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Drug Susceptibility Testing of Nontuberculous Mycobacteria

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Nontuberculous Mycobacterial Disease

Part of the book series: Respiratory Medicine ((RM))

Abstract

Drug susceptibility testing of nontuberculous mycobacteria is an important tool to guide and optimize treatment of these severe infections. Its role has long been controversial, owing to perceived discrepancies between in vitro susceptibility of mainly Mycobacterium avium complex isolates and the in vivo outcome of treatment. These discrepancies related to classic antituberculosis drugs (rifampicin, ethambutol, isoniazid); the role of these drugs in the treatment regimens is merely to prevent macrolide resistance, and their antimycobacterial activity is thus less important to treatment success. Results of tests for macrolide, aminoglycoside, fluoroquinolone, tetracycline, and oxazolidinone antibiotic susceptibility are known to predict outcomes of treatment with combination regimens containing these agents. This chapter provides a summary of known resistance mechanisms and a historical overview of susceptibility test methods and achievements, focused on in vitro-in vivo correlations derived from clinical studies.

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Literature

  1. Griffith DE, Aksamit T, Brown-Elliot BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175:367–416.

    CAS  PubMed  Google Scholar 

  2. van Ingen J, Boeree M, van Soolingen D, Mouton J. Resistance mechanisms and drug susceptibility testing of nontuberculous mycobacteria. Drug Resist Updat. 2012;15:149–61.

    PubMed  Google Scholar 

  3. Lambert PA. Cellular impermeability and uptake of biocides and antibiotics in Gram-positive bacteria and mycobacteria. J Appl Microbiol. 2002;92(Suppl):46S–54S.

    PubMed  Google Scholar 

  4. Cangelosi GA, Do JS, Freeman R, Bennett JG, Semret M, Behr MA. The two-component regulatory system mtrAB is required for morphotypic multidrug resistance in Mycobacterium avium. Antimicrob Agents Chemother. 2006;50:461–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Gao LY, Laval F, Lawson EH, Groger RK, Woodruff A, Morisaki JH, Cox JS, Daffe M, Brown EJ. Requirement for kasB in Mycobacterium mycolic acid biosynthesis, cell wall impermeability and intracellular survival: implications for therapy. Mol Microbiol. 2003;49:1547–63.

    CAS  PubMed  Google Scholar 

  6. Nguyen L, Chinnapapagari S, Thompson CJ. FbpA-Dependent biosynthesis of trehalose dimycolate is required for the intrinsic multidrug resistance, cell wall structure, and colonial morphology of Mycobacterium smegmatis. J Bacteriol. 2005;187:6603–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Nguyen HT, Wolff KA, Cartabuke RH, Ogwang S, Nguyen L. A lipoprotein modulates activity of the MtrAB two-component system to provide intrinsic multidrug resistance, cytokinetic control and cell wall homeostasis in Mycobacterium. Mol Microbiol. 2010;76:348–64.

    CAS  PubMed  Google Scholar 

  8. Philalay JS, Palermo CO, Hauge KA, Rustad TR, Cangelosi GA. Genes required for intrinsic multidrug resistance in Mycobacterium avium. Antimicrob Agents Chemother. 2004;48:3412–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ren H, Liu J. AsnB is involved in natural resistance of Mycobacterium smegmatis to multiple drugs. Antimicrob Agents Chemother. 2006;50:250–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wolff KA, Nguyen HT, Cartabuke RH, Singh A, Ogwang S, Nguyen L. Protein kinase G is required for intrinsic antibiotic resistance in mycobacteria. Antimicrob Agents Chemother. 2009;53:3515–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Howard ST, Rhoades E, Recht J, Pang X, Alsup A, Kolter R, Lyons CR, Byrd TF. Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype. Microbiology. 2006;152:1581–90.

    CAS  PubMed  Google Scholar 

  12. Schorey JS, Sweet L. The mycobacterial glycopeptidolipids: structure, function, and their role in pathogenesis. Glycobiology. 2008;18:832–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Cangelosi GA, Palermo CO, Laurent JP, Hamlin AM, Brabant WH. Colony morphotypes on Congo red agar segregate along species and drug susceptibility lines in the Mycobacterium avium-intracellulare complex. Microbiology. 1999;145(Pt 6):1317–24.

    CAS  PubMed  Google Scholar 

  14. Falkinham JO 3rd. Growth in catheter biofilms and antibiotic resistance of Mycobacterium avium. J Med Microbiol. 2007;56:250–4.

