High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure
High-Level Cefixime- and Ceftriaxone-Resistant Neisseria gonorrhoeae in France: Novel penA Mosaic Allele in a Successful International Clone Causes Treatment Failure
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DOI：
10.1128/aac.05760-11
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发表时间：
2012-03-01
影响因子：
4.9
通讯作者：
Sednaoui, Patrice
中科院分区：
文献类型：
--
作者：
Unemo, Magnus;Golparian, Daniel;Sednaoui, Patrice
最近，日本分离出第一株对广谱头孢菌素(ESCs)、头孢曲松和头孢克辛高度耐药的淋病奈瑟菌菌株(H041)，这些药物是淋病一线治疗的最后选择。在这里，我们确认并鉴定了第二株对头孢克辛和头孢曲松耐药水平较高的菌株(F89)，该菌株是在法国分离出来的，很可能导致头孢克辛治疗失败。对F89进行了6种检测：确证试验、抗菌谱(33种抗菌药)、porB测序、淋球菌多抗原序列分型(NG-MAST)、多位点序列分型(MLST)和已知淋球菌耐药决定基因(PenA、mtrR、penB、PONA和PilQ)的测序。F89被指定为MLST序列类型1901(ST1901)和NG-MAST ST1407，这是一个成功的淋球菌克隆，已在全球传播。F89对头孢克肟(MIC=4mU/ml)和头孢曲松(MIC=1~2mU/m l)有较高的耐药性，对所检测的大多数其他抗菌药物也有耐药性。一个新的Pena花叶等位基因(Pena-CI)，即Pena-XXXIV，加上青霉素结合蛋白2的A501P改变，通过转化到一组受体菌株中确定了高水平ESC抗性的主要决定因素。淋病奈瑟氏菌似乎正在成为一种超级细菌，在某些情况下，淋病可能变得无法治疗。需要对生物适合性进行调查，并加强对ESC抗性克隆及其国际传播的了解和监测。加强疾病控制活动、全世界的抗菌素耐药性控制和监测以及全球(和国家)视角的公共卫生应对计划也是至关重要的。然而，开发新的治疗策略和/或药物，最好是疫苗，对于有效的淋病管理是必不可少的。
Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA, and pilQ). F89 was assigned to MLST sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC = 4 mu g/ml) and ceftriaxone (MIC = 1 to 2 mu g/ml) and resistance to most other antimicrobials examined. A novel penA mosaic allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance, as determined by transformation into a set of recipient strains. N. gonorrhoeae appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness and enhanced understanding and monitoring of the ESC-resistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs and, ideally, a vaccine are essential to develop for efficacious gonorrhea management.