| Background:In the twenty-first century, tuberculosis (TB) remains one of the most challenging infectious diseases for global public health. According to world health organization (WHO), a total of 9.6 million new TB cases were notified globally in 2014, and 1.5 million people died from the disease, making TB the second deadliest infectious disease after the human immunodeficiency virus (HIV). The high mortality rates of TB was closely related with the emergence and wide spread of muti-drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). A lot of studies have demonstrated that survivals of drug resistant tuberculosis (DR-TB) cases are significantly lower than drug susceptible TB cases. DR-TB puts TB patients in a predicament with limited therapeutic options that are more toxic and less effective, and consequently have poorer treatment outcomes and higher mortality. Moreover, DR-TB costs more than 100 times greater compared to drug susceptible TB cases. China is one of the 22 high TB and MDR-TB burden countries in the world,1 million new TB cases,120000 MDR-TB cases and 10000 XDR-TB cases are identified every single year. The present study aimed to get the current status of drug resistance among first line anti-TB agents and their longitudinal changes, to find independent risk factors for MDR-TB and to analyze their survivals. We hope to evaluate the efficiency of the current TB control strategies and to provide evidence for early diagnosis and rational usage of anti-TB drugs for clinicians.Methods:We retrospectively analyzed the clinical and drug susceptibility test (DST) data of culture confirmed TB cases treated in Shandong Provincial Chest Hospital from January 2007 to December 2014. Statistical analysis was accomplished with the usage of SPSS software, version 16.0. Categorical variables were compared using Chi-square Test or Fisher’s exact test; continuous variables were analyzed using the Mann-Whitney U test. Chi-Square test for trends and linear regression were used to assess the changes of different drug resistance patterns over time. Unadjusted survival rates were estimated by the Kaplan-Meier method, survivals were compared using log-rank test.Results:1. A total of 5653 culture confirmed TB cases were collected among which 4622 (81.6%) were drug susceptible TB cases,1335 (23.6%) TB cases were resistant to at least one first line anti-TB drugs. There were 516 TB cases resistant to at least isoniazid (INH) and rifampicin (RFP), meeting the definition of MDR-TB, and these TB patients account for 9.1% of our sample population. The proportion of MDR-TB cases among new TB cases and retreated TB cases were 5.6% and 35.4%, respectively, the difference was statistically significant (P<0.01). And the drug resistance rates for INH, RFP, EMB and SM were 15.0%,12.4%,3.2% and 16.9%, respectively。2. There were no statistically significant changes for drug resistance rates of INH, RFP, EMB and SM, as well as for MDR-TB cases. However, the MDR-TB rates among new TB cases were increased over the 8-years study period (Chi-Square test for trends:χ2=9.209, P=0.002). And the proportion of primary MDR among all MDR-TB cases has also been increased from 30.6% in 2007 to 63.6% in 2014, increasing at a yearly rate of 4.7%(Chi-Square test for trends:χ2=26.286, P<0.01).3. TB retreatment (OR 11.27,95% CI 9.04-14.05), cavity diseases (OR 1.64,95% CI 1.33-2.02), disseminated diseases (ie. pulmonary and extrapulmonary disease) (OR 1.91,95% CI 1.40-2.61) and partial directly observed therapy (DOT) (OR 7.71,95% CI 5.74-10.35) were independent risk factors for MDR-TB. Farmers and patients with underlying chronic obstructive pulmonary disease (COPD) were also closely related to the emergence of MDR-TB.4. The mortality rate of MDR-TB cases was significantly higher than drug susceptible TB cases (7.2% vs.2.8%, P<0.001), and survival was worse in MDR-TB cases compared to drug susceptible TB cases (log-rank test:P<0.001).Conclusions:The prevalence of MDR-TB was persistently high, especially among farmers and among those between ages 18-44. The proportion of primary MDR-TB increased over the 8-year study period and MDR-TB rate was significantly higher among retreated TB cases. And survivals of MDR-TB cases were worse than drug-susceptible TB cases. TB retreatment, cavity diseases, disseminated diseases and partial DOT were independent risk factors for MDR-TB. Farmers and patients with underlying chronic obstructive pulmonary disease (COPD) were also closely related to the emergence of MDR-TB. |
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