Lina Davies Forsman1,2, Jerker Jonsson1,3, Charlotta Wagrell1, Jim Werngren4, Mikael Mansjö4, Maria Wijkander4, Ramona Groenheit4, Ulf Hammar5, Christian G Giske6, Thomas Schön7,8, Judith Bruchfeld1,2. 1. Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 2. Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden. 3. Department of Public Health Analysis and Data Management, Stockholm, Sweden. 4. Department of Microbiology, Public Health Agency of Sweden, Stockholm, Sweden. 5. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 6. Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden. 7. Department of Clinical and Experimental Medicine, Linköping University, Sweden. 8. Department of Clinical Microbiology and Infectious Diseases, Kalmar County Hospital, Sweden.
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 >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.
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)-tuberculosispatients 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-tuberculosispatients. METHODS: Clinical and demographic data of MDR-tuberculosispatients 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-tuberculosispatients. Increasing MICs of fluoroquinolones, diabetes, and age >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-tuberculosispatients. 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.
Authors: Christina Cahill; Dónal J Cox; Fiona O'Connell; Sharee A Basdeo; Karl M Gogan; Cilian Ó'Maoldomhnaigh; Jacintha O'Sullivan; Joseph Keane; James J Phelan Journal: Int J Mol Sci Date: 2021-11-10 Impact factor: 5.923