国际妇产科学杂志, 2022, 49(6): 668-674 doi: 10.12280/gjfckx.20220546

产科生理及产科疾病:综述

产科抗生素临床应用进展

潘宇霞, 项晴怡, 白晓霞,

310006 杭州,浙江大学医学院附属妇产科医院产科

Progress in Clinical Application of Antibiotics in Obstetrics

PAN Yu-xia, XIANG Qing-yi, BAI Xiao-xia,

Department of Obstetrics, Women′s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China

通讯作者: 白晓霞,E-mail:baixiaoxia@zju.edu.cn

审校者

本文编辑: 王琳

收稿日期: 2022-07-6  

Corresponding authors: BAI Xiao-xia, E-mail:baixiaoxia@zju.edu.cn

Received: 2022-07-6  

摘要

孕产妇在妊娠期、分娩期和产褥期具有独特的解剖生理特点,容易发生生殖道细菌感染,病情进展可导致早产、流产、胎膜早破、羊膜腔感染、胎儿窘迫、死胎、产褥感染及脓毒血症等不良妊娠结局。目前,抗生素作为预防和治疗细菌感染最有效的药物,广泛应用于产科临床。值得注意的是,孕产妇的合理用药既要考虑到病情本身,同时也要兼顾到妊娠期、哺乳期的母婴双重安全,因此抗生素在产科的实际临床应用中仍存在许多问题,应得到更多的关注。就如何合理使用抗生素,结合不同时期、常见病种进行综述,有助于为妊娠期和哺乳期用药指导提供更多的理论依据。

关键词: 抗菌药; 生殖道感染; 细菌感染; 产褥期感染; 孕妇

Abstract

Pregnant women have unique anatomical and physiological characteristics during pregnancy, delivery and puerperium, and are prone to genital tract bacterial infection. The progression of the disease can lead to adverse pregnancy outcomes such as premature birth, abortion, premature rupture of membranes, intra amniotic infection, fetal distress, stillbirth, puerperal infection, sepsis and so on. At present, antibiotics, as the most effective drugs to prevent and treat bacterial infections, are widely used in obstetric clinic. It is worth noting that rational use of drug for pregnant women should not only take into account the illness itself, but also take into account the safety of mother and child during pregnancy and lactation. Therefore, there are still many problems in the actual clinical application of antibiotics in obstetrics, which should be paid more attention to. This article reviews how to use antibiotics rationally, combined with different periods and common diseases, which is helpful to provide more theoretical basis for medication guidance during pregnancy and lactation.

Keywords: Anti-bacterial agents; Reproductive tract infections; Bacterial infections; Puerperal infection; Pregnant women

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本文引用格式

潘宇霞, 项晴怡, 白晓霞. 产科抗生素临床应用进展[J]. 国际妇产科学杂志, 2022, 49(6): 668-674 doi:10.12280/gjfckx.20220546

PAN Yu-xia, XIANG Qing-yi, BAI Xiao-xia. Progress in Clinical Application of Antibiotics in Obstetrics[J]. Journal of International Obstetrics and Gynecology, 2022, 49(6): 668-674 doi:10.12280/gjfckx.20220546

感染作为产科领域重要问题之一,至今仍是全球孕产妇和围生儿发病和死亡的主要原因之一。从感染部位来看,产科生殖道感染发生率高[1],一方面妊娠期女性受雌孕激素水平升高和机体免疫力下降的影响,阴道微生物群可能出现失衡、继发生殖道感染;另一方面女性下生殖道呈生理性开放,且产科有较多侵入性操作,如经阴道检查、剖宫产手术等,容易导致生殖道上行感染[2]。从病原学来看,细菌感染较为常见,大肠埃希菌、B族链球菌(group B streptococcus,GBS)及厌氧菌等均为常见致病菌[3]。众多研究表明,生殖道细菌感染可导致早产、流产、胎膜早破(premature rupture of membrane,PROM)、羊膜腔感染(intra amniotic infection,IAI)、胎儿窘迫、死胎、产褥感染、新生儿感染和孕产妇死亡等不良妊娠结局,因此及时预防和治疗生殖道细菌感染尤为重要。循证医学已证明抗生素是针对细菌感染最有效的药物,但抗生素在产科临床应用中仍存在诸多问题,如用药指征和时机、药品种类、药物对胎儿和新生儿的毒性、群体耐药性的增加等。为更好地促进产科抗生素的合理使用,减少细菌耐药,安全有效地治疗孕产妇感染,减少母儿并发症,现对产科抗生素临床应用进展进行综述。

1 抗生素在妊娠期的临床应用

1.1 妊娠合并细菌性阴道病(bacterial vaginosis,BV)

健康育龄期女性阴道微环境是由以乳杆菌为优势菌群,多种厌氧菌及需氧菌共同组成的微生态动态平衡系统,BV则是由于兼性厌氧菌及厌氧菌增多取代乳杆菌而导致的下生殖道感染[4],妊娠期妇女BV易感性增加,可通过逆行感染上生殖道导致不良妊娠结局。中华医学会及国际性病控制联盟/世界卫生组织(International Union Against Sexually Transmitted Infections/World Health Organisation,IUSTI/WHO)均推荐对有症状孕妇或无症状但既往有感染相关流产或早产病史的高危孕妇进行阴道分泌物筛查,如筛查结果阳性则进行治疗[5-6]。美国预防医学工作组(U.S. Preventive Services Task Force,USPSTF)不推荐对无症状、早产低危孕妇进行常规筛查和治疗;对无症状、早产高危孕妇是否常规筛查和治疗存在争议[7]。国内外不同指南[包括中华医学会、IUSTI/WHO、美国妇产科医师学会(American College of Obstetricians and Gynecologists,ACOG)、美国疾病控制与预防中心(Centers for Disease Control and Prevention,CDC)、加拿大妇产科医师协会(Society of Obstetricians and Gynaecologists of Canada,SOGC)]对BV的治疗方法相似,均首选甲硝唑和克林霉素[5-6,8 -10],故目前国内BV治疗方案的制定主要依据《细菌性阴道病诊治指南(2021修订版)》(具体用药方案见表1[5]),并建议在治疗1个月后进行随访,有条件者可同时完善阴道微生态检测[5]

