生殖支原体耐药机制及治疗方案的研究进展

生殖支原体是引起非淋菌性尿道炎、子宫颈炎和盆腔炎的病原体,近几年报道生殖支原体对大环内酯类和氟喹诺酮类抗生素的耐药呈逐渐增加的趋势。其对大环内酯类抗生素的耐药机制主要为23SrRNA基因突变,氟喹诺酮类耐药的机制主要为拓扑异构酶IV基因ParC以及DNA促旋酶基因GyrA的突变。随着全球范围内生殖支原体感染率的升高,如何控制生殖支原体耐药成为亟待解决的难题,新的治疗方案主要包括传统抗生素的使用及新型抗生素的开发。     

生殖支原体耐药位点与治疗研究进展

生殖支原体是引起男性非淋菌性尿道炎的重要病原体之一,主要的治疗药物包括四环素类、大环内酯类、喹诺酮类。近年来诸多研究报道,该病原体对多西环素及阿奇霉素的耐药程度日趋严重,亦不断出现莫西沙星治疗失败的案例。本文对生殖支原体耐药位点突变情况及治疗研究进展进行了综述。     

泌尿生殖系解脲支原体检出率与药敏率观察

非淋菌性泌尿生殖系感染是性传播疾病之一,近年来发病率不断上升,解脲支原体UU是引起该病的主要病原体,因此对解脲支原体的培养及耐药的研究,已成为有效治疗非淋菌性泌尿生殖系感染的重要课题。为了解绍兴地区解脲支原体的检出率及药敏情况,我院性病科对非淋菌性尿道炎疑似病例进行UU培养及药敏耐药观察,现将结果报告如下：     

非淋菌性尿道炎临床特征与治疗进展

非淋菌性尿道炎,指由淋球菌以外的其他经性接触传染的病原体引起的尿道炎,主要由沙眼衣原体、解脲支原体、人型支原体、生殖支原体感染引起。如果治疗不充分,本病可能会产生并发症。男性可合并附睾炎、前列腺炎、精囊炎,女性可合并盆腔炎性疾病等。另外,本病亦可能和男性不育、女性不孕、异位妊娠以及不良妊娠有关。本病治疗主要选用四环素类、大环内酯类和喹诺酮类药物。沙眼衣原体对上述抗生素比较敏感,临床上尚未见明显耐药。但是支原体感染对上述抗生素的敏感性不够高,已分离到抗这三类药物的耐药株,给治疗带来一定难度。     

生殖支原体对大环内酯类抗生素耐药突变位点研究

【摘要】 目的 了解生殖支原体对大环内酯类抗生素耐药相关的23S rRNA基因突变情况。 方法 就诊于我院性病门诊的91例近期应用过大环内酯类药物治疗的持续性和复发性尿道炎患者,取尿道拭子和前段尿标本进行生殖支原体（Mg）、沙眼衣原体（Ct）、解脲脲原体（Uu）等病原体检测,筛选出单一生殖支原体阳性患者标本,应用套式PCR扩增与大环内酯类抗生素耐药性相关的23S rRNA基因V区片段,扩增产物进行DNA测序,测得序列与美国国立生物信息中心已登记的生殖支原体标准株G37的相应基因序列比对。 结果 91例的标本中,Mg阳性21例,Ct阳性18例（19.8%）,Uu阳性10例,Mg与UU同时阳性2例,Ct与Uu同时阳性3例,Mg、Ct和Uu检测均为阴性者37例。21例Mg阳性标本中,18例的标本成功扩增出23S rRNA基因V区片段,除1例未发现基因突变外,其余17例均发现2058和2059位点突变,其中A2059G突变10例,A2058G突变5例,A2058T突变2例。 结论 23S rRNA基因V区片段基因突变可能与南京及周边地区Mg对大环内酯类药物耐药性相关。     

