Most-Probable-Number-Based Minimum Duration of Killing Assay for Determining the Spectrum of Rifampicin Susceptibility in Clinical Mycobacterium tuberculosis Isolates
| Autor: | Srinivasan Vijay, Nguyen Le Hoai Bao, Babak Javid, Nguyen Thuy Thuong Thuong, Nguyen Hoan Phu, Do Dang Anh Thu, Guy E. Thwaites, Le Pham Tien Trieu, Hoang Ngoc Nhung |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Tuberculosis
Multidrug tolerance medicine.drug_class Antibiotics MPN Antitubercular Agents antibiotic tolerance most probable number Microbial Sensitivity Tests rifampicin Microbiology MDK Mycobacterium tuberculosis 03 medical and health sciences Antibiotic resistance Most probable number Drug Resistance Bacterial medicine Pharmacology (medical) minimum duration of killing 030304 developmental biology Pharmacology 0303 health sciences biology 030306 microbiology antibiotic tolerance assay DNA-Directed RNA Polymerases biology.organism_classification medicine.disease 3. Good health Infectious Diseases Susceptibility Rifampin Rifampicin Bacteria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 |
| Popis: | Accurate antibiotic susceptibility testing is essential for successful tuberculosis treatment. Recent studies have highlighted the limitations of MIC-based phenotypic susceptibility methods in detecting other aspects of antibiotic susceptibilities in bacteria. Duration and peak of antibiotic exposure, at or above the MIC required for killing the bacterial population, has emerged as another important factor for determining antibiotic susceptibility. This is broadly defined as antibiotic tolerance. Accurate antibiotic susceptibility testing is essential for successful tuberculosis treatment. Recent studies have highlighted the limitations of MIC-based phenotypic susceptibility methods in detecting other aspects of antibiotic susceptibilities in bacteria. Duration and peak of antibiotic exposure, at or above the MIC required for killing the bacterial population, has emerged as another important factor for determining antibiotic susceptibility. This is broadly defined as antibiotic tolerance. Antibiotic tolerance can further facilitate the emergence of antibiotic resistance. Currently, there are limited methods to quantify antibiotic tolerance among clinical M. tuberculosis isolates. In this study, we develop a most-probable-number (MPN)-based minimum duration of killing (MDK) assay to quantify the spectrum of M. tuberculosis rifampicin susceptibility within subpopulations based on the duration of rifampicin exposure required for killing the bacterial population. MDK90–99 and MDK99.99 were defined as the minimum duration of antibiotic exposure at or above the MIC required for killing 90 to 99% and 99.99% of the initial (pretreatment) bacterial population, respectively. Results from the rifampicin MDK assay applied to 28 laboratory and clinical M. tuberculosis isolates showed that there is variation in rifampicin susceptibility among isolates. The rifampicin MDK99/99.99 time for isolates varied from less than 2 to 10 days. MDK was correlated with larger subpopulations of M. tuberculosis from clinical isolates that were rifampicin tolerant. Our study demonstrates the utility of MDK assays to measure the variation in antibiotic tolerance among clinical M. tuberculosis isolates and further expands clinically important aspects of antibiotic susceptibility testing. |
| Databáze: | OpenAIRE |
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