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- Title
Genotypic Resistance of Pyrazinamide but Not Minimum Inhibitory Concentration Is Associated With Longer Time to Sputum Culture Conversion in Patients With Multidrug-resistant Tuberculosis.
- Authors
Kuhlin, Johanna; Forsman, Lina Davies; Mansjö, Mikael; Nordvall, Michaela Jonsson; Wijkander, Maria; Wagrell, Charlotta; Jonsson, Jerker; Groenheit, Ramona; Werngren, Jim; Schön, Thomas; Bruchfeld, Judith
- Abstract
Background Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Methods Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992–2014. MIC, pDST, and whole-genome sequencing of the pncA , rpsA , and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Results Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI],.29-.82; P =.007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI,.73–1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. Conclusions In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.
- Subjects
SWEDEN; SEQUENCE analysis; CONFIDENCE intervals; PYRAZINAMIDE; SPUTUM; TREATMENT effectiveness; DESCRIPTIVE statistics; DRUG resistance in microorganisms; LONGITUDINAL method; PROPORTIONAL hazards models; MICROBIAL sensitivity tests; EVALUATION
- Publication
Clinical Infectious Diseases, 2021, Vol 73, Issue 9, pe3511
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciaa1509