Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients
Carolin Kröner, Barbara Ganster, Matthias Kappler, Ann-Christin Grimmelt, Bernd H. Belohradsky, Michael Hogardt, Gudrun Laniado, Michael Meissner, Sören Schubert, Matthias Griese
Institute for Clinical Chemistry, Molecular Diagnostics, Medical Microbiology and ygiene Department, Ludwigshafen General Hospital, Ludwigshafen, Germany.
Institute for Medical Microbiology and Infection Control, University Hospital, Johann-Wolfgang-Goethe-University, Frankfurt/Main, Germany.
Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Ludwig-Maximilians-University, Munich, Germany.
Paediatric Pneumology, Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany.
DOI: 10.4236/ojmm.2013.31006   PDF    HTML   XML   3,873 Downloads   6,703 Views   Citations


Goal of this study was to analyse the clinical course of cystic fibrosis (CF) patients with nontuberculous mycobacteria (NTM) in their respiratory secretions and to investigate the molecular epidemiology of the most prevalent NTM species by multilocus sequence analysis (MLSA). The respiratory specimen and the clinical parameters forced expiratory volume in one second (FEV1), body-mass-index (BMI), erythrocyte sedimentation rate (ESR) 1 h and immunoglobulin G (IgG) of 357 CF patients, 0 - 52.4 years, mean FEV1 2009 81.5% pred were analysed between 1998 and 2010. In 13 patients NTM were detected. 12 of 13 patients carried M. abscessus, for one patient the NTM species was not characterized. 4 patients carried a second NTM species (M. avium, M. chelonae (2x), M. intracellulare). 6 patients exhibited a significant decline in FEV1, however changes in BMI, IgG and ESR were discordant. Molecular genotyping of M. abscessus isolates revealed a unique MLSA pattern in 6 patients. 2 patients harboured identical strains, and one patient a closely related strain. Whether the presence of identical strains is attributed to the acquisition of NTM clones from common environmental sources or to patient-to-patient transmission cannot be definitely clarified. Although cross-in- fection of the three patients with identical/closely related strains in the present cohort is highly unlikely, we recommend strict hygiene measures for all CF patients harbouring NTM.

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C. Kröner, B. Ganster, M. Kappler, A. Grimmelt, B. Belohradsky, M. Hogardt, G. Laniado, M. Meissner, S. Schubert and M. Griese, "Molecular Epidemiology of Nontuberculous Mycobacteria in a German CF Center and Clinical Course of NTM Positive Patients," Open Journal of Medical Microbiology, Vol. 3 No. 1, 2013, pp. 39-47. doi: 10.4236/ojmm.2013.31006.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] K. N. Olivier, J. R. Yankaskas and M. R. Knowles, “Nontuberculous Mycobacterial Pulmonary Disease in Cystic Fibrosis,” Seminars in Respiratory Infections, Vol. 11, No. 4, 1996, pp. 272-284.
[2] K. N. Olivier, D. J. Weber, R. J. Wallace Jr., A. R. Faiz, J. H. Lee, Y. Zhang, B. A. Brown-Elliot, A. Handler, R. W. Wilson, M. S. Schechter, L. J. Edwards, S. Chakraborti and M. R. Knowles, “Nontuberculous Mycobacteria. I: Multicenter Prevalence Study in Cystic Fibrosis,” American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 6, 2003, pp. 828-834. doi:10.1164/rccm.200207-678OC
[3] R. Vankayalapati, B. Wizel, B. Samten, D. E. Griffith, H. Shams, M. R. Galland, C. F. Von Reyn, W. M. Girard, R. J. Wallace Jr. and P. F. Barnes, “Cytokine Profiles in Immunocompetent Persons Infected with Mycobacterium avium Complex,” The Journal of Infectious Diseases, Vol. 183, No. 3, 2001, pp. 478-484. doi:10.1086/318087
[4] A. Safdar, D. A. White, D. Stover, D. Armstrong and H. W. Murray, “Profound Interferon Gamma Deficiency in Patients with Chronic Pulmonary Nontuberculous Mycobacteriosis,” American Journal of Medicine, Vol. 113, No. 9, 2002, pp. 756-759. doi:10.1016/S0002-9343(02)01313-X
[5] R. E. Colombo, S. C. Hill, R. J. Claypool, S. M. Holland and K. N. Olivier, “Familial Clustering of Pulmonary Nontuberculous Mycobacterial Disease,” Chest, Vol. 137, No. 3, 2010, pp. 629-634. doi:10.1378/chest.09-1173
[6] M. L. Aitken, A. Limaye, P. Pottinger, E. Whimbey, C. H. Goss, M. R. Tonelli, G. A. Cangelosi, M. A. Dirac, K. N. Olivier, B. A. Brown-Elliott, S. McNulty and R. J. Wallace Jr., “Respiratory Outbreak of Mycobacterium abscessus Subspecies Massiliense in a Lung Transplant and Cystic Fibrosis Center,” American Journal of Respiratory and Critical Care Medicine, Vol. 185, No. 2, 2012, pp. 231-232.