表1   妊娠期、哺乳期BV的用药方案[5]

方案用药方案
推荐方案①甲硝唑400 mg,口服,2次/d,共7 d
②0.75%甲硝唑凝胶5 g,阴道给药,1次/d,共5 d
③甲硝唑阴道栓200 mg,阴道给药,1次/d,共5~7 d
④2%克林霉素软膏5 g,阴道给药,每晚1次,共7 d
替代方案①克林霉素300 mg,口服,2次/d,共7 d
②克林霉素阴道栓100 mg,阴道给药,每晚1次,共3 d

注:妊娠期首选口服全身用药,哺乳期首选阴道局部用药,如无法避免全身用药则建议延迟母乳喂养12~24 h;阴道用药期间避免性生活。

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局限性:①当前证据未发现甲硝唑和克林霉素对胎儿存在致畸作用,但甲硝唑的药品说明显示孕妇及哺乳期妇女禁用,因此临床用药要做好知情告知,减轻患者疑虑。②BV复发率高[11],目前指南对复发性BV的治疗无明确共识,临床主要通过延长用药时间或全身联合局部用药的方式治疗,近年研究多致力于寻找新的抗生素、阴道微生态制剂和免疫调节剂等,但具体治疗效果暂不明确,需寻求更多高质量临床证据支持。

1.2 妊娠期GBS感染

GBS存在于消化道和泌尿生殖道内,属条件致病菌,约10%~30%的孕妇伴有GBS定植,中国孕妇GBS定植率为11.3%[12-13]。近年来许多证据已表明,GBS感染是导致母体产褥期感染和新生儿感染或死亡的重要原因,感染GBS的早产儿死亡率可高达19.2%[14],而现有证据已明确围生期预防性使用抗生素可有效降低新生儿GBS病的发生率[15],国外已得出较为成熟的关于妊娠期GBS筛查与产时抗生素应用的相关对策[14,16 -20],我国则在此基础上结合国情制定了《预防围产期B族链球菌病(中国)专家共识》[21]。妊娠期GBS感染筛查对象包括所有孕35~37周的孕妇,筛查有效期为5周。如距筛查时间已超过5周孕妇仍未分娩则建议重复筛查;有妊娠期GBS菌尿者或既往有新生儿GBS病史者直接按GBS阳性处理;检测条件有限的机构,如孕妇合并以下危险因素,即体温≥38 ℃、早产不可避免、未足月胎膜早破(preterm premature rupture of membrane,PPROM)、胎膜破裂≥18 h,可在接诊或入院时立即完成GBS阴道-直肠拭子采样,并针对GBS进行预防性治疗[21]。妊娠期GBS感染预防性使用抗生素的指征包括:此次妊娠GBS筛查阳性,既往有新生儿GBS病史,此次妊娠期GBS菌尿,GBS定植不详但合并至少1项危险因素或既往妊娠有GBS定植史[21]。孕妇达到上述任一指征且出现PROM或进入产程,建议尽早静脉预防性使用抗生素,存在上述指征但未破膜、未进入产程的剖宫产者无需用药。

指南推荐产时针对GBS预防性应用抗生素的首选方案是静脉输注青霉素[21],在使用前常规行青霉素皮试。若皮试阴性,使用青霉素;若皮试阳性,可在头孢类抗生素不过敏或头孢唑林皮试阴性的情况下选用头孢唑林;否则根据GBS菌株对克林霉素的药敏情况进行选择,若对克林霉素敏感,选用克林霉素,若不敏感,选用万古霉素。若既往青霉素过敏者此次未行青霉素皮试,根据既往过敏表现选择,发生严重过敏反应的风险较低时选用头孢唑林,发生严重过敏反应的风险较高时,可在药敏试验显示GBS菌株对克林霉素敏感时选用克林霉素,否则静脉用万古霉素是唯一有效的抗生素选择(具体用药方案见表2[21])。值得强调的是,产程中一旦怀疑出现宫内感染,为争取良好的母婴预后,应及时换用覆盖包括GBS在内的多种微生物的广谱抗生素[22]

表2   妊娠期GBS感染的用药方案[21]

个体情况用药方案(静脉用药)
青霉素皮试阴性①青霉素G 500万单位 首剂+250~300万单位q4h至分娩
②氨苄青霉素2 g 首剂+1 g q4h至分娩
青霉素皮试阳性无头孢过敏史或头孢唑林皮试阴性头孢唑林2 g首剂+1 g q8h至分娩
有头孢严重过敏史或头孢唑林皮试阳性①克林霉素0.9 g q8h至分娩
②万古霉素20 mg/kg q8h至分娩
有青霉素过敏史且未做皮试严重过敏风险低头孢唑林2 g首剂+1 g q8h至分娩
严重过敏风险高①克林霉素0.9 g q8h至分娩
②万古霉素20 mg/kg q8h至分娩

