The incidence of Mycobacterium avium complex pulmonary disease (MACPD) has been globally increasing. The present study aims to provide a comprehensive analysis of clinical characteristics and treatment response among patients in the Amazon region of Brazil and conduct a retrospective cohort study at a prominent referral hospital in the State of Pará, Brazil, from 2012 to 2020. The M. avium group represented 58.9% of cases, followed by M. intracellulare (35.7%), M. colombiense (3.6%), and M. chimaera (1.8%). The majority of patients (73.2%) were female and with an average age of 63 years. Primary clinical manifestations included persistent cough and sputum production. The Charlson comorbidity index (CCI) averaged 2.47, with 36.3% of patients having a CCI score equal to higher than 3. Notably, over 70% of patients had received treatment for pulmonary tuberculosis before initiating treatment for MAC infection. The fibrocavitary radiologic form was the most prevalent (55.4%), frequently exhibiting a bilateral distribution (53.6%). Antimicrobial susceptibility revealed a significant prevalence of MAC resistance to drugs in the therapeutic regimen. Despite this, most of the patients experienced clinical improvement (50%). In conclusion, this study highlights a higher prevalence of MAC infections among middle-aged women, with a history of pulmonary tuberculosis treatment and presenting the fibrocavitary radiological form was predominant.
References
[1]
Dahl, V.N., Mølhave, M., Fløe, A., van Ingen, J., Schön, T., Lillebaek, T., Andersen, A.B. and Wejse, C. (2022) Global Trends of Pulmonary Infections with Nontuberculous Mycobacteria: A Systematic Review. International Journal of Infectious Diseases, 125, 120-131. https://doi.org/10.1016/j.ijid.2022.10.013
[2]
Cowman, S., van Ingen, J., Griffith, D.E. and Loebinger, M.R. (2019) Non-Tuberculous Mycobacterial Pulmonary Disease. European Respiratory Journal, 54, Article ID: 1900250. https://doi.org/10.1183/13993003.00250-2019
[3]
Nunes-Costa, D., Alarico, S., Dalcolmo, M.P., Correia-Neves, M. and Empadinhas, N. (2016) The Looming Tide of Nontuberculous Mycobacterial Infections in Portugal and Brazil. Tuberculosis, 96, 107-119. https://doi.org/10.1016/j.tube.2015.09.006
[4]
De Lima Mota, M.A., De Melo, D.M., Christyan Nunes Beserra, F.L., Nogueira Filho, G.A., Pinto, L.M., Jesus Souza, R., Silva Sousa, S.D., Mota, R.S., Justa Pires Neto, R.D. and Jesus Silva Leite, T.D.M. (2020) Clinical-Epidemiological Profile and Factors Related to the Mortality of Patients with Nontuberculous Mycobacteria Isolated at a Reference Hospital in Ceará, Northeastern Brazil. International Journal of Mycobacteriology, 9, 83-90. https://doi.org/10.4103/ijmy.ijmy_12_20
[5]
Busatto, C., Vianna, J.S., Silva, A.B.S., Basso, R., Silveira, J., Groll, A.V., Ramis, I.B. and Silva, P.E.A.D. (2020) Nontuberculous Mycobacteria in Patients with Suspected Tuberculosis and the Genetic Diversity of Mycobacterium avium in the Extreme South of Brazil. Jornal Brasileiro de Pneumologia, 46, e20190184. https://doi.org/10.36416/1806-3756/e20190184
[6]
Ministry of Health, Department of Chronic Conditions and Sexually Transmitted Infections (2023) Epidemiological Report Tuberculosis 2023 in Brasil.
[7]
Ministry of Health, Department of Chronic Conditions and Sexually Transmitted Infections (2021) Recommendations for the Diagnosis and Treatment of Diseases Caused by Non-Tuberculous Mycobacteria in Brazil.
