F Brossier1, W Sougakoff2. 1. Inserm Sorbonne universités, UPMC université Paris 06, CR7, U1135, centre d'immunologie et des maladies infectieuses, CIMI, Team E13 (bactériologie), 91, boulevard de l'hôpital, 75013 Paris, France; Centre national de référence des mycobactéries et de la résistance des mycobactéries aux antituberculeux (CNR-MyRMA), bactériologie-hygiène, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, AP-HP, 47-83, boulevard de l'hôpital, 75013 Paris, France; Hôpitaux universitaires Saint-Louis-Lariboisière, AP-HP, 2, rue Ambroise-Paré, 75010 Paris, France. Electronic address: florence.brossier@psl.aphp.fr. 2. Inserm Sorbonne universités, UPMC université Paris 06, CR7, U1135, centre d'immunologie et des maladies infectieuses, CIMI, Team E13 (bactériologie), 91, boulevard de l'hôpital, 75013 Paris, France; Centre national de référence des mycobactéries et de la résistance des mycobactéries aux antituberculeux (CNR-MyRMA), bactériologie-hygiène, hôpitaux universitaires Pitié-Salpêtrière-Charles-Foix, AP-HP, 47-83, boulevard de l'hôpital, 75013 Paris, France; Hôpitaux universitaires Saint-Louis-Lariboisière, AP-HP, 2, rue Ambroise-Paré, 75010 Paris, France.
Abstract
OBJECTIVE: Molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. We aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among Mycobacterium tuberculosis strains. MATERIALS AND METHODS: The molecular diagnosis of resistance to antituberculosis drugs in clinical samples or from in vitro cultures is based on the detection of the most common mutations in the genes involved in the development of resistance in M. tuberculosis strains (encoding either protein targets of antibiotics, or antibiotic activating enzymes) by commercial molecular kits or by sequencing. RESULTS: Three hypotheses could explain the discrepancies between the genotypic results and the phenotypic drug susceptibility testing results: a low percentage of resistant mutants precluding the detection by genotypic methods on the primary culture; a low level of resistance not detected by phenotypic testing; and other resistance mechanisms not yet characterized. DISCUSSION/ CONCLUSIONS: Molecular methods have varying sensitivity with regards to detecting antituberculosis drug resistance; that is why phenotypic susceptibility testing methods are mandatory for detecting antituberculosis drug-resistant isolates that have not been detected by molecular methods. The questionable ability of existing phenotypic and genotypic drug susceptibility testing to properly classify strains as susceptible or resistant, and at what level of resistance, was raised for several antituberculosis agents.
OBJECTIVE: Molecular methods predict drug resistance several weeks before phenotypic methods and enable rapid implementation of appropriate therapeutic treatment. We aimed to detail the most representative molecular tools used in routine practice for the rapid detection of resistance to antituberculosis drugs among Mycobacterium tuberculosis strains. MATERIALS AND METHODS: The molecular diagnosis of resistance to antituberculosis drugs in clinical samples or from in vitro cultures is based on the detection of the most common mutations in the genes involved in the development of resistance in M. tuberculosis strains (encoding either protein targets of antibiotics, or antibiotic activating enzymes) by commercial molecular kits or by sequencing. RESULTS: Three hypotheses could explain the discrepancies between the genotypic results and the phenotypic drug susceptibility testing results: a low percentage of resistant mutants precluding the detection by genotypic methods on the primary culture; a low level of resistance not detected by phenotypic testing; and other resistance mechanisms not yet characterized. DISCUSSION/ CONCLUSIONS: Molecular methods have varying sensitivity with regards to detecting antituberculosis drug resistance; that is why phenotypic susceptibility testing methods are mandatory for detecting antituberculosis drug-resistant isolates that have not been detected by molecular methods. The questionable ability of existing phenotypic and genotypic drug susceptibility testing to properly classify strains as susceptible or resistant, and at what level of resistance, was raised for several antituberculosis agents.
Authors: Liliana Rondón; Estefanía Urdániz; Cecilia Latini; Florencia Payaslian; Mario Matteo; Ezequiel J Sosa; Darío F Do Porto; Adrian G Turjanski; Sergio Nemirovsky; Graham F Hatfull; Susana Poggi; Mariana Piuri Journal: Front Microbiol Date: 2018-07-05 Impact factor: 5.640