The treatment of multidrug-resistant tuberculosis significantly increases the risk of acquired resistance to second-line drugs and upgrading the condition to extensively drug-resistant tuberculosis, according to data from a new study.
“If the results of [this study] can be generalized, then policies promoting the use of new drugs in otherwise marginally effective treatment regimens, without at least two or three other highly effective drugs, will lead rapidly to widespread acquired resistance to the new drug,” researchers with the global Preserving Effective TB Treatment Study (PETTS) wrote in Clinical Infectious Diseases.
For the prospective cohort study conducted in nine countries, the researchers enrolled 1,659 patients with confirmed MDR-TB who started treatment with second-line drugs from 2005 to 2008. Among those, 71.4% had at least one subsequent positive culture after the baseline culture and the analysis cohort included 832 individuals who had their first and last cultures tested successfully.
Sixty-six patients (7.9%) had XDR-TB at baseline and another 68 (8.9%) acquired XDR-TB during treatment. At baseline, 128 patients had fluoroquinolone resistance at baseline and another 79 (11.2%) acquired fluoroquinolone resistance during treatment. In addition, 115 patients (13.8%) had resistance to second-line injectable drugs at baseline, and another 56 (7.8%) acquired resistance.
The study included five sites that were approved by the Green Light Committee (GLC) to be part of a project to procure affordable second-line TB drugs. The researchers found that compared with non-GLC sites, the RR of acquired XDR-TB was 73% lower (RR=0.27; 95% CI, 0.16-0.47) in GLC-approved sites. Acquired fluoroquinolone resistance also was lower in the five GLC-approved countries (RR=0.28; 95% CI, 0.17-0.45), and the risk of acquired resistance to the second-line injectable drugs kanamycin (RR=0.6; 95% CI, 0.34-1.05), amikacin (RR=0.15; 95% CI, 0.06-0.39) and capreomycin (RR=0.24; 95% CI, 0.16-0.47) also was lower.
“The magnitude of acquired resistance may be even greater in programs without the socioeconomic resources of the countries participating in this study,” the researchers wrote. “Therefore, the evidence suggests that, in settings where drug-resistant TB has already become endemic, and rapid molecular tests are used selectively due to cost constraints, then new patients should be prioritized for rapid screening with these tests.”
In an accompanying editorial, C. Robert Horsburgh Jr., MD, MUS, of the Boston University School of Public Health, and Charles L. Daley, MD, of National Jewish Health in Denver, said these data indicate that acquired resistance to new drugs is inevitable if the same practices that lead to XDR-TB continue.
“It is time to invest in strengthening basic TB control programs to prevent the development of MDR-TB in the first place, enhance MDR-TB management to prevent further acquisition of drug resistance using lessons learned in the current study and roll out new drugs and regimens with caution, but roll them out expeditiously, as people are dying,” they wrote. “Failure to take these steps means that drug-resistant TB will get even worse.”
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