title: Additional treatment with clarithromycin reduces fever duration in patients with influenza.
abstract: 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.
authors.affiliation: Higashi Clinic, 589-1 Higashi-Honjou, Minabe-Cho, Hidaka-Gun, Wakayama Prefecture 645-0021, Japan. Electronic address: higashiclinic@deluxe.ocn.ne.jp.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Higashi
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: hkubo@med.tohoku.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.affiliation: Yaotome Ekimae Clinic of Internal Medicine and Pediatrics, 1-3-26 Yaotome-Chuo, Izumi-ku, Sendai 981-3135, Japan. Electronic address: hiroyasuyasuda@gmail.com.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yasuda
authors.affiliation: South Miyagi Medical Center, 38-1 Aza-nishi, Ohgawara, Shibata-gun, Miyagi Prefecture 989-1253, Japan. Electronic address: toshinkw47@gmail.com.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Electronic address: myamaya@med.tohoku.ac.jp.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D017291:Clarithromycin / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D011446:Prospective Studies; D013995:Time; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D009439:Neuraminidase; D017291:Clarithromycin
keywords: Clarithromycin; Fever; Inflammation; Influenza; Neuraminidase inhibitor