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- Davies Forsman, Lina, et al.
(författare)
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Minimum Inhibitory Concentrations of Fluoroquinolones and Pyrazinamide Susceptibility Correlate to Clinical Improvement in Multidrug-resistant Tuberculosis Patients: A Nationwide Swedish Cohort Study Over 2 Decades
- 2019
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 69:8, s. 1394-1402
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Tidskriftsartikel (refereegranskat)abstract
- Background. Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant (MDR)-tuberculosis patients is unclear. Therefore, we correlated MICs of first- and second-line tuberculosis drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-tuberculosis patients. Methods. Clinical and demographic data of MDR-tuberculosis patients in Sweden, including DST results, were retrieved from medical records from 1992 to 2014. MIC determinations were performed retrospectively for the stored individual Mycobacterium tuberculosis (Mtb) isolates using broth microdilution in Middlebrook 7H9. We fitted Cox proportional hazard models correlating MICs, DST results, and clinical variables to tSCC and treatment outcome. Results. Successful treatment outcome was observed in 83.5% (132/158) of MDR-tuberculosis patients. Increasing MICs of fluoroquinolones, diabetes, and age amp;gt;40 years were significantly associated with unsuccessful treatment outcome. Patients treated with pyrazinamide (PZA) had a significantly shorter tSCC compared to patients who were not (median difference, 27 days). Conclusions. Increasing MICs of fluoroquinolones were correlated with unsuccessful treatment outcome in MDR-tuberculosis patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatment was associated with shorter tSCC, highlighting the importance of PZA DST.
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| 2. |
- Kuhlin, Johanna, et al.
(författare)
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Genotypic resistance of pyrazinamide but not MIC is associated with longer time to sputum culture conversion in patients with multidrug-resistant tuberculosis
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 73:9, s. E3511-E3517
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: PZA resistance in multidrug-resistant tuberculosis (MDR-TB) is common and 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 was collected in this cohort study for all patients diagnosed with MDR-TB in Sweden 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 analyses, PZA gDST resistance was associated with a 29-day longer time to SCC (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.89, p=0.013 and HR 0.49, 95% CI 0.29-0.82, p=0.007, respectively). A two-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 0.73-1.31, p=0.89). Genotypic DST and MIC for PZA were not associated with treatment outcome.CONCLUSION: 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.
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