Dataset Information

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.

SUBMITTER: El Sahly HM

PROVIDER: S-EPMC3147712 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis isolates in Houston, Texas.

El Sahly Hana M HM Teeter Larry D LD Jost Kenneth C KC Dunbar Denise D Lew Justin J Graviss Edward A EA

Journal of clinical microbiology 20110608 8

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 interspers ...[more]

PMID: 21653760

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Project description:We designed this study to determine the trend of moxifloxacin resistance among multidrug-resistant tuberculosis (MDR-TB) patients from 2007 to 2013 in China to inform the composition of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment regimens. We assessed moxifloxacin resistance among MDR-TB isolates collected in national drug resistance surveys in 2007 and 2013 that included 3,634 smear-positive and 7,206 culture-positive pulmonary tuberculosis patients, respectively. Moxifloxacin susceptibility was examined by a Mycobacterium growth indicator tube (MGIT) 960 for the 2007 isolates, and by the minimum inhibitory concentration (MIC) method for the 2013 isolates, at both breakpoints 0.5 and 2.0 μg/mL. Risk factors were explored through multivariable log-binominal regression analysis. Mutations in gyrA and gyrB for part of the isolates were also studied through sequencing. Of 401 MDR strains isolated in 2007, moxifiloxacin resistance could be determined for 319 (79.6%): 41 (12.9%) and 10 (3.1%) were resistant at 0.5 and 2.0 μg/mL, respectively. Of 365 MDR strains isolated in 2013, 338 (92.6%) could be analyzed: 140 (41.4%) and 79 (23.4%) were resistant at 0.5 and 2.0 μg/mL. For patients in 2007, no characteristics were significantly associated with moxifloxacin resistance. For patients in 2013, patients aged ≥60 years (adjusted prevalence ratio [aPR], 1.46; 95% confidence interval [CI], 1.10 to 1.93) were more likely to have resistance at 0.5 μg/mL, whereas those residing in eastern China compared to those in central China had an increased risk of resistance at both 0.5 (aPR, 1.85; 95% CI, 1.38 to 2.48) and 2.0 μg/mL (aPR, 2.14; 95% CI, 1.35 to 3.40). Sequencing results were obtained for 245 and 266 MDR-TB isolates in 2007 and 2013, respectively. In total, 34 of 38 (89.5%) and 89 of 104 (85.6%) of 2007 and 2013 moxifloxacin-resistant (0.5 μg/mL) MDR-TB strains had mutations in the gyrA and gyrB gene, respectively. Asp94Gly was the most common mutation among 2007 (11 of 38, 28.9%) and 2013 isolates (24 of 104, 23.1%) and conferred high-level moxifloxacin resistance. Moxifloxacin resistance among MDR-TB patients in China increased from modest to high from 2007 to 2013. Moxifloxacin should be used carefully as a potentially effective drug for composing MDR/RR-TB regimens especially for elderly patients in China. Individual susceptibility testing especially rapid molecular-based assays should be conducted to confirm the susceptibility to moxifloxacin. IMPORTANCE China is one of the high-burden countries for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). Moxifloxacin is one of the critical antituberculosis drugs for MDR/RR-TB treatment. Susceptibility to moxifloxacin is therefore very important to compose effective regimens and to provide protection against development of resistance of companion drugs such as bedaquiline and linezolid. There are, however, no nationally representative data on moxifloxacin resistance among MDR/RR-TB cases in China. Therefore, we assessed the resistance prevalence for moxifloxacin among MDR-TB strains isolated in national drug resistance surveys in 2007 and 2013 that covered 72 sites around the country. We demonstrate that the prevalence of moxifloxacin resistance in MDR-TB isolates increased from modest to high, which should prompt the national tuberculosis program to use moxifloxacin cautiously in second-line regimens to treat MDR/RR-TB unless susceptibility can be laboratory-confirmed.

Project description:BackgroundLevofloxacin (LVX) and Moxifloxacin (MXF) are the cornerstones for treatment of multidrug-resistant tuberculosis (MDR-TB). China is one of the highest MDR- and fluoroquinolones (FQ)-resistant TB burdens countries. DNA gyrase encoded by gyr genes is the main target of FQ in Mycobacterium tuberculosis (MTB). The prevalence and molecular characterization of LVX- and MXF-resistant MTB strains from southern China were examined in this study.MethodsDrug susceptibility testing (DST) of 400 MTB clinical isolates was evaluated by proportion method on Löwenstein-Jensen (LJ) medium against ten drugs. The sequencing of entire gyrA and gyrB genes and multiplex PCR were performed to distinguish the prevalence of mutant types in Beijing and non-Beijing genotypes.ResultsThree hundred and twenty-one out of four hundred (80.25%) drug-resistant isolates (resistant > one drug) were categorized as 83/321 (25.80%) MDR, 174/321 (54.20%) pre-XDR and 64/321 (19.93%) XDR-MTB. Overall, 303/400 (75.75%) LVX- and 292/400 (73.00%) MXF-resistant (R) MTB strains were identified. Two hundred seventy-one out of three hundred and three (89.43%) resistant strains carried mutations in gyrA and 91/303 (30.03%) in gyrB. Interestingly, 18 novel mutations were detected in gyrA and gyrB genes. Mutations at (A90, D94) and (T500, G510, G512) frequently existed in QRDR(s) of gyrA and gyrB respectively in 286/400 (71.50%) LVXRMXFR strains. The novel mutations in- and out-side the QRDR of gyrA (L105R, A126E, M127K, D151T, V165A) and gyrB (D461H, N499S, G520A) increased the sensitivity and consistency of genotypic tests. Notably, 25 LVXRMXFR strains were found with unknown resistance mechanisms.ConclusionsMutations in QRDR(s) were concomitantly associated with Beijing and non-Beijing genotypes. The prevalence of resistance and cross-resistance between LVX and MXF in MTB isolates from southern China was immensely higher than other countries. Our valuable findings provide the substantial implications to improve the reliability of genotypic diagnostic tests relying on potential resistance conferring mutations in entire gyr genes.

Dataset Information

Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis isolates in Houston, Texas.

Publications

Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis isolates in Houston, Texas.

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