title: Retrospective investigation of combination therapy with clarithromycin and levofloxacin for pulmonary Mycobacterium avium complex disease.
abstract: BACKGROUND
  Fluoroquinolones are often used for the treatment of refractory Mycobacterium avium complex (MAC) disease when the clinical efficacy of the recommended regimen, which includes clarithromycin (CAM), rifampicin (RFP), and ethambutol (EB), is insufficient. However, recent in vitro and in vivo studies have suggested that fluoroquinolones decreased the antibacterial activity of CAM when they were administered in combination. In this study, we retrospectively investigated the influence of the combination of CAM and levofloxacin (LVFX) on clinical outcomes for pulmonary MAC disease patients.
  
  
  METHODS
  Pulmonary MAC disease patients from 2010 to 2012 were divided into two groups, those who received LVFX together with CAM (LVFX group) and those who received CAM without LVFX (control group). The number of patients who showed improvement was evaluated at 1, 3, 6 and 12 months after the start of therapy based on bacteriological examination (culture and smear examination) and the bacilli negative conversion rate.
  
  
  RESULTS
  There were no significant differences between the LVFX group (n = 18, 64.5 ± 6.5 years old) and the control group (n = 57, 71.0 ± 7.0 years old) in terms of gender, age, etiologic agent, baseline culture examination score, concomitant medication, and dosage of each drug. The clinical outcomes in the LVFX group were inferior to those in the control group at all endpoints and observational periods, and we found a significant difference in the percent improvement of the smear examination by fluorescence microscopy method (38 % vs. 83 %) and the bacilli negative conversion rate (38 % vs. 79 %) at 3 months. Our study suggests that the combination of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment. There was no significant difference between both groups in terms of frequency of adverse events.
  
  
  CONCLUSIONS
  The possibility that combined administration of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment was suggested.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimomura
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Airi
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Pharmacy, Chemotherapy Research Institute, Kaken Hospital, 6-1-14 Konodai, Ichikawa, Chiba 272-0827 Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Imanaka
authors.affiliation: Department of Respiratory medicine, Chemotherapy Research Institute, Kaken Hospital, 6-1-14 Konodai, Ichikawa, Chiba 272-0827 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Majima
authors.affiliation: Department of Respiratory medicine, Chemotherapy Research Institute, Kaken Hospital, 6-1-14 Konodai, Ichikawa, Chiba 272-0827 Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Masuyama
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Tsugumichi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Aoyama
keywords: Bacilli negative conversion rate; Clarithromycin; Clinical efficacy; Levofloxacin; Mycobacterium avium complex
references.citation: Chest. 2012 Dec;142(6):1482-8
references.pmid: 22628488
references.citation: Antimicrob Agents Chemother. 2007 Nov;51(11):4071-6
references.pmid: 17709469
references.citation: Biopharm Drug Dispos. 2011 Oct;32(7):389-97
references.pmid: 21812004
references.citation: Kekkaku. 2000 Jul;75(7):471-6
references.pmid: 10944891
references.citation: Antimicrob Agents Chemother. 2013 May;57(5):2281-5
references.pmid: 23478956
references.citation: Am J Respir Crit Care Med. 1999 Sep;160(3):866-72
references.pmid: 10471610
references.citation: Am J Ther. 2004 Nov-Dec;11(6):433-42
references.pmid: 15543082
references.citation: Int J Antimicrob Agents. 2011 Apr;37(4):296-301
references.pmid: 21353489
references.citation: Tuberc Respir Dis (Seoul). 2014 Oct;77(4):161-6
references.pmid: 25368661
references.citation: Thorax. 2003 Mar;58(3):246-51
references.pmid: 12612305
references.citation: J Infect Chemother. 2012 Apr;18(2):146-51
references.pmid: 21927844
references.citation: Kekkaku. 2005 Jan;80(1):1-7
references.pmid: 15839056
references.citation: Kekkaku. 1997 Jan;72(1):1-7
references.pmid: 9038009
references.citation: Chest. 2004 Aug;126(2):566-81
references.pmid: 15302746
references.citation: Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1766-72
references.pmid: 8665032
references.citation: Thorax. 2008 Jul;63(7):627-34
references.pmid: 18250184
references.citation: Kekkaku. 2001 Apr;76(4):357-62
references.pmid: 11398326
references.citation: Kekkaku. 2008 Dec;83(12):779-84
references.pmid: 19172823