Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995–2003

Huang, Tung Po; Kunin, Calvin M.; Lee, Susan Shin Jung; Chen, Yao Shen; Tu, Hui Zin; Liu, Yung Ching

doi:10.1093/jac/dki353

Cited by 79 publications

(65 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The existing level of moxifloxacin resistance is comparable to the low prevalence of MDR-TB (0.64%) in Houston (10). We found a statistically significant association between moxifloxacin resistance and MDR-TB, confirming findings from other geographic regions (5,14,15,33). Hence, one can hypothesize that the usefulness of the drug will be compromised in regions of significant MDR-TB prevalence, such as certain areas of the former Soviet Union where MDR-TB constitutes as much as 28% of all new cases, according to World Health Organization statistics (http://www.who.int/tb/publications/global_report/2010 /en/index.html).…”

Section: Discussionsupporting

confidence: 86%

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

et al. 2011

View full text Add to dashboard Cite

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...

show abstract

Section: Discussionsupporting

confidence: 86%

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

et al. 2011

View full text Add to dashboard Cite

show abstract

“…It is not associated with resistance to the fluoroquinolones. It appears to be most commonly seen in strains from Asia, where the presence of this polymorphism is observed in most of the clinical isolates sequenced (8,21).…”

Section: Discussionmentioning

confidence: 99%

Pyrosequencing for Rapid Detection of Mycobacterium tuberculosis Resistance to Rifampin, Isoniazid, and Fluoroquinolones

et al. 2009

View full text Add to dashboard Cite

After isoniazid and rifampin (rifampicin), the next pivotal drug class in Mycobacterium tuberculosis treatment is the fluoroquinolone class. Mutations in resistance-determining regions (RDR) of the rpoB, katG, and gyrA genes occur with frequencies of 97%, 50%, and 85% among M. tuberculosis isolates resistant to rifampin, isoniazid, and fluoroquinolones, respectively. Sequences are highly conserved, and certain mutations correlate well with phenotypic resistance. We developed a pyrosequencing assay to determine M. tuberculosis genotypic resistance to rifampin, isoniazid, and fluoroquinolones. We characterized 102 M. tuberculosis clinical isolates from the Philippines for susceptibility to rifampin, isoniazid, and ofloxacin by using the conventional submerged-disk proportion method and validated our pyrosequencing assay using these isolates. DNA was extracted and amplified by using PCR primers directed toward the RDR of the rpoB, katG, and gyrA genes, and pyrosequencing was performed on the extracts. The M. tuberculosis H37Rv strain (ATCC 25618) was used as the reference strain. The sensitivities and specificities of pyrosequencing were 96.7% and 97.3%, 63.8% and 100%, and 70.0% and 100% for the detection of resistance to rifampin, isoniazid, and ofloxacin, respectively. Pyrosequencing is thus a rapid and accurate method for detecting M. tuberculosis resistance to these three drugs.Rifampin (rifampicin), isoniazid, and the fluoroquinolones are the most important initial drug markers for extensively drug-resistant Mycobacterium tuberculosis strains, defined as multidrug-resistant (MDR) isolates (resistant to both isoniazid and rifampin) with additional resistance to a fluoroquinolone and to one of the injectable drugs (2). The fluoroquinolones have become an essential part of treatment regimens for MDR tuberculosis (7,25). Due to their potency and safety, the newgeneration fluoroquinolones are now even being evaluated as first-line medications for tuberculosis (3,13,20). Wang et al. further suggested that routine fluoroquinolone resistance testing may have a clinical impact by showing a significant correlation between development of fluoroquinolone and first-line M. tuberculosis drug resistance in an area in which resistant strains are highly endemic (28).The spontaneous acquisition of DNA sequence mutations is the primary genetic basis for the development of M. tuberculosis drug resistance (14). Since sequences are highly conserved, certain mutations correlate well with phenotypic resistance, and a limited number of mutations account for the majority of phenotypic resistance to the important antituberculosis medications, various methods of genotypic testing have successfully been used for the rapid detection of M. tuberculosis resistance (16,22). The sites that most frequently contain mutations associated with phenotypic resistance, called resistance-determining regions (RDR), differ depending on the drug tested. Among rifampin-resistant isolates worldwide, 95 to 97% harbor mutations in the rifampin RDR, an 81-bp ...

