Prevalence of pyrazinamide resistance across the spectrum of drug resistant phenotypes of Mycobacterium tuberculosis

Whitfield, Michael G.; Streicher, Elizabeth M.; Dolby, Tania; Simpson, John; Sampson, Samantha L.; Helden, Paul D. van; Rie, Annelies Van; Warren, Robin M.

doi:10.1016/j.tube.2016.05.003

Cited by 17 publications

(16 citation statements)

References 11 publications

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“…Nevertheless, among the 37 MDR-TB isolates included in the current cohort, 25/37 (65.6%) were resistant to PZA. This is similar to the PZA resistance prevalence of 31% to 89% among MDR-TB reported in other studies (9,30). Considering the high cost of PCR sequencing and the high PZA resistance rate among MDR-TB in not only our locality but also other regions (31), we have suggested an algorithm for selectively applying direct pncA PCR sequencing in respiratory specimens or culture isolates.…”

Section: Discussionsupporting

confidence: 85%

Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

et al. 2019

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An in-house-developed pncA sequencing assay for analysis of pyrazinamide (PZA) resistance was evaluated using 162 archived Mycobacterium tuberculosis complex (MTBC) isolates with phenotypic PZA susceptibility profiles that were well defined by analysis of Bactec MGIT 960 PZA kit and PZase activity data. Preliminary results showed 100% concordance between pncA sequencing and phenotypic PZA drug susceptibility test (DST) results among archived isolates. Also, 637 respiratory specimens were prospectively collected, and 158 were reported as MTBC positive by the Abbott Realtime MTB assay (96.3% sensitivity [95% confidence interval {CI}: 92.2% to 98.7%]; 100% specificity [95% CI: 99.2% to 100.0%]). Genotypic and phenotypic PZA resistance profiles of these 158 MTBC-positive specimens were analyzed by pncA sequencing and Bactec MGIT 960 PZA kit, respectively. For analysis of PZA resistance, pncA sequencing detected pncA mutations in 5/5 (100%) phenotypic PZA-resistant respiratory specimens within 4 working days. No pncA mutations were detected among PZA-susceptible specimens. Combining archived isolates with prospective specimens, 27 were identified as phenotypic PZA resistant with pncA mutation. Among these 27 samples, 6/27 (22.2%) phenotypic PZA-resistant strains carried novel pncA mutations without rpsA and panD mutations. These included 5 with mutations (a deletion [Del] at 383T [Del383T], Del 380 to 390, insertion of A [A Ins] at position 127, A Ins at position 407, and G Ins at position 508) in pncA structural genes and 1 with a mutation (T-12C) at the pncA promoter region. All six of these strains had no or reduced PZase activities, indicating that the novel mutations might confer PZA resistance. Additionally, 25/27 phenotypic PZA-resistant strains were confirmed multidrug-resistant tuberculosis (MDR-TB) strains. As PZA is commonly used in MDR-TB treatment regimens, direct pncA sequencing will rapidly detect PZA resistance and facilitate judicious use of PZA in treating PZA-susceptible MDR-TB.

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Section: Discussionsupporting

confidence: 85%

Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

et al. 2019

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“…In a recent study, the prevalence of PZA resistance was 0%–9% in cases of drug-sensitive TB, and 31%–89% among MDR-TB isolates. The study found a significant increase in the prevalence of PZA-resistant TB with increased resistance to other drugs (3031). Further studies studying the prevalence, cause, and relation between MDR-TB and PZA-resistant TB are warranted.…”

Section: Discussionmentioning

confidence: 99%

The Rate of Drug-Resistant Tuberculosis in Korean Children and Adolescents Since 2007

et al. 2017

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The incidence of drug-resistant tuberculosis (DR-TB) in pediatric populations is a critical indicator of national TB management and treatment strategies. Limited data exist regarding the rate of pediatric DR-TB. In this study, we aimed to analyze the status of DR-TB in Korean children from 2007 to 2013. We analyzed specimens submitted to the Korean Institute of Tuberculosis using Mycobacterium tuberculosis culture and drug susceptibility tests (DSTs) from January 2007 through December 2013. Specimens from patients ≤ 19 years of age were included. Among the 2,690 cases, 297 cases were excluded because of insufficient data, leaving 2,393 cases for the final analysis. In total, resistance to one or more TB drugs was 13.5%. The resistance rates of each of the drugs were as follows: isoniazid (INH) 10.2%, rifampin (RFP) 5.1%, ethambutol (EMB) 3.7%, and pyrazinamide (PZA) 3.1%. The resistance rate of multidrug-resistant TB (MDR-TB) was 4.2%, and that of extensively drug-resistant TB (XDR-TB) was 0.8%. The overall drug resistance rate demonstrated significant increase throughout the study period (P < 0.001) but showed no significant difference compared to previous study from 1999 to 2007. The drug resistance rate of PZA in ≤ 15 years of age group was significantly greater than that of > 15 years (P < 0.001). The drug resistance rate has increased throughout the study period.

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“…undiagnosed [75] which, together with the strong association between ethambutol resistance and MDR-TB, [68] undermines the efficacy of standardised MDR treatment regimens. Ineffective treatment of MDR-TB has allowed the emergence of additional resistance, culminating in XDR-TB, which we termed programmatic selection.…”

Section: Researchmentioning

confidence: 99%

Tuberculosis research in South Africa over the past 30 years: From bench to bedside

et al. 2019

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0. The South African Medical Research Council Centre for Tuberculosis Research has a rich history of high-impact research that has influenced our understating of this hyper-epidemic which is further exacerbated by the emergence and spread of drug-resistant forms of the disease. This review aims to summarise the past 30 years of research conducted in the Centre which has influenced the way that tuberculosis (TB) is diagnosed and treated. The review includes the development of new technologies for rapid screening of people with probable TB and the repurposing of human diagnostics for wildlife conservation.

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Prevalence of pyrazinamide resistance across the spectrum of drug resistant phenotypes of Mycobacterium tuberculosis

Abstract: Pyrazinamide resistance is largely unknown in the spectrum of drug resistant phenotypes. We summarize data on PZA resistance in clinical isolates from South Africa. PZA DST should be performed when considering its inclusion in treatment of patients with rifampicin-resistant TB or MDR-TB.

Cited by 17 publications

References 11 publications

Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing

The Rate of Drug-Resistant Tuberculosis in Korean Children and Adolescents Since 2007

Tuberculosis research in South Africa over the past 30 years: From bench to bedside

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