Amoxicillin-clavulanate Alone or in Combination With Ciprofloxacin in Low-Risk Febrile Neutropenic Adult Patients: A Prospective, Double-blind, Randomized, Non-Inferiority Multicenter, Phase III Clinical Trial.

Inclusion Criteria:

• Patient ≥ 18 years old
• Treated for a solid cancer or a hematological malignancy
• Presented with low-risk* febrile neutropenia due to chemotherapy with an expectedduration of neutropenia ≤ 7 days
• Neutropenia is defined by an absolute neutrophil count ≤ 500/mm3.
• Fever is defined by temperature ≥ 38.3° or ≥ 38° twice during a 1-hour interval.
• Signing informed consent *Low risk is defined by MASCC score ≥ 21

Exclusion Criteria:

• Hypersensitivity to the active substances: amoxicillin-clavulanic, ciprofloxacin,penicillins, to other quinolones or to one of the excipient
• History of severe immediate hypersensitivity reaction to another beta-lactam
• History of jaunditis/hepatic impairment related to amoxicillin/clavulanic
• Concomitant administration of ciprofloxacin and tizanidine.
• Clinical signs of focal infection including history of untreated dental abscess.
• Signs of sepsis or organ failure.
• Severe immune deficiency other than the current cancer, except controlled-HIVinfection
• Gastrointestinal symptoms requiring intravenous treatment (mucositis, vomiting, severediarrhea...).
• Known aminotransferase serum levels > 5 x normal values.
• Known renal insufficiency defined as creatinine clearance of < 30 mL/min (MDRD).
• Antibiotherapy within 24h before enrollment. Prophylactic use of amoxicillin is anexclusion criterium whereas prophylactic use of trimethoprim-sulfamethoxazole (cotrimoxazole) and penicillin G (Oracilline®) are not and will be considered in theanalysis.
• History of infection or colonization due to bacteria resistant to experimental drugsin the previous year
• Can be enrolled in the study only once.
• Patients not benefiting from a Social Security scheme or not benefiting from itthrough a third party.
• Persons benefiting from enhanced protection, namely minors, persons deprived of theirliberty by a judicial or administrative decision, persons staying in a health orsocial institution, adults under legal protection, and finally patients in emergencies
• Pregnant or breastfeeding women, women at age to procreate and not using effectivecontraception (either hormonal / mechanical : oral, injection, subcutaneous,implantable, intrauterine device, or surgical : tubal ligation, hysterectomy, totalovariectomy).