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Direct Determination of Pyrazinamide (PZA) Susceptibility by Sputum Microscopic Observation Drug Susceptibility (MODS) Culture at Neutral pH: the MODS-PZA Assay.

Alcántara, R; Fuentes, P; Marin, L; Kirwan, DE; Gilman, RH; Zimic, M; Sheen, P (2020) Direct Determination of Pyrazinamide (PZA) Susceptibility by Sputum Microscopic Observation Drug Susceptibility (MODS) Culture at Neutral pH: the MODS-PZA Assay. J Clin Microbiol, 58 (5). ISSN 1098-660X https://doi.org/10.1128/JCM.01165-19
SGUL Authors: Kirwan, Daniela Elisa

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Abstract

Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of Mycobacterium tuberculosis However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH. Here, for the first time, MODS culture at neutral pH was evaluated using high PZA concentrations (400 and 800 μg/ml) to determine PZA susceptibility directly from sputum samples. Sputum samples were cultured with PZA for up to 21 days at 37°C. Plate reading was performed at two time points: R1 (mean, 10 days) and R2 (mean, 13 days) for each PZA concentration. A consensus reference test, composed of MGIT-PZA, pncA sequencing, and the classic Wayne test, was used. A total of 182 samples were evaluated. The sensitivity and specificity for 400 μg/ml ranged from 76.9 to 89.7 and from 93.0 to 97.9%, respectively, and for 800 μg/ml ranged from 71.8 to 82.1 and from 95.8 to 98.6%, respectively. Compared to MGIT-PZA, our test showed a similar turnaround time (medians of 10 and 12 days for PZA-sensitive and -resistant isolates, respectively). In conclusion, MODS-PZA is presented as a fast, simple, and low-cost DST that could complement the MODS assay to evaluate resistance to the principal first-line antituberculosis drugs. Further optimization of test conditions would be useful in order to increase its performance.

Item Type: Article
Additional Information: Copyright © 2020 Alcántara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Keywords: MODS, drug susceptibility, pyrazinamide, sputum, tuberculosis, drug susceptibility, MODS, pyrazinamide, sputum, tuberculosis, 06 Biological Sciences, 07 Agricultural and Veterinary Sciences, 11 Medical and Health Sciences, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: J Clin Microbiol
ISSN: 1098-660X
Language: eng
Dates:
DateEvent
May 2020Published
23 April 2020Published Online
27 February 2020Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
099805/Z/112/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
0687-01-10Grand Challenge CanadaUNSPECIFIED
037-22014FONDECyT-PeruUNSPECIFIED
UNSPECIFIEDMedical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 32132191
Web of Science ID: WOS:000535797600015
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112046
Publisher's version: https://doi.org/10.1128/JCM.01165-19

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