    PubMed  Google Scholar 

  15. Nguyen L, Thompson CJ. Foundations of antibiotic resistance in bacterial physiology: the mycobacterial paradigm. Trends Microbiol. 2006;14:304–12.

    CAS  PubMed  Google Scholar 

  16. Stephan J, Mailaender C, Etienne G, Daffe M, Niederweis M. Multidrug resistance of a porin deletion mutant of Mycobacterium smegmatis. Antimicrob Agents Chemother. 2004;48:4163–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Danilchanka O, Pavlenok M, Niederweis M. Role of porins for uptake of antibiotics by Mycobacterium smegmatis. Antimicrob Agents Chemother. 2008;52:3127–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. van Ingen J, Ferro BE, Hoefsloot W, Boeree MJ, van Soolingen D. Drug treatment of pulmonary nontuberculous mycobacterial disease in HIV-negative patients: the evidence. Expert Rev Anti Infect Ther. 2013;11(10):1065–77.

    PubMed  Google Scholar 

  19. Schmalstieg AM, Srivastava S, Belkaya S, Deshpande D, Meek C, Leff R, van Oers NSC, Gumbo T. The antibiotic resistance arrow of time: Efflux pump induction is a general first step in the evolution of mycobacterial drug resistance. Antimicrob Agents Chemother. 2012;56:4806–15.

    PubMed  PubMed Central  Google Scholar 

  20. Silva PE, Bigi F, Santangelo MP, Romano MI, Martin C, Cataldi A, Ainsa JA. Characterization of P55, a multidrug efflux pump in Mycobacterium bovis and Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2001;45:800–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Ramon-Garcia S, Martin C, Ainsa JA, De Rossi E. Characterization of tetracycline resistance mediated by the efflux pump Tap from Mycobacterium fortuitum. J Antimicrob Chemother. 2006;57:252–9.

    CAS  PubMed  Google Scholar 

  22. De Rossi E, Blokpoel MC, Cantoni R, Branzoni M, Riccardi G, Young DB, De Smet KA, Ciferri O. Molecular cloning and functional analysis of a novel tetracycline resistance determinant, tet(V), from Mycobacterium smegmatis. Antimicrob Agents Chemother. 1998;42:1931–7.

    PubMed  PubMed Central  Google Scholar 

  23. Sander P, De Rossi E, Boddinghaus B, Cantoni R, Branzoni M, Bottger EC, Takiff H, Rodriquez R, Lopez G, Riccardi G. Contribution of the multidrug efflux pump LfrA to innate mycobacterial drug resistance. FEMS Microbiol Lett. 2000;193:19–23.

    CAS  PubMed  Google Scholar 

  24. Li XZ, Zhang L, Nikaido H. Efflux pump-mediated intrinsic drug resistance in Mycobacterium smegmatis. Antimicrob Agents Chemother. 2004;48:2415–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Briffotaux J, Huang W, Wang X, Gicquel B. MmpS5/MmpL5 as an efflux pump in Mycobacterium species. Tuberculosis. 2017;107:13–9.

    CAS  PubMed  Google Scholar 

  26. Alexander DC, Vasireddy R, Vasireddy S, et al. The emergence of mmpT5 variants during bedaquiline treatment of Mycobacterium intracellulare Lung Disease. J Clin Microbiol. 2017;55:574–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Bhatt K, Banerjee SK, Chakraborti PK. Evidence that phosphate specific transporter is amplified in a fluoroquinolone resistant Mycobacterium smegmatis. Eur J Biochem. 2000;267:4028–32.

    CAS  PubMed  Google Scholar 

  28. Morris RP, Nguyen L, Gatfield J, Visconti K, Nguyen K, Schnappinger D, Ehrt S, Liu Y, Heifets L, Pieters J, Schoolnik G, Thompson CJ. Ancestral antibiotic resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2005;102:12200–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Flores AR, Parsons LM, Pavelka MS Jr. Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiology. 2005;151:521–32.

    CAS  PubMed  Google Scholar 

  30. Nash DR, Wallace RJ Jr, Steingrube VA, Udou T, Steele LC, Forrester GD. Characterization of beta-lactamases in Mycobacterium fortuitum including a role in beta-lactam resistance and evidence of partial inducibility. Am Rev Respir Dis. 1986;134:1276–82.

