Report of Expert Consultations on Rapid Molecular Testing to Detect Drug-Resistant Tuberculosis in the United States

Executive summary

Rapid drug-susceptibility tests are a pressing public health and diagnostic need because of the rise in multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR TB) globally (1). Published studies (2,3) suggest that, compared to conventional culture-based methods, the rapid detection of rifampin-resistance using molecular methods can enable earlier initiation of effective therapy and thereby reduce periods of infectiousness of MDR TB cases by as much as six weeks and improve patient outcomes; both of which may have a large impact on efforts to control MDR TB. It is estimated that preventing a single case of MDR TB would save the U.S. health care system more than $250,000 (4). In recognition of the importance of rapid drug-susceptibility testing, the Advisory Council for the Elimination of Tuberculosis (ACET) passed a resolution in June 2008 that stated —

Be it resolved that ACET recommends that the Director of CDC fund and expedite implementation of currently available rapid drug-resistance assays in selected qualified reference labs to quickly identify drug-resistant TB, reduce transmission, and prevent further acquired drug resistance; such that by the end of 2008, labs are able to provide this assay for optimal patient care.

In response to the ACET resolution, CDC convened an expert panel to examine the current status of rapid drug resistance testing in the United States, published evidence, and current guidelines and to provide guidance and make recommendations to CDC for developing a system to provide access to rapid drug-susceptibility testing to all TB Control programs in the United States. The panel included clinicians; control officials; laboratorians; and representatives from the TB Regional Training and Medical Consultation Centers, ACET, National TB Controllers Association, Association of Public Health Laboratories, and CDC. This report to the Director of the Division of TB Elimination describes general principles and considerations for molecular drug-resistance testing service from clinical, laboratory, and public health perspectives; possible scenarios for providing a molecular drug-resistance testing service; and recommendations for CDC.

To ensure access to state-of-the-art testing, the panel recommends that CDC establish regional laboratories to provide molecular drug-resistance testing services to state and local TB programs. The panel recommends that molecular drug-resistance testing be available for one AFB smear-positive or NAA-positive respiratory specimen or one M. tuberculosis culture from each TB patient or TB suspect (estimate testing 15,000 to 20,000 samples per year). A phased approach to developing and implementing a molecular drug-resistance testing service would be prudent. As an initial step, the expert panel strongly recommends that CDC immediately establish a service to provide molecular drug resistance testing for TB suspects and patients at high-risk of having MDR TB and those deemed high priority by the state or local TB program(estimate testing 2,500 samples per year). CDC is encouraged to explore using supplements to existing cooperative agreements to provide sufficient new funds to existing, proficient molecular drug-resistance testing laboratories to allow them to expand their capacities to meet this need. CDC, state TB programs, and partners should aggressively work towards establishing the protocols and procedures for (a) identifying patients for whom the testing would be of benefit, (b) submitting specimens to the molecular drug-resistance testing laboratories, (c) reporting results, and (d) additional testing to determine the susceptibility of rifampin-resistant samples to first-line and second-line anti-tuberculosis drugs.

For any approach, it will be essential to route requests for, and reports of, the molecular drug-resistance testing through the local or state TB control program because this would (a) provide early engagement of the TB Control Program in potential TB cases, (b) improve communications between TB clinicians, controllers, and laboratorians, (c) reinforce the important role played by state and local TB Programs and laboratories, (d) engage a person knowledgeable about molecular drug-resistance testing for TB early in the decision process, and (e) avoid excessive and inappropriate ordering of the molecular drug-resistance tests. The molecular drug-resistance testing services should be aligned or coordinated with the services of the TB Regional Training and Medical Consultation Centers to facilitate access to advice on the appropriate use and interpretation of molecular drug-resistance tests and on treatment of patients with drug-resistant TB. Another essential feature is that the detection of drug resistance must immediately trigger expedited (reflex) testing for susceptibility to first and second line anti-TB drugs by conventional culture-based methods and molecular genetic methods.

New funds will be needed for the molecular drug-resistance testing program. Funds in the current TB Elimination Cooperative Agreements should not be redirected to the molecular drug-resistance testing program.