初始治疗注意事项
对于确诊患有尿道炎且有症状的患者(黏液脓性分泌物,革兰氏染色每高倍视野中多形核白细胞 [PMN]≥2 个,尿液白细胞酯酶检测结果呈阳性,或尿沉渣中每高倍视野中 PMN≥10 个),在得出检查结果之前,应针对淋球菌性 (GU) 和非淋球菌性尿道炎 (NGU) 两者进行假定性治疗。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com[37]International Union against Sexually Transmitted Infections. 2016 European Guideline on the management of non-gonococcal urethritis. 2016. http://www.iusti.org/ (last accessed 10 October 2016).http://www.iusti.org/regions/europe/pdf/2016/2016EuropeanNGUGuideline.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/27147267?tool=bestpractice.com[38]Horner P, Blee K, O'Mahony C, et al; Clinical Effectiveness Group of the British Association for Sexual Health and HIV. 2015 UK national guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2015 May 22. [Epub ahead of print]http://www.bashh.org/documents/UK%20National%20Guideline%20on%20the%20Management%20of%20Non-gonococcal%20Urethritis%202015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26002319?tool=bestpractice.com 治疗期间患者应避免性生活。如果不能确诊尿道炎,则应推迟治疗,除非认为患者感染风险高且不太可能返回随访。
对于所有的尿道炎患者,应尽力确保对患者前 60 天内的性伴侣进行评估,并对其采用推荐的方案进行治疗。 [
]In people with sexually transmitted infections, what are the best strategies for partner notification?http://cochraneclinicalanswers.com/doi/10.1002/cca.676/full显示答案 对于有衣原体或淋病感染的异性恋患者,应考虑性伴侣加速治疗,但无法确保患者前 60 天内的所有性伴侣都得到评估和治疗。具体做法是在患者的性伴侣未经医疗人员检查的情况下,通过患者将药物或处方给其性伴侣。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com加快性伴疗法的法律可能因国家而不同。患者应联系当地卫生部门,确定这一做法在当地是否合法。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com[39]Hogben M. Partner notification for sexually transmitted diseases. Clin Infect Dis. 2007;44:S160-S174.http://cid.oxfordjournals.org/content/44/Supplement_3/S160.longhttp://www.ncbi.nlm.nih.gov/pubmed/17342669?tool=bestpractice.com[40]Golden MR, Whittington WL, Handsfield HH, et al. Effect of expedited treatment of sex partners on recurrent or persistent gonorrhea or chlamydial infection. N Engl J Med. 2005;352:676-685.http://content.nejm.org/cgi/content/full/352/7/676http://www.ncbi.nlm.nih.gov/pubmed/15716561?tool=bestpractice.com[41]The American College of Obstetricians and Gynecologists. Committee opinion no. 506: expedited partner therapy in the management of gonorrhea and chlamydia by obstetrician-gynecologists. Obstet Gynecol. 2011;118:761-766.http://www.ncbi.nlm.nih.gov/pubmed/21860319?tool=bestpractice.com 这些做法有争议,原因在于尽管它们可有效减少淋病和衣原体尿道炎的传播,但却失去了面对面接触、咨询、检测其他性传播疾病,或发现抗生素过敏的机会。CDC: expedited partner therapy
尿道炎会促进艾滋病的传播。对艾滋病毒感染者和非艾滋病毒感染者的治疗方法相同。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
初期革兰氏染色提示淋病
如果初始革兰氏染色提示淋病,则建议采用针对 GU 和 NGU 的
