scholarly journals Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System

2016 ◽  
Vol 54 (5) ◽  
pp. 1276-1281 ◽  
Author(s):  
Anne-Marie Demers ◽  
Amour Venter ◽  
Sven O. Friedrich ◽  
Gabriel Rojas-Ponce ◽  
Daniel Mapamba ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Direct Method ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
Indirect Methods ◽  
Future Studies ◽  
Patient Screening ◽  
Phenotypic Methods ◽  
Direct And Indirect Methods

Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster. Agreement between the direct and indirect methods varied from 90 to 100% in each laboratory. The median times for obtaining PZA results from the time when the specimen was collected ranged from 11 to 16 days for the direct test and 18 to 95 days for the indirect test across laboratories. The direct method is accurate and reproducible across laboratories. It can be expected to accelerate results in >50% of cases, but it cannot replace indirect DST for PZA. Phenotypic methods remain the gold standard for DST in drug trials. If future studies can optimize the method to decrease the number of uninterpretable results, direct MGIT DST could be the new phenotypic DST standard for clinical trials, providing more rapid detection of resistance to new drugs in experimental regimens.

scholarly journals TB Elimination Requires Discovery and Development of Transformational Agents

2020 ◽  
Vol 10 (7) ◽  
pp. 2605 ◽  
Author(s):  
Christian Lienhardt ◽  
Mario C. Raviglione
Keyword(s):  
Rapid Detection ◽  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
The World ◽  
Health Organization ◽  
Combination Regimens

The World Health Organization (WHO) End Tuberculosis (TB) Strategy has set ambitious targets to reduce 2015 TB incidence and deaths by 80% and 90%, respectively, by the year 2030. Given the current rate of TB incidence decline (about 2% per year annually), reaching these targets will require new transformational tools and innovative ways to deliver them. In addition to improved tests for early and rapid detection of TB and universal drug-susceptibility testing, as well as novel vaccines for improved prevention, better, safer, shorter and more efficacious treatments for all forms of TB are needed. Only a handful of new drugs are currently in phase II or III clinical trials, and a few combination regimens are being tested, mainly for drug-resistant TB. In this article, capitalising on an increasingly rich medicine pipeline and taking advantage of new methodological designs with great potential, the main areas where progress is needed for a transformational improvement of treatment of all forms of TB are described.

scholarly journals Sensititre MYCOTB MIC Plate for Testing Mycobacterium tuberculosis Susceptibility to First- and Second-Line Drugs

2013 ◽  
Vol 58 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Jongseok Lee ◽  
Derek T. Armstrong ◽  
Willy Ssengooba ◽  
Jeong-ae Park ◽  
Yeuni Yu ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Susceptibility Testing ◽  
Critical Concentration ◽  
Microtiter Plate ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Second Line ◽  
Content Type ◽  
The Republic ◽  
Phenotypic Methods

ABSTRACTForMycobacterium tuberculosis, phenotypic methods for drug susceptibility testing of second-line drugs are poorly standardized and technically challenging. The Sensititre MYCOTB MIC plate (MYCOTB) is a microtiter plate containing lyophilized antibiotics and configured for determination of MICs to first- and second-line antituberculosis drugs. To evaluate the performance of MYCOTB forM. tuberculosisdrug susceptibility testing using the Middlebrook 7H10 agar proportion method (APM) as the comparator, we conducted a two-site study using archivedM. tuberculosisisolates from Uganda and the Republic of Korea. Thawed isolates were subcultured, and dilutions were inoculated into MYCOTB wells and onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, and 21; APM results were read at 21 days. A total of 222 isolates provided results on both platforms. By APM, 106/222 (47.7%) of isolates were resistant to at least isoniazid and rifampin. Agreement between MYCOTB and APM with respect to susceptibility or resistance was ≥92% for 7 of 12 drugs when a strict definition was used and ≥96% for 10 of 12 drugs when agreement was defined by allowing a ± one-well range of dilutions around the APM critical concentration. For ethambutol, agreement was 80% to 81%. For moxifloxacin, agreement was 83% to 85%; incorporating existing DNA sequencing information for discrepant analysis raised agreement to 91% to 96%. For MYCOTB, the median time to plate interpretation was 10 days and interreader agreement was ≥95% for all drugs. MYCOTB provided reliable results forM. tuberculosissusceptibility testing of first- and second-line drugs except ethambutol, and results were available sooner than those determined by APM.

