Infection and Drug Resistance (Dec 2018)

Prevalence of nontuberculous mycobacteria and high efficacy of D-cycloserine and its synergistic effect with clarithromycin against Mycobacterium fortuitum and Mycobacterium abscessus

  • Khosravi AD,
  • Mirsaeidi M,
  • Farahani A,
  • Tabandeh MR,
  • Mohajeri P,
  • Shoja S,
  • Hoseini Lar KhosroShahi SR

Journal volume & issue
Vol. Volume 11
pp. 2521 – 2532

Abstract

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Azar Dokht Khosravi,1,2 Mehdi Mirsaeidi,3 Abbas Farahani,1,2 Mohammad Reza Tabandeh,4 Parviz Mohajeri,5,6 Saeed Shoja,7 Seyedeh Roghayeh Hoseini Lar KhosroShahi8 1Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 2Department of Microbiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; 3Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, USA; 4Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran; 5Department of Microbiology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran; 6Nosocomial Infection Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran; 7Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran; 8Tuberculosis Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Background: The prevalence of pulmonary disease caused by nontuberculous mycobacteria (NTM) is reportedly on the rise in the world. Some of the species are resistant to various antibiotics; hence, limited treatment options are available. The aims of this study were to investigate the prevalence of NTM and to determine the effect of D-cycloserine against Mycobacterium fortuitum and Mycobacterium abscessus isolated from clinical specimens to find out the synergistic effect of D-cycloserine and clarithromycin.Methods: A total of 95 nonduplicate pulmonary isolates of NTM were collected from three major Regional Tuberculosis (TB) Centers. NTM isolates were identified by conventional tests and PCR sequence analysis of the rpoB gene. PCR sequencing of erm-41 was performed for detecting the inducible resistance to macrolides. In vitro susceptibilities and activities of D-cycloserine-clarithromycin combinations were accessed using the broth microdilution method.Results: Among 714-positive acid-fast bacilli from TB-suspected cases, 95 isolates were identified as NTM (13.3%). The prevalence of identified isolates was as follows: M. fortuitum 46 (48.4%), Mycobacterium simiae 16 (16.8%), Mycobacterium kansasii 15 (15.7%), M. abscessus 7 (7.3%), Mycobacterium thermoresistibile 4 (4.2%), Mycobacterium elephantis 3 (3.2%), Mycobacterium porcinum 2 (2.1%), and Mycobacterium chimaera 2 (2.1%). In addition, rpoB sequence analysis could identify all NTM isolates. The effect of D-cycloserine was better than that of clarithromycin. The synergistic effect of D-cycloserine with clarithromycin was observed for six (100%) and five (71.5%) strains of M. fortuitum and M. abscessus, respectively.Conclusion: In the present study, we demonstrated a wide range of NTM in processed samples from different provinces of Iran. Our observations indicated that D-cycloserine was very active against M. abscessus and M. fortuitum; hence, D-cycloserine, either alone or in combination with clarithromycin, may be promising for the treatment of M. abscessus- and M. fortuitum-associated diseases.Keywords: nontuberculous mycobacteria, in vitro activity, D-cycloserine, Mycobacterium fortuitum, Mycobacterium abscessus

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