[Figure caption and citation for the preceding image starts]: 尿道分泌物革兰氏染色查见革兰氏阴性双球菌和多形核白细胞改编自公共卫生图片库,疾病预防与控制中心(Jacobs N,1974 年) [Citation ends].假定性二联疗法(即使用作用机制不同的两种抗生素)。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com[29]Bignell C, Unemo M; European STI Guidelines Editorial Board. 2012 European guideline on the diagnosis and treatment of gonorrhoea in adults. Int J STD AIDS. 2013;24:85-92.https://www.bashh.org/documents/3920.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24400344?tool=bestpractice.com[37]International Union against Sexually Transmitted Infections. 2016 European Guideline on the management of non-gonococcal urethritis. 2016. http://www.iusti.org/ (last accessed 10 October 2016).http://www.iusti.org/regions/europe/pdf/2016/2016EuropeanNGUGuideline.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/27147267?tool=bestpractice.com感染淋病奈瑟菌的患者常合并感染沙眼衣原体;因此,二联疗法方案应同时涵盖这两种微生物(如头孢菌素加阿奇霉素或多西环素)。
美国疾病预防控制中心 (CDC) 建议的一线治疗方案是肌肉注射头孢曲松加阿奇霉素,最好在医务人员的直接观察下同时给药。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com作为次选抗生素,阿奇霉素优于多西环素,因其可作为单药治疗,且淋球菌对多西环素的耐药性发生率较高;但多西环素可用于对阿奇霉素过敏的患者。
如果无法使用头孢曲松,则口服头孢克肟联合阿奇霉素是合适的替代方案。可用于替代头孢曲松加阿奇霉素的其他单剂量注射用头孢菌素包括头孢唑肟、头孢西丁(与丙磺舒一起给药)和头孢噻肟。不推荐任何其他口服头孢菌素。
对于头孢菌素过敏的患者,可考虑口服吉米沙星或单次肌肉注射庆大霉素加高剂量阿奇霉素(即 2 g,单次给药);[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com然而,胃肠道不良作用可能限制这些方案的使用。大观霉素是另一种替代选择;不过,它在许多国家/地区无法获得。
妊娠女性应使用一线药物头孢曲松加阿奇霉素进行治疗。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com阿奇霉素的替代药物包括阿莫西林和红霉素,因为多西环素不建议用于妊娠期。大观霉素是另一种替代选择;不过,它在许多国家/地区无法获得。若患者对头孢菌素过敏、大观霉素无法获得或存在其他因素导致无法使用这些方案进行治疗,则建议咨询传染病专科医生。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
初期革兰氏染色不提示淋病
这些患者最初只针对非淋菌性尿道炎进行治疗。建议使用阿奇霉素或多西环素进行假定性治疗,因为这些药物可高效治疗沙眼衣原体感染。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com欧洲指南建议使用多西环素作为一线药物治疗来最大限度地减小诱发生殖支原体对大环内酯抗微生物药物产生耐药性的风险。[37]International Union against Sexually Transmitted Infections. 2016 European Guideline on the management of non-gonococcal urethritis. 2016. http://www.iusti.org/ (last accessed 10 October 2016).http://www.iusti.org/regions/europe/pdf/2016/2016EuropeanNGUGuideline.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/27147267?tool=bestpractice.com一项研究表明,使用阿奇霉素治疗后的衣原体残存率比使用多西环素后高。[42]Seña AC, Lensing S, Rompalo A, et al. Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis infections in men with nongonococcal urethritis: predictors and persistence after therapy. J Infect Dis. 2012;206:357-365.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490700/http://www.ncbi.nlm.nih.gov/pubmed/22615318?tool=bestpractice.com其他研究则发现,阿奇霉素和多西环素对(无论是由何种病原体导致的)NGU 的治愈率不存在差异,尽管这两种药物对生殖支原体感染的治疗失败率都很高(分别为 40% 和 30%)。[43]Manhart LE, Gillespie CW, Lowens MS, et al. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin Infect Dis. 2013;56:934-942.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588116/http://www.ncbi.nlm.nih.gov/pubmed/23223595?tool=bestpractice.com阿奇霉素被认为对治疗生殖支原体相关性 NGU 可能更有效,尽管有治疗失败的报道。