注:严重过敏风险低指既往过敏时出现胃肠道不适、头痛、阴道炎、无全身症状的非荨麻疹性斑丘疹或不伴皮疹的瘙痒;严重过敏风险高指既往过敏时出现I型超敏反应或罕见的迟发过敏反应:瘙痒性皮疹、荨麻疹、皮肤即刻潮红、低血压、血管性水肿、呼吸窘迫、嗜酸性粒细胞增多、全身症状/药物诱发的超敏反应综合征、Stevens-Johnson综合征或中毒性表皮坏死松解症等。q4h:每4小时1次,q8h:每8小时1次。

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GBS菌尿指妊娠期行中段尿液培养显示GBS阳性,不论孕周大小和菌落计数多少,均提示严重阴道-直肠GBS定植[23],发生胎膜早破和早产风险增加,因此建议预防性使用抗生素[21]:有泌尿系统感染症状者立即治疗;每毫升GBS菌落计数≥104个菌落形成单位(colony forming unit,CFU),即≥104 CFU/mL,应立即治疗,且在产程中预防性应用抗生素;GBS菌落计数<104 CFU/mL,且无症状,只需在产程中预防性应用抗生素。首选青霉素,口服或静脉用药4~7 d,若青霉素皮试阳性,则根据药敏试验选择敏感抗生素,但不建议使用克林霉素[24]。治疗后建议停药1周复查尿培养评估治疗效果,并在之后每月复查尿培养。

局限性:①由于我国关于孕妇GBS筛查和预防GBS感染相关指南形成较晚,国内部分医院缺乏GBS筛查的意识,未形成规范治疗观念,导致潜在性GBS未能及时发现,有可能增加不良妊娠结局的发生,需结合共识逐步规范临床实践。②严格的循证医学研究推动产科学发展,目前国内仍缺乏GBS定植及发病相关数据,后期需积极开展多中心高质量临床研究。③国内GBS菌株对抗生素的敏感性及耐药性尚不明确,有研究显示其对青霉素类、头孢菌素类、万古霉素仍有较高敏感性,但对克林霉素已形成明显的耐药性[25],为兼顾抗生素使用的有效性及合理性,青霉素仍可作为预防和治疗GBS感染的首选药物,克林霉素需谨慎选用。

1.3 IAI

IAI是指羊膜腔内的胎盘、胎膜、羊水、蜕膜、胎儿、脐带的任一部位或成分的感染,常见病原体包括GBS、大肠埃希菌和支原体等[26],多为混合感染。足月分娩产妇中IAI发生率为2%~5%,IAI可引起剖宫产率增加、产后出血、子宫内膜炎、败血症及孕产妇死亡等并发症,也可导致胎儿及新生儿出现胎儿窘迫、肺炎、脑膜炎、败血症、神经麻痹、死胎和死产等不良结局[27]

临床型IAI诊断标准为:母体体温升高(≥37.8 ℃)并伴有胎儿基线心率≥160次/min、母体心率≥100次/min、母体外周血白细胞计数≥15×109/L或核左移、阴道分泌物有异味及子宫底压痛,具备其中任何2项及以上即可诊断[28],但上述诊断标准间具有较强的联动性且客观性不足,容易导致临床医生过度治疗。因此2016年ACOG和美国儿科学会的专家小组提出用“宫内炎症或感染或两者兼而有之(inflammation, intrauterine infection or both,Triple I)”来代替临床型IAI[29],2017年ACOG在此基础上提出了新的IAI诊断标准[27],将IAI分为孤立性母体发热、可疑的IAI、确诊的IAI(具体内容见表3[27,29]),更为强调胎心基线、血液检查和阴道分泌物。诸多证据表明PROM、羊水胎粪污染、GBS感染和多次阴道检查等会增加IAI发生率[26],因此临床工作中需警惕上述高危因素的发生甚至叠加导致的效应,将合并上述高危因素的孕妇作为IAI的重点排查人群。

表3   IAI分类和特点[27,29]

类别特点
孤立性母体发热产妇口腔温度为39 ℃或更高时都应该记录为发热;如果口腔温度为38~39 ℃,30 min内重复测量,如果体温仍在38 ℃以上,则记录为发热
可疑的IAI不明原因的发热加上以下任何一项:
①胎心率基线升高(>160次/min,持续10 min或更长时间,不包括加速、减速、显著变异时期)
②没有使用皮质类固醇的情况下母体白细胞计数>15×109/L
③阴道窥器明确显示从宫颈口流出脓液
确诊的IAI以上表现加上以下任何一项:
①羊水革兰染色阳性、羊水低葡萄糖水平
②羊水培养阳性结果
③胎盘病理显示感染

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治疗上,除非可明确发热原因(如脱水、硬膜外镇痛、甲亢、环境温度升高、存在其他感染病灶等),孤立性母体发热可考虑使用抗生素,可疑或确诊的IAI推荐及时使用抗生素,且尽量选用广谱抗生素[27]。指南首选抗生素是氨苄青霉素联合庆大霉素,存在轻度青霉素过敏反应可选用头孢唑林联合庆大霉素,严重青霉素过敏反应可选用克林霉素或万古霉素联合庆大霉素,其余可供替代的抗生素方案有氨苄西林舒巴坦、哌拉西林他唑巴坦、头孢替坦、头孢西丁、厄他培南(具体方案见表4[27])。至于产后是否需要继续使用抗生素有待研究,ACOG认为经阴道分娩者产后不需要常规使用抗生素,经剖宫产分娩者建议至少追加1次抗生素(克林霉素或甲硝唑)[27,30],临床中产后抗生素使用时间及种类需根据感染是否持续存在决定,持续存在感染的患者,抗生素可使用至临床感染证据消失后24~48 h停药。

表4   IAI的用药方案[27]

