Mycobacterium tuberculosis drug-resistance testing: challenges, recent developments and perspectives.
Drug-resistance testing, or antimicrobial susceptibility testing (AST), is mandatory for Mycobacterium tuberculosis in cases of failure on standard therapy. We reviewed the different methods and techniques of phenotypic and genotypic approaches. Although multiresistant and extensively drug-resistant (MDR/XDR) tuberculosis is present worldwide, AST for M. tuberculosis (AST-MTB) is still mainly performed according to the resources available rather than the drug-resistance rates. Phenotypic methods, i.e. culture-based AST, are commonly used in high-income countries to confirm susceptibility of new cases of tuberculosis. They are also used to detect resistance in tuberculosis cases with risk factors, in combination with genotypic tests. In low-income countries, genotypic methods screening hot-spot mutations known to confer resistance were found to be easier to perform because they avoid the culture and biosafety constraint. Given that genotypic tests can rapidly detect the prominent mechanisms of resistance, such as the rpoB mutation for rifampicin resistance, we are facing new challenges with the observation of false-resistance (mutations not conferring resistance) and false-susceptibility (mutations different from the common mechanism) results. Phenotypic and genotypic approaches are therefore complementary for obtaining a high sensitivity and specificity for detecting drug resistances and susceptibilities to accurately predict MDR/XDR cure and to gather relevant data for resistance surveillance. Although AST-MTB was established in the 1960s, there is no consensus reference method for MIC determination against which the numerous AST-MTB techniques can be compared. This information is necessary for assessing in vitro activity and setting breakpoints for future anti-tuberculosis agents.
Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden; Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Linköping University, Sweden; European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC), ESCMID, Basel, Switzerland.
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Schön
Emerging Bacterial Pathogens Unit, Div. of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
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Miotto
Department of Medicine, University of Cambridge, Cambridge, UK.
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Köser
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC), ESCMID, Basel, Switzerland; Unidade de Microbiologia Médica, Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, UNL, Lisboa, Portugal.
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Viveiros
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC), ESCMID, Basel, Switzerland; Institut für Medizinische Mikrobiologie, Nationales Zentrum für Mykobakterien, Universität Zürich, Zürich, Switzerland.
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Böttger
European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Mycobacterial Infections (ESGMYC), ESCMID, Basel, Switzerland; National Reference Center for Mycobacteria and Antimycobacterial Resistance, Paris, France; APHP, Hôpital Lariboisière, Laboratory of Bacteriology, Paris, France; University Paris Diderot, INSERM IAME UMR1137, Sorbonne Paris Cité, Paris, France. Electronic address: emmanuelle.cambau@aphp.fr.
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Cambau
D000995:Antitubercular Agents / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D024881:Drug Resistance, Bacterial; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods* / Q000639:trends; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods* / Q000639:trends; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics*; D010641:Phenotype
D000995:Antitubercular Agents; D012321:DNA-Directed RNA Polymerases; C105078:RNA polymerase beta subunit
Antimicrobial susceptibility testing; Critical concentration; Critical proportion; Genetic resistance; Hot spot mutations; Minimum inhibitory concentration