TB: Rapid Test for Multidrug Resistance Shows Promise

Bridget M. Kuehn

September 15, 2017

A rapid test that can detect tuberculosis (TB) resistance to multiple drugs showed promise in a study published September 14 in the New England Journal of Medicine.

The test accurately detects resistance to isoniazid, fluoroquinolones, and aminoglycosides, according to lead author, Yingda Linda Xie, MD, a clinical fellow in the Tuberculosis Research Section at the National Institute of Allergy and Infectious Disease, and colleagues. This could aid in the implementation of a new shorter treatment regimen — including fluoroquinolones and aminoglycosides — for multidrug-resistant TB (MDR-TB), which is resistant to rifampicin and isoniazid.

It may also aid in identification and proper treatment of extensively drug resistant TB (XDR-TB). The Centers for Disease Control and Prevention defines XDR-TB as resistant to rifampicin and isoniazid in addition to any fluoroquinolone and at least one of the injectable medications commonly used as second-line TB therapies.  

The results have generated a lot of excitement in the field.

"It's a great step forward," said Gerald Friedland, MD, a member of the Infectious Diseases Society of America and a professor emeritus of medicine, epidemiology and public health at Yale School of Medicine, New Haven, Connecticut, who was not involved in the development of the test. "It's well appreciated that excellent TB diagnostics have been neglected and it has impeded tuberculosis control and treatment success globally."  

Drug-resistant strains of tuberculosis have been a growing threat globally, with more than half a million cases annually testing positive for drug resistance, according to the World Health Organization (WHO). Failure to test for drug resistance before initiating treatment and ineffective treatment have contributed to the spread of resistant strains.

Additionally, treatment regimens for patients who are identified as having resistant strains of tuberculosis can last a gruelling 20 months or more and are costly. As result, many patients never complete their treatments. In 2016, the WHO recommended a 9- to 12-month regimen for eligible patients with MDR-TB who have undergone testing with a DNA-based test for resistant strains.

Now, Dr Xie and colleagues show that the experimental rapid test can reliably detect mutations in Mycobacterium tuberculosis linked to resistance to isoniazid, fluoroquinolones, and aminoglycosides.

The multicenter study included 308 patients from South Korea and China who were positive for tuberculosis based on a culture test. Sputum samples from participants were tested with the experimental assay and a rapid test for rifampicin resistance. The results were then compared to standard methods for drug resistance testing. When DNA sequencing was used as the standard for comparison, the experimental test was 99.6% specific for resistance to all the target drugs and 98.1% sensitive for resistance to isoniazid, 95.8% sensitive for fluoroquinolones, 92.7% sensitive for kanamycin, and 96.8% sensitive for amikacin.

The experimental rapid test can deliver results in 2 hours without much technical expertise or laboratory equipment, which might allow same-day decisions about which therapies to use, the authors write. Additionally, existing equipment used for rifampin-resistance testing might be adapted to run this test.

"Our ability to rapidly diagnose the presence of TB and at the same time the presence of resistance, either MDR or XDR, will be greatly enhanced by approval and distribution of this diagnostic test," Eric Goosby, MD, a professor at the University of California San Francisco School of Medicine and UN Secretary General's special advisor on TB, told Medscape Medical News. Dr Goosby was an unpaid advisor to the investigators who developed a similar rifampicin-only test in 2007-2008.

Dr Goosby and Dr Friedland agreed that the new test offers advantages over the existing option. Patients may be able to get a same-day diagnosis and receive appropriate treatment, reducing the likelihood of exposing others, Dr Goosby said. The test also requires less technical skill to perform and is safer for laboratory technicians, who will not have to handle the bacteria, Dr Friedland said. As a result, it may be more accessible to smaller hospitals and clinics, Dr Goosby suggested.

"The ultimate test is how this works in the real world, not the laboratory setting," Dr Friedland cautioned. "How widely available and distributed will it be?" He explained that global resources for tuberculosis control have remained flat and that more resources are needed to control the spread of tuberculosis.

But both Dr Friedland and Dr Goosby were optimistic that the new test would help.

Study authors report grants from the test-maker Cepheid, as well as holding patents for molecular technologies to detect tuberculosis. Dr. Friedland reported no relevant conflicts. Dr. Goosby was an unpaid adviser to the investigators who developed the rifampicin resistance rapid test in 2007- 2008.

N Engl J Med. 2017;377:1043-1054. Abstract

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