[8]
Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F., Holland, S.M., Horsburgh, R., Huitt, G., Iademarco, M.F., Iseman, M., Olivier, K., Ruoss, S., Von Reyn, C.F., Wallace, R.J. and Winthrop, K. (2007) An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases. American Journal of Respiratory and Critical Care Medicine, 175, 367-416. https://doi.org/10.1164/rccm.200604-571ST
[9]
Daley, C.L., Iaccarino, J.M., Lange, C., Cambau, E., Wallace Jr., R.J., Andrejak, C., Böttger, E.C., Brozek, J., Griffith, D.E., Guglielmetti, L., Huitt, G.A., Knight, S.L., Leitman, P., Marras, T.K., Olivier, K.N., Santin, M., Stout, J.E., Tortoli, E., van Ingen, J., Wagner, D. and Winthrop, K.L. (2020) Treatment of Nontuberculous Mycobacterial Pulmonary Disease: An Official ATS/ERS/ESCMID/IDSA Clinical Practice Guideline. European Respiratory Journal, 56, Article ID: 2000535. https://doi.org/10.1183/13993003.00535-2020
[10]
Gebert, M.J., Delgado-Baquerizo, M., Oliverio, A.M., Webster, T.M., Nichols, L.M., Honda, J.R., Chan, E.D., Adjemian, J., Dunn, R.R. and Fierer, N. (2018) Ecological Analyses of Mycobacteria in Showerhead Biofilms and Their Relevance to Human Health. mBio, 9, e01614-18. https://doi.org/10.1128/mBio.01614-18
[11]
Lipman, M., Kunst, H., Loebinger, M.R., Milburn, H.J. and King, M. (2021) Non Tuberculous Mycobacteria Pulmonary Disease: Patients and Clinicians Working Together to Improve the Evidence Base for Care. International Journal of Infectious Diseases, 113, S73-S77. https://doi.org/10.1016/j.ijid.2021.03.064
[12]
Brown-Elliott, B.A., Nash, K.A. and Wallace Jr., R.J. (2012) Antimicrobial Susceptibility Testing, Drug Resistance Mechanisms, and Therapy of Infections with Nontuberculous Mycobacteria. Clinical Microbiology Reviews, 25, 545-582. https://doi.org/10.1128/CMR.05030-11
[13]
Falkinham III, J.O. (2018) Challenges of NTM Drug Development. Frontiers in Microbiology, 9, Article 1613. https://doi.org/10.3389/fmicb.2018.01613
[14]
Nonaka, M., Matsuyama, M., Sakai, C., Matsumura, S., Arai, N., Nakajima, M., Saito, T. and Hizawa, N. (2023) Risk Factors for Clinical Progression in Patients with Pulmonary Mycobacterium avium Complex Disease without Culture-Positive Sputum: A Single-Center, Retrospective Study. European Journal of Medical Research, 28, Article No. 186. https://doi.org/10.1186/s40001-023-01152-0
[15]
Kumagai, S., Ito, A., Hashimoto, T., Marumo, S., Tokumasu, H., Kotani, A., Yamaki, H., Shirata, M., Furuuchi, K., Fukui, M. and Ishida, T. (2017) Development, and Validation of a Prognostic Scoring Model for Mycobacterium avium Complex Lung Disease: An Observational Cohort Study. BMC Infectious Diseases, 17, Article No. 436. https://doi.org/10.1186/s12879-017-2544-0
[16]
Zweijpfenning, S., Kops, S., Magis-Escurra, C., Boeree, M.J., van Ingen, J. and Hoefsloot, W. (2017) Treatment and Outcome of Non-Tuberculous Mycobacterial Pulmonary Disease in a Predominantly Fibro-Cavitary Disease Cohort. Respiratory Medicine, 131, 220-224. https://doi.org/10.1016/j.rmed.2017.08.031
