Microbiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-Analysis

doi:10.1016/j.chest.2017.04.166

Chest

Volume 152, Issue 1, July 2017, Pages 120-142

https://doi.org/10.1016/j.chest.2017.04.166 Get rights and content

Background

Pulmonary disease caused by nontuberculous mycobacteria (NTM) is steadily increasing worldwide.

Methods

A systematic review of non-Mycobacterium avium complex studies published prior to October 2016 was conducted with respect to microbiological and clinical outcomes of current treatment regimens.

Results

We retrieved 352 citations, which yielded 24 studies eligible for evaluation. Sixteen studies were retrospective chart reviews, three studies were prospective, and only five studies were randomized. The weighted average proportion of sputum culture conversion (SCC) after subtracting posttreatment relapses for patients with M abscessus was 41.2% (95% CI, 28.6%-54.5%) but was 69.8% (95% CI, 41.0%-91.9%) with subspecies M massiliense in macrolide-containing regimens, 80.2% (95% CI, 58.4%-95.2%) in patients with M kansasii, 32.0% (95% CI, 16.5%-49.8%) for M xenopi (MX) and 54.4% (95% CI, 34.7%-73.4%) for M malmoense. SCCs in the total of 55 patients who underwent lung resection and had MX or M abscessus was high at 75.9%.

The risk of bias was low in four of five randomized studies. However, heterogeneous use of outcome parameters (eight definitions of “relapse,” eight of “treatment success,” and four of “cure”) hampered comparison of nonrandomized studies as well as producing possible bias by a posteriori exclusion (13.3%) and uncompleted treatment of participants (25.3%).

Conclusions

As a sustained microbiological response without surgery is unsatisfactory in treating M abscessus, MX, and M malmoense, functional and quality of life aspects should be given more emphasis in the individual evaluation of treatment outcome. Further, properly planned studies with sufficient power are needed, as are new drugs or better-tolerated application of current antibiotics, or both.

Section snippets

Study Search

We searched studies published in English, French, German, Italian, or Spanish through September 30, 2016 (see e-Appendix 1 for details). Initially, all NTM species were included in our search criteria; our final selection, however, included only articles concerning individual non-MAC species for which a microbiological treatment outcome was reported.

Assessment of Study Quality

The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.¹⁴ Risk of bias

Results

Figure 1 presents a flow diagram of the literature search results: In the selection process, 352 abstracts were identified, 87 of which were read in full text (Fig 1). Finally, 24 studies published in peer-reviewed journals could be included in the review.17, 18, 19, 20, 21, 22, 23, 24, 25, 37, 38, 39, 40, 41 Two BTS studies on MX²⁵ and M malmoense³³ provide additional information on cases reported in an earlier (2001) BTS study.³⁶ To avoid double counting, the 2001 publication was not included.

Discussion

Unlike pulmonary TB, the treatment decision for NTM-PD is highly complex and depends on (in addition to the presumed clinical benefits to the individual patients) the identity of the respective NTM pathogen and the respective radiographic findings. Cavitary disease deserves particular attention here; it is clearly a more deadly threat than nodular/bronchiectatic forms of NTM disease. Cavitary disease is frequent not only in cases of M xenopi, M malmoense, and M kansasii²¹ but has been also been

Acknowledgments

Author contributions: R. D. guarantees the integrity of the work, contributed to study selection and review, conducted the statistical analysis, and wrote the manuscript. F. R., E. R., L. W., and J. S. reviewed and amended the manuscript and approved the final decision for submission. A. N. contributed to study selection and review and approved the final decision for submission.

Financial/nonfinancial disclosures: The authors have reported to CHEST the following: R. D. has received fees for

