Transcript Document

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
16th 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
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
MDDR
Request/Approval
MDDR Isolate Received
Conventional
DST
Molecular
Analysis
Molecular Results
(Interim Report)
Molecular + Conventional DST
Results (Final Report)
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)
Agreement Between Molecular and Conventional
Testing
Drug
No. of Isolates with Both
MDDR and Conventional
Results
No. of Discordant
Results Between
MDDR and
Conventional Methods
Percent
Agreement
Between
Methods
RMP
229
6
97.4%
INH
228
18
92.1%
Association of RMP or INH Resistance
with Submission Criteria
Submission Criterion
Association of Detection of RMP or INH
Resistance with Testing Method
MDDR
Conventional
Known MDR
p < 0.001
p < 0.001
Previous Treatment
p = 0.585
p = 0.312
Foreign Born
p = 0.064
p = 0.271
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
Acknowledgements

Angela M. Starks , PhD, Team Lead, Laboratory
Capacity

Beverly Metchock, Dr. P.H. , D(ABMM), Team Lead,
Reference Team