OBJECTIVE: To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa. DESIGN: Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance. RESULTS: MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB). CONCLUSION: An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.
OBJECTIVE: To determine the extent of pyrazinamide (PZA) resistance in isolates from previously treated patients from the Western Cape, South Africa. DESIGN: Drug-resistant isolates, isolates resistant to one or more drugs other than PZA (PZA resistance is not routinely determined) (n = 127), and drug-susceptible (n = 47) clinical isolates of Mycobacterium tuberculosis from previously treated patients from the Western Cape were phenotypically (BACTEC MGIT 960) and genotypically (pncA gene sequencing) analysed for PZA resistance. RESULTS: MGIT analysis found that 68 of the 127 drug-resistant isolates were PZA-resistant. Nearly all (63/68) PZA-resistant isolates had diverse nucleotide changes scattered throughout the pncA gene, and five PZA-resistant isolates had no pncA mutations. Of the 47 phenotypically susceptible isolates, 46 were susceptible to PZA, while one isolate was PZA-monoresistant (OR = 53.0, 95% CI = 7.1-396.5). A pncA polymorphism (Thr114Met) that did not confer PZA resistance was also identified. PZA resistance was strongly associated with multidrug-resistant tuberculosis (MDR-TB). CONCLUSION: An alarmingly high proportion of South African drug-resistant M. tuberculosis isolates are PZA-resistant, indicating that PZA should not be relied upon in managing patients with MDR-TB in the Western Cape. A method for the rapid detection of PZA resistance would be beneficial in managing patients with suspected drug resistance.
Authors: Nontuthuko E Maningi; Luke T Daum; John D Rodriguez; Halima M Said; Remco P H Peters; John Osei Sekyere; Gerald W Fischer; James P Chambers; P Bernard Fourie Journal: J Clin Microbiol Date: 2018-04-25 Impact factor: 5.948
Authors: G E Louw; R M Warren; N C Gey van Pittius; C R E McEvoy; P D Van Helden; T C Victor Journal: Antimicrob Agents Chemother Date: 2009-05-18 Impact factor: 5.191
Authors: Michael G Whitfield; Robin M Warren; Elizabeth M Streicher; Samantha L Sampson; Frik A Sirgel; Paul D van Helden; Alexandra Mercante; Melisa Willby; Kelsey Hughes; Kris Birkness; Glenn Morlock; Annelies van Rie; James E Posey Journal: J Clin Microbiol Date: 2015-08-19 Impact factor: 5.948
Authors: Alistair D Calver; Alecia A Falmer; Megan Murray; Odelia J Strauss; Elizabeth M Streicher; Madelene Hanekom; Thelma Liversage; Mothusi Masibi; Paul D van Helden; Robin M Warren; Thomas C Victor Journal: Emerg Infect Dis Date: 2010-02 Impact factor: 6.883