1. Comparison of Molecular and Conventional Methods for Detection of Multidrug-Resistant Tuberculosis in the United States, 2009 to 2011 Mitchell A. Yakrus, MS, MPH Microbiologist Laboratory Branch 16 th Annual Conference The Union-North American Region February 25, 2012 National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination

2. Background  CDC’s DTBE Laboratory Branch provides a service for the molecular detection of drug resistance (MDDR) to rapidly identify multidrug-resistant isolates of Mycobacterium tuberculosis complex (MTBC)  DNA sequencing of 9 genetic loci associated with resistance to first and second-line drugs  Concurrently perform growth-based conventional drug susceptibility testing (DST)  Agar proportion for 12 first and second-line antituberculosis drugs  MGIT 960 for pyrazinamide  MTBC isolates must meet specific criteria before submission for MDDR

3. Molecular Analysis Conventional DST Molecular Results (Interim Report) MDDR Isolate Received Molecular + Conventional DST Results (Final Report) MDDR Request/Approval

4. Methods  Received 285 requests for MDDR testing from 43 public health laboratories from September 2009 to February 2011  Analyzed agreement between molecular and conventional results for rifampin (RMP) and isoniazid (INH)  Examined submission criteria as indicated on request forms for possible association with resistance to RMP or INH  Isolate known to be multi-drug resistant (MDR)  Patient previously treated for tuberculosis (TB)  Patient from an area with a high rate of drug resistance (foreign born)

5. Agreement Between Molecular and Conventional Testing DrugNo. of Isolates with Both MDDR and Conventional Results No. of Discordant Results Between MDDR and Conventional Methods Percent Agreement Between Methods RMP229697.4% INH2281892.1%

6. Association of RMP or INH Resistance with Submission Criteria Submission CriterionAssociation of Detection of RMP or INH Resistance with Testing Method MDDRConventional Known MDRp < 0.001 Previous Treatmentp = 0.585p = 0.312 Foreign Bornp = 0.064p = 0.271

7. Summary  MDDR was highly concordant with drug resistance results from growth-based conventional testing  Detection of resistance to RMP or INH was not significantly associated with specific submission criteria with the exception of whether isolates were submitted as known MDR  Further analysis of the association of submission criteria with results is needed to optimize testing algorithms  Need to collect clinical outcome data for patients to measure impact of rapidly identifying drug resistance and discordant results

8. Acknowledgements  Angela M. Starks, PhD, Team Lead, Laboratory Capacity  Beverly Metchock, Dr. P.H., D(ABMM), Team Lead, Reference Team