Colangeli R, et al. - Whether any correlations between the minimum inhibitory concentration (MIC) of a drug below the standard resistance breakpoint and the relapse risk for tuberculosis after treatment can be determined by analyzing pretreatment isolates of Mycobacterium tuberculosis obtained from patients who subsequently had a relapse or were cured, was investigated. A greater risk of relapse was observed in relation to higher MIC values vs lower MIC values in pretreatment isolates of M. tuberculosis with decrements of MIC values of isoniazid or rifampin below standard resistance breakpoints.

Methods

• This study comprised development cohort and validation cohort.
• Researchers analyzed data from the Tuberculosis Trials Consortium Study 22 (development cohort), to evaluate relapse and cure isolates to determine the MIC values of isoniazid and rifampin that were below the standard resistance breakpoint (0.1 μg per milliliter for isoniazid and 1.0 μg per milliliter for rifampin).
• They generated predictive relapse models by integrating this analysis with clinical, radiologic, and laboratory data; these models were validated by analyzing data from the DMID 01-009 study (validation cohort).

Results

• Data showed that, in the relapse group and in the cure group, the mean (±SD) MIC of isoniazid below the breakpoint was 0.0334±0.0085 μg per milliliter and 0.0286±0.0092 μg per milliliter, respectively, in the development cohort; a higher value in the relapse group by a factor of 1.17 (P=0.02) was represented.
• Representing a higher value in the relapse group by a factor of 1.53 (P < 0.001), the observed corresponding MIC values of rifampin were 0.0695±0.0276 and 0.0453±0.0223 μg per milliliter, respectively.
• In a multivariable analysis that included other significant between-group differences, higher MIC values were shown to be related to relapse.
• The generated area under the curve (AUC) was 0.779 in an analysis of receiver-operating-characteristic curves of relapse based on these MIC values.
• They found that, in the development cohort, 0.875 was the AUC in a multivariable model that included MIC values.
• Reslapse was also predicted in the validation cohort by the MIC values either alone or combined with other patient characteristics, with AUC values of 0.964 and 0.929, respectively.
• Findings revealed that the use of a model score for the MIC values of isoniazid and rifampin to achieve 75.0% sensitivity in cross-validation analysis predicted relapse with a specificity of 76.5% in the development cohort and a sensitivity of 70.0% and a specificity of 100% in the validation cohort.