    CAS  PubMed  Google Scholar 

  31. Lefebvre AL, Le Moigne V, Bernut A, Veckerlé C, Compain F, Herrmann JL, Kremer L, Arthur M, Mainardi JL. Inhibition of the β-Lactamase BlaMab by avibactam improves the in vitro and in vivo efficacy of imipenem against Mycobacterium abscessus. Antimicrob Agents Chemother. 2017;61. https://doi.org/10.1128/AAC.02440-16.

  32. Adjei MD, Heinze TM, Deck J, Freeman JP, Williams AJ, Sutherland JB. Acetylation and nitrosation of ciprofloxacin by environmental strains of mycobacteria. Can J Microbiol. 2007;53:144–7.

    CAS  PubMed  Google Scholar 

  33. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat. 2010;13:151–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Ripoll F, Pasek S, Schenowitz C, Dossat C, Barbe V, Rottman M, Macheras E, Heym B, Herrmann JL, Daffe M, Brosch R, Risler JL, Gaillard JL. Non mycobacterial virulence genes in the genome of the emerging pathogen Mycobacterium abscessus. PLoS One. 2009;4:–e5660.

    Google Scholar 

  35. Ho II, Chan CY, Cheng AF. Aminoglycoside resistance in Mycobacterium kansasii, Mycobacterium avium-M. intracellulare, and Mycobacterium fortuitum: are aminoglycoside-modifying enzymes responsible? Antimicrob Agents Chemother. 2000;44:39–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Baysarowich J, Koteva K, Hughes DW, Ejim L, Griffiths E, Zhang K, Junop M, Wright GD. Rifamycin antibiotic resistance by ADP-ribosylation: structure and diversity of Arr. Proc Natl Acad Sci U S A. 2008;105:4886–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Nash KA, Brown-Elliott BA, Wallace RJ Jr. A novel gene, erm(41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae. Antimicrob Agents Chemother. 2009;53:1367–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Brown-Elliott BA, Hanson K, Vasireddy S, Iakhiaeva E, Nash KA, Vasireddy R, Parodi N, Smith T, Gee M, Strong A, Barker A, Cohen S, Muir H, Slechta ES, Wallace RJ Jr. Absence of a functional erm gene in isolates of Mycobacterium immunogenum and the Mycobacterium mucogenicum group, based on in vitro clarithromycin susceptibility. J Clin Microbiol. 2015;53:875–8.

    PubMed  PubMed Central  Google Scholar 

  39. Dey A, Verma AK, Chatterji D. Role of an RNA polymerase interacting protein, MsRbpA, from Mycobacterium smegmatis in phenotypic tolerance to rifampicin. Microbiology. 2010;156:873–83.

    CAS  PubMed  Google Scholar 

  40. Griffith DE, Brown-Elliott BA, Langsjoen B, Zhang Y, Pan X, Girard W, Nelson K, Caccitolo J, Alvarez J, Shepherd S, Wilson R, Graviss EA, Wallace RJ Jr. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2006;174:928–34.

    CAS  PubMed  Google Scholar 

  41. Meier A, Heifets L, Wallace RJ Jr, Zhang Y, Brown BA, Sander P, Bottger EC. Molecular mechanisms of clarithromycin resistance in Mycobacterium avium: observation of multiple 23S rDNA mutations in a clonal population. J Infect Dis. 1996;174:354–60.

    CAS  PubMed  Google Scholar 

  42. Bastian S, Veziris N, Roux AL, Brossier F, Gaillard JL, Jarlier V, Cambau E. Assessment of clarithromycin susceptibility in strains belonging to the Mycobacterium abscessus group by erm(41) and rrl sequencing. Antimicrob Agents Chemother. 2011;55:775–81.

    CAS  PubMed  Google Scholar 

  43. Long KS, Munck C, Andersen TM, Schaub MA, Hobbie SN, Bottger EC, Vester B. Mutations in 23S rRNA at the peptidyl transferase center and their relationship to linezolid binding and cross-resistance. Antimicrob Agents Chemother. 2010;54:4705–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Brown-Elliott BA, Iakhiaeva E, Griffith DE, Woods GL, Stout JE, Wolfe CR, Turenne CY, Wallace RJ Jr. In vitro activity of amikacin against isolates of Mycobacterium avium complex with proposed MIC breakpoints and finding of a 16S rRNA gene mutation in treated isolates. J Clin Microbiol. 2013;51:3389–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Olivier KN, Griffith DE, Eagle G, et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med. 2017;195(6):814–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Prammananan T, Sander P, Brown BA, Frischkorn K, Onyi GO, Zhang Y, Bottger EC, Wallace RJ Jr. A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis. 1998;177:1573–81.

