对孕妇进行筛查,以预防新生儿B族链球菌感染
B 族链球菌 (GBS) 是新生儿脓毒症的一种主要病因,出生前从产妇阴道定植的细菌中获得该细菌。一些研究显示,对带菌者和高危人群进行针对定植的积极筛查联合产时应用抗生素可以降低早发型B族链球菌感染的发病率,并且在美国这是推荐的预防手段。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com[39]Royal College of Obstetricians and Gynaecologists. The prevention of early onset neonatal group B streptococcal disease. Green-top guideline no. 36. September 2017. http://www.rcog.org.uk/ (last accessed 18 september 2017).http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14821/fullhttp://www.ncbi.nlm.nih.gov/pubmed/28901693?tool=bestpractice.com[40]American College of Obstetricians and Gynaecologists. Prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2011;117:1019-1027.http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Prevention_of_Early-Onset_Group_B_Streptococcal_Disease_in_Newbornshttp://www.ncbi.nlm.nih.gov/pubmed/21422882?tool=bestpractice.com[41]Powers RJ, Wirtschafter D; Perinatal Quality Improvement Panel of the California Perinatal Quality Care Collaborative. Prevention of group B streptococcus early-onset disease: a toolkit by the California Perinatal Quality Care Collaborative. J Perinatol. 2010;30:77-87.http://www.ncbi.nlm.nih.gov/pubmed/19657350?tool=bestpractice.com[53]Taminato M, Fram D, Torloni MR, et al. Screening for group B streptococcus in pregnant women: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2011;19:1470-1478.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-11692011000600026&lng=en&nrm=iso&tlng=enhttp://www.ncbi.nlm.nih.gov/pubmed/22249684?tool=bestpractice.com然而,这在一篇系统评价中受到争议,该系统评价总结道,尽管给予B族链球菌定植产妇预防性抗生素治疗似乎降低了早发型B族链球菌病的发病率,但是这可能是由研究设计和实施的偏倚造成的。[42]Ohlsson A, Shah VS. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2014;(6):CD007467.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007467.pub4/fullhttp://www.ncbi.nlm.nih.gov/pubmed/24915629?tool=bestpractice.com美国疾病预防控制中心 (CDC)推荐一种筛查方案来预防早发型B族链球菌感染。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com该筛查方案获得了美国儿科学会和美国妇产科医师协会的认可和支持。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com[40]American College of Obstetricians and Gynaecologists. Prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2011;117:1019-1027.http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Prevention_of_Early-Onset_Group_B_Streptococcal_Disease_in_Newbornshttp://www.ncbi.nlm.nih.gov/pubmed/21422882?tool=bestpractice.com
自从应用 B族链球菌筛查和产时抗生素预防以来,早发型B族链球菌感染的发病率下降了 80%。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com[25]Chen KT, Ringer S, Cohen AP, et al. The role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis, J Perinatol. 2002;22:653-657.http://www.nature.com/jp/journal/v22/n8/full/7210818a.htmlhttp://www.ncbi.nlm.nih.gov/pubmed/12478449?tool=bestpractice.com在这段时期,B族链球菌分离株对大环内酯类抗生素的耐药性有所增强。[54]Larsen JW, Serve JL. Group B streptococcus and pregnancy: a review. Am J Obstet Gynecol. 2008;198:440-448.http://www.ncbi.nlm.nih.gov/pubmed/18201679?tool=bestpractice.com产时抗生素治疗未能降低晚发型疾病的发病率。
尽管引入了 B 族链球菌筛查,但是B族链球菌感染仍继续发生,不过,与基于风险的筛查方案相比,普遍筛查方案使早发型B族链球菌病的发病率出现更大程度的降低,原因在于后者错失了产时抗生素给药的机会。[8]Schrag SJ, Zell ER, Lynfield R, et al. A population-based comparison of strategies to prevent early-onset group B streptococcal disease in neonates. N Engl J Med. 2002;347:233-239.http://www.nejm.org/doi/full/10.1056/NEJMoa020205#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/12140298?tool=bestpractice.com[41]Powers RJ, Wirtschafter D; Perinatal Quality Improvement Panel of the California Perinatal Quality Care Collaborative. Prevention of group B streptococcus early-onset disease: a toolkit by the California Perinatal Quality Care Collaborative. J Perinatol. 2010;30:77-87.http://www.ncbi.nlm.nih.gov/pubmed/19657350?tool=bestpractice.com大多数病例(如果遵循筛查策略)见于 B族链球菌培养筛查结果为阴性 (64%) 的产妇所生的婴儿,大多数这些产妇有产时危险因素。[55]Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005;115:1240-1246.http://www.ncbi.nlm.nih.gov/pubmed/15867030?tool=bestpractice.com在妊娠 35-37 周时试验结果为阴性的产妇中,大约有 4%-6% 的产妇在足月分娩时出现培养结果阳性。[56]Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol. 1996;88:811-815.http://www.ncbi.nlm.nih.gov/pubmed/8885919?tool=bestpractice.com[57]Valkenburg-van den Berg AW, Houtman-Roelofsen RL, Oostvogel PM, et al. Timing of group B streptococcus screening in pregnancy: a systematic review. Gynecol Obstet Invest. 2010;69:174-183.http://www.ncbi.nlm.nih.gov/pubmed/20016190?tool=bestpractice.com