个体情况用药方案(静脉用药)
无青霉素过敏氨苄青霉素2 g q6h+庆大霉素2 mg/kg 首剂+5 mg/kg q24h
轻度青霉素过敏头孢唑林2 g q8h +庆大霉素2 mg/kg 首剂+5 mg/kg q24h
严重青霉素过敏①克林霉素0.9 g q8h+庆大霉素2 mg/kg 首剂+5 mg/kg q24h
②万古霉素1.0 g q12h+庆大霉素2 mg/kg 首剂+5 mg/kg q24h
其他代替方案①氨苄西林舒巴坦3 g q6h
②哌拉西林他唑巴坦3.375 g q6h或4.5 g q8h
③头孢替坦2 g q12h
④头孢西丁2 g q8h
⑤厄他培南1 g q24h

注:经阴道分娩者产后不需要常规使用抗生素;剖宫产分娩建议至少追加一次抗生素(克林霉素0.9 g或甲硝唑0.5 g覆盖厌氧菌)。q6h:每6小时1次;q8h:每8小时1次;q12h:每12小时1次;q24h:每24小时1次。

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局限性:因为临床病情评估的不确定性,高危因素的早期识别以及适时的产时抗生素干预尤为重要,制定更明确且敏感的IAI诊断标准有利于快速识别病情,及时使用恰当抗生素治疗,提高母胎治疗效果。国内已有研究显示大肠埃希菌、GBS为IAI的常见致病菌,且大肠埃希菌对青霉素类、头孢菌素类抗生素有较高的耐药性[31],GBS对克林霉素有较高的耐药性,故选择抗生素时需结合临床症状、高危因素、感染途径,考虑最可能的致病菌种类及药敏情况,减缓耐药菌的增长。

1.4 PROM

PROM是指胎膜在临产前发生的自发性破裂,发生率为2%~8%[32],发生在37周前称为PPROM。PROM与IAI互相影响,互为因果,PPROM还是早产的主要原因之—,早产及宫内感染可导致新生儿的各种严重并发症,包括新生儿呼吸窘迫综合征、脑室内出血、坏死性小肠结肠炎和败血症等[28,33]

由于PROM常合并GBS感染、IAI,因此如临床怀疑或明确诊断IAI、符合GBS感染预防用药指征则建议参考相应指南使用抗生素[21,26]。结合孕周,目前证据不支持足月PROM在没有达到GBS感染或IAI用药指征的前提下常规预防性使用抗生素[28]。针对PPROM,不足孕34周的孕妇建议及早开始针对GBS感染的预防性抗生素治疗,最早可于孕20周开始[32];而对孕34~36+6周孕妇的处理仍有不同意见,ACOG建议同足月PROM处理[32],而国内研究多认为要尽早预防性使用抗生素[34]

目前推荐的有循证医学证据的有效抗生素治疗为氨苄青霉素联合红霉素静脉滴注48 h,后改为阿莫西林联合肠溶红霉素口服连续5 d,青霉素过敏的孕妇,则可单独口服红霉素10 d(具体用药见表5[28,32])。近年来国内外提出用阿奇霉素代替红霉素[35],两者同为大环内酯类,作用类似,但阿奇霉素服用方法简单、胃肠道耐受性更好,且发生临床型IAI可能性更小。因为氨苄青霉素联合克拉维酸钾类抗生素有增加新生儿坏死性小肠结肠炎的风险,应避免使用[32]

表5   PROM的用药方案[28,32]

个体情况用药方案
无青霉素过敏一阶段:氨苄青霉素2 g+红霉素250 mg q6h(或阿奇霉素500 mg 1次/d)静脉滴注48 h
二阶段:阿莫西林250 mg+肠溶红霉素333 mg q8h(或阿奇霉素500 mg 1次/d)口服 5 d
青霉素过敏红霉素250 mg q8h(或阿奇霉素500 mg 1次/d)口服,共10 d

注:q6h:每6小时1次;q8h:每8小时1次。

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局限性:目前临床关于长时间足月PROM抗生素使用多是基于临床经验,缺乏用药时机方面的高质量研究,需进一步开展,以期有效预防感染的同时减少胎儿抗生素的暴露及耐药性的产生。其次对于近足月PROM期待治疗或引产时限仍存在争议,因此抗生素使用最佳方案也有待进一步探索。最后国内临床研究发现PROM孕妇羊水培养病原菌以大肠埃希菌、GBS多见,对青霉素类、头孢菌素类、红霉素类抗生素耐药明显[36],故强调针对PPROM和PROM孕妇,需排除IAI或GBS感染后,才能按照PROM预防感染方案用药,减少抗生素的滥用。

1.5 早产

早产指妊娠满28周或新生儿出生体质量≥1 000 g且妊娠不满37周的分娩。根据原因,早产可分为自发性早产和治疗性早产,前者包括胎膜完整、不伴随胎膜早破的早产(占50%)和PROM后早产(占25%),后者则是因妊娠合并症或并发症需提前终止妊娠者(占25%)[37]。生殖道感染、PROM与自发性早产存在密切关联,近年来先兆早产孕妇提倡完善下生殖道分泌物筛查,包括白带常规、GBS培养、支原体培养及一般细菌培养等,如符合PROM或GBS感染用药指征则按照相关建议治疗。而对于一般胎膜完整且排除生殖道感染的早产不推荐常规应用抗生素[37]。紧急宫颈环扎作为治疗早产的手段在临床上广为应用,但围手术期是否需要预防性使用抗生素仍不确定,临床多根据具体病情及手术情况实行个性化用药方案[38]

