Acquired Drug Resistance in Mycobacterium tuberculosis and Poor Outcomes among Patients with Multidrug-Resistant Tuberculosis

Abstract

Rates and risk factors for acquired drug resistance and association with outcomes among patients with multidrug-resistant tuberculosis (MDR TB) are not well defined. In an MDR TB cohort from the country of Georgia, drug susceptibility testing for second-line drugs (SLDs) was performed at baseline and every third month. Acquired resistance was defined as any SLD whose status changed from susceptible at baseline to resistant at follow-up. Among 141 patients, acquired resistance in Mycobacterium tuberculosis was observed in 19 (14%); prevalence was 9.1% for ofloxacin and 9.8% for capreomycin or kanamycin. Baseline cavitary disease and resistance to >6 drugs were associated with acquired resistance. Patients with M. tuberculosis that had acquired resistance were at significantly increased risk for poor treatment outcome compared with patients without these isolates (89% vs. 36%; p<0.01). Acquired resistance occurs commonly among patients with MDR TB and impedes successful treatment outcomes.

Keywords: MDR TB; Mycobacterium tuberculosis; XDR TB; acquired drug resistance; antimicrobial resistance; bacteria; extensively drug-resistant tuberculosis; multidrug resistance; multidrug-resistant tuberculosis; treatment outcomes; tuberculosis and other mycobacteria.

Figure 1

Cohort diagram of patients with multidrug-resistant tuberculosis (MDR TB) depicting rates of acquired drug resistance, Georgia, March 2009–October 2012. XDR TB, extensively drug-resistant tuberculosis; OFL, ofloxacin; S, susceptible; CAP, capreomycin; KAN, kanamycin; R, resistant.

Figure 2

Final treatment outcomes for patients with multidrug-resistant tuberculosis (MDR TB), by acquired drug resistance status, Georgia, March 2009–October 2012. LFU, loss to follow up. *15 of 44 patients were culture positive at time of LFU, including all 6 patients with acquired resistance.