疾病发病率的差异和对同一文献的解读差异导致不同国家采用不同的预防方案。[2]Phares CR, Lynfield R, Farley M, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA. 2008;229:2056-2065.http://jama.ama-assn.org/cgi/content/full/299/17/2056http://www.ncbi.nlm.nih.gov/pubmed/18460666?tool=bestpractice.com[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com[23]Schuchat A. Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev. 1998;11:497-513.http://cmr.asm.org/cgi/content/full/11/3/497http://www.ncbi.nlm.nih.gov/pubmed/9665980?tool=bestpractice.com[40]American College of Obstetricians and Gynaecologists. Prevention of early-onset group B streptococcal disease in newborns. Obstet Gynecol. 2011;117:1019-1027.http://www.acog.org/Resources_And_Publications/Committee_Opinions/Committee_on_Obstetric_Practice/Prevention_of_Early-Onset_Group_B_Streptococcal_Disease_in_Newbornshttp://www.ncbi.nlm.nih.gov/pubmed/21422882?tool=bestpractice.com[45]Colbourn TE, Asseburg C, Bojke L, et al. Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. BMJ. 2007;335:655.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995477/http://www.ncbi.nlm.nih.gov/pubmed/17848402?tool=bestpractice.com[53]Taminato M, Fram D, Torloni MR, et al. Screening for group B streptococcus in pregnant women: a systematic review and meta-analysis. Rev Lat Am Enfermagem. 2011;19:1470-1478.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-11692011000600026&lng=en&nrm=iso&tlng=enhttp://www.ncbi.nlm.nih.gov/pubmed/22249684?tool=bestpractice.com[58]Shah V, Ohlsson A; Canadian Task Force on Preventive Health Care. Prevention of early-onset group B streptococcal (GBS) infection in the newborn: systematic review and recommendations CTFPHC technical report 01-6. May 2001. http://www.canadiantaskforce.ca (last accessed 18 September 2017).https://canadiantaskforce.ca/wp-content/uploads/2016/09/2002-streptococcal-systematic-review-and-recommendations-en.pdf[59]Colbourn T, Asseburg C, Bojke L, et al. Prenatal screening and treatment strategies to prevent group B streptococcal and other bacterial infections in early infancy: cost-effectiveness and expected value of information analyses. Health Technol Assess. 2007;11:1-226.http://www.ncbi.nlm.nih.gov/pubmed/17651659?tool=bestpractice.com[60]Daniels J, Gray J, Pattison H, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess. 2009;13:1-178.http://www.ncbi.nlm.nih.gov/pubmed/19778493?tool=bestpractice.com[61]Kotarski J, Heczko PB, Lauterbach R, et al. Polish Gynecological Society's recommendations regarding diagnosis and prevention of Streptococcus agalactiae infection in pregnant women and newborns [in Polish]. Ginekol Pol. 2008;79:221-223.http://www.ncbi.nlm.nih.gov/pubmed/18592860?tool=bestpractice.com[62]Yudin MH, van Schalkwyk J, Van Eyk N, et al. Antibiotic therapy in preterm premature rupture of the membranes. J Obstet Gynaecol Can. 2009;31:863-867, 868-874.http://www.ncbi.nlm.nih.gov/pubmed/19941711?tool=bestpractice.com[63]Queensland Health Statewide Maternity and Neonatal Clinical Guidelines Program. Early onset group B streptococcal disease. November 2010. http://www.health.qld.gov.au (last accessed 18 September 2017).http://www.health.qld.gov.au/qcg/documents/g_gbs5-0.pdf[64]Committee on Infectious Diseases; Committee on Fetus and Newborn, Baker CJ, Byington CL, et al. Policy statement - recommendations for the prevention of perinatal group B streptococcal (GBS) disease. Pediatrics. 2011;128:611-616.http://pediatrics.aappublications.org/content/128/3/611.longhttp://www.ncbi.nlm.nih.gov/pubmed/21807694?tool=bestpractice.com[65]Money D, Allen VM; Society of Obstetrician and Gynaecologists of Canada. The prevention of early-onset neonatal group B streptococcal disease. J Obstet Gynaecol Can. 2013;35:939-951.https://sogc.org/wp-content/uploads/2013/09/October2013-CPG298-ENG-Online_Final.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/24165063?tool=bestpractice.com
