Incidence of Moxifloxacin Resistance in Clinical Mycobacterium tuberculosis Isolates in Houston, Texas

Abstract

Comprehensive data on the prevalence of quinolone resistance in Mycobacterium tuberculosis clinical isolates in the United States are scarce. By use of a systematic population-based approach, M. tuberculosis strains from tuberculosis (TB) cases were collected in Harris County, TX, in 2007 to 2008. The susceptibilities of M. tuberculosis isolates to moxifloxacin and ofloxacin were determined by the agar proportion indirect susceptibility method. Spoligotyping and 12-locus mycobacterial interspersed repetitive unit (MIRU12)-based genotyping of M. tuberculosis isolates were performed, and the gyrA, gyrB, Rv2686c, Rv2687c, and Rv2688c genes in quinolone-resistant and year-of-diagnosis-matched M. tuberculosis isolates were sequenced. Susceptibility testing was performed on 557 M. tuberculosis isolates, of which 10 (1.8%) were resistant to moxifloxacin. There was 100% concordance between ofloxacin and moxifloxacin susceptibilities. A quinolone was prescribed to at least 5 (50%) patients in the period preceding TB diagnosis. Multidrug-resistant TB (MDR-TB) was significantly associated with quinolone resistance (P ‫؍‬ 0.01). Mutations in the quinolone resistance-determining region of gyrA were found for 50% of the resistant isolates. No other presumptive quinolone resistance-associated mutations were identified. We conclude that the incidence of moxifloxacin-resistant TB is low in Harris County and is associated with MDR-TB. Previous exposure to quinolones is common among patients with moxifloxacin resistance and warrants more careful evaluation.The antituberculosis drug pipeline is extremely slow: it has been more than 40 years since rifampin was introduced for wide clinical use. While fluoroquinolones were initially indicated and widely used for nonmycobacterial infections, their antituberculosis properties were recognized early and described in the literature (16). Their tolerability and relative low to moderate cost have made them an attractive target for development as antituberculosis drugs. The newer quinolones, such as sparfloxacin, gatifloxacin, and moxifloxacin, have better in vitro activity against Mycobacterium tuberculosis clinical isolates than older quinolones, such as ofloxacin, levofloxacin and ciprofloxacin, as suggested by lower MICs, a higher ratio of the peak serum drug concentration to the MIC, and a higher ratio of the 24-h area under the curve to the MIC (11,22,(27)(28)(29)36). In vivo studies in animal models and humans have corroborated these findings (19,34). Due in part to the side effects observed with sparfloxacin (phototoxicity) and gatifloxacin (dysglycemia), moxifloxacin has been the quinolone most favored in clinical antimycobacterial testing (4). Plans for further development of moxifloxacin as an antituberculosis agent to shorten the course of tuberculosis (TB) chemotherapy are under way, and clinicians are using the medication when there is intolerance or resistance to first-line antituberculosis agents.However, another dynamic can potentially affect the use of moxifloxacin in TB tre...

Molecular Diagnosis of Fluoroquinolone Resistance in Mycobacterium tuberculosis

“…The variability might also be due to selection bias, since the vast majority of studies were made retrospectively. Regarding the substitutions in GyrA, those at position D94 were the most frequent, followed by A90V and S91P (Table 4), as previously reported (11,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

“…The second major result of our study is that FQ r isolates harbored more substitutions in GyrA or GyrB than is generally reported in the literature (93% versus an average of 81% in the 13 studies providing both gyrA and gyrB sequence data; P ϭ 0.02) ( Tables 2 and 4) (11,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Among these substitutions found in the FQ r isolates, we observed a higher proportion in GyrB than was previously published (11.5% versus an average of 3%) (11).…”

“…The previously published studies in this field of investigation have some limitations: (i) most studies evaluated the performance of molecular diagnosis for FQ r isolates only (11,(16)(17)(18), (ii) most studies were performed on retrospectively chosen isolates with a high prevalence of FQ resistance (most were Ͼ50%) (11), and (iii) only half of the studies included sequencing of gyrA/gyrB (11,(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). To our knowledge, the present study is the largest study published that was performed prospectively, apart from that by Hu et al (28), which was performed prospectively and included fewer isolates selected from a population in which the prevalence of FQ resistance was similar to that studied here (14 versus 12%).…”

Fluoroquinolone resistance in non-multidrug-resistant tuberculosis—a surveillance study in New South Wales, Australia, and a review of global resistance rates

“…There were 11 studies from 10 countries identified by our search strategy that were included in this review, including this current surveillance study (Table 1). 11,13,[27][28][29][30][31][32][33][34] The studies were carried out between 1995 and 2013. Study populations were diverse, including TB patients from field clinics, hospitals, and our study which included all TB patients from a country state.…”

An Impact of Biofield Treatment: Antimycobacterial Susceptibility Potential Using BACTEC 460/MGIT-TB System

“…Due to its wide distribution pattern, can easily invade to an intracellular compartment of Mycobacterium and produce strong effects like macrophages without cross-resistance to antitubercular drugs [26][27][28]. Among them, moxifloxacin resistance to MDR-TB is very low [29] and highly effective to isoniazide and rifampicin resistance cases. The main targets of its bactericidal actions to DNA gyrase and topoisomerase IV [30].…”