High incidence of fluoroquinolone resistance and effect of efflux pump inhibitors on moxifloxacin resistance among Mycobacterium tuberculosis isolates causing urinary tract infection in Taiwan

Abstract

This study explored the prevalence of urinary tract tuberculosis (UTB) and whether efflux pump activation accounts for resistance to moxifloxacin in Taiwan. Of 3034 patients with culture-confirmed TB from 2005–2012, 47 patients (1.5%) with UTB were included in this study. Minimum inhibitory concentrations (MICs) of moxifloxacin were determined in the presence and absence of efflux pump inhibitors (EPIs), including verapamil, reserpine and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). EPI responders were defined as isolates with at least a four-fold reduction in MICs in the presence of EPIs. Among the 47 isolates, 24 (51.1%) were resistant to ofloxacin and 22 (46.8%) were resistant to moxifloxacin by the agar proportion method. Among the 22 moxifloxacin-resistant isolates, 19 (86.4%) had low-level resistance (MIC = 1.0–2.0 mg/L). Patients with prior exposure to fluoroquinolones were more likely than non-exposed patients to have moxifloxacin-resistant isolates [14/22 (63.6%) vs. 8/25 (32.0%); P = 0.030]. All 3 isolates with high-level moxifloxacin resistance (MIC ≥ 4.0 mg/L) had mutations in the gyrA or gyrB genes; however, among the 19 isolates with low-level resistance, only 1 (5.3%) had a mutation in the gyrA gene. Among the 19 isolates with low-level moxifloxacin resistance, 16 isolates (84.2%) were EPIs responders, but none of the high-level resistant isolates were EPIs responders. Approximately one-half (46.8%) of the isolates from patients with UTB were resistant to moxifloxacin, and activation of efflux pumps accounted for most low-level moxifloxacin-resistant isolates.