生殖支原体及解脲脲原体在男性不同人群中的感染与定植研究

目的了解生殖支原体及解脲脲原体在男性不同人群中的流行状况,分析生殖支原体及解脲脲原体与男性非淋菌性尿道炎的相关性。方法病例对照研究结合横断面研究,采集性病门诊非淋菌性尿道炎患者、性病门诊无尿道炎的就诊者、男男性接触者及健康体检者4组人群的尿道拭子标本,运用培养法和套式PCR法检测解脲脲原体,套式PCR和产物DNA测序检测生殖支原体。结果生殖支原体检出率非淋菌性尿道炎患者组为25.0％,无尿道炎的就诊者组6.4％,男男性接触者组5.5％,健康体检者组未检出。各组与健康体检者组比较差异均有统计学意义,而非淋菌性尿道炎患者与无尿道炎的就诊者、非淋菌性尿道炎患者与男男性接触者比较,P均<0.01,无尿道炎的就诊者与男男性接触者比较,P>0.05。多因素回归分析发现,尿道炎与生殖支原体阳性率显著相关,P=0.004,OR=6.754,95％CI1.833～24.893。解脲脲原体PCR阳性率在非淋菌性尿道炎患者、无尿道炎的就诊者、健康体检者组间差异无统计学意义。男男性接触者组的解脲脲原体阳性率明显低于其他三组。结论生殖支原体与非淋菌性尿道炎高度相关,男性高危性行为人群中生殖支原体的感染率较普通人群高。解脲脲原体定植在男性非淋菌性尿道炎患者、性行为高危人群及普通人群间无差异,与非淋菌性尿道炎无相关性。     

欧洲、澳大利亚、英国生殖支原体感染诊疗指南介绍

【摘要】 生殖支原体可导致非淋菌性尿道炎、宫颈炎等泌尿生殖道感染甚至附睾炎、盆腔炎、早产等并发症。由于近年来生殖支原体感染率的升高以及多种常用治疗药物耐药的普遍出现,2016年欧洲、2017年澳大利亚性健康联盟、2018年英国性健康与HIV协会分别颁布了生殖支原体感染的诊疗指南,就其感染的临床表现、诊断、患者与性伴的治疗、随访等方面给出了建议,对我国生殖支原体感染的诊治有重要的指导意义。     

生殖支原体与临床疾病关系研究进展

自从1981年生殖支原体首次从非淋菌性尿道炎（non-gonococcal urethritis，NGU）患者尿道分泌物中分离以来，有关生殖支原体的研究日益增多：从基因蛋白组、生物学性状、培养特性等基础研究到致病性、耐药性、治疗等临床研究都取得了较大的成果。本文就近年来有关生殖支原体感染与临床疾病关系的研究进展进行综述。     

解脲支原体耐药机制研究进展

解脲支原体是引起非淋球茵性生殖道感染的主要病原体之一。四环素类、大环内酯类、喹诺酮类抗生素是治疗解脲支原体感染的主要有效药物。随着解脲支原体对不同抗生素的耐药情况日趋严重，国内外对解脲支原体的耐药机制研究逐渐增多。tetM的核糖体保护作用是解脲支原体对四环素的主要耐药机制。喹诺酮类的主要耐药机制与编码DNA促旋酶和拓扑异构酶Ⅳ亚单位的基因突变有关。外膜蛋白对药物的低通透性（外排抗性机制）、靶位的修饰改变及酶修饰引起抗生素结构改变是大环内酯类的主要耐药机制。但解脲支原体对大环内酯类抗生素耐药机制的研究未见报道。     

泌尿生殖系病人的尿素分解支原体和淋球菌的培养诊断

在性传播性疾病中,非淋菌性炎症占很大比例,其发病数是淋病病人数的1.5～2倍。其病原体多种多样,尿素分解支原体(Ureaplasma Urealyticum)和衣原体是主要的泌尿生殖系非淋菌性炎症的病原体。苏联资料表明,尿素分解支原体占非淋菌性尿道炎病人的67.6％,占淋病后尿道炎病人的74.6％。本文报道278例泌尿生殖系患者的尿素分解支     

