Discordance of Drug Susceptibility Test Data between the CDC Mycobacteriology Laboratory and Local Public Health Laboratories Participating in Tuberculosis Clinical Trials, TBTC, CDC

BACKGROUND: Multi drug resistant Tuberculosis (MDR-TB) is a serious public health concern in many parts of the world. As per the WHO- 2010 global report on Surveillance and response 3.6% of all incident TB cases globally are multidrug resistant. In this regard, there is an increasing demand for timely, reliable and comprehensive drug susceptibility testing (DST) as MDR-TB surveillance is being geared up. The intent of this analysis is to determine whether there is a need to continue routine confirmatory DST testing at CDC in addition to just sending the isolates for genotyping. Analysis is done by measuring the discordance between the results of laboratory DST at CDC and the local labs drug type, drug testing concentrations, and study sites. METHODS: The data for this analysis was provided by the Tuberculosis Trials Consortium (TBTC), CDC. Data for this analysis was collected over nearly two decades (1993-2011), gathered from 7 clinical trials. Discordance between the local and CDC lab DST results was measured using Kappa statistic. Sensitivity and specificity analysis was done by taking the CDC DST lab results as the gold standard. Discordance levels were calculated by local sites and baseline drug resistance for each antibiotic in each study was measured. RESULTS: Average Kappa values for inter rater agreement for all the studies was 0.6444 whereas the overall level of discordance across all studies is 7.786%. Drug resistance at baseline was highest for Isoniazid and Streptomycin (except Study 23 and 22). CONCLUSION: Though the current results show few DST result discordances between local and CDC labs, it is better to continue to send isolates to the centralized lab (CDC) in view of the worldwide threat of drug resistant TB epidemic, the recommendations of the current literature and the benefits of reliable confirmatory testing services and availability of other molecular diagnostic methods