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com[44]Bradshaw CS, Chen MY, Fairley CK. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS One. 2008;3:e3618.http://www.ncbi.nlm.nih.gov/pubmed/18978939?tool=bestpractice.com[45]Jensen JS, Bradshaw CS, Tabrizi SN, et al. Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with inducible macrolide resistance. Clin Infect Dis. 2008;47:1546-1553.http://cid.oxfordjournals.org/content/47/12/1546.longhttp://www.ncbi.nlm.nih.gov/pubmed/18990060?tool=bestpractice.com[46]Maeda S, Yasuda M, Ito S, et al. Azithromycin treatment for nongonococcal urethritis negative for chlamydia trachomatis, mycoplasma genitalium, mycoplasma hominis, ureaplasma parvum, and ureaplasma urealyticum. Int J Urol. 2009;16:215-216.http://www.ncbi.nlm.nih.gov/pubmed/19228227?tool=bestpractice.com[47]Bradshaw CS, Jensen JS, Tabrizi SN, et al. Azithromycin failure in Mycoplasma genitalium urethritis. Emerg Infect Dis. 2006;12:1149-1152.http://www.ncbi.nlm.nih.gov/pubmed/16836839?tool=bestpractice.com[48]Mena LA, Mroczkowski TF, Nsuami M, et al. A randomized comparison of azithromycin and doxycycline for the treatment of mycoplasma genitalium-positive urethritis in men. Clin Infect Dis. 2009;48:1649-1654.http://www.ncbi.nlm.nih.gov/pubmed/19438399?tool=bestpractice.com[49]Schwebke JR, Rompalo A, Taylor S, et al. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial. Clin Infect Dis. 2011;52:163-170.http://cid.oxfordjournals.org/content/52/2/163.longhttp://www.ncbi.nlm.nih.gov/pubmed/21288838?tool=bestpractice.com适合的替代方案包括红霉素、左氧氟沙星或氧氟沙星。
妊娠女性应使用一线药物阿奇霉素进行治疗。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com阿奇霉素的替代药物是阿莫西林或红霉素。多西环素和喹诺酮不建议用于妊娠期。如果患者存在任何因素导致无法使用这些方案进行治疗,则建议咨询传染病专科医生。
如果培养和/或聚合酶链反应 (PCR) 随后确诊淋病(通常在 1-2 日内),则应添加适合的抗淋球菌抗生素(如头孢菌素)。[37]International Union against Sexually Transmitted Infections. 2016 European Guideline on the management of non-gonococcal urethritis. 2016. http://www.iusti.org/ (last accessed 10 October 2016).http://www.iusti.org/regions/europe/pdf/2016/2016EuropeanNGUGuideline.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/27147267?tool=bestpractice.com[38]Horner P, Blee K, O'Mahony C, et al; Clinical Effectiveness Group of the British Association for Sexual Health and HIV. 2015 UK national guideline on the management of non-gonococcal urethritis. Int J STD AIDS. 2015 May 22. [Epub ahead of print]http://www.bashh.org/documents/UK%20National%20Guideline%20on%20the%20Management%20of%20Non-gonococcal%20Urethritis%202015.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/26002319?tool=bestpractice.com
随访
