Additional treatment with clarithromycin reduces fever duration in patients with influenza

Background: Influenza virus infection-induced inflammatory responses are associated with fever and other symptoms. Although macrolide antibiotics (macrolides) provide anti-inflammatory effects, these effects have not been well studied in influenza patients. Methods: We examined the effects of clarithromycin on influenza symptoms. A randomized, prospective, and open-label study was performed between December 2010 and March 2011 and between December 2012 and March 2013 in patients with pandemic A/H1 2009 influenza or seasonal influenza virus infections. Patients aged >15 years received either neuraminidase inhibitors (control group) or clarithromycin plus neuraminidase inhibitors (clarithromycin group). Body temperature and other symptoms were recorded for 5 days after initiating treatment. Serum interleukin (IL)-6 and IL-8 levels were also measured. Results: Herein, 79 patients were enrolled over the two influenza seasons, and data from 63 patients were analyzed. All patients showed fever and other symptoms, including rhinorrhea (n=38), cough (n=50), sore throat (n=39), arthralgia or myalgia (n=46), and general malaise (n=50). Fever duration was approximately 42% shorter in patients with temperatures ≥38.5 °C (p=0.02), decreasing from 42. h to 24. h. Among patients with pandemic influenza infections (n=20), the rhinorrhea improvement rate was higher in the clarithromycin group (p=0.03; 88% vs. 20%). Serum IL-6 levels decreased 5 days after treatment, but no differences between the two groups were detected. Conclusions: Clarithromycin may have the additional clinical benefit of improving fever, the main symptom of influenza, in patients treated with neuraminidase inhibitors.