Efficacy of clarithromycin-naproxen-oseltamivir combination therapy versus oseltamivir alone in hospitalized pediatric influenza patients

Purpose This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. Methods This prospective, single-blind study included children aged 1–18 years hospitalized with influenza, in MacKay Children’s Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. Results Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients’ baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 hours vs. 32.1 hours, p=0.002). The decrease in the virus titer from days 1 to 3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p=0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. Conclusion The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.