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Genotypic resistanc...
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Kuhlin, JohannaDepartment of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
(author)
Genotypic resistance of pyrazinamide but not MIC is associated with longer time to sputum culture conversion in patients with multidrug-resistant tuberculosis
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2020-10-03
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Oxford University Press,2021
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LIBRIS-ID:oai:DiVA.org:liu-173446
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-173446URI
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https://doi.org/10.1093/cid/ciaa1509DOI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Funding: Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20150508]; Swedish National Research Council [540-2013-8707, 2016-02043]
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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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Davies Forsman, LinaDepartment of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
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Mansjö, MikaelDepartment of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden
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Jonsson Nordvall, MichaelaLinköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk mikrobiologi(Swepub:liu)micjo69
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Wijkander, MariaDepartment of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden
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Wagrell, CharlottaDepartment of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
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Jonsson, JerkerDepartment of Public Health Analysis and Data Management, Public Health Agency of Sweden, Stockholm, Sweden
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Groenheit, RamonaDepartment of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden
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Werngren, JimDepartment of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden
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Schön, Thomas,1973-Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Infektionskliniken i Östergötland,Department of Infectious Diseases and Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden(Swepub:liu)thosc49
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Bruchfeld, JudithDepartment of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
(author)
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Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, SwedenDepartment of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
(creator_code:org_t)
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In:Clinical Infectious Diseases: Oxford University Press73:9, s. E3511-E35171058-48381537-6591
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