• Safety: No serious medical complication due to infection (death, treatment in ICU [Intensive Care Unit], potentially life-threatening complication) (non-inferiority-design, limit 3.5%)
  
• Efficacy: Response without rehospitalization or changing randomized antibiotics (non-inferiority design, limit 10%)
  

• Improved prediction of low-risk episodes of fever and neutropenia
  
• Description of characteristics of low-risk episodes of fever and neutropenia
  
• Description of characteristics of high-risk episodes of fever and neutropenia (observational study part)
  

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.

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