Molecular detection methods of resistance to antituberculosis drugs in Mycobacterium tuberculosis. 2017

F Brossier, and W Sougakoff, and
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.

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. 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. 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.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D004269 DNA, Bacterial Deoxyribonucleic acid that makes up the genetic material of bacteria. Bacterial DNA
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000995 Antitubercular Agents Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. Anti-Tuberculosis Agent,Anti-Tuberculosis Agents,Anti-Tuberculosis Drug,Anti-Tuberculosis Drugs,Antitubercular Agent,Antitubercular Drug,Tuberculostatic Agent,Tuberculostatic Agents,Antitubercular Drugs,Agent, Anti-Tuberculosis,Agent, Antitubercular,Agent, Tuberculostatic,Anti Tuberculosis Agent,Anti Tuberculosis Agents,Anti Tuberculosis Drug,Anti Tuberculosis Drugs,Drug, Anti-Tuberculosis,Drug, Antitubercular
D024881 Drug Resistance, Bacterial The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS). Antibiotic Resistance, Bacterial,Antibacterial Drug Resistance
D025202 Molecular Diagnostic Techniques MOLECULAR BIOLOGY techniques used in the diagnosis of disease. Molecular Testing,Molecular Diagnostic Technics,Molecular Diagnostic Testing,Diagnostic Technic, Molecular,Diagnostic Technics, Molecular,Diagnostic Technique, Molecular,Diagnostic Techniques, Molecular,Diagnostic Testing, Molecular,Molecular Diagnostic Technic,Molecular Diagnostic Technique,Technic, Molecular Diagnostic,Technics, Molecular Diagnostic,Technique, Molecular Diagnostic,Techniques, Molecular Diagnostic,Testing, Molecular,Testing, Molecular Diagnostic

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