2 抗生素在分娩期和围手术期的临床应用

2.1 经阴道分娩

对多数孕妇而言,阴道分娩是最理想的分娩方式,然而一项针对2016—2020年全国阴道分娩并发症的调查显示,近年来阴道分娩并发症发生率呈上升趋势,其中产后出血发生率为3.7%~5.7%,产科裂伤发生率为8.9%~11.9%,严重会阴裂伤(涉及产科相关肛门括约肌损伤,包括Ⅲ、Ⅳ度会阴裂伤)发生率约为0.06%~0.07%[39]。结合相关指南,阴道正常分娩、阴道侧切及阴道助产不伴严重会阴裂伤者不推荐常规预防性使用抗生素,阴道分娩伴严重会阴裂伤,建议单次预防性使用抗生素[38],推荐使用可覆盖革兰阴性杆菌、肠球菌属、链球菌属、厌氧菌的抗生素,如二代头孢菌素(头孢呋辛、头孢替坦)、克林霉素、头霉素类(头孢西丁)或甲硝唑等[40]。因胎盘残留或产后出血而行刮宫术或宫腔球囊填塞的产妇,目前尚无数据推荐预防性应用抗生素[38]

局限性:经阴道分娩是否需要使用抗生素与其并发症严重程度关系紧密,因此临床需强调阴道分娩后产科医师对会阴组织结构的充分评估,提高严重会阴裂伤的临床识别率和诊断率,进而把握抗生素使用指征、种类及剂量[41],达到预防或控制感染、避免抗生素滥用的目的。

2.2 经剖宫产分娩

剖宫产是产后感染重要的独立危险因素,现行指南已明确建议对所有剖宫产女性预防性应用抗生素,除非其已经接受了广谱抗生素治疗(如IAI)[38]。选用抗生素的目标覆盖菌群需包括革兰阴性杆菌、肠球菌属、GBS和厌氧菌[42]。建议在术前60 min内预防给药,如需紧急分娩,则建议在切皮后尽快给药,如考虑预防性应用抗生素对胎儿有风险,可选择在断脐时使用[38]。剖宫产分娩推荐单剂量预防性使用抗生素,一代、二代头孢菌素是首选的一线抗生素;对于有明显青霉素或头孢菌素过敏史的患者,克林霉素联合氨基糖苷类的单剂量组合是合理的替代方案;针对非选择性剖宫产患者,建议在标准抗生素预防方案中加入阿奇霉素(具体用药方案见表6[38,42])。

表6   剖宫产的抗生素预防用药方案[38,42]

个体情况用药方案
无明显青霉素或头孢菌素①头孢呋辛1.5 g 静脉滴注,临时1次
过敏史②头孢唑林2.0 g 静脉滴注,临时1次
有明显青霉素或头孢菌素克林霉素0.9 g+氨基糖苷类5 mg/kg 静脉滴注,临时1次
过敏史①头孢呋辛1.5 g 静脉滴注,临时1次

注:针对非选择性剖宫产患者,建议在标准抗生素预防方案中加入阿奇霉素(500 mg),输注时间超过1 h;如手术时间超过3 h或超过所用药物半衰期的2倍以上,或成人出血量超过1 500 mL,可在术中追加1次;清洁-污染手术及污染手术的预防用药时间为24 h,必要时延长至48 h。

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局限性:许多抗生素被证明能有效预防剖宫产产后感染,包括头孢唑林、头孢替坦、头孢呋辛、氨苄西林、哌拉西林、头孢西丁和氨苄西林舒巴坦等[38],目前临床多遵循单药单剂量预防性使用抗生素,可降低医疗成本、药品毒性和细菌耐药风险,但仍有研究提出应联合使用抗生素预防剖宫产术后感染,尤其是非选择性剖宫产,加用阿奇霉素、庆大霉素或甲硝唑会取得更好的临床效果[43-44],在临床工作中需进一步收集相关研究证据。

3 抗生素在产褥期的临床应用

产褥感染是指分娩时及产褥期生殖道受病原菌侵袭引起的局部或全身感染,发生率为1.0%~7.2%[45],多表现为急性子宫内膜炎、子宫肌炎、脓毒血症及败血症、切口感染,是产妇的主要死亡原因之一。产褥感染的发生与妊娠期及分娩期患者的病情和临床决策有关,相较于后期抗感染治疗,在前期及时筛查产褥感染高危患者并进行有效预防性干预更为重要。针对产褥感染,治疗性使用抗生素需全面考虑感染严重程度、感染途径、病原学分布和耐药性分析,后两者依赖于细菌培养及药敏试验等检验技术,而获取检验结果需要一定时间,因此当病原学未知时,临床往往需经验性选用广谱高效抗生素,特别是重症脓毒血症,强调“黄金1小时”的抗感染原则[46-47]。而在取得病原学证据后,应及时根据药敏试验和治疗反应调整用药方案,如更换敏感抗生素或降阶梯治疗[47]。经验性用药需明确感染来源及可能的致病菌,产科因素感染来源多见于IAI、感染性流产、子宫内膜炎、伤口感染,常见致病菌包括大肠埃希菌、A族链球菌(group A streptococci,GAS)、GBS、葡萄菌属、厌氧菌以及混合感染[48],因此抗生素需覆盖厌氧和需氧的革兰阳性菌和阴性菌。针对一般细菌轻症感染,多选用青霉素类+氨基糖苷类、二代/三代头孢菌素类+甲硝唑或克林霉素,重症感染直接选用碳青霉烯类或含酶抑制剂复合物(如哌拉西林他唑巴坦)。针对耐药菌[如耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus,MRSA)、耐万古霉素肠球菌(vancomycin resisitant Enterococcus,VRE)、产超广谱β-内酰胺酶大肠埃希菌(extended spectrum beta-lactamases Escherichia coli,ESBLs E.coli)、铜绿假单胞菌],一般选用含酶抑制剂复合物或碳青霉烯类,考虑联合用药时可增加氨基糖苷类或喹诺酮类(具体用药方案见表7[48-50])。