生殖支原体感染及其抗菌药物的研究现状

生殖支原体是性传播疾病的病原体之一,与非淋菌性尿道炎及女性宫颈炎等疾病密切相关.诊断生殖支原体感染的方法主要有培养、分子生物学及血清学法.目前治疗生殖支原体感染主要是阿奇霉素,但已经出现耐阿奇霉素的生殖支原体临床菌株的报道.针对生殖支原体的治疗药物的药效学研究平台主要有药物敏感性体外实验和动物模型.

Abstract：

Mycoplasma genitalium (Mg), a pathogen of sexually transmitted disease, is closely related with nongonococcal urethritis and cervicitis. The diagnosis of Mg infection mainly depends on culture,molecular biological and serological methods. Mg infection is primarily treated with azithromycin, but there have been reports on the resistance of Mg to azithromycin. Pharmacodynamic research on antibiotics against Mg is mainly through in vitro drug susceptibility testing and animal model experiment.     

性病门诊235例患者生殖支原体感染分析

目的研究分析我院皮肤性病门诊患者生殖支原体(Mg)的感染情况。方法收集2015年2—10月就诊于皮肤性病门诊疑似泌尿生殖系统感染的患者235例(男165例,女70例),采集男性尿道或女性宫颈分泌物分别进行超显微镜检、淋球菌培养、支原体培养、生殖道沙眼衣原体聚合酶链反应(PCR)检测和生殖支原体实时荧光核酸恒温扩增检测技术(SAT)检测。结果 235例患者中各种微生物检出情况分别为Mg 17例(7.23%),解脲脲原体(Uu)72例(30.64%),人型支原体(Mh)22例(9.36%),生殖道沙眼衣原体(Ct)10例(4.26%),淋球菌6例(2.55%),上述检测项目全部阴性122例(51.91%)。Mg阳性的17例患者中单一感染7例(41.18%),混合感染10例(58.82%),其中Mg+Uu感染6例,Mg+Uu+Mh感染4例。结论 Mg可单一感染,也可混合感染,临床上应加强对性病门诊患者Mg的筛查。Mg生长条件要求高,培养成功率低,SAT检测是目前可以选择用来检测Mg的方法之一。     

451例STD患者的生殖支原体感染

为了解性传播疾病（STD）患者中感染生殖支原体（Mg)的状况及其临床意义，在本所的STD门诊部收集451例患者的尿道（宫颈）分泌物作了Mg检测。标本接种于改良的SP－4培养基作Mg分离培养，并同时用聚合酶链反应（PCR）进行Mg检测，以PCR结果作为最终判断依据。患者中69例非淋病性尿道炎（NGU）病人还作了咽部拭子的Mg检测。结果证明，Mg阳性患者有67例（14．9％），其中NGU 59例（20．6％），其他STD仅8例（4．9％），二者差异有统计学显著性（P＜0．0001），表明Mg感染与NGU发生关系密切。尿道（宫颈）分泌物及咽拭子同时检测Mg的69例NGU病人中，7例在二部位均检出Mg，提示有口淫的可能性。     

生殖支原体感染的研究进展

生殖支原体(Mg)是一种越来越受到重视的性传播感染病原体。Mg可以引起男性无症状和/或有症状尿道炎,并与女性宫颈炎和盆腔炎密切相关。Mg对HIV感染的获得和传播有重要作用。常用DNA扩增方法检测Mg。Mg感染的治疗可选用阿奇霉素和多西环素。     