    CAS  PubMed  Google Scholar 

  47. Klein JL, Brown TJ, French GL. Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations. Antimicrob Agents Chemother. 2001;45:3056–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. van Ingen J, Kohl TA, Kranzer K, Hasse B, Keller PM, Katarzyna Szafrańska A, Hillemann D, Chand M, Schreiber PW, Sommerstein R, Berger C, Genoni M, Rüegg C, Troillet N, Widmer AF, Becker SL, Herrmann M, Eckmanns T, Haller S, Höller C, Debast SB, Wolfhagen MJ, Hopman J, Kluytmans J, Langelaar M, Notermans DW, Ten Oever J, van den Barselaar P, Vonk ABA, Vos MC, Ahmed N, Brown T, Crook D, Lamagni T, Phin N, Smith EG, Zambon M, Serr A, Götting T, Ebner W, Thürmer A, Utpatel C, Spröer C, Bunk B, Nübel U, Bloemberg GV, Böttger EC, Niemann S, Wagner D, Sax H. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;17:1033–41.

    PubMed  Google Scholar 

  49. Stinear TP, Seemann T, Harrison PF, Jenkin GA, Davies JK, Johnson PD, Abdellah Z, Arrowsmith C, Chillingworth T, Churcher C, Clarke K, Cronin A, Davis P, Goodhead I, Holroyd N, Jagels K, Lord A, Moule S, Mungall K, Norbertczak H, Quail MA, Rabbinowitsch E, Walker D, White B, Whitehead S, Small PL, Brosch R, Ramakrishnan L, Fischbach MA, Parkhill J, Cole ST. Insights from the complete genome sequence of Mycobacterium marinum on the evolution of Mycobacterium tuberculosis. Genome Res. 2008;18(5):729–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Matsumoto CK, Bispo PJ, Santin K, Nogueira CL, Leão SC. Demonstration of plasmid-mediated drug resistance in Mycobacterium abscessus. J Clin Microbiol. 2014;52:1727–9 [Epub ahead of print]

    Google Scholar 

  51. Canetti G, Froman S, Grosset J, Hauduroy P, Langerova M, Mahler HT, Meissner G, Mitchison DA, Sula L. Mycobacteria: laboratory methods for testing drug sensitivity and resistance. Bull World Health Organ. 1963;29:565–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Runyon EH. Anonymous mycobacteria in pulmonary disease. Med Clin North Am. 1959;43:273–90.

    CAS  PubMed  Google Scholar 

  53. Middlebrook G, Cohn ML. Bacteriology of tuberculosis: laboratory methods. Am J Public Health Nations Health. 1958;48:844–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. van Ingen J, van der Laan T, Dekhuijzen PNR, Boeree MJ, van Soolingen D. In vitro drug susceptibility of 2275 clinical nontuberculous Mycobacterium isolates of 49 species in the Netherlands. Int J Antimicrob Agents. 2010;35:169–73.

    PubMed  Google Scholar 

  55. Research Committee of the British Thoracic Society. First randomised trial of treatments for pulmonary disease caused by M. avium intracellulare, M. malmoense, and M. xenopi in HIV negative patients: rifampicin, ethambutol and isoniazid versus rifampicin and ethambutol. Thorax. 2001;56:167–72.

    Google Scholar 

  56. Wallace RJ Jr, Dalovisio JR, Pankey GA. Disk diffusion testing of susceptibility of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents. Antimicrob Agents Chemother. 1979;16:611–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Stone MS, Wallace RJ Jr, Swenson JM, Thornsberry C, Christensen LA. Agar disk elution method for susceptibility testing of Mycobacterium marinum and Mycobacterium fortuitum complex to sulfonamides and antibiotics. Antimicrob Agents Chemother. 1983;24:486–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Snider DE Jr, Good RC, Kilburn JO, Laskowski LF Jr, Lusk RH, Marr JJ, Reggiardo Z, Middlebrook G. Rapid drug-susceptibility testing of Mycobacterium tuberculosis. Am Rev Respir Dis. 1981;123:402–6.

