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      Clinical characteristics and treatment outcomes of patients with macrolide-resistant Mycobacterium avium complex pulmonary disease: a systematic review and meta-analysis

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          Abstract

          Background

          Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD).

          Methods

          We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale.

          Results

          Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14–30%), and the one-year all-cause mortality was 10% (95% CI, 5–20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types.

          Conclusions

          Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.

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          Most cited references17

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          British Thoracic Society Guideline for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD)

          Charles S. Haworth, John C.G. Banks, Toby Capstick … (2017)
          The full guideline for the management of non-tuberculous mycobacterial pulmonary disease is published in Thorax. The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline.
          Article 0 comments Cited 107 times – based on 0 reviews     Review now
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            Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study

            David Griffith, Gina L. Eagle, Rachel Thomson … (2018)
            Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).
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              Treatment Outcomes of Mycobacterium avium Complex Lung Disease: A Systematic Review and Meta-analysis

              Nakwon Kwak, Jimyung Park, Eunyoung Kim … (2017)
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                Author and article information

                Contributors
                Youngmok Park: 0mokfv@yuhs.ac
                Eun Hye Lee: hieunhye@yuhs.ac
                Inkyung Jung: ijung@yuhs.ac
                Goeun Park: labbios@yuhs.ac
                Young Ae Kang:
                ORCID: http://orcid.org/0000-0002-7783-5271
                mdkang@yuhs.ac
                Journal
                Journal ID (nlm-ta): Respir Res
                Journal ID (iso-abbrev): Respir. Res
                Title: Respiratory Research
                Publisher: BioMed Central (London )
                ISSN (Print): 1465-9921
                ISSN (Electronic): 1465-993X
                Publication date (Electronic): 18 December 2019
                Publication date PMC-release: 18 December 2019
                Publication date (Print): 2019
                Volume: 20
                Electronic Location Identifier: 286
                Affiliations
                [1 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Division of Pulmonology, Department of Internal Medicine, Severance Hospital, , Yonsei University College of Medicine, ; 50-1 Yonsei-ro, Seodaemun-Gu, 03722 Seoul, Republic of Korea
                [2 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Division of Biostatistics, Department of Biomedical Systems Informatics, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                Author information
                http://orcid.org/0000-0002-7783-5271
                Article
                Publisher ID: 1258
                DOI: 10.1186/s12931-019-1258-9
                PMC ID: 6921583
                PubMed ID: 31852452
                SO-VID: 4ec1343e-de43-4ff5-be2a-a966f2b4fdde
                Copyright © © The Author(s). 2019
                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 : 26 April 2019
                Date accepted : 9 December 2019
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2019

                ScienceOpen disciplines: Respiratory medicine
                Keywords: mycobacterium avium complex,mycobacterium avium-intracellulare infection,macrolides,drug resistance,clarithromycin
                Data availability:
                ScienceOpen disciplines: Respiratory medicine
                Keywords: mycobacterium avium complex, mycobacterium avium-intracellulare infection, macrolides, drug resistance, clarithromycin

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