生殖支原体与黏液脓性宫颈炎相关性的研究

目的 探讨生殖支原体与女性非衣原体非淋球菌感染的黏液脓性宫颈炎的相关性。方法 对象包括性病门诊就诊的女性非衣原体非淋球菌感染的黏液脓性宫颈炎患者226例及健康体检人群118例。采集宫颈拭子标本，运用PCR检测生殖支原体。一般情况、病史和性行为等采用问卷调查。结果生殖支原体在非衣原体非淋球菌感染的黏液脓性宫颈炎患者中的检出率为11.06%（25/226），健康体检人群中的检出率为0.85%（1/118），两组间差异有统计学意义（χ2 = 11.58，P < 0.001）。分析226例黏液脓性宫颈炎患者显示，有异位妊娠史、宫颈糜烂、附件压痛及宫颈内管分泌物镜检多型核白细胞≥10个/油镜视野的患者生殖支原体的感染率分别为27.78%，16.36%，18.28%，14.12%，而无异位妊娠史、宫颈糜烂、附件压痛及宫颈内管分泌物镜检多型核白细胞 < 10个/油镜视野的患者分别为9.62%，6.03%，6.02%，1.79%，生殖支原体的感染率差异在四组人群间均有统计学意义（P < 0.05），而多性伴数和宫颈口有黏液脓性分泌物在两组间差异均具有统计学意义（P < 0.01）。结论 性病门诊就诊的非衣原体非淋球菌感染黏液脓性宫颈炎患者中，生殖支原体感染率高于普通人群。     

Mycoplasma genitalium: a cause of male urethritis?

BACKGROUND--Male urethritis may be caused by mycoplasmas. Since Mycoplasma genitalium has previously been isolated from the urethra of two men with non-gonococcal urethritis (NGU), it was the aim of the study further to elucidate its role by measuring the prevalence of this organism in men with NGU. MATERIAL AND METHODS--The polymerase chain reaction was used. Two different sequences of the gene coding for the main adhesin MgPa were amplified. Urethral, rectal, and throat samples from 99 male sexually transmitted disease (STD) patients with and without urethritis were studied. RESULTS--M genitalium DNA was demonstrated in 17/99 (17%) of the urethral swabs, but in none of the rectal and throat swabs. Significantly more patients with urethritis (13/52) were positive for M genitalium DNA than were patients without urethritis (4/47) (p < 0.03). In those with urethritis M genitalium DNA was found more often in Chlamydia trachomatis negative NGU (12/34) than in those with chlamydial NGU (1/14) (p = 0.05). Attempts to culture M genitalium from the PCR positive specimens were unsuccessful. CONCLUSION--M genitalium DNA was found significantly more often in male STD patients with non-chlamydial NGU than in men with chlamydial urethritis (p = 0.05) and in men without urethritis (p = 0.003), suggesting that M genitalium may be a cause of NGU. M genitalium DNA was not demonstrated in any of the throat or rectal swabsindicating that the urogenital tract is probably the primary site of infection or colonisation of this species.     

生殖支原体致病性及其感染的治疗进展

生殖支原体是男女生殖道及直肠感染的重要性病病原体,可通过黏附上皮细胞激发宿主的免疫反应,导致局部炎症.近年来,随着大环内酯类耐药菌株的广泛流行,早期使用阿奇霉素治疗生殖支原体感染的疗效明显下降.喹诺酮类的莫西沙星等可提高生殖支原体感染的治愈率,然而随之而来的喹诺酮类耐药菌株的出现,其治疗失败病例开始出现.更为严重的是,已经出现对大环内酯及喹诺酮类同时耐药的多重耐药菌株的报道.多西环素、原始霉素等也可用于生殖支原体感染的治疗,但存在细菌清除率低或每天多次服药的不足,因此,有必要寻找新的治疗药物及更佳的治疗方案.     