    CAS  PubMed  Google Scholar 

  59. Heifets LB, Iseman MD, Lindholm-Levy PJ. Determination of MICs of conventional and experimental drugs in liquid medium by the radiometric method against Mycobacterium avium complex. Drugs Exp Clin Res. 1987;13:529–38.

    CAS  PubMed  Google Scholar 

  60. Hoffner SE, Svenson SB, Kallenius G. Synergistic effects of antimycobacterial drug combinations on Mycobacterium avium complex determined radiometrically in liquid medium. Eur J Clin Microbiol. 1987;6:530–5.

    CAS  PubMed  Google Scholar 

  61. Hansen KT, Clark RB, Sanders WE. Effects of different test conditions on the susceptibility of Mycobacterium fortuitum and Mycobacterium chelonae to amikacin. J Antimicrob Chemother. 1994;33:483–94.

    CAS  PubMed  Google Scholar 

  62. Yew WW, Piddock LJ, Li MS, Lyon D, Chan CY, Cheng AF. In-vitro activity of quinolones and macrolides against mycobacteria. J Antimicrob Chemother. 1994;34:343–51.

    CAS  PubMed  Google Scholar 

  63. Clinical Laboratory Standards Institute. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes – approved standard. 2nd ed. Wayne, PA: Clinical Standards Institute. CLSI document M24-A2; 2011.

    Google Scholar 

  64. Drobniewski F, Rusch-Gerdes S, Hoffner S. Antimicrobial susceptibility testing of Mycobacterium tuberculosis (EUCAST document E.DEF 8.1)--report of the Subcommittee on Antimicrobial Susceptibility Testing of Mycobacterium tuberculosis of the European Committee for Antimicrobial Susceptibility Testing (EUCAST) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Clin Microbiol Infect. 2007;13:1144–56.

    CAS  PubMed  Google Scholar 

  65. Piersimoni C, Nista D, Bornigia S, De Sio G. Evaluation of a new method for rapid drug susceptibility testing of Mycobacterium avium complex isolates by using the mycobacteria growth indicator tube. J Clin Microbiol. 1998;36:64–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Hombach M, Somoskövi A, Hömke R, Ritter C, Böttger EC. Drug susceptibility distributions in slowly growing non-tuberculous mycobacteria using MGIT 960 TB eXiST. Int J Med Microbiol. 2013;303:270–6.

    CAS  PubMed  Google Scholar 

  67. Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol Microbiol Scand B Microbiol Immunol. 1971;217(Suppl):211.

    Google Scholar 

  68. Swenson JM, Thornsberry C, Silcox VA. Rapidly growing mycobacteria: testing of susceptibility to 34 antimicrobial agents by broth microdilution. Antimicrob Agents Chemother. 1982;22:186–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Swenson JM, Wallace RJ Jr, Silcox VA, Thornsberry C. Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. Antimicrob Agents Chemother. 1985;28:807–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Wallace RJ Jr, Nash DR, Steele LC, Steingrube V. Susceptibility testing of slowly growing mycobacteria by a microdilution MIC method with 7H9 broth. J Clin Microbiol. 1986;24:976–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Woods GL, Williams-Bouyer N, Wallace RJ Jr, Brown-Elliott BA, Witebsky FG, Conville PS, Plaunt M, Hall G, Aralar P, Inderlied C. Multisite reproducibility of results obtained by two broth dilution methods for susceptibility testing of Mycobacterium avium complex. J Clin Microbiol. 2003;41:627–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Flynn CM, Kelley CM, Barrett MS, Jones RN. Application of the Etest to the antimicrobial susceptibility testing of Mycobacterium marinum clinical isolates. J Clin Microbiol. 1997;35:2083–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Fabry W, Schmid EN, Ansorg R. Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium kansasii. Chemotherapy. 1995;41:247–52.

    CAS  PubMed  Google Scholar 

  74. Fabry W, Schmid EN, Ansorg R. Comparison of the E test and a proportion dilution method for susceptibility testing of Mycobacterium avium complex. J Med Microbiol. 1996;44:227–30.

    CAS  PubMed  Google Scholar 

  75. Hoffner SE, Klintz L, Olsson-Liljequist B, Bolmstrom A. Evaluation of Etest for rapid susceptibility testing of Mycobacterium chelonae and M. fortuitum. J Clin Microbiol. 1994;32:1846–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Werngren J, Olsson-Liljequist B, Gezelius L, Hoffner SE. Antimicrobial susceptibility of Mycobacterium marinum determined by E-test and agar dilution. Scand J Infect Dis. 2001;33:585–8.

