口服抗生素是尿路感染 (UTI) 的主要治疗措施。在选择合适的抗生素时,了解当地微生物耐药特点十分重要。[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com 治疗决策取决于UTI是单纯性还是复杂性。 复杂性感染病例可包括以下任意条件:男性、怀孕、导尿、留置尿管、复发性尿路感染病史、结构或功能性膀胱异常、耐药菌感染史、既往单纯性膀胱炎治疗失败、糖尿病或免疫抑制状态。 这类患者需要更长的疗程。
单纯性急性膀胱炎
急性非复杂性膀胱炎的一线治疗是为期 3-5 天的呋喃妥因,为期 3 天的甲氧苄啶/磺胺甲噁唑 (TMP/SMX) 或单用甲氧苄啶。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com[35]Zalmanovici Trestioreanu A, Green H, Paul M, et al. Antimicrobial agents for treating uncomplicated urinary tract infection in women. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD007182.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007182.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20927755?tool=bestpractice.com[36]Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) - report 2017. Nov 2017 [internet publication].https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/656611/ESPAUR_report_2017.pdf[37]National Institute for Health and Care Excellence. Urinary tract infection (lower): antimicrobial prescribing. Oct 2018 [internet publication].https://www.nice.org.uk/guidance/ng109 这些药物疗效相似;然而,如果当地引起非复杂性膀胱炎的病原体耐药率超过 20%,则不应将 TMP/SMX 或甲氧苄啶作为一线治疗药物。[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com 葡萄糖-6-磷酸脱氢酶 (glucose-6-phosphate dehydrogenase, G6PD) 缺乏症患者不应使用呋喃妥因,因为存在发生溶血性贫血的风险。
如果患者对呋喃妥因或 TMP/SMX 过敏,或者对呋喃妥因或 TMP/SMX 的细菌耐药性在当地普遍较高,那么,建议采用磷霉素单次剂量治疗。[38]Falagas ME, Vouloumanou EK, Togias AG, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010 Sep;65(9):1862-77.http://www.ncbi.nlm.nih.gov/pubmed/20587612?tool=bestpractice.com 一项荟萃分析表明,磷霉素治疗急性非复杂性膀胱炎的有效性与其他抗生素类似。[38]Falagas ME, Vouloumanou EK, Togias AG, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010 Sep;65(9):1862-77.http://www.ncbi.nlm.nih.gov/pubmed/20587612?tool=bestpractice.com 然而,一项研究将呋喃妥因的 5 天用药疗程与单剂磷霉素进行比较,发现使用呋喃妥因时,临床和微生物缓解情况更好。[39]Huttner A, Kowalczyk A, Turjeman A, et al. Effect of 5-day nitrofurantoin vs single-dose fosfomycin on clinical resolution of uncomplicated lower urinary tract infection in women: a randomized clinical trial. JAMA. 2018 May 1;319(17):1781-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134435/http://www.ncbi.nlm.nih.gov/pubmed/29710295?tool=bestpractice.com 除特定病例外,不建议使用 pivmecillinam 之外的其他替代药物(例如头孢菌素或氨基青霉素类)进行经验性治疗。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com 与呋喃妥因、TMP/SMX (甲氧苄氨嘧啶-磺胺甲基异噁唑) 或磷霉素相比,β-内酰胺制剂具有较高的生态附加损害风险(耐药病原体的选择、定植或感染耐多药病原体,后续感染 [例如艰难梭菌] 风险较高)。[30]Chu CM, Lowder JL. Diagnosis and treatment of urinary tract infections across age groups. Am J Obstet Gynecol. 2018 Jul;219(1):40-51.http://www.ncbi.nlm.nih.gov/pubmed/29305250?tool=bestpractice.com 由于存在负面的生态影响,氟喹诺酮不再适合作为非复杂性膀胱炎抗微生物治疗,应保留用于其他用途。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com
在管理非复杂性尿路感染时,不同治疗方案(经验性抗生素治疗、根据中段尿培养结果开具针对性药物延迟治疗)对症状的控制效果类似。[31]Little P, Moore MV, Turner S, et al. Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ. 2010 Feb 5;340:c199.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2817051/http://www.ncbi.nlm.nih.gov/pubmed/20139214?tool=bestpractice.com 抗生素相对安慰剂而言具有明显优势。[40]Falagas MEK. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect. 2009 Feb;58(2):91-102.http://www.ncbi.nlm.nih.gov/pubmed/19195714?tool=bestpractice.com
如果患者在经过 2-3 天的治疗后没有改善,则需要进行进一步评估。如尚未检查,应通过尿液分析确诊。在更换抗生素之前,应留取尿培养以便指导下一步治疗。
对于既往发生过膀胱炎再次复发的病例,治疗此次复发以及之后可能的复发时均可考虑患者的起始治疗。 在这种情况下,应在女性产生症状前提供抗生素处方并详细指导其使用。 患者信息手册会在这方面提供帮助。[41]Tucker MK, Sirotenko GA, Keating KN, et al. Educating patients with uncomplicated UTIs: the effect of an educational brochure on patient knowledge. Postgrad Med. 2004 Dec;116(suppl 6):3-10.http://www.ncbi.nlm.nih.gov/pubmed/19667682?tool=bestpractice.com
非那吡啶可用作抗生素之外的辅助治疗,缓解症状。需注意的是,它可能导致葡萄糖-6-磷酸脱氢酶缺乏症患者发生溶血。
复杂性急性膀胱炎
