The combination of amoxicillin-clavulanate (AC) and a fluoroquinolone (FQ) is currently recommended for the treatment for outpatients with hematologic malignancies presenting with chemotherapy-induced fever (CIF), if the expected duration of neutropenia is < 7 days. However, infections due to Pseudomonas aeruginosa (naturally resistant to AC) are rare in this population. Furthermore, FQ might result in severe adverse events, and to the selection of bacterial resistance.

The investigators hypothesize that monotherapy with AC is non-inferior to the reference treatment AC + FQ in the outpatient treatment of CIF in adult hematology patients.

Method: Pragmatic, multicentre, randomized clinical trial, controlled in two parallel groups, with stratified randomization according to the type of haematological disorder. The study will include 1,526 adult patients with one of the following haematological disorders: (1) lymphoma of all histology types treated with the goal of remission; (2) myelodysplasia treated with azacytidine; (3) acute myeloblastic leukemia receiving non-intensive care, with a basal neutrophils count > 1000/mm3. The participants will be randomized prior to chemotherapy to receive either Amoxicillin-clavulanate 1g/152 mg tid. (AC) or Amoxicillin-clavulanate 1g/152 mg tid. and Ciprofloxacin 500 mg bid. (AC+C) orally for 7 days, to be taken in case of CIF. Only the first episode of CIF of each patient will be included in the analysis. The main evaluation criterion will be clinical success, defined as apyrexia 4 days after the first antibiotic dose, without modification of antibiotic treatment. The main secondary evaluation criteria (recorded at Day 14) will be fever recurrence, hospital admission, modification of antibiotic treatment, treatment with a beta-lactamine antibiotic efficient against P. aeruginosa, duration of antibiotic treatment, bacteraemia, inefficiency of the study treatment against the identified bacteria, and adverse events of FQ.

Inclusion Criteria:

1. Adult patients (≥ 18 years) with one of the following haematological disorders (in whom chemotherapy regimens are expected to provoke neutropenia lasting <7 days) (1) lymphoma of all histological types treated with the goal of remission; (2) myelodysplasia treated with azacytidine; (3) acute myeloblastic leukaemia, treated with a non-intensive scheme (azacytidine, azacytidine+venetoclax, other oral treatment against molecular targets)
2. Written informed consent
3. Patient able to understand all information related to the study and able to follow the protocol procedures (phone call and completion of the patient follow-up form (electronic or paper))
4. Affiliated to or beneficiary of the welfare care

Exclusion Criteria:

• 1. Patient under legal protection 2. Patient deprived of liberty by judicial or administrative decision 3. Patient who is the investigator, any member of the study team, or a relative directly involved in the trial, including assistant physicians, pharmacists, study coordinators, etc… 4. Participation in another interventional clinical trial 5. Impossible collection of informed consent (including non-francophone patient, or cognitive disorders) 6. Body mass index (BMI) > 30 7. Basal neutrophils count < 1000/mm3 (on the latest available blood test performed < 1 month before inclusion) 8. Aminotransferase serum levels > 5 X normal values (on the latest available blood test performed < 1 month before inclusion) 9. Creatinine clearance < 30 mL/min (on the latest available blood test performed < 1 month before inclusion) 10. Previous treatment with CAR-T cells 11. Previous allogeneic or autogeneic bone-marrow transplantation 12. Chronic obstructive pulmonary disease (COPD) 13. Previous invasive fungal infection 14. Allergy to one of the study medications 15. Contraindication to fluoroquinolones:

  1. hypersensitivity to ciprofloxacin, to other quinolones, or to any of the following excipients (microcrystalline cellulose, crospovidone, anhydrous colloidal silica, magnesium stearate, hypromellose, macrogol, titanium dioxide),
  2. treatment with tizanidine,
  3. previous hypersensitivity to any quinolone,
  4. previous tendonitis attributed to any fluoroquinolone,
  5. epilepsy 16. Contraindication to amoxicillin-clavulanate 17. QT prolongation (defined as a QT interval > 0.45 seconds for males and > 0.47 seconds for females) 18. Antibiotic prophylaxis (with the exception of the combination sulfamethoxazole and trimethoprim) 19. Pregnant or breastfeeding women, 20. Women not using contraception 21. Patient treated with anti-psychotic drug