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Clin Infect Dis. 2018 Dec 18. doi: 10.1093/cid/ciy1068. [Epub ahead of print]

Minimum inhibitory concentrations of fluoroquinolones and pyrazinamide susceptibility correlate to clinical improvement in MDR-TB patients - a nationwide Swedish cohort study over two decades.

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Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
Department of Public Health Analysis and Data Management, The Public Health Agency of Sweden, Stockholm, Sweden.
Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden.
Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Sweden.
Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Sweden.



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 tuberculosis (MDR-TB) patients is unclear. Therefore, we correlated MICs of first-and second-line TB drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-TB patients.


Clinical and demographic data of MDR-TB patients in Sweden 1992-2014 including DST results were retrieved from medical records. MIC determinations were performed retrospectively for the stored individual 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.


Successful treatment outcome was observed in 83.5% (132/158) of MDR-TB patients. Increasing MICs of fluoroquinolones, diabetes and age > 40 years were significantly associated with unsuccessful treatment outcome. Patients treated with PZA had a significantly shorter tSCC compared to patients were not (median difference 27 days).


Increasing MICs of fluoroquinolones were correlated to unsuccessful treatment outcome in MDR-TB patients. Further studies, including MIC testing and clinical outcome data to define clinical Mtb breakpoints, are warranted. PZA treatmentwas associated with shorter tSCC, highlighting the importance of PZA DST.


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