    CAS  PubMed  Google Scholar 

  77. Woods GL, Bergmann JS, Witebsky FG, Fahle GA, Boulet B, Plaunt M, Brown BA, Wallace RJ Jr, Wanger A. Multisite reproducibility of Etest for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. J Clin Microbiol. 2000;38:656–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Mougari F, Loiseau J, Veziris N, Bernard C, Bercot B, Sougakoff W, Jarlier V, Raskine L, Cambau E. French National Reference Center for Mycobacteria. Evaluation of the new GenoType NTM-DR kit for the molecular detection of antimicrobial resistance in non-tuberculous mycobacteria. J Antimicrob Chemother. 2017;72:1669–77.

    CAS  PubMed  Google Scholar 

  79. Truffot-Pernot C, Ji B, Grosset J. Effect of pH on the in vitro potency of clarithromycin against Mycobacterium avium complex. Antimicrob Agents Chemother. 1991;35:1677–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Heginbothom ML, Lindholm-Levy PJ, Heifets LB. Susceptibilities of Mycobacterium malmoense determined at the growth optimum pH (pH 6.0). Int J Tuberc Lung Dis. 1998;2:430–4.

    CAS  PubMed  Google Scholar 

  81. Lounis N, Vranckx L, Gevers T, Kaniga K, Andries K. In vitro culture conditions affecting minimal inhibitory concentration of bedaquiline against M. tuberculosis. Med Mal Infect. 2016;46:220–5.

    CAS  PubMed  Google Scholar 

  82. Veenemans J, Mouton JW, Kluytmans JA, Donnely R, Verhulst C, van Keulen PH. Effect of manganese in test media on in vitro susceptibility of Enterobacteriaceae and Acinetobacter baumannii to tigecycline. J Clin Microbiol. 2012;50(9):3077–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Wallace RJ Jr, Wiss K, Bushby MB, Hollowell DC. In vitro activity of trimethoprim and sulfamethoxazole against the nontuberculous mycobacteria. Rev Infect Dis. 1982;4:326–31.

    CAS  PubMed  Google Scholar 

  84. Tison F, Tacquet A, Guillaume J, Devulder B. Unsuitability of the basic coletsos medium for the measurement of sensitivity to cycloserine. Inactivation of cycloserine by sodium pyruvate. Ann Inst Pasteur Lille. 1963;14:117–24.

    CAS  PubMed  Google Scholar 

  85. Wallace RJ Jr, Wiss K. Susceptibility of Mycobacterium marinum to tetracyclines and aminoglycosides. Antimicrob Agents Chemother. 1981;20:610–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Davis CE Jr, Carpenter JL, Trevino S, Koch J, Ognibene AJ. In vitro susceptibility of Mycobacterium avium complex to antibacterial agents. Diagn Microbiol Infect Dis. 1987;8:149–55.

    CAS  PubMed  Google Scholar 

  87. Rynearson TK, Shronts JS, Wolinsky E. Rifampin: in vitro effect on atypical mycobacteria. Am Rev Respir Dis. 1971;104:272–4.

    CAS  PubMed  Google Scholar 

  88. Watt B, Edwards JR, Rayner A, Grindey AJ, Harris G. In vitro activity of meropenem and imipenem against mycobacteria: development of a daily antibiotic dosing schedule. Tuber Lung Dis. 1992;73:134–6.

    CAS  PubMed  Google Scholar 

  89. Woods GL, Bergmann JS, Witebsky FG, Fahle GA, Wanger A, Boulet B, Plaunt M, Brown BA, Wallace RJ Jr. Multisite reproducibility of results obtained by the broth microdilution method for susceptibility testing of Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium fortuitum. J Clin Microbiol. 1999;37:1676–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Schon T, Chryssanthou E. Minimum inhibitory concentration distributions for Mycobacterium avium complex – towards evidence-based susceptibility breakpoints. Int J Infect Dis. 2017;55:122–4.

    PubMed  Google Scholar 

  91. Goldman KP. Treatment of unclassified mycobacterial infection of the lungs. Thorax. 1968;23:94–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Research Committee of the British Thoracic Society. Pulmonary disease caused by Mycobacterium avium-intracellulare in HIV-negative patients: five-year follow-up of patients receiving standardised treatment. Int J Tuberc Lung Dis. 2002;6:628–34.

