Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
Open Access / Peer-Reviewed / Research Article
Efficacy of Combination Therapy with Oseltamivir Phosphate and Azithromycin for Influenza: A Multicenter, Open-Label, Randomized Study
Hiroshi Kakeya, Masafumi Seki, Koichi Izumikawa, Kosuke Kosai, Yoshitomo Morinaga, Shintaro Kurihara, Shigeki Nakamura, Yoshifumi Imamura, Taiga Miyazaki, Misuzu Tsukamoto, Katsunori Yanagihara, Takayoshi Tashiro, Shigeru Kohno
Published: March 14, 2014 / DOI: 10.1371/journal.pone.0091293
Abstract
Background
Macrolides have antibiotic and immunomodulatory activities, which may have a favorable effect on the clinical outcome of patients with infections, including influenza. This study aimed to evaluate the effects of combination therapy with an anti-influenza agent, oseltamivir, and a single-dose formulation of azithromycin (AZM), which has been used for influenza-related secondary pneumonia, on influenza patients. The primary endpoint was a change in the expression levels of inflammatory cytokines. Secondary endpoints were the time required for resolution of influenza-related symptoms, incidence of complications, and adverse reactions.
Methods
Patients with seasonal influenza were enrolled in this multicenter, open-label, randomized study. Patients were stratified according to the presence of a high risk factor and were randomized to receive combination therapy with oseltamivir plus an extended-release formulation of AZM (combo-group) or oseltamivir monotherapy (mono-Group).
Results
We enrolled 107 patients and randomized them into the mono-group (56 patients) or the combo-group (51 patients). All patients were diagnosed with influenza A infection, and none of the patients had comorbid pneumonia. Statistically significant differences were not observed in the expression levels of inflammatory cytokines and chemokines between the 2 groups. The maximum temperature in the combo-group was lower than that in the mono-group on day 3 through day 5 (p = 0.048), particularly on day 4 (p = 0.037).
Conclusion
To our knowledge, this is the first prospective, randomized, clinical trial of oseltamivir and AZM combination therapy for influenza. Although the difference in inflammatory cytokine expression level was not statistically significant, combination therapy showed an early resolution of some symptoms.
Name of registry
University hospital Medical Information Network (UMIN).
Trial Registration no: UMIN000005371
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Citation: Kakeya H, Seki M, Izumikawa K, Kosai K, Morinaga Y, et al. (2014) Efficacy of Combination Therapy with Oseltamivir Phosphate and Azithromycin for Influenza: A Multicenter, Open-Label, Randomized Study. PLoS ONE 9(3): e91293. doi:10.1371/journal.pone.0091293
Editor: D. William Cameron, University of Ottawa, Canada
Received: September 24, 2013; Accepted: February 7, 2014; Published: March 14, 2014
Copyright: ? 2014 Kakeya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by a Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology (No. 23591151 and No. 25461516) as well as by the Japanese Ministry of Health, Labour and Welfare Sciences Research Grants (H25-Shinko-ippan-006). The nonprofit corporation Nagasaki Evaluation Organization for Clinical Interventions (NEOCI; Nagasaki, Japan) and Pfizer Inc. also provided grants for this study, but the sponsors were not involved in the design of the study; enrollment of patients; data collection, analysis, and interpretation; or preparation of the manuscript.
Competing interests: Shigeru Kohno received an honorarium, consultation fees, and research grants from Pfizer Inc., Dainippon Sumitomo Pharma Co., Merck Sharp & Dohme, Astellas Pharma Inc., Taisho Toyama Pharmaceutical Co., and Daiichi Sankyo Co. This study was partly funded by Pfizer Inc. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.
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Open Access / Peer-Reviewed / Research Article
Efficacy of Combination Therapy with Oseltamivir Phosphate and Azithromycin for Influenza: A Multicenter, Open-Label, Randomized Study
Hiroshi Kakeya, Masafumi Seki, Koichi Izumikawa, Kosuke Kosai, Yoshitomo Morinaga, Shintaro Kurihara, Shigeki Nakamura, Yoshifumi Imamura, Taiga Miyazaki, Misuzu Tsukamoto, Katsunori Yanagihara, Takayoshi Tashiro, Shigeru Kohno
Published: March 14, 2014 / DOI: 10.1371/journal.pone.0091293
Abstract
Background
Macrolides have antibiotic and immunomodulatory activities, which may have a favorable effect on the clinical outcome of patients with infections, including influenza. This study aimed to evaluate the effects of combination therapy with an anti-influenza agent, oseltamivir, and a single-dose formulation of azithromycin (AZM), which has been used for influenza-related secondary pneumonia, on influenza patients. The primary endpoint was a change in the expression levels of inflammatory cytokines. Secondary endpoints were the time required for resolution of influenza-related symptoms, incidence of complications, and adverse reactions.
Methods
Patients with seasonal influenza were enrolled in this multicenter, open-label, randomized study. Patients were stratified according to the presence of a high risk factor and were randomized to receive combination therapy with oseltamivir plus an extended-release formulation of AZM (combo-group) or oseltamivir monotherapy (mono-Group).
Results
We enrolled 107 patients and randomized them into the mono-group (56 patients) or the combo-group (51 patients). All patients were diagnosed with influenza A infection, and none of the patients had comorbid pneumonia. Statistically significant differences were not observed in the expression levels of inflammatory cytokines and chemokines between the 2 groups. The maximum temperature in the combo-group was lower than that in the mono-group on day 3 through day 5 (p = 0.048), particularly on day 4 (p = 0.037).
Conclusion
To our knowledge, this is the first prospective, randomized, clinical trial of oseltamivir and AZM combination therapy for influenza. Although the difference in inflammatory cytokine expression level was not statistically significant, combination therapy showed an early resolution of some symptoms.
Name of registry
University hospital Medical Information Network (UMIN).
Trial Registration no: UMIN000005371
_____
Citation: Kakeya H, Seki M, Izumikawa K, Kosai K, Morinaga Y, et al. (2014) Efficacy of Combination Therapy with Oseltamivir Phosphate and Azithromycin for Influenza: A Multicenter, Open-Label, Randomized Study. PLoS ONE 9(3): e91293. doi:10.1371/journal.pone.0091293
Editor: D. William Cameron, University of Ottawa, Canada
Received: September 24, 2013; Accepted: February 7, 2014; Published: March 14, 2014
Copyright: ? 2014 Kakeya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was supported by a Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology (No. 23591151 and No. 25461516) as well as by the Japanese Ministry of Health, Labour and Welfare Sciences Research Grants (H25-Shinko-ippan-006). The nonprofit corporation Nagasaki Evaluation Organization for Clinical Interventions (NEOCI; Nagasaki, Japan) and Pfizer Inc. also provided grants for this study, but the sponsors were not involved in the design of the study; enrollment of patients; data collection, analysis, and interpretation; or preparation of the manuscript.
Competing interests: Shigeru Kohno received an honorarium, consultation fees, and research grants from Pfizer Inc., Dainippon Sumitomo Pharma Co., Merck Sharp & Dohme, Astellas Pharma Inc., Taisho Toyama Pharmaceutical Co., and Daiichi Sankyo Co. This study was partly funded by Pfizer Inc. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.
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