表7   产褥感染的抗生素用药方案[48-50]

可能致病菌用药方案
一般细菌轻症①青霉素类(氨苄青霉素)+氨基糖苷类(庆大霉素)+甲硝唑/克林霉素
②二代或三代头孢菌素类(头孢噻肟或头孢曲松)+甲硝唑/替硝唑
重症①碳青霉烯类(亚胺培南、美罗培南)
②含酶抑制剂复合物(哌拉西林他唑巴坦)
耐药菌轻症含酶抑制剂复合物(增加剂量和频次)
重症或菌血症碳青霉烯类
联合用药①含酶抑制剂复合物+氨基糖苷类或喹诺酮类
②碳青霉烯类(亚胺培南、美罗培南)+氨基糖苷类或喹诺酮类
MRSA万古霉素、替考拉宁、替加环素
VRE氟喹诺酮类(左氧氟沙星、莫西沙星)
CRE替加环素或替加环素+碳青霉烯类

注:CRE 耐碳青霉烯肠杆菌(carbapenem-resistant Enterobacteriaceae)。

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局限性:产褥感染的部位多样、致病菌复杂,这要求临床医生熟悉生殖道感染常见微生物及其敏感抗生素,而不同地域存在差异性,因此在临床治疗中需收集相关数据,研究当地流行病学特点,为经验性治疗提供可靠参考。其次,产褥感染病情进展快速,原发感染如未得到及时正确的干预,可能进展为重症感染,甚至导致患者死亡,因此产褥感染需注重多学科合作,提高救治成功率[49]。最后,产褥感染联合用药或广谱抗生素使用频率高,治疗时需严格按照指征、规范合理使用抗生素,警惕耐药菌的快速增长。

4 结语

产科抗生素合理应用的重点在于:①有无指征;②给药方案是否适宜;③妊娠期/哺乳期涉及母胎安全,有无充分权衡利弊,做好知情告知。抗生素在产科使用的目的可分为预防性和治疗性,预防性使用抗生素的目的是预防特定病原菌所致的或特定人群可能发生的感染或预防手术部位感染[51],重点在于用药对象的筛查和指征的把控,作为前期处理环节,其恰当与否和母婴预后关系紧密,对感染是否发生及严重程度均有重大影响,因此需保持动态关注。治疗性使用抗生素是为了缓解或解除症状、改善预后,其中经验性治疗需立足于当地微生物流行模式和耐药性特征,针对性治疗则依赖细菌培养和药敏试验的检验技术支持,故未来需注重进行高质量的临床研究,完善国内或本地域相关流行病学数据,探索基于我国或本地域感染现状的抗生素合理使用方案,更好地服务于临床工作。

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[J]. JAMA, 2020, 323(13):1286-1292. doi: 10.1001/jama.2020.2684.

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Bacterial vaginosis is common and is caused by a disruption of the microbiological environment in the lower genital tract. In the US, reported prevalence of bacterial vaginosis among pregnant women ranges from 5.8% to 19.3% and is higher in some races/ethnicities. Bacterial vaginosis during pregnancy has been associated with adverse obstetrical outcomes including preterm delivery, early miscarriage, postpartum endometritis, and low birth weight.To update its 2008 recommendation, the USPSTF commissioned a review of the evidence on the accuracy of screening and the benefits and harms of screening for and treatment of bacterial vaginosis in asymptomatic pregnant persons to prevent preterm delivery.This recommendation applies to pregnant persons without symptoms of bacterial vaginosis.The USPSTF concludes with moderate certainty that screening for asymptomatic bacterial vaginosis in pregnant persons not at increased risk for preterm delivery has no net benefit in preventing preterm delivery. The USPSTF concludes that for pregnant persons at increased risk for preterm delivery, the evidence is conflicting and insufficient, and the balance of benefits and harms cannot be determined.The USPSTF recommends against screening for bacterial vaginosis in pregnant persons not at increased risk for preterm delivery. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for bacterial vaginosis in pregnant persons at increased risk for preterm delivery. (I statement).

Vaginitis in Nonpregnant Patients: ACOG Practice Bulletin, Number 215

[J]. Obstet Gynecol, 2020, 135(1):e1-e17. doi: 10.1097/AOG.0000000000003604.

DOI:10.1097/AOG.0000000000003604.      URL     [本文引用: 1]

Workowski KA, Bachmann LH, Chan PA, et al.

Sexually Transmitted Infections Treatment Guidelines, 2021

[J]. MMWR Recomm Rep, 2021, 70(4):1-187. doi: 10.15585/mmwr.rr7004a1.

DOI:10.15585/mmwr.rr7004a1      PMID:34292926      [本文引用: 1]

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11-14, 2019. The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health care providers can use these guidelines to assist in prevention and treatment of STIs.

Yudin MH, Money DM. No.

211-Screening and Management of Bacterial Vaginosis in Pregnancy

[J]. J Obstet Gynaecol Can, 2017, 39(8):e184-e191. doi: 10.1016/j.jogc.2017.04.018.