    Google Scholar 

  93. Hoffner SE, Heurlin N, Petrini B, Svenson SB, Kallenius G. Mycobacterium avium complex develop resistance to synergistically active drug combinations during infection. Eur Respir J. 1994;7:247–50.

    CAS  PubMed  Google Scholar 

  94. Chaisson RE, Benson CA, Dube MP, et al. Clarithromycin therapy for bacteremic Mycobacterium avium complex disease. A randomized, double-blind, dose-ranging study in patients with AIDS. AIDS Clinical Trials Group Protocol 157 Study Team. Ann Intern Med. 1994;121:905–11.

    CAS  PubMed  Google Scholar 

  95. Sison JP, Yao Y, Kemper CA, Hamilton JR, Brummer E, Stevens DA, Deresinski SC. Treatment of Mycobacterium avium complex infection: do the results of in vitro susceptibility tests predict therapeutic outcome in humans? J Infect Dis. 1996;173:677–83.

    CAS  PubMed  Google Scholar 

  96. Wallace RJ Jr, Brown BA, Griffith DE, Girard WM, Murphy DT. Clarithromycin regimens for pulmonary Mycobacterium avium complex: the first 50 patients. Am J Respir Crit Care Med. 1996;153:1766–72.

    PubMed  Google Scholar 

  97. Tanaka E, Kimoto T, Tsuyuguchi K, et al. Effect of clarithromycin regimen for Mycobacterium avium complex pulmonary disease. Am J Respir Crit Care Med. 1999;160:866–72.

    CAS  PubMed  Google Scholar 

  98. Ahn CH, Lowell JR, Ahn SS, Ahn SI, Hurst GA. Short-course chemotherapy for pulmonary disease caused by Mycobacterium kansasii. Am Rev Respir Dis. 1983;128:1048–50.

    CAS  PubMed  Google Scholar 

  99. Ahn CH, Wallace RJ Jr, Steele LC, Murphy DT. Sulfonamide-containing regimens for disease caused by rifampin-resistant Mycobacterium kansasii. Am Rev Respir Dis. 1987;135:10–6.

    CAS  PubMed  Google Scholar 

  100. Wallace RJ Jr, Dunbar D, Brown BA, Onyi G, Dunlap R, Ahn CH, Murphy DT. Rifampin-resistant Mycobacterium kansasii. Clin Infect Dis. 1994;18:736–43.

    CAS  PubMed  Google Scholar 

  101. Shitrit D, Baum GL, Priess R, et al. Pulmonary Mycobacterium kansasii infection in Israel, 1999–2004: clinical features, drug susceptibility, and outcome. Chest. 2006;129:771–6.

    PubMed  Google Scholar 

  102. van Ingen J, Totten SE, Heifets LB, Boeree MJ, Daley CL. Drug susceptibility testing and pharmacokinetics question current treatment regimens in Mycobacterium simiae complex disease. Int J Antimicrob Agents. 2012;39:173–6.

    PubMed  Google Scholar 

  103. van Ingen J, Hoefsloot W, Mouton JW, Boeree MJ, van Soolingen D. Synergistic activity of rifampicin and ethambutol against slow growing nontuberculous mycobacteria is currently of questionable clinical significance. Int J Antimicrob Agents. 2013;42:80–2.

    PubMed  Google Scholar 

  104. Aubry A, Chosidow O, Caumes E, Robert J, Cambau E. Sixty-three cases of Mycobacterium marinum infection: clinical features, treatment, and antibiotic susceptibility of causative isolates. Arch Intern Med. 2002;162:1746–52.

    PubMed  Google Scholar 

  105. Ljungberg B, Christensson B, Grubb R. Failure of doxycycline treatment in aquarium-associated Mycobacterium marinum infections. Scand J Infect Dis. 1987;19:539–43.

    CAS  PubMed  Google Scholar 

  106. Floto RA, Olivier KN, Saiman L, Daley CL, Herrmann J-L, Nick JA, Noone PG, Bilton D, Corris P, Gibson RL, Hempstead SE, Koetz K, Sabadosa KA, Sermet-Gaudelus I, Smyth AR, van Ingen J, Wallace RJ, Winthrop KL, Marshall BC, Haworth CSUS. Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus recommendations for the management of non-tuberculous mycobacteria in individuals with cystic fibrosis. Thorax. 2016;71(Suppl 1):1–22.