氟喹诺酮治疗复杂性急性膀胱炎推荐用于如下情境:当地耐药性小于 10%;患者病情不严重,且全部治疗可经口服进行;或患者对 β-内酰胺抗菌素有严重过敏反应。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/ 由于氟喹诺酮在一些泌尿科患者中的使用率较高,使其在这一特定群体中成功治疗的可能性较小,因此,如果患者在过去 6 个月内使用了氟喹诺酮,则不建议将其作为一线治疗。[42]van der Starre WE, van Nieuwkoop C, Paltansing S, et al. Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection. J Antimicrob Chemother. 2011 Mar;66(3):650-6.https://academic.oup.com/jac/article/66/3/650/728616http://www.ncbi.nlm.nih.gov/pubmed/21123286?tool=bestpractice.com 在对氟喹诺酮过敏或耐药的情况下,第三代头孢菌素(例如头孢泊肟)将是合适的首选药物。
具有全身症状、需要住院的复杂性 UIT 患者应首先静脉输注抗生素进行治疗,例如,青霉素加氨基糖苷;第二代头孢菌素加氨基糖苷类;或第三代头孢菌素。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/ 随着病情改善,患者的治疗方案可改为微生物对之敏感的口服抗微生物药物,完成治疗过程。[34]Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.http://www.ncbi.nlm.nih.gov/pubmed/21292654?tool=bestpractice.com
需要进行尿常规、尿培养及药敏检测并根据药敏结果修改治疗方案。
非那吡啶可用作抗生素之外的辅助治疗,缓解症状。需注意的是,它可能导致葡萄糖-6-磷酸脱氢酶缺乏症患者发生溶血。
妊娠患者急性膀胱炎
对于复杂性感染的妊娠人群,一般不建议使用氟喹诺酮、四环素和甲氧苄啶/磺胺甲噁唑。因此对于这些患者来说,一线抗生素是呋喃妥因,但由于存在新生儿溶血性贫血的理论风险,应避免在妊娠晚期使用。[43]Sheffield JS, Cunningham FG. Urinary tract infection in women. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1085-92.http://www.ncbi.nlm.nih.gov/pubmed/16260529?tool=bestpractice.com 替代药物包括头孢菌素和青霉素。[1]European Association of Urology. Guidelines on urological infections. 2018 [internet publication].http://uroweb.org/guideline/urological-infections/ 经证明,磷霉素与其他治疗选择一样有效,也可考虑用作妊娠期间的恰当选择。[44]Estebanez A, Pascual R, Gil V, et al. Fosfomycin in a single dose versus a 7-day course of amoxicillin-clavulanate for the treatment of asymptomatic bacteriuria during pregnancy. Eur J Clin Microbiol Infect Dis. 2009 Dec;28(12):1457-64.http://www.ncbi.nlm.nih.gov/pubmed/19768649?tool=bestpractice.com[45]Usta TA, Dogan O, Ates U, et al. Comparison of single-dose and multiple-dose antibiotics for lower urinary tract infection in pregnancy. Int J Gynecol Obstet. 2011 Sep;114(3):229-33.http://www.ncbi.nlm.nih.gov/pubmed/21696732?tool=bestpractice.com
复发性膀胱炎
需要向慢性复发性尿路感染患者提供预防性抗生素(甲氧苄氨嘧啶/磺胺甲噁唑或呋喃妥因),采取每天服用或性交后服用的方案。 性生活后排尿可能有帮助。[46]Foxman B, Frerichs RR. Epidemiology of urinary tract infection: II. Diet, clothing, and urination habits. Am J Public Health. 1985 Nov;75(11):1314-7.http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=4051067http://www.ncbi.nlm.nih.gov/pubmed/4051067?tool=bestpractice.com 长期使用呋喃妥因时应当谨慎,因为存在肺损伤的风险。[47]Santos JM, Batech M, Pelter MA, et al. Evaluation of the risk of nitrofurantoin lung injury and its efficacy in diminished kidney function in older adults in a large integrated healthcare system: a matched cohort study. J Am Geriatr Soc. 2016 Apr;64(4):798-805.http://www.ncbi.nlm.nih.gov/pubmed/27100576?tool=bestpractice.com
根据一项系统回顾,马尿酸乌洛托品可能有效,尤其是对无解剖异常患者短期预防。[48]Lee BS, Bhuta T, Simpson JM, et al. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;(10):CD003265.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003265.pub3/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23076896?tool=bestpractice.com
一些针对每日口服高剂量蔓越莓的研究发现,其片剂或提取物可使UTI发生率轻中度减低20%~30%,但是不同研究间结果不尽相同。[49]Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2012 Oct 17;(10):CD001321.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001321.pub5/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23076891?tool=bestpractice.com[50]Wang CH, Fang CC, Chen NC, et al. Cranberry-containing products for prevention of urinary tract infections in susceptible populations: a systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Jul 9;172(13):988-96.http://www.ncbi.nlm.nih.gov/pubmed/22777630?tool=bestpractice.com 如果患者想要尝试蔓越莓汁,医生不应阻止其饮食中添加合理剂量的蔓越莓汁。
对于未来可能发作的病例,患者初始的治疗也可考虑。 在这种情况下,应在女性产生症状前提供抗生素处方并详细指导其使用。 患者信息手册会在这方面提供帮助。[41]Tucker MK, Sirotenko GA, Keating KN, et al. Educating patients with uncomplicated UTIs: the effect of an educational brochure on patient knowledge. Postgrad Med. 2004 Dec;116(suppl 6):3-10.http://www.ncbi.nlm.nih.gov/pubmed/19667682?tool=bestpractice.com