DOI:10.1016/j.jogc.2017.04.018      PMID:28729110      [本文引用: 1]

To review the evidence and provide recommendations on screening for and management of bacterial vaginosis in pregnancy.The clinical practice options considered in formulating the guideline.Outcomes evaluated include antibiotic treatment efficacy and cure rates, and the influence of the treatment of bacterial vaginosis on the rates of adverse pregnancy outcomes such as preterm labour and delivery and preterm premature rupture of membranes.Medline, EMBASE, CINAHL, and Cochrane databases were searched for articles, published in English before the end of June 2007 on the topic of bacterial vaginosis in pregnancy.The evidence obtained was rated using the criteria developed by the Canadian Task Force on Preventive Health Care.Guideline implementation will assist the practitioner in developing an approach to the diagnosis and treatment of bacterial vaginosis in pregnant women. Patients will benefit from appropriate management of this condition.These guidelines have been prepared by the Infectious Diseases Committee of the SOGC, and approved by the Executive and Council of the SOGC.The Society of Obstetricians and Gynaecologists of Canada.There is currently no consensus as to whether to screen for or treat bacterial vaginosis in the general pregnant population in order to prevent adverse outcomes, such as preterm birth.Copyright © 2017. Published by Elsevier Inc.

Tomás M, Palmeira-de-Oliveira A, Simöes S, et al.

Bacterial vaginosis: Standard treatments and alternative strategies

[J]. Int J Pharm, 2020, 587:119659. doi: 10.1016/j.ijpharm.2020.119659.

DOI:10.1016/j.ijpharm.2020.119659      URL     [本文引用: 1]

Ding Y, Wang Y, Hsia Y, et al.

Systematic Review and Meta-Analyses of Incidence for Group B Streptococcus Disease in Infants and Antimicrobial Resistance, China

[J]. Emerg Infect Dis, 2020, 26(11):2651-2659. doi: 10.3201/eid2611.181414.

DOI:10.3201/eid2611.181414      PMID:33079042      [本文引用: 1]

We performed a systematic review and meta-analysis of the incidence, case-fatality rate (CFR), isolate antimicrobial resistance patterns, and serotype and sequence type distributions for invasive group B Streptococcus (GBS) disease in infants <1-89 days of age in China. We searched the PubMed/Medline, Embase, Wanfang, and China National Knowledge Infrastructure databases for research published during January 1, 2000-March 16, 2018, and identified 64 studies. Quality of included studies was assessed by using Cochrane tools. Incidence and CFR were estimated by using random-effects meta-analyses. Overall incidence was 0.55 (95% CI 0.35-0.74) cases/1,000 live births, and the CFR was 5% (95% CI 3%-6%). Incidence of GBS in young infants in China was higher than the estimated global incidence (0.49 cases/1,000 live births) and higher than previous estimates for Asia (0.3 cases/1,000 live births). Our findings suggest that implementation of additional GBS prevention efforts in China, including maternal vaccination, could be beneficial.

Puopolo KM, Lynfield R, Cummings JJ, et al.

Management of Infants at Risk for Group B Streptococcal Disease

[J]. Pediatrics, 2019, 144(4):e20192350. doi: 10.1542/peds.2019-2350.

DOI:10.1542/peds.2019-2350      URL     [本文引用: 1]

Prevention of Group B Streptococcal Early-Onset Disease in Newborns: ACOG Committee Opinion, Number 797

[J]. Obstet Gynecol, 2020, 135(2):e51-e72. doi: 10.1097/AOG.0000000000003668.

DOI:10.1097/AOG.0000000000003668.      URL     [本文引用: 2]

Nanduri SA, Petit S, Smelser C, et al.

Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance

[J]. JAMA Pediatr, 2019, 173(3):224-233. doi: 10.1001/jamapediatrics.2018.4826.

DOI:10.1001/jamapediatrics.2018.4826      PMID:30640366      [本文引用: 1]

Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development.To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development.This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018.Group B Streptococcus isolated from a normally sterile site.Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance.The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally.The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.

Verani JR, McGee L, Schrag SJ, et al.

Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010

[J]. MMWR Recomm Rep, 2010, 59(RR-10):1-36.

PMID:21088663      [本文引用: 1]

Despite substantial progress in prevention of perinatal group B streptococcal (GBS) disease since the 1990s, GBS remains the leading cause of early-onset neonatal sepsis in the United States. In 1996, CDC, in collaboration with relevant professional societies, published guidelines for the prevention of perinatal group B streptococcal disease (CDC. Prevention of perinatal group B streptococcal disease: a public health perspective. MMWR 1996;45[No. RR-7]); those guidelines were updated and republished in 2002 (CDC. Prevention of perinatal group B streptococcal disease: revised guidelines from CDC. MMWR 2002;51[No. RR-11]). In June 2009, a meeting of clinical and public health representatives was held to reevaluate prevention strategies on the basis of data collected after the issuance of the 2002 guidelines. This report presents CDC's updated guidelines, which have been endorsed by the American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, the American College of Nurse-Midwives, the American Academy of Family Physicians, and the American Society for Microbiology. The recommendations were made on the basis of available evidence when such evidence was sufficient and on expert opinion when available evidence was insufficient. The key changes in the 2010 guidelines include the following: • expanded recommendations on laboratory methods for the identification of GBS, • clarification of the colony-count threshold required for reporting GBS detected in the urine of pregnant women, • updated algorithms for GBS screening and intrapartum chemoprophylaxis for women with preterm labor or preterm premature rupture of membranes, • a change in the recommended dose of penicillin-G for chemoprophylaxis, • updated prophylaxis regimens for women with penicillin allergy, and • a revised algorithm for management of newborns with respect to risk for early-onset GBS disease. Universal screening at 35-37 weeks' gestation for maternal GBS colonization and use of intrapartum antibiotic prophylaxis has resulted in substantial reductions in the burden of early-onset GBS disease among newborns. Although early-onset GBS disease has become relatively uncommon in recent years, the rates of maternal GBS colonization (and therefore the risk for early-onset GBS disease in the absence of intrapartum antibiotic prophylaxis) remain unchanged since the 1970s. Continued efforts are needed to sustain and improve on the progress achieved in the prevention of GBS disease. There also is a need to monitor for potential adverse consequences of intrapartum antibiotic prophylaxis (e.g., emergence of bacterial antimicrobial resistance or increased incidence or severity of non-GBS neonatal pathogens). In the absence of a licensed GBS vaccine, universal screening and intrapartum antibiotic prophylaxis continue to be the cornerstones of early-onset GBS disease prevention.

