Detection of Pyrazinamide Heteroresistance in Mycobacterium tuberculosis

Heteroresistance is defined as the coexistence of both susceptible and resistant bacteria in a bacterial population. Previously published data show that it may occur in 9 to 57% of Mycobacterium tuberculosis isolates for various drugs. Pyrazinamide (PZA) is an important first-line drug used for trea...

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Vydáno v:Antimicrobial agents and chemotherapy Ročník 65; číslo 9; s. e0072021
Hlavní autoři: Werngren, Jim, Mansjö, Mikael, Glader, Mikaela, Hoffner, Sven, Davies Forsman, Lina
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 17.08.2021
Témata:
Amidohydrolases - genetics
Antitubercular Agents - pharmacology
Antitubercular Agents - therapeutic use
Drug Resistance, Bacterial - genetics
Humans
Microbial Sensitivity Tests
Mutation
Mycobacterium tuberculosis - genetics
Pyrazinamide - pharmacology
Tuberculosis, Multidrug-Resistant - drug therapy
Mycobacterium tuberculosis
heteroresistance
Wayne's test
whole-genome sequencing
method evaluation
pyrazinamide
drug susceptibility testing
BACTEC MGIT 960
ISSN:1098-6596, 1098-6596
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Shrnutí:Heteroresistance is defined as the coexistence of both susceptible and resistant bacteria in a bacterial population. Previously published data show that it may occur in 9 to 57% of Mycobacterium tuberculosis isolates for various drugs. Pyrazinamide (PZA) is an important first-line drug used for treatment of both drug-susceptible and PZA-susceptible multidrug-resistant TB. Clinical PZA resistance is defined as a proportion of resistant bacteria in the isolate exceeding 10%, when the drug is no longer considered clinically effective. The ability of traditional drug susceptibility testing techniques to detect PZA heteroresistance has not yet been evaluated. The aim of this study was to compare the capacity of Bactec MGIT 960, Wayne's test, and whole-genome sequencing (WGS) to detect PZA-resistant subpopulations in bacterial suspensions prepared with different proportions of mutant strains. Both Bactec MGIT 960 and WGS were able to detect the critical level of 10% PZA heteroresistance, whereas Wayne's test failed to do so, with the latter falsely reporting highly resistant samples as PZA susceptible. Failure to detect drug-resistant subpopulations may lead to inadvertently weak treatment regimens if ineffective drugs are included, with the risk of treatment failure with the selective growth of resistant subpopulations. We need clinical awareness of heteroresistance as well as evaluation of new diagnostic tools for their capacity to detect heteroresistance in TB.
Bibliografie:ObjectType-Article-1
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ISSN:1098-6596
1098-6596
DOI:10.1128/AAC.00720-21