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Drug-susceptibility testing useful in guiding treatment for MDR and XDR TB
The use of drug susceptibility testing for ethambutol, pyrazinamide and second-line tuberculosis drugs appears to yield valuable information in directing treatment selection for multidrug-resistant and extensively drug-resistant tuberculosis, according to recent findings.
In the individual-patient meta-analysis, researchers identified observational studies of patient groups that included at least 25 patients with MDR or XDR TB. The analysis included 8,955 patients.
Participating centers supplied clinical and demographic patient characteristics, information on initial in vitro drug susceptibility testing results to first- and second-line agents, detailed treatment regimen information, and treatment outcomes. Drug susceptibility testing data were available for the following drugs: pyrazinamide; ethambutol; injectables, including streptomycin, kanamycin, amikacin and capreomycin (Capastat, Lilly); fluoroquinolones, including ofloxacin, levofloxacin and other later-generation fluoroquinolones; and drugs from group 4, including ethionamide (Trecator, Wyeth Pharmaceuticals), prothionamide, cycloserine (Seromycin, Purdue GMP) and para-aminosalicylic acid. Treatment success was defined as the attainment of a cure or completion of therapy, whereas treatment failure encompassed failure, relapse or death.
The researchers found that the odds of treatment success with an individual drug was consistently and significantly linked to in vitro susceptibility to the drug. These findings persisted in various adjusted and sensitivity analyses. Ethambutol, pyrazinamide and group 4 drugs had adjusted treatment success odds ranging from 1.7 to 2.3, and second-line injectables and fluoroquinolones had adjusted odds ranging from 2.4 to 4.6.
According to the researchers, these findings are important, but further investigation using more uniform laboratory methods is needed.
“[Drug susceptibility testing] for [ethambutol], [pyrazinamide] and many second-line tuberculosis drugs using currently available methods appears to provide useful information that should be used by clinicians in selecting drugs for MDR tuberculosis treatment,” the researchers wrote. “However, additional studies are needed to improve, standardize and validate the laboratory methods and clinical concentrations for these tests.”
Disclosure: The researchers report no relevant financial disclosures.