scholarly journals Comparative Performance of Genomic Methods for the Detection of Pyrazinamide Resistance and Heteroresistance in Mycobacterium tuberculosis

2021 ◽  
Author(s):  
Michael G. Whitfield ◽  
David M. Engelthaler ◽  
Christopher Allender ◽  
Megan Folkerts ◽  
Tim H. Heupink ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Susceptibility Testing ◽  
High Sensitivity ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Comparative Performance ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Targeted Deep Sequencing ◽  
Phenotypic Methods

Background: Pyrazinamide is an important component of both drug-susceptible and drug-resistant tuberculosis treatment regimens. Although approximately 50% of rifampicin resistant isolates are also resistant to pyrazinamide, pyrazinamide susceptibility testing is not routinely performed due to the challenging nature of the assay. We investigated the diagnostic accuracy of genotypic and phenotypic methods, and explored the occurrence of pyrazinamide heteroresistance. Methods: We assessed pyrazinamide susceptibility among 358 individuals enrolled in the South African EXIT-RIF cohort using Sanger and targeted deep sequencing (TDS) of the pncA gene, whole genome sequencing (WGS), and phenotypic drug-susceptibility testing. We calculated the diagnostic accuracy of the different methods, and investigated the prevalence and clinical impact of pncA heteroresistance. True pyrazinamide susceptibility status was assigned to each isolate using the Koser classification and expert rules. Results: We observed 100% agreement across genotypic methods for detection of pncA fixed mutations, only TDS confidently identified three isolates (0.8%) with minor variants. For the 355 (99.2%) isolates that could be assigned true pyrazinamide status with confidence, phenotypic DST had a sensitivity of 96.5% (95% CI: 93.8-99.3%) and specificity of 100% (95% CI: 100-100%); both Sanger sequencing and WGS had a sensitivity of 97.1% (95% CI: 94.6-99.6%) and specificity of 97.8% (95% CI: 95.7-99.9%); and TDS, sensitivity of 98.8% (95% CI: 97.2-100%) and specificity of 97.8% (95% CI: 95.7-99.9%). Conclusions: We demonstrate high sensitivity and specificity for pyrazinamide susceptibility testing among all assessed genotypic methods. The prevalence of pyrazinamide heteroresistance in Mtb isolates was lower than that identified for other first-line drugs.

scholarly journals Clinical Management of Drug-Resistant Tuberculosis in Resource Constrained Settings

2013 ◽  
Vol 5 ◽  
pp. CMT.S6560
Author(s):  
Domingo Palmero ◽  
Viviana Ritacco
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
New Drugs ◽  
Drug Resistant ◽  
Resource Constrained ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Repurposed Drugs ◽  
Culture Identification

Drug-resistant forms of tuberculosis (TB), particularly multi- and extensively drug-resistant TB, represent an important obstacle to global control of the disease. Recently, new drugs, repurposed drugs, and new drug combinations have been evaluated, with a number showing promise for the treatment of drug-resistant TB. Additionally, a range of methods for accelerating mycobacterial culture, identification, and drug susceptibility testing have been developed, and several in-house and commercial genotyping methods for speeding drug resistance detection have become available. Despite these significant achievements in drug development and diagnostics, drug-resistant TB continues to be difficult to diagnose and treat. Significant international efforts are still needed, especially in the field of clinical and operational research, to translate these encouraging developments into effective patient cure and make them readily available to resource-constrained settings, where they are most needed.

Accuracy of molecular drug susceptibility testing amongst tuberculosis patients in Karakalpakstan, Uzbekistan

2021 ◽  
Author(s):  
Horacio Gil ◽  
Hasmik Margaryan ◽  
Ismailov Azamat ◽  
Bekturdieva Ziba ◽  
Halmuratov Bayram ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Tuberculosis Patients
Sign in / Sign up

Export Citation Format

Share Document