[7] J. M. Kilby, P. H. Gilligan, J. R. Yankaskas, W. E. Highsmith Jr., L. J. Edwards and M. R. Knowles, “Nontuberculous Mycobacteria in Adult Patients with Cystic Fibrosis,” Chest, Vol. 102, No. 1, 1992, pp. 70-75. doi:10.1378/chest.102.1.70
[8] M. L. Aitken, W. Burke, G. McDonald, C. Wallis, B. Ramsey and C. Nolan, “Nontuberculous Mycobacterial Disease in Adult Cystic Fibrosis Patients,” Chest, Vol. 103, No. 4, 1993, pp. 1096-1099. doi:10.1378/chest.103.4.1096
[9] K. N. Olivier, D. J. Weber, J. H. Lee, A. Handler, G. Tudor, P. L. Molina, J. Tomashefski and M. R. Knowles, “Nontuberculous Mycobacteria. II: Nested-Cohort Study of Impact on Cystic Fibrosis Lung Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 6, 2003, pp. 835-840. doi:10.1164/rccm.200207-679OC
[10] I. Levy, G. Grisaru-Soen, L. Lerner-Geva, E. Kerem, H. Blau, L. Bentur, M. Aviram, J. Rivlin, E. Picard, A. Lavy, Y. Yahav and G. Rahav, “Multicenter Cross-Sectional Study of Nontuberculous Mycobacterial Infections among Cystic Fibrosis Patients, Israel,” Emerging Infectious Diseases, Vol. 14, No. 3, 2008, pp. 378-384. doi:10.3201/eid1403.061405
[11] S. Razvi and L. Saiman, “Nontuberculous Mycobacteria in Cystic Fibrosis,” The Pediatric Infectious Disease Journal, Vol. 26, No. 3, 2007, pp. 263-264. doi:10.1097/01.inf.0000256964.30181.df
[12] K. N. Olivier, “The Natural History of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis,” Paediatric Respiratory Reviews, Vol. 5, No. A, 2004, pp. S213-S216.
[13] D. Schewe, M. Kappler and M. Griese, “Instructions for Infection Control in Outpatient Care of Patients with Cystic Fibrosis,” European Journal of Medical Research, Vol. 10, No. 8, 2005, pp. 345-351.
[14] K. De Boeck, F. Vermeulen, S. Wanyama and M. Thomas, “Inhaled Corticosteroids and Lower Lung Function Decline in Young Children with Cystic Fibrosis,” European Respiratory Journal, Vol. 37, No. 5, 2011, pp. 1091-1095. doi:10.1183/09031936.00077210
[15] P. K. Kent, “Public Health Mycobacteriology: A Guide for the Level III Laboratory,” US Department of Health and Human Services, Centers for Disease Control, Atlanta, 2011, in Print.
[16] E. Richter, J. Beer, R. Diel, D. Hillemann, H. Hoffmann, M. Klotz, H. Mauch and S. Rüsch-Gerdes, “MIQ 05: Qualit?tsstandards in der Mikrobiologisch-Infektiologischen Diagnostik-Tuberkulose und Mykobakteriose,” Elsevier, Urban & Fischer, 2011, pp. 11-45.
[17] P. Kirschner, B. Springer, U. Vogel, A. Meier, A. Wrede, M. Kiekenbeck, F. C. Bange and E. C. Bottger, “Genotypic Identification of Mycobacteria by Nucleic Acid Sequence Determination: Report of a 2-Year Experience in a Clinical Laboratory,” Journal of Clinical Microbiology, Vol. 31, No. 11, 1993, pp. 2882-2889.
