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Rates of MDR and XDR TB on the rise
Researchers from the CDC have found higher overall levels of extensively drug-resistant tuberculosis than expected in eight countries, as well as a high prevalence of resistance to at least one second-line drug among those with multidrug-resistant tuberculosis.
“Drug-resistant TB is more difficult and costly to treat and more often fatal,” Tracy Dalton, PhD, of the CDC, said in a press release. “Internationally, it is particularly worrisome in areas with fewer resources and less access to effective therapies. As more individuals are diagnosed with and treated for drug-resistant TB, more resistance to second-line drugs is expected to emerge. So far, extensively drug-resistant TB has been reported in 77 countries worldwide, but exact prevalence remains unclear.”
The researchers conducted a prospective cohort study from 2005 to 2008. Patients with confirmed pulmonary MDR TB who were starting second-line treatment were enrolled. The patients were from one of eight countries: Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea and Thailand.
Among the 1,278 patients enrolled, 43.7% had resistance to at least one second-line drug, ranging from 33.3% in Thailand to 62% in Latvia. Fluoroquinolone resistance was seen in 12.9% of the patients and 20% of patients were resistant to at least one second-line injectable drug. The prevalence of resistance to oral second-line drugs was 27.1%. XDR TB was seen in 6.7% of patients.
The strongest risk factor for resistance was previous treatment for MDR TB with any second-line drug. Patients in the hospital at time of enrollment were at risk for resistance to fluoroquinolones and second-line injectable drugs, as well as for XDR TB. Fluoroquinolone resistance and XDR TB were more common in women. Patients with HIV infection had less fluoroquinolone resistance. Unemployment, a history of imprisonment, alcohol abuse and tobacco use were also risk factors for resistance to second-line injectable drugs.
“Social factors should be taken into account in the management of TB,” Dalton said in the press release. “Our country-specific results can be extrapolated to guide in-country policy for laboratory capacity and for designing effective treatment recommendations for MDR TB.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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This study provides significant insight into the factors associated with resistance to second-line TB drugs, as it included data from diverse sites and employed a standardized protocol for drug susceptibility testing that was performed in a single laboratory. On one hand, the finding that the strongest risk factor for resistance to second-line drugs was treatment with second-line drugs is not surprising, as this is consistent with multiple prior studies of drug-resistant TB. On the other hand, it is intriguing that only 15% of the patients whose isolates were resistant to a second-line drug had a history of exposure to a second-line drug. This suggests that one or more major causes of resistance to second-line anti-TB drugs remain to be identified. These could include infection with a strain resistant to a second-line drug, unrecorded treatment with a second-line drug (perhaps for an indication other than TB), or others. The study emphasizes the need to strengthen TB treatment programs in order to decrease the frequency of selecting for drug resistance during treatment. This is even more imperative as new drugs become available for treatment of drug-resistant and drug-susceptible TB in order to minimize the frequency of selecting strains resistant to the new drugs.