[17]
Kim, E.Y., Chi, S.Y., Oh, I.J., Kim, K.S., Kim, Y.I., Lim, S.C., Kim, Y.C. and Kwon, Y.S. (2011) Treatment Outcome of Combination Therapy Including Clarithromycin for Mycobacterium avium Complex Pulmonary Disease. The Korean Journal of Internal Medicine, 26, 54-59. https://doi.org/10.3904/kjim.2011.26.1.54
[18]
Charlson, M.E., Pompei, P., Ales, K.L. and Mackenzie, C.R. (1987) A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation. Journal of Chronic Diseases, 40, 373-383. https://doi.org/10.1016/0021-9681(87)90171-8
[19]
van Ingen, J., Aksamit, T., Andrejak, C., Böttger, E.C., Cambau, E., Daley, C.L., Griffith, D.E., Guglielmetti, L., Holland, S.M., Huitt, G.A., Koh, W.J., Lange, C., Leitman, P., Marras, T.K., Morimoto, K., Olivier, K.N., Santin, M., Stout, J.E., Thomson, R., Tortoli, E., Wallace Jr., R.J., Winthrop, K.L. and Wagner, D. for NTM-NET (2018) Treatment Outcome Definitions in Nontuberculous Mycobacterial Pulmonary Disease: An NTM-NET Consensus Statement. European Respiratory Journal, 51, Article ID: 1800170. https://doi.org/10.1183/13993003.00170-2018
[20]
Kim, H., Kim, S.H., Shim, T.S., Kim, M.N., Bai, G.H., Park, Y.G., Lee, S.H., Chae, G.T., Cha, C.Y., Kook, Y.H. and Kim, B.J. (2005) Differentiation of Mycobacterium Species by Analysis of the Heat-Shock Protein 65 Gene (hsp65). International Journal of Systematic and Evolutionary Microbiology, 55, 1649-1656. https://doi.org/10.1099/ijs.0.63553-0
[21]
Adékambi, T., Colson, P. and Drancourt, M. (2003) rpoB-Based Identification of Nonpigmented and Late-Pigmenting Rapidly Growing Mycobacteria. Journal of Clinical Microbiology, 41, 5699-5708. https://doi.org/10.1128/JCM.41.12.5699-5708.2003
[22]
Clinical and Laboratory Standards Institute (2018) Susceptibility Testing of Mycobacteria, Nocardiae, and other Aerobic Actinomycetes: Approved Standard. 3rd Edition, CLSI, Wayne, PA.
[23]
BRASIL (2007) Ministério da Saúde. Introdução à Estatística Espacial para a Saúde Pública/Ministério da Saúde. Fundação Oswaldo Cruz, Brasília, Brasil. http://www.escoladesaude.pr.gov.br/arquivos/File/TEXTOS_CURSO_VIGILANCIA/capacitacao_e_atualizacao_em_geoprocessamento_em_saude_3.pdf
[24]
Yamamura, M., Freitas, I.M.D., Santo, M., Chiaravalloti, F., Popolin, M.A.P., Arroyo, L.H., et al. (2016) Análise espacial das internações evitáveis por tuberculose em Ribeirão Preto, SP (2006-2012). Revista de Saúde Pública, 50, Article 20. https://doi.org/10.1590/S1518-8787.2016050006049
[25]
Bhatt, S.P., Nanda, S. and Kintzer Jr., J.S. (2009) The Lady Windermere Syndrome. Primary Care Respiratory Journal, 18, 334-336. https://doi.org/10.4104/pcrj.2009.00019
[26]
Chan, E.D. and Iseman M.D. (2010) Slender, Older Women Appear to be More Susceptible to Nontuberculous Mycobacterial Lung Disease. Gender Medicine, 7, 5-18. https://doi.org/10.1016/j.genm.2010.01.005
[27]
