Research on gonococcal resistance to antibiotics including new quinolone

淋球菌对新型喹诺酮类抗生素耐药性的研究

• 批准号: 12671542
• 负责人: TANAKA Masatoshi
• 金额: $ 1.28万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671542/
• 关键词: Neisseria gonorrhoeae; prevalence rate; quinolone resistance; tetracycline resistance; penicillin resistance; cephem resistance; penicillinase-produding; Mechanism of resistance; 薬剤感受性; 薬剤耐性; DNAジャイレース; トポイソメラーゼIV; ペニシリ耐性; 栄養要求型

I. Prevalence of antibiotic-resistant Neisseria gonorrhoeae : We determined the MIC for 208 N. gonorrhoeae isolates in 2001 in Fukuoka city. The prevalence rates of quinolone resistance (CPFX MIC≧1 μg/ml), penicillin resistance (PCG MIC≧2 μg/ml), and tetracycline resistance (TC MIC≧2 μg/ml) in those isolates were 64.4%, 13.4%, and 13.9%, respectively. The prevalence rate of penicillinase-producing N. gonorrhoeae (PPNG) was only 1.4% in those isolates. There were no isolates resistant to spectinomycin (SPCM MIC≧128 μg/ml) or intermediately resistant to cefixime (CFIX MIC≧0.5 μg/ml) in those isolates. However, the prevalence rate of reduced susceptibility to CFIX with MIC of 0.125 to 0.25 μg/ml was relatively higher (23.6%) in 2001 as compared with that (1.6%) in 1995-96. These results indicate that the prevalence rate of quinolone resistance in the isolates in 2001 was remarkably high and that the isolates in 2001 showed reduced susceptibility to CFIX.II. Mechanism of resistance to cefi … More xime : We examined the genetic mechanisms of chromosomally mediated resistance to CFIX. Chromosomally mediated penicillin (a variety of β-lactam antibiotics) resistance in N. gonorrhoeae occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. The first step in transformation to high-level penicillin resistance is mediated by the penA gene, which encodes altered forms of PBP2. Therefore, we analyzed mutations in the penA gene of the 6 gonococcal isolates intermediately resistant (CFIX MIC=0.5 μg/ml) and 3 susceptible (CFIX MIC; ≦0.001 to 0.004 μg/ml) to CFIX, PCR and direct DNA sequencing were performed to identify mutations in a region including the transpeptidase domain of the penA gene. All 6 isolates intermediately resistant to CFIX had same 33 amino acid substitutions through position 323 to 480 within the region of the transpeptidase domain of PBP2. However, no single alteration was identified in the same region of the PBP2 of the 3 susceptible isolates. Our data suggest that multiple alterations in PBP2 play an essential role in conferring cefixime resistance to N. gonorrhoeae. Less

I.耐药淋球菌的流行：我们测定了208 N. 2001年在福冈市的淋病分离株。耐喹诺酮类药物（CPFX MIC ≥ 1 μg/ml）、青霉素类药物（PCG MIC ≥ 2 μg/ml）和四环素类药物（TC MIC ≥ 2 μg/ml）的检出率分别为64.4%、13.4%和13.9%。产青霉素酶N.淋球菌（PPNG）仅占1.4%。未发现对大观霉素耐药（SPCM MIC ≤ 128 μg/ml）或对头孢克肟中度耐药（CFIX MIC ≤ 0.5 μg/ml）的菌株。但2001年对CFIX敏感性降低（MIC为0.125 ~ 0.25 μg/ml）的发生率（23.6%）较1995 ~ 1996年（1.6%）相对较高。结果表明，2001年分离株对喹诺酮类药物的耐药率较高，2001年分离株对CFIX. II的敏感性降低。头孢菌素耐药机制 ...更多信息 xime：我们研究了染色体介导的对CFIX耐药性的遗传机制。染色体介导的N.淋病部分地通过青霉素结合蛋白（PBP）的改变和外膜通透性的降低而发生。转化为高水平青霉素抗性的第一步是由编码PBP 2改变形式的佩纳基因介导的。因此，我们分析了6株对CFIX中度耐药（CFIX MIC=0.5 μg/ml）和3株敏感（CFIX MIC = 0.001 - 0.004 μg/ml）的淋球菌分离株的佩纳基因突变，进行PCR和直接DNA测序以鉴定包括佩纳基因转肽酶结构域的区域中的突变。对CFIX具有中等抗性的所有6个分离株在PBP 2的转肽酶结构域区域内的位置323至480处具有相同的33个氨基酸取代。然而，在3个敏感分离物的PBP 2的相同区域中未鉴定到单一的改变。我们的数据表明，PBP 2的多重改变在赋予头孢克肟耐药性中起着重要作用。淋病少

项目成果

Tanaka M, et al.: "A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan"J Infect Chemother. 8. 81-86 (2002)

Tanaka M 等人：“淋病奈瑟菌分离株对头孢烯的敏感性显着降低，以及日本单剂量治疗淋球菌感染的抗生素方案的选择”J Infect Chemother。

Tanaka M, et al.: "Clinical and fundamental investigations on the treatment of Neisseria gonorrhoeae infections"Nishinihon J Urol. 64. 324-337 (2002)

Tanaka M 等人：“淋病奈瑟菌感染治疗的临床和基础研究”Nishinihon J Urol。

Tanaka M, (他7名): "A remarkable reduction in the susceptibility of Neisseria gonorrhoeae isolates to cephems and the selection of antibiotic regimens for the single-dose treatment of gonococcal infection in Japan"J Infect Chemother. 8. 81-86 (2002)

Tanaka M，（其他 7 名）：“淋病奈瑟菌分离株对头孢烯的敏感性显着降低，以及日本单剂量治疗淋球菌感染的抗生素方案的选择”J Infect Chemother（2002 年）。 ）

田中正利, (他10名): "淋菌感染症の治療に関する臨床的および基礎的検討"西日泌尿. 64. 324-337 (2002)

Masatoshi Tanaka，（和其他 10 人）：“淋球菌感染治疗的临床和基础研究”Nishinichi Urinary Journal 64. 324-337 (2002)。

田中正利: "STDと薬剤耐性-淋菌-"日性感染症会誌. 13. 44-58 (2002)

Masatoshi Tanaka：“STD 和耐药性 - 淋病奈瑟菌 -”日本性传染病学会杂志 13. 44-58 (2002)。