Retrospective investigation of combination therapy with clarithromycin and levofloxacin for pulmonary Mycobacterium avium complex disease

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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.

Conclusion

The possibility that combined administration of CAM and LVFX causes unfavorable clinical outcomes for pulmonary MAC disease treatment was suggested.

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Most cited references 15

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Mycobacterium avium complex pulmonary disease in patients without HIV infection.

John Field, Dina Fisher, Annette L. Cowie (2004)

Mycobacterium avium complex (MAC) is ubiquitous. It is found in various freshwater and saltwater sources around the world, including hot water pipes. Although the organism was identified in the 1890s, its potential to cause human disease was only recognized 50 years later. Only a minority of people exposed to the organism will acquire MAC lung disease, usually those with underlying lung disease or immunosuppression. MAC may, however, cause progressive parenchymal lung disease and bronchiectasis in patients without underlying lung disease, particularly in middle-aged and elderly women. Preliminary data suggest that the interferon-gamma pathways may be deficient in elderly women with MAC lung disease. Other groups of patients who are more likely to harbor MAC in their lungs include patients with a cystic fibrosis or an abnormal alpha(1)-antiproteinase gene and patients with certain chest wall abnormalities. Treatment results continue to be disappointing, and the mortality of patients with MAC lung disease remains high. A PubMed search identified 38 reports of the treatment of MAC lung disease. Apart from the British Thoracic Society study, the only published controlled investigation, the studies published since 1994 have included a macrolide, either clarithromycin or azithromycin, usually in combination with ethambutol and a rifamycin. If success is defined as eradication of the organism without relapse over a period of several years after treatment has been discontinued, the reported treatment success rate with the macrolide containing regimens is approximately 55%. The prolonged treatment period, side effects, and possibly reinfection rather than relapse are responsible for the high failure rate.

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Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M avium complex lung disease.

Won-Jung Koh, Byeong-Ho Jeong, Kyeongman Jeon … (2012)

Mycobacterium avium and Mycobacterium intracellulare are grouped together as the M avium complex; however, little is known about the clinical impact of this species differentiation. This study compared the clinical features and prognoses of patients with M avium and M intracellulare lung disease. From 2000 to 2009, 590 patients were given a new diagnosis of M avium complex lung disease; 323 (55%) had M avium lung disease, and 267 (45%) had M intracellulare lung disease. Compared with the patients with M avium lung disease, the patients with M intracellulare lung disease were more likely to have the following characteristics: older age (64 vs 59 years, P = .002), a lower BMI (19.5 kg/m² vs 20.6 kg/m², P < .001), respiratory symptoms such as cough (84% vs 74%, P = .005), a history of previous treatment for TB (51% vs 31%, P < .001), the fibrocavitary form of the disease (26% vs 13%, P < .001), smear-positive sputum (56% vs 38%, P < .001), antibiotic therapy during the 24 months of follow-up (58% vs 42%, P < .001), and an unfavorable microbiologic response after combination antibiotic treatment (56% vs 74%, P = .001). Patients with M intracellulare lung disease exhibited a more severe presentation and had a worse prognosis than patients with M avium lung disease in terms of disease progression and treatment response. Therefore, species differentiation between M avium and M intracellulare may have prognostic and therapeutic implications.

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In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan

Y Kohno, H. Ohno, Y. Miyazaki … (2007)

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Author and article information

Contributors

Hitoshi Shimomura: shimoshimo@rs.tus.ac.jp

Airi Ono: aoringo.akaringo25@gmail.com

Keiko Imanaka: imanaka@kaken-hp.or.jp

Toru Majima: tmajima@kaken-hp.or.jp

Hidenori Masuyama: masuyama@kaken-hp.or.jp

Tsugumichi Sato: tsugusato@rs.tus.ac.jp

Takao Aoyama: t-aoyama@rs.noda.tus.ac.jp

Journal

Journal ID (nlm-ta): J Pharm Health Care Sci

Journal ID (iso-abbrev): J Pharm Health Care Sci

Title: Journal of Pharmaceutical Health Care and Sciences

Publisher: BioMed Central (London )

ISSN (Electronic): 2055-0294

Publication date (Electronic): 3 September 2015

Publication date PMC-release: 3 September 2015

Publication date Collection: 2015

Volume: 1

Electronic Location Identifier: 24

Affiliations

[ ]Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510 Japan

[ ]Department of Pharmacy, Chemotherapy Research Institute, Kaken Hospital, 6-1–14 Konodai, Ichikawa, Chiba 272-0827 Japan

[ ]Department of Respiratory medicine, Chemotherapy Research Institute, Kaken Hospital, 6-1–14 Konodai, Ichikawa, Chiba 272-0827 Japan

Article

Publisher ID: 25

DOI: 10.1186/s40780-015-0025-4

PMC ID: 4728750

SO-VID: 6ee58387-a195-4c23-8bd8-4516ec0fd575

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 6 May 2015

Date accepted : 20 August 2015

Funding

Funded by: FundRef , ᅟ;

Award ID: ᅟ

Award Recipient : Hitoshi Shimomura

Custom metadata

Keywords: mycobacterium avium complex,levofloxacin,clarithromycin,clinical efficacy,bacilli negative conversion rate

Data availability:

Keywords: mycobacterium avium complex, levofloxacin, clarithromycin, clinical efficacy, bacilli negative conversion rate

Retrospective investigation of combination therapy with clarithromycin and levofloxacin for pulmonary Mycobacterium avium complex disease

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Most cited references 15

Mycobacterium avium complex pulmonary disease in patients without HIV infection.

Clinical significance of the differentiation between Mycobacterium avium and Mycobacterium intracellulare in M avium complex lung disease.

In Vitro and In Vivo Activities of Novel Fluoroquinolones Alone and in Combination with Clarithromycin against Clinically Isolated Mycobacterium avium Complex Strains in Japan

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