title: Analysis of drug treatment outcome in clarithromycin-resistant Mycobacterium avium complex lung disease.
abstract: BACKGROUND
  Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.
  
  
  METHODS
  Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 μg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings.
  
  
  RESULTS
  Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found.
  
  
  CONCLUSIONS
  Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan. tkskdt@jikei.ac.jp.|Division of Respiratory Disease, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8461, Japan. tkskdt@jikei.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Kadota
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Matsui
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirose
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Saito
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Akaba
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Akashi
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Atsuhisa
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Akagawa
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.|Asthma and Allergy Center, National Hospital Organization Tokyo National Hospital, 3-1-1, Takeoka, Kiyose-shi, Tokyo, 204-8585, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D017291:Clarithromycin / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015999:Multivariate Analysis; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000302:isolation & purification*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies; D012307:Risk Factors; D012709:Serum Albumin / Q000032:analysis; D013183:Sputum / Q000382:microbiology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D012709:Serum Albumin; D017963:Azithromycin; D002097:C-Reactive Protein; D017291:Clarithromycin
references.citation: Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1376-95
references.pmid: 10764337
references.citation: N Engl J Med. 1994 Feb 10;330(6):438-9
references.pmid: 8284019
references.citation: Am J Respir Crit Care Med. 1994 May;149(5):1335-41
references.pmid: 8173775
references.citation: J Infect Dis. 1995 Mar;171(3):747-50
references.pmid: 7876634
references.citation: Clin Infect Dis. 1996 Apr;22 Suppl 1:S3-13; discussion S13-4
references.pmid: 8785253
references.citation: Am J Respir Crit Care Med. 1996 Jun;153(6 Pt 1):1766-72
references.pmid: 8665032
references.citation: Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1829-32
references.pmid: 9620913
references.citation: Am J Respir Crit Care Med. 1999 Sep;160(3):866-72
references.pmid: 10471610
references.citation: Am J Respir Crit Care Med. 2006 Oct 15;174(8):928-34
references.pmid: 16858014
references.citation: Respir Med. 2007 Jan;101(1):130-8
references.pmid: 16750618
references.citation: Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416
references.pmid: 17277290
references.citation: Ann Thorac Surg. 2008 Jun;85(6):1887-92; discussion 1892-3
references.pmid: 18498789
references.citation: Am J Respir Crit Care Med. 2008 Dec 1;178(11):1139-47
references.pmid: 18723437
references.citation: Am J Respir Crit Care Med. 2009 Nov 1;180(9):896-902
references.pmid: 19661243
references.citation: Am J Respir Crit Care Med. 2010 Oct 1;182(7):977-82
references.pmid: 20508209
references.citation: Am J Respir Crit Care Med. 2010 Oct 1;182(7):970-6
references.pmid: 20538958
references.citation: N Engl J Med. 2011 Aug 25;365(8):689-98
references.pmid: 21864166
references.citation: Curr Opin Infect Dis. 2012 Apr;25(2):218-27
references.pmid: 22327466
references.citation: J Infect Chemother. 2012 Apr;18(2):146-51
references.pmid: 21927844
references.citation: J Infect Chemother. 2012 Aug;18(4):436-43
references.pmid: 22205543
references.citation: Am J Respir Crit Care Med. 2012 Sep 15;186(6):559-65
references.pmid: 22744719
references.citation: Cochrane Database Syst Rev. 2012;11:CD002203
references.pmid: 23152214
references.citation: JAMA. 2013 Mar 27;309(12):1251-9
references.pmid: 23532241
references.citation: JAMA. 2013 Mar 27;309(12):1260-7
references.pmid: 23532242
references.citation: Antimicrob Agents Chemother. 2013 May;57(5):2281-5
references.pmid: 23478956
references.citation: Ann Thorac Surg. 2013 Jul;96(1):287-91
references.pmid: 23618520