show abstract

“…More than half of the MDR-TB strains examined in this study had mutations in gyrA (66.7%). The rates of FQ resistance among MDR-TB patients also have been found to be high in other countries in the region as well: 51.4% in the Philippines (46), 22.2% in Taiwan (47), and 25.1% in China (Shanghai) (20). The rates in countries on other continents are lower, e.g., 4.1% in the United States and Canada (48) and 4.3% in MDR-TB patients in Russia (49).…”

Section: Figmentioning

confidence: 97%

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

et al. 2016

View full text Add to dashboard Cite

h Fluoroquinolones (FQs) are broad-spectrum antibiotics recommended for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients. FQ resistance, caused by mutations in the gyrA and gyrB genes of Mycobacterium tuberculosis, is increasingly reported worldwide; however, information on mutations occurring in strains from the Indian subcontinent is scarce. Hence, in this study, we aimed to characterize mutations in the gyrA and gyrB genes of acid-fast bacillus (AFB) smear-positive sediments or of M. tuberculosis isolates from AFB smear-negative samples from patients in India suspected of having MDR-TB. A total of 152 samples from patients suspected of having MDR-TB were included in the study. One hundred forty-six strains detected in these samples were characterized by sequencing of the gyrA and gyrB genes. The extracted DNA was subjected to successive amplifications using a nested PCR protocol, followed by sequencing. A total of 27 mutations were observed in the gyrA genes of 25 strains, while no mutations were observed in the gyrB genes. The most common mutations occurred at amino acid position 94 (13/27 [48.1%]); of these, the D94G mutation was the most prevalent. The gyrA mutations were significantly associated with patients with rifampin (RIF)-resistant TB. Heterozygosity was seen in 4/27 (14.8%) mutations, suggesting the occurrence of mixed populations with different antimicrobial susceptibilities. A high rate of FQ-resistant mutations (17.1%) was obtained among the isolates of TB patients suspected of having MDR-TB. These observations emphasize the need for accurate and rapid molecular tests for the detection of FQ-resistant mutations at the time of MDR-TB diagnosis.T reatment of multidrug-resistant tuberculosis (MDR-TB) patients, with strains resistant to rifampin (RIF) and isoniazid (INH), is further complicated by the presence of fluoroquinolone (FQ) resistance, due to prolonged, limited, and expensive treatment options (1, 2). A recent meta-analysis of the responses to treatment of 6,724 MDR-TB patients from 26 centers revealed that the frequency of treatment success was 64%, while that for patients with MDR-TB plus FQ resistance was only 48% (3). This clearly indicates the need for routine molecular screening for FQ resistance-associated molecular markers so that the treatment of such patients can be optimized without delay. Many such patients develop extensively drug resistant tuberculosis (XDR-TB), defined as MDR-TB plus resistance to any one FQ and any of the aminoglycosides/cyclic peptides (A-CP) (4). This poses an even more serious threat to TB management, since only 40% of XDR-TB patients have successful treatment outcomes (2). Previous studies have suggested that 5.4% (95% confidence interval [95% CI], 3.4 to 7.5%) of MDR-TB cases may actually be XDR-TB (2).FQs are oral antibacterial agents that have activity against Mycobacterium tuberculosis (5, 6). Hence, FQs are recommended for the treatment of MDR-TB patients and patients with intolerance to RIF (2). FQs are also being evaluated in ...

show abstract

Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995–2003

Cited by 79 publications

References 33 publications

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

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

Pyrosequencing for Rapid Detection of Mycobacterium tuberculosis Resistance to Rifampin, Isoniazid, and Fluoroquinolones

Sequence Analysis of Fluoroquinolone Resistance-Associated Genes gyrA and gyrB in Clinical Mycobacterium tuberculosis Isolates from Patients Suspected of Having Multidrug-Resistant Tuberculosis in New Delhi, India

Contact Info

Product

Resources

About