[18] J. Makinen, M. Marjamaki, H. Marttila and H. Soini, “Evaluation of a Novel Strip Test, GenoType Mycobacterium CM/AS, for Species Identification of Mycobacterial Cultures,” Clinical Microbiology and Infection, Vol. 12, No. 5, 2006, pp. 481-483. doi:10.1111/j.1469-0691.2006.01380.x
[19] A. Roth, U. Reischl, A. Streubel, L. Naumann, R. M. Kroppenstedt, M. Habicht, M. Fischer and H. Mauch, “Novel Diagnostic Algorithm for Identification of Mycobacteria Using Genus-Specific Amplification of the 16S-23S rRNA Gene Spacer and Restriction Endonucleases," Journal of Clinical Microbiology, Vol. 38, No. 3, 2000, pp. 1094-1104.
[20] E. Macheras, A. L. Roux, S. Bastian, S. C. Leao, M. Palaci, V. Sivadon-Tardy, C. Gutierrez, E. Richter, S. Rusch-Gerdes, G. Pfyffer, T. Bodmer, E. Cambau, J. L. Gaillard and B. Heym, “Multilocus Sequence Analysis and rpoB Sequencing of Mycobacterium abscessus (Sensu Lato) Strains,” Journal of Clinical Microbiology, Vol. 49, No. 2, 2011, pp. 491-499. doi:10.1128/JCM.01274-10
[21] T. Adekambi, P. Colson and M. Drancourt, “rpoB-Based Identification of Nonpigmented and Late-Pigmenting Rapidly Growing Mycobacteria,” Journal of Clinical Microbiology, Vol. 41, No. 12, 2003, pp. 5699-5708. doi:10.1128/JCM.41.12.5699-5708.2003
[22] V. A. Steingrube, J. L. Gibson, B. A. Brown, Y. Zhang, R. W. Wilson, M. Rajagopalan and R. J. Wallace Jr., “PCR Amplification and Restriction Endonuclease Analysis of a 65-Kilodalton Heat Shock Protein Gene Sequence for Taxonomic Separation of Rapidly Growing Mycobacteria,” Journal of Clinical Microbiology, Vol. 33, No. 1, 1995, pp. 149-153.
[23] M. A. Yakrus, S. M. Hernandez, M. M. Floyd, D. Sikes, W. R. Butler and B. Metchock, “Comparison of Methods for Identification of Mycobacterium abscessus and M. chelonae Isolates,” Journal of Clinical Microbiology, Vol. 39, No. 11, 2001, pp. 4103-4110. doi:10.1128/JCM.39.11.4103-4110.2001
[24] Y. Zhang, M. A. Yakrus, E. A. Graviss, N. WilliamsBouyer, C. Turenne, A. Kabani and R. J. Wallace Jr., “Pulsed-Field Gel Electrophoresis Study of Mycobacterium abscessus Isolates Previously Affected by DNA Degradation,” Journal of Clinical Microbiology, Vol. 42, No. 12, 2004, pp. 5582-5587. doi:10.1128/JCM.42.12.5582-5587.2004
[25] F. Ripoll, S. Pasek, C. Schenowitz, C. Dossat, V. Barbe, M. Rottman, E. Macheras, B. Heym, J. L. Herrmann, M. Daffe, R. Brosch, J. L. Risler and J. L. Gaillard, “Non Mycobacterial Virulence Genes in the Genome of the Emerging Pathogen Mycobacterium abscessus,” PLoS One, Vol. 4, No. 6, 2009, e5660. doi:10.1371/journal.pone.0005660
[26] D. G. Higgins, A. J. Bleasby and R. Fuchs, “CLUSTAL V: Improved Software for Multiple Sequence Alignment,” Computer Applications in the Biosciences, Vol. 8, No. 2, 1992, pp. 189-191.
