Report of Expert Consultations on Rapid Molecular Testing to Detect Drug-Resistant Tuberculosis in the United States
The emergence and spread of drug-resistant strains of Mycobacterium tuberculosis are greatly complicating tuberculosis (TB) control efforts in many countries. An estimated 511,000 cases of multidrug-resistant TB (MDR TB; caused by strains resistant to at least isoniazid and rifampin) occurred globally in 2007 (1). In the United States, a total of 125 cases of MDR TB were reported in 2007 (1.2% of culture-positive cases with susceptibility testing performed) as well as 2 cases of extensively drug resistant TB (XDR TB) (5). MDR TB is significantly more difficult and expensive to treat than drug-susceptible 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).
The management of drug-resistant TB cases starts with a reliable diagnosis, which is obtained by isolating M. tuberculosis bacteriafrom clinical specimens and conducting drug-susceptibility tests. The susceptibility of bacteria to a particular drug is usually determined by attempting to grow the bacteria in or on media containing that drug. The agar and liquid culture proportion methods are used by most laboratories in the United States that perform susceptibility testing of M. tuberculosis bacteria (6,7). Because of the slow growth of M. tuberculosis bacteria and the requirement for isolation before drug-susceptibility testing, the agar proportion method typically requires six to eight weeks to provide results while the liquid culture methods can provide results in four to five weeks. Molecular methods can reduce the time required for detection of drug resistance to one to two days. Because of the earlier detection of resistance and earlier initiation of effective therapy, the use of rapid molecular methods for detecting rifampin resistance may reduce periods of infectiousness of MDR TB cases by as much as six weeks, reduce the further spread of MDR TB, and improve treatment outcomes (2,3).
In recognition of the importance of rapid drug-susceptibility testing, a proposed revision of the Diagnostic Standards and Classification of Tuberculosis in Adults and Children (7) is likely to support the use of rapid molecular drug-resistance tests for AFB smear-positive sputum sediments from TB patients who are suspected to have drug-resistant disease or who are from a region or population with a high prevalence of drug resistance. In addition, 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 and the proposed revision of the diagnostic standards (7), 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-resistance testing. The expert panel included clinicians; control officials; laboratorians; and representatives from the ACET, TB Regional Training and Medical Consultation Centers (RTMCC), National TB Controllers Association (NTCA), Association of Public Health Laboratories (APHL), and CDC.