with fever in severe chemotherapy-induced neutropenia at low risk for medical complications, oral antibiotics in an outpatient setting after an initial phase of intravenous antibiotics and in-hospital observation for 8 to 22 hours, is not inferior as to safety and efficacy compared to continued intravenous antibiotics given in-hospital.

Sex

All

Minimum age

1 Year

Maximum age

18 Years

Inclusion Criteria:

* Chemotherapy because of malignancy
* Severe neutropenia (absolute neutrophil count ≤ 0.5x10E9/L)
* Fever (axillary temperature ≥ 38.5°C once or ≥ 38.0°C during ≥ 2 hours)
* Able to swallow oral medication
* Written informed consent from patients and/or parents

Exclusion Criteria:

* Status post myeloablative chemotherapy
* Diagnosis: acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or B-cell Non-Hodgkin lymphoma
* Bone marrow involvement by malignancy ≥ 25%
* Any comorbidity requiring hospitalization: \[1\] mean arterial blood pressure \< 50 mmHg (up to 10 years) / \< 60 mmHg (older than 10 years); \[2\] oxygen saturation \< 94% at room air; \[3\] radiologically defined pneumonia; \[4\] focal bacterial infection; \[5\] blood cultures taken at presentation reported positive at reassessment; \[6\] need for inpatient treatment or observation due to any other reason, as judged by the physician in charge
* Ever shaking chills
* Ever axillary temperature ≥ 39.5°C
* Antibacterial treatment before presentation with fever and neutropenia (except for prevention against Pneumocystis jiroveci \[formerly P. carinii\] pneumonia)
* Modification or de novo institution of a prophylaxis against P. jiroveci pneumonia
* Modification or de novo institution of a therapy with G-CSF or GM-CSF.
* Allergy to ciprofloxacin and/or amoxicillin
* Serum creatinine level above the upper limit of normal range

• BACKGROUNDAmmann RA. SPOG 2003 FN: Risikobeurteilung und risikoadaptierte Behandlung bei Kindern und Jugendlichen mit Fieber in Neutropenie. Paediatrica 16(1): 28-31, 2005.
• BACKGROUNDAmmann RA, Simon A, de Bont ES. Low risk episodes of fever and neutropenia in pediatric oncology: Is outpatient oral antibiotic therapy the new gold standard of care? Pediatr Blood Cancer. 2005 Sep;45(3):244-7. doi: 10.1002/pbc.20287. No abstract available. PMID 15747334
• RESULTAmmann RA, Bodmer N, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kuhne T, Popovic MB, Luthy AR, Aebi C. Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study. J Clin Oncol. 2010 Apr 20;28(12):2008-14. doi: 10.1200/JCO.2009.25.8988. Epub 2010 Mar 15. PMID 20231680
• RESULTBrack E, Bodmer N, Simon A, Leibundgut K, Kuhne T, Niggli FK, Ammann RA. First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study. Pediatr Blood Cancer. 2012 Sep;59(3):423-30. doi: 10.1002/pbc.24076. Epub 2012 Jan 23. PMID 22271702
• RESULTLuthi F, Leibundgut K, Niggli FK, Nadal D, Aebi C, Bodmer N, Ammann RA. Serious medical complications in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study. Pediatr Blood Cancer. 2012 Jul 15;59(1):90-5. doi: 10.1002/pbc.23277. Epub 2011 Aug 11. PMID 21837771
• RESULTAgyeman P, Aebi C, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kuhne T, Beck Popovic M, Leibundgut K, Bodmer N, Ammann RA. Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study. Pediatr Infect Dis J. 2011 Jul;30(7):e114-9. doi: 10.1097/INF.0b013e318215a290. PMID 21394050