FLUOROQUINOLONE ANTIBIOTIC AGAINST BLOOD CUUTURE ISOLATE

针对血培养分离物的氟喹诺酮类抗生素

• 批准号: 6414338
• 负责人: DANIEL P. FEDORKO
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6414338
• 关键词: DNA topoisomerases; Streptococcus mitis; antibiotics; bacterial genetics; drug resistance; gene mutation; microorganism culture

Thirty-seven strains of viridans streptococci isolated from blood cultures on bone marrow transplant (BMT) recipients during the past 4 years and 39 strains of viridans streptococci isolated from non-BMT patients were tested for fluoroquinolone susceptibility. Of the five strains from BMT patients that were resistant to levofloxacin, trovafloxacin, and/or grepafloxacin, one isolate (NIH-(R02) demonstrated high-level resistance to multiple fluoroquinolones tested. DNA gyrase A is one of the major targets for quinolone antibiotics. The amino acid sequence within the quinolone resistance-determining region (QRDR) of the gyrase A of NIH-(R02) was determined. When compared with ten sensitive strains of S. mitis, NIH-(R02) carried a single point mutation in the "GKYHPHGDS" box within the QRDR of the gyrA gene (serine to leucine replacement). The mechanism of fluoroquinolone resistance in this isolate of S. mitis is thus likely similar to the previously reported mechanisms in S. pneumoniae.We will sequence the QRDR of the parC subunit of topoisomerase IV (parC gene) of NIH-(R02) and the ten sensitive strains to search for additional point mutations that may confer resistance to the quinolone antibiotics in the viridans group of streptococci.

对过去 4 年中从骨髓移植 (BMT) 受者血培养中分离的 37 株草绿色链球菌和从非 BMT 患者中分离的 39 株草绿色链球菌进行了氟喹诺酮敏感性测试。在来自 BMT 患者的对左氧氟沙星、曲伐沙星和/或格帕沙星耐药的 5 株菌株中，一种分离株 (NIH-(R02)) 对所测试的多种氟喹诺酮类药物表现出高水平耐药性。DNA 旋转酶 A 是喹诺酮类抗生素的主要靶标之一。喹诺酮类耐药决定区域内的氨基酸序列 测定了NIH-(R02)的促旋酶A的(QRDR)。与轻链球菌的 10 种敏感菌株相比，NIH-(R02) 在 gyrA 基因 QRDR 内的“GKYHPHGDS”盒中携带单点突变（丝氨酸替换为亮氨酸）。因此，该轻链球菌分离株的氟喹诺酮类耐药机制可能与之前报道的机制相似 我们将对 NIH-(R02) 的拓扑异构酶 IV 的 parC 亚基（parC 基因）和 10 种敏感菌株的 QRDR 进行测序，以寻找可能赋予草绿色链球菌群对喹诺酮类抗生素耐药性的其他点突变。