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生殖支原体治疗的新视野

New Horizons in Mycoplasma genitalium Treatment.

作者信息

Bradshaw Catriona S, Jensen Jorgen S, Waites Ken B

机构信息

Central Clinical School, Monash University.

Melbourne Sexual Health Centre, Alfred Hospital, Melbourne, Australia.

出版信息

J Infect Dis. 2017 Jul 15;216(suppl_2):S412-S419. doi: 10.1093/infdis/jix132.

Abstract

Mycoplasmagenitalium is an important sexually transmitted pathogen responsible for both male and female genital tract disease. Appreciation of its significance in human disease has been hampered by its slow growth in culture, difficulty in isolating it, and lack of commercial molecular-based tests for rapid detection. Comparatively few in vitro data on antimicrobial susceptibility are available due to the scarcity of clinical isolates and difficulty in performing susceptibility tests to determine minimum inhibitory concentrations for M. genitalium. Antimicrobial agents that inhibit protein synthesis such as macrolides, along with fluoroquinolones that inhibit DNA replication, have been the treatments of choice for M. genitalium infections. Even though international guidelines recommend azithromycin as first-line treatment, rapid spread of macrolide resistance as well as emergence of quinolone resistance has occurred. Increasing rates of treatment failure have resulted in an urgent need for new therapies and renewed interest in other classes such as aminocyclitols, phenicols, and streptogramins as treatment alternatives. Limited data for new investigational antimicrobials such as the ketolide solithromycin suggest that this drug may eventually prove useful in management of some resistant M. genitalium infections, although it is not likely to achieve cure rates >80% in macrolide-resistant strains, in a similar range as recently reported for pristinamycin. However, agents with completely new targets and/or mechanisms that would be less likely to show cross-resistance with currently available drugs may hold the greatest promise. Lefamulin, a pleuromutilin, and new nonquinolone topoisomerase inhibitors are attractive possibilities that require further investigation.

摘要

生殖支原体是一种重要的性传播病原体,可导致男性和女性生殖道疾病。由于其在培养中生长缓慢、难以分离,且缺乏基于分子的快速检测商业测试,人们对其在人类疾病中的重要性认识不足。由于临床分离株稀缺以及难以进行药敏试验以确定生殖支原体的最低抑菌浓度,关于抗菌药物敏感性的体外数据相对较少。抑制蛋白质合成的抗菌药物(如大环内酯类)以及抑制DNA复制的氟喹诺酮类一直是治疗生殖支原体感染的首选药物。尽管国际指南推荐阿奇霉素作为一线治疗药物,但大环内酯类耐药性的迅速传播以及喹诺酮类耐药性的出现已经发生。治疗失败率的不断上升迫切需要新的治疗方法,人们也重新关注氨基环醇类、酚类和链阳菌素类等其他类别作为替代治疗方法。关于新型研究性抗菌药物(如酮内酯类索利霉素)的有限数据表明,这种药物最终可能被证明对治疗一些耐药生殖支原体感染有用,尽管在大环内酯类耐药菌株中它不太可能达到>80%的治愈率,与最近报道的 pristinamycin 的治愈率范围相似。然而,具有全新靶点和/或机制且不太可能与现有药物产生交叉耐药性的药物可能最有前景。截短侧耳素类的 lefamulin 和新型非喹诺酮类拓扑异构酶抑制剂是有吸引力的可能性,需要进一步研究。

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