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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
Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
Karolinska Inst, Sweden; Publ Hlth Agcy Sweden, Sweden.
Karolinska Inst, Sweden.
Publ Hlth Agcy Sweden, Sweden.
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2019 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 69, no 8, p. 1394-1402Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS INC , 2019. Vol. 69, no 8, p. 1394-1402
Keywords [en]
treatment outcome; drug-resistant tuberculosis; cohort study; drug regimen; pyrazinamide
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:liu:diva-161386DOI: 10.1093/cid/ciy1068ISI: 000490004300018PubMedID: 30561569OAI: oai:DiVA.org:liu-161386DiVA, id: diva2:1367480
Note

Funding Agencies|Swedish Heart Lung FoundationSwedish Heart-Lung Foundation [20150508]; Swedish Research CouncilSwedish Research Council [540-2013-8797]

Available from: 2019-11-04 Created: 2019-11-04 Last updated: 2019-11-04

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CiteExportLink to record
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Citation style
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