Epidemiological cut-off values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis
Author(s)
Type
Journal Article
Abstract
Drug susceptibility testing of M. tuberculosis is rooted in a binary susceptible/resistant paradigm. While there are considerable advantages in measuring the minimum inhibitory concentrations (MICs) of a panel of drugs for an isolate, it is necessary to measure the epidemiological cut-off values (ECOFF/ECVs) to permit comparison with qualitative data. Here we present ECOFF/ECVs for 13 anti-tuberculosis compounds, including bedaquiline and delamanid, derived from 20 637 clinical isolates collected by 14 laboratories based in 11 countries on five continents. Each isolate was incubated for 14 days on a dry 96-well broth microdilution plate and then read. Resistance to most of the drugs due to prior exposure is expected and the MIC distributions for many of the compounds are complex, and therefore a phenotypically wild-type population could not be defined. Since a majority of samples also underwent genetic sequencing, we defined a genotypically wild-type population and measured the MIC of the 99th percentile by direct measurement and via fitting a Gaussian using interval regression. The proposed ECOFF/ECVs were then validated by comparing with the MIC distributions of high-confidence genetic variants that confer resistance and with qualitative drug susceptibility tests obtained via the Mycobacterial Growth Indicator Tube (MGIT) system or Microscopic-Observation Drug Susceptibility (MODS) assay. These ECOFF/ECVs will inform and encourage the more widespread adoption of broth microdilution: this is a cheap culture-based method that tests the susceptibility of 12–14 antibiotics on a single 96-well plate and so could help personalise the treatment of tuberculosis.
Date Issued
2022-10
Date Acceptance
2022-02-22
Citation
European Respiratory Journal, 2022, 60 (4)
ISSN
0903-1936
Publisher
European Respiratory Society
Journal / Book Title
European Respiratory Journal
Volume
60
Issue
4
Copyright Statement
Copyright ©The authors 2022.
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000911502500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
ASSAY
BREAKPOINTS
DISTRIBUTIONS
DRUG-SUSCEPTIBILITY
Life Sciences & Biomedicine
MYCOBACTERIUM-TUBERCULOSIS
MYCOTB MIC PLATE
PREDICTION
RESISTANCE
Respiratory System
Science & Technology
TOOL
Publication Status
Published
Article Number
2200239
Date Publish Online
2022-03-17