CDC 建议,确诊为非复杂性泌尿生殖系统淋病且已进行任何推荐或替代治疗的患者无需进行治愈检测。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com具体确诊为衣原体感染、淋病或毛滴虫感染的男性应在治疗后 3 个月接受复查,因为据报道再感染率很高,无论其性伴侣是否接受过治疗。
妊娠女性应接受复查以确定是否治愈。复查优先选择使用核酸扩增试验 (NAAT),例如对尿道分泌物和/或尿沉渣进行连接酶链反应 (LCR) 或 PCR 检测。建议在治疗后 3-4 周进行衣原体感染治愈检测,并在第 3 个月进行复查。建议在第 3 个月进行淋病复查。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
复发性或持续性尿道炎
确认是否存在尿道炎的客观体征。如果没有尿道炎的客观证据,长期或重复使用抗菌药物效果有限。此时应对患者进行(重新)评估,以确认尿道炎是否有非感染性原因(例如创伤、经尿道使用设备或仪器、异物插入尿道、包括杀精剂在内的化学刺激)。
如果患者没有可靠地完成初始治疗,或因接触未经治疗的性伴侣再次暴露,则可采用初始治疗方案进行复治。
在以下患者中应考虑到治疗失败:[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
疑似治疗失败的淋球菌性尿道炎患者应使用推荐的方案(头孢曲松加阿奇霉素)进行复治,因为再感染的可能性大于真正的治疗失败。如果治疗失败的可能性更大,应获取样本进行培养和药敏试验。对于这些患者,可以考虑使用吉米沙星或庆大霉素加高剂量阿奇霉素(即 2 g,单次给药)。如果头孢克肟加阿奇霉素被用作初治方案,则可以使用头孢曲松加高剂量阿奇霉素。应在复治后 7-14 天进行治愈检测(通过培养、NAAT 和药敏试验)。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
对于疑似治疗失败且最初使用多西环素进行治疗的 NGU 患者,应给予阿奇霉素(即 1 g,单次给药),因为持续性或复发性 NGU 的最常见病因是生殖支原体感染。如果阿奇霉素治疗失败,建议使用莫西沙星,因为在阿奇霉素治疗失败的病例中,尚未发现更高剂量的阿奇霉素可有效治疗生殖支原体感染。在阴道毛滴虫感染率高的地区,与女性发生性行为且有持续性或复发性尿道炎的男性应使用甲硝唑或替硝唑进行假定性治疗。在接受针对生殖支原体或阴道毛滴虫的假定性治疗后有持续性或复发性 NGU 的患者应转诊至专科医生处进行治疗。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
治疗失败时,应咨询传染病专家。在许多国家,这类病例应向政府卫生主管部门报告。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com
曾有过耐四环素类药物的解脲支原体和耐大环内酯的生殖支原体的报道。[1]Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64:1-137.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/26042815?tool=bestpractice.com[10]Yokoi S, Maeda S, Kubota Y, et al. The role of Mycoplasma genitalium and Ureaplasma urealyticum biovar 2 in postgonococcal urethritis. Clin Infect Dis. 2007;45:866-871.http://cid.oxfordjournals.org/content/45/7/866.longhttp://www.ncbi.nlm.nih.gov/pubmed/17806051?tool=bestpractice.com[44]Bradshaw CS, Chen MY, Fairley CK. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS One. 2008;3:e3618.http://www.ncbi.nlm.nih.gov/pubmed/18978939?tool=bestpractice.com[45]Jensen JS, Bradshaw CS, Tabrizi SN, et al. Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with inducible macrolide resistance. Clin Infect Dis. 2008;47:1546-1553.http://cid.oxfordjournals.org/content/47/12/1546.longhttp://www.ncbi.nlm.nih.gov/pubmed/18990060?tool=bestpractice.com[46]Maeda S, Yasuda M, Ito S, et al. Azithromycin treatment for nongonococcal urethritis negative for chlamydia trachomatis, mycoplasma genitalium, mycoplasma hominis, ureaplasma parvum, and ureaplasma urealyticum. Int J Urol. 2009;16:215-216.http://www.ncbi.nlm.nih.gov/pubmed/19228227?tool=bestpractice.com[47]Bradshaw CS, Jensen JS, Tabrizi SN, et al. Azithromycin failure in Mycoplasma genitalium urethritis. Emerg Infect Dis. 2006;12:1149-1152.http://www.ncbi.nlm.nih.gov/pubmed/16836839?tool=bestpractice.com但由于缺少确认性检测手段,因此上述情况仅仅是临床怀疑。由于这类病原体难以培养,通常难以获知其耐药情况,因此不太可能获得其药敏资料。
针对难治性病例,最后一步应排除疱疹性尿道炎等少见病因。