RESUMO
Exploring the influence of pyrazinamide exposure and susceptibility on treatment response is crucial for optimizing the management of multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the association between pyrazinamide exposure, susceptibility, and response to MDR-TB treatment, as well as find clinical thresholds for pyrazinamide. A prospective multi-center cohort study of participants with MDR-TB using pyrazinamide was conducted in three TB-designated hospitals in China. Univariate and multivariate analyses were applied to investigate the associations. Classification and Regression Tree (CART) analysis was used to identify clinical thresholds, which were further evaluated by multivariate analysis and receiver operating characteristic (ROC) curves. The study included 143 patients with MDR-TB. The exposure/susceptibility ratio of pyrazinamide was associated with two-month culture conversion (adjusted risk ratio (aRR), 1.1; 95% confidence interval (CI), 1.07-1.20), six-month culture conversion (aRR, 1.1; 95% CI, 1.06-1.16), treatment success (aRR, 1.07; 95% CI, 1.03-1.10), as well as culture conversion time (adjusted hazard ratio (aHR) 1.18; 95% CI,1.14-1.23). The threshold for optimal improvement in sputum culture results at the sixth month of treatment was determined to be a pyrazinamide AUC0-24h/MIC ratio of 7.8. In conclusion, the exposure/susceptibility ratio of pyrazinamide is associated with the treatment response of MDR-TB, which may change in different Group A drug-based regimens.
RESUMO
OBJECTIVE: To analyze epidemiological features of severe acute respiratory syndrome (SARS) in Haidian district, Beijing. METHODS: Each SARS case was interviewed by trained investigator using standardized questionnaire followed a descriptive analysis. RESULTS: Four hundred and three SARS cases were identified and 27 of them died from March 18 and May 31, 2003. The incidence rate of SARS was 18.0/100,000 with case fatality rate as 6.7% in Haidian district, Beijing. Seventy-four percent of patients were adults with higher risk in age group of 20 - 29 year. SARS patients were scattered around in 32 out of 33 streets and villages in this district. The disease appeared to be sporadic but the case of outbreaks in family or university only seen in three streets. The course of SARS epidemic in this district could be divided into three phases: initial-which last for days, peak-21 days and then rapid decline-for 26 days. Number of patients having had a history of close contact to other SARS were gradually decreasing along with the process of the epidemics (trend chi(2) = 8.800, P = 0.003). Seventy-two point seven percent of the SARS cases had been exposed to the injection in the hospital settings. When the epidemics came to a rapid decline, 85.7% of the patients diagnosed during that period could be traced down to have had the history of contacting SARS cases within their own families. The distribution of occupation was also showed significantly different in the three respective stages (chi(2) = 36.41, P < 0.01). Among the patients who could not be identified as having confirmed contact history, 26.6% having had outward activities and 47.6% of them visited hospitals, especially during the peak stage. CONCLUSION: The intensity of SARS epidemic among the residents of Haidian district was recognized as similar to the other parts of Beijing. Nosocomial infection in hospital settings was most important cause responsible for the transmission of SARS in this district.
