low-risk fever and neutropenia in children with cancer: safety and efficacy of oral antibiotics in an outpatient setting

Conditions: Fever; Neutropenia; Cancer

Summary: 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.

details on antimicrobial therapy * at presentation with fn (fever and neutropenia) and during an initial inpatient observation period of 8 to 22 hours, empirical intravenous broad-spectrum antibiotics are given. type and dosage are chosen by the treating physician. * patients randomized to continued intravenous antibiotics continue with these antibiotics. * patients randomized to oral antibiotics receive a combination of oral ciprofloxacin (25 to 30 mg/kg/day, top dose 1500 mg/day) plus oral amoxicillin (65 to 80 mg/kg/day, top dose 2250 mg/day), both given in two doses per day. * in both groups, the study gives guidelines (for certain situations) and rules (for other situations) when to change and when to stop antibiotics. details on clinical and laboratory controls * during antibiotic therapy, patients are seen daily, either as inpatients or as outpatients according to randomization. complete blood counts are performed at least every second day. * after stopping antibiotic therapy and until resolution of severe neutropenia (if applicable), patients are seen every other day, with a complete blood count. * patients randomized to outpatient management have the possibility to contact at any time of the day (and night) a pediatric oncologist in case of problems, in order to discuss necessity for emergency control and/or rehospitalization.

Eligibility criteria:
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

Keywords: children oral antibiotics outpatient treatment fever and neutropenia