Danley, J., Kwait, R., Peterson, D.D., Sendecki, J., Vaughn, B., Nakisbendi, K., Sawicki, J. and Lande, L. (2014) Normal Estrogen, but Low Dehydroepiandrosterone Levels, in Women with Pulmonary Mycobacterium avium Complex. A Preliminary Study. Annals of the American Thoracic Society, 11, 908-914. https://doi.org/10.1513/AnnalsATS.201312-422OC
[28]
Koh, W.J., Jeong, B.H., Jeon, K., Lee, N.Y., Lee, K.S., Woo, S.Y., Shin, S.J. and Kwon, O.J. (2012) Clinical Significance of the Differentiation between Mycobacterium avium and Mycobacterium Intracellulare in M. avium Complex Lung Disease. Chest, 142, 1482-1488. https://doi.org/10.1378/chest.12-0494
[29]
Schweitzer, M.D., Salamo, O., Campos, M., Schraufnagel, D.E., Sadikot, R. and Mirsaeidi, M. (2017) Body Habitus in Patients with and without Bronchiectasis and Non-Tuberculous Mycobacteria. PLOS ONE, 12, e0185095. https://doi.org/10.1371/journal.pone.0185095
[30]
Fusco da Costa, A.R., Falkinham, J.O., Lopes, M.L., Barretto, A.R., Felicio, J.S., Sales, L.H., et al. (2013) Occurrence of Nontuberculous Mycobacterial Pulmonary Infection in an Endemic Area of Tuberculosis. PLOS Neglected Tropical Diseases, 7, e2340. https://doi.org/10.1371/journal.pntd.0002340
[31]
Lima, C.A., Gomes, H.M., Oelemann, M.A., Ramos, J.P., Caldas, P.C., Campos, C.E., et al. (2013) Nontuberculous Mycobacteria in Respiratory Samples from Patients with Pulmonary Tuberculosis in the State of Rondônia, Brazil. Memórias do Instituto Oswaldo Cruz, 108, 457-462. https://doi.org/10.1590/S0074-0276108042013010
[32]
Hwang, J.A., Kim, S., Jo, K.W. and Shim, T.S. (2017) Natural History of Mycobacterium avium Complex Lung Disease in Untreated Patients with Stable Course. European Respiratory Journal, 49, Article ID: 1600537. https://doi.org/10.1183/13993003.00537-2016
[33]
Sadamatsu, H., Takahashi, K., Tashiro, H., Kusaba, K., Haraguchi, T., Kurihara, Y., Komiya, N., Nakashima, C., Nakamura, T., Kimura, S. and Sueoka-Aragane, N. (2021) A Low Body Mass Index Is Associated with Unsuccessful Treatment in Patients with Mycobacterium avium Complex Pulmonary Disease. Journal of Clinical Medicine, 10, Article 1576. https://doi.org/10.3390/jcm10081576
[34]
Gochi, M., Takayanagi, N., Kanauchi, T., Ishiguro, T., Yanagisawa, T. and Sugita, Y. (2015) Retrospective Study of the Predictors of Mortality and Radiographic Deterioration in 782 Patients with Nodular/Bronchiectatic Mycobacterium avium Complex Lung Disease. BMJ Open, 5, e008058. https://doi.org/10.1136/bmjopen-2015-008058
[35]
Kitada, S., Uenami, T., Yoshimura, K., Tateishi, Y., Miki, K., Miki, M., et al. (2012) Long-Term Radiographic Outcome of Nodular Bronchiectatic Mycobacterium avium Complex Pulmonary Disease. The International Journal of Tuberculosis and Lung Disease, 16, 660-664. https://doi.org/10.5588/ijtld.11.0534
[36]
Loebinger, M.R., Quint, J.K., van der Laan, R., Obradovic, M., Chawla, R., Kishore, A. and van Ingen, J. (2023) Risk Factors for Nontuberculous Mycobacterial Pulmonary Disease: A Systematic Literature Review and Meta-Analysis. Chest, 164, 1115-1124. https://doi.org/10.1016/j.chest.2023.06.014
