Efficacy of Levofloxacin Versus Amoxicillin/Clavulanate and Ciprofloxacin in the Outpatient Management of Low-Risk Febrile Neutropenia in Children with Cancer; A Randomised Control Study

Abstract

Background and Aims Outpatient management of low-risk fever and neutropenia should be implemented if close monitoring is accessible and patient compliance is feasible. the use of Amoxicillin/ Clavulanate plus ciprofloxacin, Levofloxacin, and Moxifloxacin for the treatment of low-risk febrile neutropenia. There are not enough studies assessing the tolerance, safety, and efficacy of these agents in children. In this study, we aimed to assess the efficacy and safety of single-agent Levofloxacin versus the Augmentin /ciprofloxacin regimen used in our institute. Methods This is a randomized prospective interventional 2 arm study of low-risk febrile neutropenia patients presenting to the emergency department at the National Cancer Institute, Cairo University starting from December 2021 to July 2022.Eligible patients were children<18 years with haematological malignancies or haemopoietic and Low-risk febrile neutropenia without aetiological diagnosis. Lottery method was used to randomly enrol patients (1:1) to both arms. Patients were randomized to double agent ciprofloxacin and amoxicillin-clavulanic acid in comparison to single-agent levofloxacin. Follow up of the outpatient cases at; Day 1: Start oral antibiotics, obtain guardians contacts, and assure compliance, Day 3: Follow up the patient clinically and follow up count, and Day 7: Resolution of infection and stopping of antibiotics regardless of neutropenia. Primary outcomes included Safe marrow recovery and improvement of fever in all eligible patients. Drug-related side effects encountered in both arms of the study were reported. Results A preliminary analysis of the first 120 patients (60 in each group) was done. 100% of patients achieved marrow recovery in both arms by D7. Fever subsided in 100% on the Levofloxacin arm compared to 60% in the group receiving Augmentin/Ciprofloxacin. only one patient on the double agent arm was upgraded to HR and admitted to the inpatient. Levofloxacin was tolerable in all patients with no significant side effects apart from insomnia reported by the parents in 1 patient, while patients in the double agent arm; 4 had diarrhoea, 2 nausea and 2 complained of bad drug taste. Conclusions Levofloxacin has better efficacy and can be administered safely in children with low-risk FN, however close follow-up for long-term side effects and monitoring of possible emerging bacterial resistance is warranted.