    Google Scholar 

  107. Jarand J, Levin A, Zhang L, Huitt G, Mitchell JD, Daley CL. Clinical and microbiologic outcomes in patients receiving treatment for Mycobacterium abscessus pulmonary disease. Clin Infect Dis. 2011;52:565–71.

    PubMed  Google Scholar 

  108. Jeon K, Kwon OJ, Lee NY, Kim BJ, Kook YH, Lee SH, Park YK, Kim CK, Koh WJ. Antibiotic treatment of Mycobacterium abscessus lung disease: a retrospective analysis of 65 patients. Am J Respir Crit Care Med. 2009;180:896–902.

    CAS  PubMed  Google Scholar 

  109. Koh WJ, Jeon K, Lee NY, Kim BJ, Kook YH, Lee SH, Park YK, Kim CK, Shin SJ, Huitt GA, Daley CL, Kwon OJ. Clinical significance of differentiation of Mycobacterium massiliense from Mycobacterium abscessus. Am J Respir Crit Care Med. 2011;183:405–10.

    PubMed  Google Scholar 

  110. Harada T, Akiyama Y, Kurashima A, et al. Clinical and Microbiological Differences between Mycobacterium abscessus and Mycobacterium massiliense Lung Diseases. J Clin Microbiol. 2012;50:3556–61.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Wallace RJ, Swenson JM, Silcox VA, Bulen MG. Treatment of nonpulmonary infections due to Mycobacterium fortuitum and Mycobacterium chelonei on the basis of in vitro susceptibilities. J Infect Dis. 1985;152:500–14.

    PubMed  Google Scholar 

  112. Mouton JW, Brown DF, Apfalter P, Canton R, Giske CG, Ivanova M, Macgowan AP, Rodloff A, Soussy CJ, Steinbakk M, Kahlmeter G. The role of pharmacokinetics/ pharmacodynamics in setting clinical MIC breakpoints: the EUCAST approach. Clin Microbiol Infect. 2011;18:E37–45.

    Google Scholar 

  113. van Ingen J, Egelund EF, Levin A, Totten SE, Boeree MJ, Mouton JW, Aarnoutse R, Heifets LB, Peloquin CA, Daley CL. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Respir Crit Care Med. 2012;186:559–65.

    PubMed  Google Scholar 

  114. Koh WJ, Jeong BH, Jeon K, Lee SY, Shin SJ. Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2012;186:797–802.

    CAS  PubMed  Google Scholar 

  115. Magis-Escurra C, Alffenaar JW, Hoefnagels I, Dekhuijzen PN, Boeree MJ, van Ingen J, Aarnoutse RE. Pharmacokinetic studies in patients with nontuberculous mycobacterial lung infections. Int J Antimicrob Agents. 2013;42:256–61.

    CAS  PubMed  Google Scholar 

  116. Ferro BE, van Ingen J, Wattenberg M, van Soolingen D, Mouton JW. Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease. J Antimicrob Chemother. 2015;70(10):2838–43.

    CAS  PubMed  Google Scholar 

  117. Ferro BE, Srivastava S, Deshpande D, Sherman CM, Pasipanodya JG, van Soolingen D, Mouton JW, van Ingen J, Gumbo T. Amikacin pharmacokinetics/pharmacodynamics in a novel hollow fiber Mycobacterium abscessus disease model. Antimicrob Agents Chemother. 2016;60(3):1242–8.

    CAS  PubMed Central  Google Scholar 

  118. Ferro BE, Srivastava S, Deshpande D, Pasipanodya JG, van Soolingen D, Mouton JW, van Ingen J, Gumbo T. Moxifloxacin’s limited efficacy in the Hollow-Fiber Model of Mycobacterium abscessus disease. Antimicrob Agents Chemother. 2016;60:3779–85. https://doi.org/10.1128/AAC.02821-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ferro BE, Srivastava S, Deshpande D, Pasipanodya JG, van Soolingen D, Mouton JW, van Ingen J, Gumbo T. Tigecycline is highly efficacious against mycobacterium abscessus pulmonary disease. Antimicrob Agents Chemother. 2016;60:2895–900. https://doi.org/10.1128/AAC.03112-15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands

    Jakko van Ingen

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  1. Professor of Medicine, University of Texas Health Science Center, Tyler, TX, USA

    David E. Griffith

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van Ingen, J. (2019). Drug Susceptibility Testing of Nontuberculous Mycobacteria. In: Griffith, D. (eds) Nontuberculous Mycobacterial Disease. Respiratory Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-93473-0_3

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