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Acquired resistance to second-line drugs increased mortality in TB
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Patients with tuberculosis who acquire resistance to second-line drugs were more likely to die than those without resistance, according to CDC researchers.
“The probability of death during TB treatment was significantly greater among TB cases with acquired resistance to second-line drugs than among cases with baseline resistance to the same drugs and cases without resistance to those drugs, indicating the need for more vigilant clinical monitoring and timely repeat drug susceptibility tests during the course of treatment,” the researchers wrote in Clinical Infectious Diseases.
The researchers used data from the National TB Surveillance System (NTSS) to identify a subset of cases of culture-confirmed TB in which the patient had both initial and final drug susceptibility tests for second-line injectable drugs (n=2,329) and fluoroquinolones (n=1,187). They compared the death rates between patients with acquired resistance and those without.
Forty-nine patients (2.1%) developed resistance to at least one second-line injectable drug: 35 acquired resistance to capreomycin (Capastat, Akorn), 16 to kanamycin and seven to amikacin. Fifty-five patients (2.4%) had initial resistance to the second-line injectable drugs. Among those who acquired resistance, 13 patients (26.5%) died during treatment compared with 10 patients (18.2%) with initial resistance to the drugs and 222 patients (10%) who did not acquire resistance. After controlling for age, mortality rate was significantly higher among those with acquired resistance (adjusted HR=2.8; 95% CI, 1.4-5.4).
Thirty-two patients (2.7%) developed resistance to at least one fluoroquinolone: 20 acquired resistance to ciprofloxacin and 14 to ofloxacin. Forty-six patients (3.9%) had initial resistance to fluoroquinolones. Twelve patients (37.5%) who acquired resistance died during treatment vs. one patient (2.2%) who had initial resistance and 121 patients (10.9%) of patients who did not acquire resistance. After controlling for age, those with acquired resistance had a twofold greater mortality risk than those without (adjusted HR=1.9; 95% CI, 1-3.6).
In both groups, high mortality was also associated with illicit drug use, positive HIV status, multidrug-resistant TB at treatment initiation, extrapulmonary disease and directly observed therapy.
“Providers should consider the possibility of emergence of acquired resistance to second-line drugs and monitor drug susceptibility tests results in cases with increased risk of acquired resistance to second-line drugs, including individuals with MDR-TB, positive HIV status or extrapulmonary disease,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.
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