Avalos Elisea, Catanzaro Donald, Catanzaro Antonino, Ganiats Theodore, Brodine Stephanie, Alcaraz John, Rodwell Timothy
Department of Family and Preventive Medicine, University of California San Diego, La Jolla, California, United States of America.
Department of Biological Sciences, University of Arkansas, Fayetteville Arkansas, United States of America.
PLoS One. 2015 Mar 27;10(3):e0120470. doi: 10.1371/journal.pone.0120470. eCollection 2015.
The detection of mutations in the gyrA and gyrB genes in the Mycobacterium tuberculosis genome that have been demonstrated to confer phenotypic resistance to fluoroquinolones is the most promising technology for rapid diagnosis of fluoroquinolone resistance.
In order to characterize the diversity and frequency of gyrA and gyrB mutations and to describe the global distribution of these mutations, we conducted a systematic review, from May 1996 to April 2013, of all published studies evaluating Mycobacterium tuberculosis mutations associated with resistance to fluoroquinolones. The overall goal of the study was to determine the potential utility and reliability of these mutations as diagnostic markers to detect phenotypic fluoroquinolone resistance in Mycobacterium tuberculosis and to describe their geographic distribution.
Forty-six studies, covering four continents and 18 countries, provided mutation data for 3,846 unique clinical isolates with phenotypic resistance profiles to fluoroquinolones. The gyrA mutations occurring most frequently in fluoroquinolone-resistant isolates, ranged from 21-32% for D94G and 13-20% for A90V, by drug. Eighty seven percent of all strains that were phenotypically resistant to moxifloxacin and 83% of ofloxacin resistant isolates contained mutations in gyrA. Additionally we found that 83% and 80% of moxifloxacin and ofloxacin resistant strains respectively, were observed to have mutations in the gyrA codons interrogated by the existing MTBDRsl line probe assay. In China and Russia, 83% and 84% of fluoroquinolone resistant strains respectively, were observed to have gyrA mutations in the gene regions covered by the MTBDRsl assay.
Molecular diagnostics, specifically the Genotype MTBDRsl assay, focusing on codons 88-94 should have moderate to high sensitivity in most countries. While we did observe geographic differences in the frequencies of single gyrA mutations across countries, molecular diagnostics based on detection of all gyrA mutations demonstrated to confer resistance should have broad and global utility.
结核分枝杆菌基因组中gyrA和gyrB基因的突变检测已被证明可赋予对氟喹诺酮类药物的表型耐药性，这是快速诊断氟喹诺酮耐药性最有前景的技术。
为了描述gyrA和gyrB基因突变的多样性和频率，并描述这些突变的全球分布，我们在1996年5月至2013年4月期间对所有已发表的评估结核分枝杆菌与氟喹诺酮耐药性相关突变的研究进行了系统综述。该研究的总体目标是确定这些突变作为诊断标志物检测结核分枝杆菌表型氟喹诺酮耐药性的潜在效用和可靠性，并描述其地理分布。
46项研究覆盖四大洲18个国家，提供了3846株对氟喹诺酮类药物具有表型耐药谱的独特临床分离株的突变数据。在耐氟喹诺酮类药物的分离株中最常出现的gyrA突变，按药物分类，D94G为21 - 32%，A90V为13 - 20%。所有对莫西沙星表型耐药的菌株中有87%以及对氧氟沙星耐药的分离株中有8