[27] D. E. Griffith, T. Aksamit, B. A. Brown-Elliott, A. Catanzaro, C. Daley, F. Gordin, S. M. Holland, R. Horsburgh, G. Huitt, M. F. Iademarco, M. Iseman, K. Olivier, S. Ruoss, C. F. von Reyn, R. J. Wallace Jr. and K. Winthrop, “An Official ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Nontuberculous Mycobacterial Diseases,” American Journal of Respiratory and Critical Care Medicine, Vol. 175, No. 4, 2007, pp. 367-416. doi:10.1164/rccm.200604-571ST
[28] L. Leitritz, M. Griese, A. Roggenkamp, A. M. Geiger, V. Fingerle and J. Heesemann, “Prospective Study on Nontuberculous Mycobacteria in Patients with and without Cystic Fibrosis,” Medical Microbiology and Immunology, Vol. 193, No. 4, 2004, pp. 209-217. doi:10.1007/s00430-003-0195-9
[29] C. R. Esther Jr., M. M. Henry, P. L. Molina and M. W. Leigh, “Nontuberculous Mycobacterial Infection in Young Children with Cystic Fibrosis,” Pediatric Pulmonology, Vol. 40, No. 1, 2005, pp. 39-44. doi:10.1002/ppul.20222
[30] M. Renna, C. Schaffner, K. Brown, S. Shang, M. H. Tamayo, K. Hegyi, N. J. Grimsey, D. Cusens, S. Coulter, J. Cooper, A. R. Bowden, S. M. Newton, B. Kampmann, J. Helm, A. Jones, C. S. Haworth, R. J. Basaraba, M. A. DeGroote, D. J. Ordway, D. C. Rubinsztein and R. A. Floto, “Azithromycin Blocks Autophagy and May Predispose Cystic Fibrosis Patients to Mycobacterial Infection,” Journal of Clinical Investigation, Vol. 121, No. 9, 2011, pp. 3554-3563. doi:10.1172/JCI46095
[31] B. Petrini, “Mycobacterium abscessus: An Emerging Rapid-Growing Potential Pathogen,” APMIS, Vol. 114, No. 5, 2006, pp. 319-328. doi:10.1111/j.1600-0463.2006.apm_390.x
[32] D. E. Griffith, “Emergence of Nontuberculous Mycobacteria as Pathogens in Cystic Fibrosis” American Journal of Respiratory and Critical Care Medicine, Vol. 167, No. 6, 2003, pp. 810-812. doi:10.1164/rccm.2301001
[33] C. Pierre-Audigier, A. Ferroni, I. Sermet-Gaudelus, M. Le Bourgeois, C. Offredo, H. Vu-Thien, B. Fauroux, P. Mariani, A. Munck, E. Bingen, D. Guillemot, G. Quesne, V. Vincent, P. Berche and J. L. Gaillard, “Age-Related Prevalence and Distribution of Nontuberculous Mycobacterial Species among Patients with Cystic Fibrosis,” Journal of Clinical Microbiology, Vol. 43, No. 7, 2005, pp. 3467-3470. doi:10.1128/JCM.43.7.3467-3470.2005
[34] S. M. Holland, E. M. Eisenstein, D. B. Kuhns, M. L. Turner, T. A. Fleisher, W. Strober and J. I. Gallin, “Treatment of Refractory Disseminated Nontuberculous Mycobacterial Infection with Interferon Gamma. A Preliminary Report,” The New England Journal of Medicine, Vol. 330, No. 19, 1994, pp. 1348-1355. doi:10.1056/NEJM199405123301904
[35] H. Mussaffi, J. Rivlin, I. Shalit, M. Ephros and H. Blau, “Nontuberculous Mycobacteria in Cystic Fibrosis Associated with Allergic Bronchopulmonary Aspergillosis and Steroid Therapy,” European Respiratory Journal, Vol. 25, No. 2, 2005, pp. 324-328. doi:10.1183/09031936.05.00058604
[36] F. C. Bange, B. A. Brown, C. Smaczny, R. J. Wallace Jr. and E. C. Bottger, “Lack of Transmission of Mycobacterium abscessus among Patients with Cystic Fibrosis Attending a Single Clinic,” Clinical Infectious Diseases, Vol. 32, No. 11, 2001, pp. 1648-1650. doi:10.1086/320525
[37] J. L. Sampaio, C. Viana-Niero, D. de Freitas, A. L. Hofling-Lima and S. C. Leao, “Enterobacterial Repetitive Intergenic Consensus PCR Is a Useful Tool for Typing Mycobacterium chelonae and Mycobacterium abscessus Isolates,” Diagnostic Microbiology and Infectious Disease, Vol. 55, No. 2, 2006, pp. 107-118. doi:10.1016/j.diagmicrobio.2006.01.006
[38] K. A. Harris, D. T. Kenna, C. Blauwendraat, J. C. Hartley, J. F. Turton, P. Aurora and G. L. Dixon, “Molecular Fingerprinting of Mycobacterium abscessus Strains in a Cohort of Pediatric Cystic Fibrosis Patients,” Journal of Clinical Microbiology, Vol. 50, No. 5, 2012, pp. 17581761. doi:10.1128/JCM.00155-12
[39] L. Saiman and J. Siegel, “Infection Control in Cystic Fibrosis,” Clinical Microbiology Reviews, Vol. 17, No. 1, 2004, pp. 57-71. doi:10.1128/CMR.17.1.57-71.2004

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