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The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression.
Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed.
MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression.
A pharmacologic approach to treatment of Mycobacterium abscessus pulmonary disease
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Mycobacterium abscessus est un complexe de mycobactéries non tuberculeuses à croissance rapide responsable d’infections pulmonaires, comprenant les sous-espèces abscessus, massiliense et bolletii. Elles se différencient essentiellement par l’existence d’une résistance naturelle inductible aux macrolides, présente dans la plupart des souches de Mycobacterium abscessus spp abscessus et Mycobacterium abscessus spp bolletii, mais absente pour Mycobacterium abscessus spp massiliense. La thérapie repose sur un traitement long associant plusieurs antibiotiques, dont certains en perfusion intraveineuse. Cependant, le pronostic du traitement de ces infections est mauvais, le taux de guérison ne dépassant pas 40 %. De plus en plus de données de pharmacodynamie et de pharmacocinétique vis-à-vis de M. abscessus sont publiées. Elles montrent que l’inefficacité de la thérapie est le fait d’une résistance importante de la bactérie, notamment aux macrolides, couplée à une pharmacocinétique non favorable. D’autres molécules aux caractéristiques plus intéressantes et la forme inhalée des antibiotiques sont des pistes d’avenir.
Mycobacterium abscessus is a fast-growing non-tuberculous mycobacteria complex causing pulmonary infections, comprising the subspecies abscessus, massiliense and bolletii. Differences are based predominantly on natural inducible macrolide resistance, active in most Mycobacterium abscessus spp abscessus species and in Mycobacterium abscessus spp bolletii but inactive in Mycobacterium abscessus spp massiliense. Therapy consists in long-term treatment, combining multiple antibiotics. Prognosis is poor, as only 40% of patients experience cure. Pharmacodynamic and pharmacokinetic data on M. abscessus have recently been published, showing that therapy ineffectiveness might be explained by intrinsic bacterial resistance (macrolides…) and by the unfavorable pharmacokinetics of the recommended antibiotics. Other molecules and inhaled antibiotics are promising.
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This retrospective multicenter cohort study included pwCF from five CF centers in Israel. PwCF aged older than 6 who had at least one positive NTM airway culture in the past two years and were treated with ETI for at least one year were included. The annual NTM and bacterial isolations, pulmonary function tests, and body mass index were analyzed before and after ETI treatment.
Fifteen pwCF were included (median age 20.9 years, 73.3% females, 80% pancreatic insufficient). In nine patients (66%) NTM isolations were eradicated following treatment with ETI. Seven of them had MABC. The median time between the first NTM isolation and treatment with ETI was 2.71 years (0.27-10.35 years). Eradication of NTM was associated with improved pulmonary function tests (p<0.05).
For the first time, we report successful eradication of NTM, including MABC, following treatment with ETI in pwCF. Additional studies are needed to assess whether treatment with ETI can result in the long-term eradication of NTM.
Treatment Approaches to Mycobacterium abscessus Pulmonary Disease
2023, Clinics in Chest Medicine
Treatment of the Less Common Nontuberculous Mycobacterial Pulmonary Disease
2023, Clinics in Chest Medicine

View all citing articles on Scopus

: FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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Chest

Original Research: Chest InfectionsMicrobiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-Analysis

Background

Methods

Results

Conclusions

Section snippets

Study Search

Assessment of Study Quality

Results

Discussion

Acknowledgments

Int J Infect Dis

J Clin Epidemiol

J Microbiol Immunol Infect

Respir Med

Respir Med

Respir Med

Tuber Lung Dis

Drug Resist Updat

Clin Chest Med

An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases [published correction appears in

Am J Respir Crit Care Med.

Burden and trends of hospitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, 2005-2011

BMC Infect Dis

Prevalence of nontuberculous mycobacterial pulmonary disease, Germany, 2009-2014

Emerg Infect Dis

Nontuberculous mycobacteria in cystic fibrosis and non-cystic fibrosis bronchiectasis

Semin Respir Crit Care Med

Pulmonary disease caused by nontuberculous mycobacteria

Expert Rev Respir Med

Current opinions in the treatment of pulmonary nontuberculous mycobacteria in non-cystic fibrosis patients: Mycobacterium abscessus group, Mycobacterium avium complex, and Mycobacterium kansasii

Curr Treat Options Infect Dis

Emended description of Mycobacterium abscessus, Mycobacterium abscessus subsp. abscessus and Mycobacteriumabscessus subsp. bolletii and designation of Mycobacteriumabscessus subsp. massiliense comb. nov

Int J Syst Evol Microbiol

Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative patients: the evidence

Expert Rev Anti Infect Ther

Advances in the management of pulmonary disease due to Mycobacterium abscessus complex

Int J Tuberc Lung Dis

The rising incidence and clinical relevance of Mycobacterium malmoense: a review of the literature

Int J Tuberc Lung Dis

Management of opportunist mycobacterial infections: Joint Tuberculosis Committee Guidelines 1999. Subcommittee of the Joint Tuberculosis Committee of the British Thoracic Society

Thorax

Pulmonary Mycobacterium xenopi infection in non-HIV-infected patients: a systematic review

Int J Tuberc Lung Dis

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

BMJ

Sulfonamide-containing regimens for disease caused by rifampin-resistant Mycobacterium kansasii

Am Rev Respir Dis

Original Research: Chest Infections
Microbiological and Clinical Outcomes of Treating Non-Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Review and Meta-Analysis