caa a22 4500 606156577 CHVBK 20210128100609.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s10096-014-2262-0 doi (NATIONALLICENCE)springer-10.1007/s10096-014-2262-0 Automated liquid culture system misses isoniazid heteroresistance in Mycobacterium tuberculosis isolates with mutations in the promoter region of the inhA gene [Elektronische Daten] [Z. Zhang, J. Lu, Y. Wang, Y. Pang, Y. Zhao] Heteroresistance in Mycobacterium tuberculosis isolates remains the major challenge for phenotypic drug susceptibility testing (DST) methods to detect drug resistance. The aim of this study was to investigate the abilities of phenotypic DST methods to identify the isoniazid (INH) heteroresistance in M. tuberculosis. We found that the broth dilution method was able to detect INH resistance if 0.5% resistant bacteria with mutations in the katG and oxyR-ahpC regions were present, while the detection limit ranged from 1 to 10% for the INH-resistant strains harboring inhA mutations, which was associated with the different mutant types. Additionally, MGIT DST was able to find the recommended 1% INH resistance due to katG mutations. In contrast, MGIT DST detected resistance in suspensions with 20% resistant bacteria with inhA mutations. Statistical analysis revealed that the ability of the broth dilution method to detect heteroresistance was better than that of the MGIT DST (p = 0.004). When we further pairwise compared the two methods for detecting heteroresistance according to different mutant loci, the broth dilution method found more heteroresistance due to inhA mutations than MGIT DST (p = 0.001), while the differences for katG and oxyR-ahpC mutations were both not statistically significant (p > 0.05). In conclusion, our findings demonstrate that MGIT DST fails to detect INH heteroresistance in M. tuberculosis isolates with mutations in the promoter region of inhA. In addition, the broth dilution method is more sensitive than MGIT DST in finding INH heteroresistance, indicating that this method may serve as an alternative method to detect the heteroresistance of M. tuberculosis. Springer-Verlag Berlin Heidelberg, 2014 Zhang Z. Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China aut Lu J. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China aut Wang Y. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Chang Bai Road, Changping District, 102206, Beijing, People's Republic of China aut Pang Y. Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China aut Zhao Y. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Chang Bai Road, Changping District, 102206, Beijing, People's Republic of China aut European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/3(2015-03-01), 555-560 0934-9723 34:3<555 2015 34 10096 https://doi.org/10.1007/s10096-014-2262-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10096-014-2262-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Z. Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China aut NATIONALLICENCE 700 1- Lu J. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China aut NATIONALLICENCE 700 1- Wang Y. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Chang Bai Road, Changping District, 102206, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Pang Y. Respiratory Diseases Department of Nanlou, Chinese People's Liberation Army General Hospital, Beijing, China aut NATIONALLICENCE 700 1- Zhao Y. National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, No. 155, Chang Bai Road, Changping District, 102206, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- European Journal of Clinical Microbiology & Infectious Diseases Springer Berlin Heidelberg 34/3(2015-03-01), 555-560 0934-9723 34:3<555 2015 34 10096