为减少错失预防治疗机会的次数,对筛查方案进行评估,确定了以下有待改善的方面:[66]Van Dyke MK, Phares CR, Lynfield R, et al. Evaluation of universal antenatal screening for group B streptococcus. N Engl J Med. 2009;360:2626-2636.http://www.nejm.org/doi/full/10.1056/NEJMoa0806820#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/19535801?tool=bestpractice.com
如何进行筛查
除了此次妊娠期间患有 B族链球菌菌尿症的孕妇或者以前生产的婴儿患有B族链球菌病的孕妇,所有孕妇都必须在妊娠 35-37 周时接受阴道和直肠培养。
使用棉签从阴道和直肠下段采集样本,然后投入增菌培养液内培养,并置于选择性培养基之上。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com[67]Public Health England. Standards for microbiology investigations. September 2014. https://www.gov.uk (last accessed 18 September 2017).https://www.gov.uk/government/collections/standards-for-microbiology-investigations-smi在培养之前,将样本保存在 4℃(39.2℉)的温度条件下,并且在采集之后 24 小时内进行处理,则培养的敏感性最高。样本应投入适当的增菌培养液内,并在 35℃-37℃(95℉-99℉)的温度条件下孵化 18-24 小时,以促进 B族链球菌恢复。此外还可以使用直接平板 (direct plate)。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com已发现自行采样是临床医生采样的一种准确、可接受的替代选择。[68]Price D, Shaw E, Howard M, et al. Self-sampling for group B streptococcus in women 35 to 37 weeks pregnant is accurate and acceptable: a randomized cross-over trial. J Obstet Gynaecol Can. 2006;28:1083-1088.http://www.ncbi.nlm.nih.gov/pubmed/17169231?tool=bestpractice.com
对于对青霉素或头孢菌素有严重过敏反应高风险的青霉素过敏孕妇,应对产前 B族链球菌分离株进行药敏试验。来自存在严重过敏反应高风险的青霉素过敏患者的分离株,如果对克林霉素敏感或者对红霉素耐药,则检查其是否存在克林霉素诱导耐药[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com
将从孕妇采集的尿液样本送检时,临床医生应告知实验室。纯粹培养或混合培养的集落形成单位≥10^4 表示尿液检测结果阳性,应予以报告。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com
检测结果阳性时的做法
对于所有出现 B族链球菌定植的产妇,皆应给予产时抗生素治疗。此外,存在以下情况的产妇也需要接受产时抗生素预防:
检测结果阴性时的做法
仅对存在以下情况的产妇进行产时抗生素预防:
未进行筛查时的做法
存在以下情况的产妇需要接受产时抗生素预防:
分娩发动时 B族链球菌携带的筛查
通过培养进行筛查的相关困难,孕妇妊娠 35-37 周时筛查结果为阴性但在分娩时转变为阳性的可能性(大约 4%),以及妊娠 35-37 周时筛查结果为阳性但在分娩时转变为阴性的可能性(大约 13%),已促使一些研究者寻找更多可以在分娩发动时实施的快速诊断试验。[56]Yancey MK, Schuchat A, Brown LK, et al. The accuracy of late antenatal screening cultures in predicting genital group B streptococcal colonization at delivery. Obstet Gynecol. 1996;88:811-815.http://www.ncbi.nlm.nih.gov/pubmed/8885919?tool=bestpractice.comPCR 检测是一种可行的方法,具有较高的敏感性和特异性,可以在 30-45 分钟内完成。[69]Bergeron MG, Danbing KE, Menard C, et al. Rapid detection of group B streptococci in pregnant women at delivery. N Engl J Med. 2000;343:175-179.http://www.nejm.org/doi/full/10.1056/NEJM200007203430303#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/10900276?tool=bestpractice.com然而,任何可用的试验都并不足够精确,也不符合成本效益。此外,在实际临床实践中每周 7 天、每天 24 小时进行 PCR 检测所需的后勤工作量非常大,从而阻碍了在许多机构使用该方法。[60]Daniels J, Gray J, Pattison H, et al. Rapid testing for group B streptococcus during labour: a test accuracy study with evaluation of acceptability and cost-effectiveness. Health Technol Assess. 2009;13:1-178.http://www.ncbi.nlm.nih.gov/pubmed/19778493?tool=bestpractice.com即时检验 (point-of-care test) 也正在开发之中,但当前还没有一种即时检验被投入常规使用或者被任何国家指南所支持。任何此类产品的使用都必须经由当地评估和支持。
如果在此前 5 周内未对 B族链球菌状态进行评估,则应在早产分娩发动时或早产胎膜早破时进行 B族链球菌筛查。应开始给予抗生素治疗,随后如果出现筛查结果阴性,或者孕妇没有进入真正的分娩且胎膜完整,则应停药。如果孕妇仍未分娩,则应在妊娠 35-37 周时重复进行筛查。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com
CDC指南现在支持在这种情况下使用核酸扩增试验(如果可用)。对于在进行试验时 B族链球菌定植状态未知,无产时危险因素(体温>38.0℃ [>100.4℉] 或羊膜破裂时间超过 18 个小时),且足月分娩的产妇,核酸扩增试验可以用于在产时检测阴道直肠样本。对于产时核酸扩增试验结果阳性或者随后出现产时危险因素(不论核酸扩增试验结果如何)的产妇,推荐给予抗生素预防。[9]Verani JR, McGee L, Schrag SJ, et al. Prevention of perinatal group B streptococcal disease - revised guidelines from CDC, 2010. MMWR. 2010;59:1-36.http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5910a1.htmhttp://www.ncbi.nlm.nih.gov/pubmed/21088663?tool=bestpractice.com