Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.
Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.
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DOI：
10.1186/s12879-015-1029-2
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发表时间：
2015-08-21
影响因子：
3.7
通讯作者：
Unemo M
中科院分区：
文献类型：
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作者：
Unemo M
淋球菌已经对所有药物产生了抗菌素耐药性(AMR)，目前被推荐用于淋病的经验性单一治疗。在体外，包括对最后一种选择头孢曲松的高水平耐药性和用头孢曲松治疗咽部淋病的零星失败已经出现。对此，几个特别高收入的地区或国家引入了经验性双重抗菌疗法(头孢曲松250-1000 mg加阿奇霉素1-2 mg)。这些治疗方案目前看来是有效的，应该在当地有质量保证的AMR数据不支持其他治疗方案的所有环境中考虑。然而，在有限的地理区域实施的双重抗菌疗法不会完全防止耐药性的出现，不幸的是，很可能只是一个何时出现治疗失败的问题，而不是这些双重抗菌疗法是否会出现治疗失败的问题。因此，对于单一疗法或至少包括在新的双重治疗方案中的新的负担得起的抗菌剂是必要的，这可能需要考虑用于所有新开发的抗菌剂。最近开发的几种抗菌药值得更多地关注未来可能治疗淋病的药物。体外活性研究检查地理、时间和遗传上不同的淋球菌分离株，包括多药耐药株，特别是对头孢曲松和阿奇霉素具有耐药性的菌株，是重要的。此外，了解目前和正在出现的(体外诱导/选择和体内出现)这些抗菌药的遗传耐药机制的效果和生物学适合性，预测耐药性的出现，进行时间-杀伤曲线分析以评估抗菌活性，适当的小鼠实验，以及遗传和表型实验室参数与临床治疗结果之间的相关性，也将是有价值的。随后，经过适当设计的随机对照临床试验评估了肛门淋病以及重要的咽部淋病的疗效、理想剂量、毒性、不良反应、成本和药代动力学/药效学数据，即因为治疗失败最初出现在这个解剖部位。最后，今后第一次就诊时的治疗最好是个人化，即通过新颖的快速表型AMR测试和/或遗传护理点AMR测试，包括检测淋球菌，这将改善淋病和AMR的管理和公共卫生控制。尽管如此，现在肯定是重新审视开发淋球菌疫苗的挑战的合适时机。
Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250–1000 mg plus azithromycin 1–2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed, randomized controlled clinical trials evaluating efficacy, ideal dose, toxicity, adverse effects, cost, and pharmacokinetic/pharmacodynamics data for anogenital and, importantly, also pharyngeal gonorrhoea, i.e. because treatment failures initially emerge at this anatomical site. Finally, in the future treatment at first health care visit will ideally be individually-tailored, i.e. by novel rapid phenotypic AMR tests and/or genetic point of care AMR tests, including detection of gonococci, which will improve the management and public health control of gonorrhoea and AMR. Nevertheless, now is certainly the right time to readdress the challenges of developing a gonococcal vaccine.