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2010 至 2012 年日本京都和大阪地区淋病奈瑟菌分离株的耐药性和分子分型:首例高水平头孢曲松耐药菌株(H041)鉴定后的强化监测

Antimicrobial resistance and molecular typing of Neisseria gonorrhoeae isolates in Kyoto and Osaka, Japan, 2010 to 2012: intensified surveillance after identification of the first strain (H041) with high-level ceftriaxone resistance.

机构信息

National Institute of Infectious Diseases, Tokyo, Japan.

出版信息

Antimicrob Agents Chemother. 2013 Nov;57(11):5225-32. doi: 10.1128/AAC.01295-13. Epub 2013 Aug 12.

Abstract

In 2009, the first high-level ceftriaxone-resistant Neisseria gonorrhoeae strain (H041) was isolated in Kyoto, Japan. The present study describes an intensified surveillance (antimicrobial resistance and molecular typing) of Neisseria gonorrhoeae isolates in Kyoto and its neighboring prefecture Osaka, Japan, in 2010 to 2012, which was initiated after the identification of H041. From April 2010 to March 2012, 193 N. gonorrhoeae isolates were collected and the MICs (μg/ml) to six antimicrobials, including ceftriaxone, were determined. All isolates showed susceptibility to ceftriaxone and cefixime (MIC values, <0.5 μg/ml), and spectinomycin. The rates of resistance (intermediate susceptibility) to azithromycin, penicillin G, and ciprofloxacin were 3.6% (19.7%), 24.4% (71.0%), and 78.2% (0.5%), respectively. Multilocus sequence typing (MLST) showed that 40.9%, 19.2%, and 17.1% of isolates belonged to ST1901, ST7359, and ST7363, respectively. Furthermore, N. gonorrhoeae multiantigen sequence typing (NG-MAST) revealed that 12 (63%) of the 19 isolates with decreased susceptibility to ceftriaxone (MIC > 0.064 μg/ml) were of ST1407. NG-MAST ST1407 was also the most prevalent ST (16.1%; 31 of 193 isolates). In those NG-MAST ST1407 strains, several mosaic type penA alleles were found, including SF-A type (penicillin binding protein 2 allele XXXIV) and its derivatives. These were confirmed using transformation of the penA mosaic alleles as critical determinants for enhanced cefixime and ceftriaxone MICs. The intensified surveillance in Kyoto and Osaka, Japan, did not identify any dissemination of the high-level ceftriaxone-resistant N. gonorrhoeae strain H041, suggesting that H041 might have caused only a sporadic case and has not spread further.

摘要

2009 年,首例头孢曲松高度耐药淋病奈瑟菌(H041)株在日本京都被分离出来。本研究描述了日本京都及其邻近的大阪府 2010 年至 2012 年对淋病奈瑟菌分离株的强化监测(抗微生物耐药性和分子分型),该监测是在 H041 鉴定后启动的。从 2010 年 4 月至 2012 年 3 月,共收集了 193 株淋病奈瑟菌分离株,并测定了 6 种抗菌药物(包括头孢曲松)的 MIC(μg/ml)。所有分离株均对头孢曲松和头孢克肟(MIC 值<0.5μg/ml)和大观霉素敏感。对阿奇霉素、青霉素 G 和环丙沙星的耐药率(中介敏感性)分别为 3.6%(19.7%)、24.4%(71.0%)和 78.2%(0.5%)。多位点序列分型(MLST)显示,40.9%、19.2%和 17.1%的分离株分别属于 ST1901、ST7359 和 ST7363。此外,淋病奈瑟菌多抗原序列分型(NG-MAST)显示,19 株对头孢曲松(MIC>0.064μg/ml)中介敏感性降低的分离株中有 12 株(63%)为 ST1407。NG-MAST ST1407 也是最常见的 ST(16.1%;193 株分离株中有 31 株)。在这些 NG-MAST ST1407 菌株中,发现了几种镶嵌型 penA 等位基因,包括 SF-A 型(青霉素结合蛋白 2 等位基因 XXXIV)及其衍生物。通过转化 penA 镶嵌等位基因作为提高头孢克肟和头孢曲松 MIC 的关键决定因素,证实了这一点。日本京都和大阪的强化监测并未发现高水平头孢曲松耐药淋病奈瑟菌 H041 的传播,表明 H041 可能只引起了散发病例,并未进一步传播。

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