Tetracycline treatment does not eradicate Mycoplasma genitalium

OBJECTIVES: To study the treatment efficacy of tetracyclines and azithromycin in Mycoplasma genitalium positive patients attending an STD clinic. METHODS: All M genitalium positive patients (34 men and 26 women) attending an STD clinic during a 6 month period were treated with antibiotics. All patients known to be partners of M genitalium positive patients and those who were M genitalium positive, but not initially treated, were treated with azithromycin. Patients with urethritis and/or cervicitis were treated with tetracyclines before their M genitalium status was known. RESULTS: 10 of 14 women (71%) and 10 of 16 men (63%) treated with tetracyclines were M genitalium positive at follow up, whereas all patients treated with azithromycin (16 men and 20 women) were M genitalium negative, at the 4 week follow up visit. CONCLUSIONS: These results suggest that tetracyclines are not sufficient to eradicate M genitalium. Randomised controlled treatment trials are urgently needed.     

Mycoplasma genitalium: prevalence, clinical significance, and transmission

OBJECTIVES: To study the prevalence, symptoms and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in STD clinic attendees and in partners of M genitalium infected patients. METHODS: M genitalium and C trachomatis were detected by polymerase chain reaction from urethral and endocervical swab specimens in a cross sectional study among 445 female and 501 male STD clinic attendees. Partners of 26 female and 26 male M genitalium positive index patients were examined. RESULTS: The prevalence of C trachomatis and M genitalium was 4% and 6.3%, respectively, among the women and 5.4% and 6%, respectively, among the men. Dual infections were uncommon. M genitalium was strongly associated with urethritis in both men and women and with cervicitis in women. Among M genitalium infected men, symptomatic urethritis was more common than asymptomatic urethritis. M genitalium and C trachomatis were not associated with symptoms of urethritis or cervicitis in women. Of 26 male partners of M genitalium positive female index patients, 38% were positive, and 77% of the negative partners had symptoms of urethritis. The concordance rate for 22 female partners of male index patients was 45%. For both men and women the M genitalium prevalence was significantly higher in partners of M genitalium positive index patients than in M genitalium negative index patients with urethritis and/or cervicitis. CONCLUSIONS: M genitalium is associated with urethritis in both men and women and with cervicitis in women. A high concordance rate was found among sexual partners of M genitalium infected patients, indicating that the infection is sexually transmitted.     

2016 European guideline on Mycoplasma genitalium infections

Mycoplasma genitalium infection contributes to 10–35% of non‐chlamydial non‐gonococcal urethritis in men. In women, M. genitalium is associated with cervicitis and pelvic inflammatory disease (PID). Transmission of M. genitalium occurs through direct mucosal contact. Asymptomatic infections are frequent. In women, symptoms include vaginal discharge, dysuria or symptoms of PID – abdominal pain and dyspareunia. In men, urethritis, dysuria and discharge predominates. Besides symptoms, indication for laboratory test is a high‐risk sexual behaviour. Diagnosis is achievable only through nucleic acid amplification testing (NAAT). If available, NAAT diagnosis should be followed with an assay for macrolide resistance. Therapy for M. genitalium is indicated if M. genitalium is detected or on an epidemiological basis. Doxycycline has a low cure rate of 30–40%, but does not increase resistance. Azithromycin has a cure rate of 85–95% in macrolide susceptible infections. An extended course appears to have a higher cure rate. An increasing prevalence of macrolide resistance, most likely due to widespread use of azithromycin 1 g single dose without test of cure, is drastically decreasing the cure rate. Moxifloxacin can be used as second‐line therapy, but resistance is increasing. Uncomplicated M. genitalium infection should be treated with azithromycin 500 mg on day one, then 250 mg on days 2–5 (oral), or josamycin 500 mg three times daily for 10 days (oral). Second line treatment and treatment for uncomplicated macrolide resistant M. genitalium infection is moxifloxacin 400 mg od for 7–10 days (oral). For third line treatment of persistent M. genitalium infection after azithromycin and moxifloxacin doxycycline 100 mg two times daily for 14 days can be tried and may cure 30%. Pristinamycin 1 g four times daily for 10 days (oral) has a cure rate of app. 90%. Complicated M. genitalium infection (PID, epididymitis) is treated with moxifloxacin 400 mg od for 14 days.