To our knowledge, this is the first study to address the development and internally validation of risk score to the shorter sputum smear and culture conversions among patients with MDR-TB. In addition, this is the first study to address the development of clinical risk score to predict time-to sputum smear and culture conversions.
At the end of treatment, 89% of our patients converted their culture, which was comparable to the conversion rates reported in Ethiopia (88.6%) , South Africa (89%) , USA (85%) , South Korea (91.7%) , and Peru (92%) , but higher than those reported in China (76.3%) , and Indonesia (81%) . Nevertheless, the median culture conversion observed in our sample was comparable to those reported in the literature, ranging from 30 days to 91 days [2,4,5].
In parallel, 90.2% of our patients achieved to sputum smear conversion in a median of 59 days. This median time to conversion was comparable to those previously reported in South Korea (56 days) , Peru (59 days)  and Dominican Republic (60 days) , but less days than in USA (93 days) , China (91.5 days)  and Ethiopia (72 days) . Possible reasons for these discrepancies are selection bias, differences in MDR-TB regimens, genetic background, and differences between health-care systems.
The role of culture conversion as a biomarker of treatment success has been overlooked in many studies [10,17]. Our finding agreed with the literature report that patients who achieved earlier culture conversion were more likely to have successful MDR-TB treatment. Although, the higher rates of culture conversion in the present study are encouraging, additional efforts should be made to increase the rate of successful MDR-TB treatment up to 80% as recommended by the WHO.
Independently to the treatment outcomes, we found that the lower colony count of initial culture and previously treatment for TB were associated with more rapid culture conversion. While similar result had been found that the colony count of initial culture is predictive to the culture conversion , the majority of studies reported the colony count of initial sputum smear as predictor of culture conversion instead of colony count of initial culture [4,5]. In this study, the history of TB treatment was found to be associated to more rapid culture conversion, unlike to the study conducted by Holtz et al . This association may be explained by the interaction between HIV infection and the metabolism of TB drugs . Many literature data have been shown that in patients who infected by HIV infection, the absorption rate of MDR-TB drugs is lower compared to those without HIV infection [19,20]. In fact, among the 146 patients who were previously treated for TB, 14% are HIV positive compared to the 26 new cases patients in whom 54% are HIV positive.
Only the higher BMI was associated with a rapid smear conversion, after adjusted to the MDR-TB treatment outcomes. The impact of underweight on MDR-TB treatment outcomes is well established, and possible reasons are malnutrition, lower immunity or poor absorption from gastrointestinal tract [7,8,21].
We have developed a clinical prognostic risk score for both time-to initial sputum smear and culture conversions. Risk scores had a good discriminative capacity and the identified thresholds optimized well the separation of the Kaplan Meier curves. Using the risk scores, we would be able to compare the predictive power of each biomarker (time-to initial sputum smear and culture conversions) to detect patients with higher chance to achieve treatment success during Treatment course. Because few patients converted their sputum smear or culture after three months, the time-dependent AUC were estimated only at the first three times visits after the initiation of MDR-TB treatment. Despite the absence of significance probably due to lack of power, we found that the predictive power of culture was higher than sputum smear, and the best discriminative capacity was reached at three months. Moreover, the time-dependent positive and negative predictive values for culture conversion were higher than sputum smear conversion. For example, the positive predictive value at three months of 91% indicate that patients who converted their culture at three months will have a 91% of chance to achieve successful MDR-TB treatment. These finding suggest that the culture is more sensitive to detect patients with higher probability of treatment success than sputum smear, and the optimal time point is three months. Similar results were found in Ethiopia that the validity of culture conversion is significantly higher than smear conversion in predicting MDR-TB treatment outcomes, and the optimum times for culture and smear conversion together is four months . The slight difference concerning the optimal time point may be explained by the differences in MDR-TB regimens and the statistical models used to handle data. Nevertheless, future prospective cohort studies will be need to decide on the optimal time point of sputum smear and culture measurement.
Despite the higher discriminative capacity of our prognostic risk score in predicting smear and culture conversions, we need to externally validated it on independent samples including non-Guinean patients to establish her generalizability. Retrospective design, and some missing parameters such as diabetes status, smoking and alcohol use, and biomarkers were limits of this study, they might be further used to improve prognostic risk score.