Prevention of Early-onset Neonatal Group B Streptococcal Disease: Green-top Guideline No.36

[J]. BJOG, 2017, 124(12):e280-e305. doi: 10.1111/1471-0528.14821.

DOI:10.1111/1471-0528.14821      URL     [本文引用: 1]

Nicolle LE, Gupta K, Bradley SF, et al.

Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America

[J]. Clin Infect Dis, 2019, 68(10):e83-e110. doi: 10.1093/cid/ciy1121.

DOI:10.1093/cid/ciy1121      URL     [本文引用: 1]

Queensland Clinical Guidelines.

Early onset group B

[EB/OL]. (2020-04-01)[2021-07-01]. http://www.health.qld.gov.au/qcq.

URL     [本文引用: 1]

US Preventive Services Task Force, Owens DK, Davidson KW, et al.

Screening for Asymptomatic Bacteriuria in Adults: US Preventive Services Task Force Recommendation Statement

[J]. JAMA, 2019, 322(12):1188-1194. doi: 10.1001/jama.2019.13069.

DOI:10.1001/jama.2019.13069      PMID:31550038      [本文引用: 1]

Among the general adult population, women (across all ages) have the highest prevalence of asymptomatic bacteriuria, although rates increase with age among both men and women. Asymptomatic bacteriuria is present in an estimated 1% to 6% of premenopausal women and an estimated 2% to 10% of pregnant women and is associated with pyelonephritis, one of the most common nonobstetric reasons for hospitalization in pregnant women. Among pregnant persons, pyelonephritis is associated with perinatal complications including septicemia, respiratory distress, low birth weight, and spontaneous preterm birth.To update its 2008 recommendation, the USPSTF commissioned a review of the evidence on potential benefits and harms of screening for and treatment of asymptomatic bacteriuria in adults, including pregnant persons.This recommendation applies to community-dwelling adults 18 years and older and pregnant persons of any age without signs and symptoms of a urinary tract infection.Based on a review of the evidence, the USPSTF concludes with moderate certainty that screening for and treatment of asymptomatic bacteriuria in pregnant persons has moderate net benefit in reducing perinatal complications. There is adequate evidence that pyelonephritis in pregnancy is associated with negative maternal outcomes and that treatment of screen-detected asymptomatic bacteriuria can reduce the incidence of pyelonephritis in pregnant persons. The USPSTF found adequate evidence of harms associated with treatment of asymptomatic bacteriuria (including adverse effects of antibiotic treatment and changes in the microbiome) to be at least small in magnitude. The USPSTF concludes with moderate certainty that screening for and treatment of asymptomatic bacteriuria in nonpregnant adults has no net benefit. The known harms associated with treatment include adverse effects of antibiotic use and changes to the microbiome. Based on these known harms, the USPSTF determined the overall harms to be at least small in this group.The USPSTF recommends screening pregnant persons for asymptomatic bacteriuria using urine culture. (B recommendation) The USPSTF recommends against screening for asymptomatic bacteriuria in nonpregnant adults. (D recommendation).

中华医学会围产医学分会, 中华医学会妇产科学分会产科学组.

预防围产期B族链球菌病(中国)专家共识

[J]. 中华围产医学杂志, 2021, 24(8):561-566. doi: 10.3760/cma.j.cn113903-20210716-00638.

DOI:10.3760/cma.j.cn113903-20210716-00638.      [本文引用: 8]

Committee Opinion No.

712: Intrapartum Management of Intraamniotic Infection

[J]. Obstet Gynecol, 2017, 130(2):e95-e101. doi: 10.1097/AOG.0000000000002236.

DOI:10.1097/AOG.0000000000002236.      URL     [本文引用: 1]

Allen VM, Yudin MH. No.

276-Management of Group B Streptococcal Bacteriuria in Pregnancy

[J]. J Obstet Gynaecol Can, 2018, 40(2):e181-e186. doi: 10.1016/j.jogc.2017.11.025.

DOI:10.1016/j.jogc.2017.11.025      URL     [本文引用: 1]

Smaill FM, Vazquez JC.

Antibiotics for asymptomatic bacteriuria in pregnancy

[J]. Cochrane Database Syst Rev, 2019, 2019(11): CD000490. doi: 10.1002/14651858.CD000490.pub4.

DOI:10.1002/14651858.CD000490.pub4      URL     [本文引用: 1]

金英, 张正银, 黄韵, .

孕晚期妇女生殖道B族链球菌的耐药性和耐药基因检测情况分析

[J]. 中国妇幼保健, 2020, 35(23):4435-4437. doi: 10.19829/j.zgfybj.issn.1001-4411.2020.23.011.

DOI:10.19829/j.zgfybj.issn.1001-4411.2020.23.011      [本文引用: 1]

陈晓丹, 侯红瑛.

羊膜腔感染诊断与治疗

[J]. 中华产科急救电子杂志, 2020, 9(4):204-207. doi: 10.3877/cma.j.issn.2095-3259.2020.04.004.

DOI:10.3877/cma.j.issn.2095-3259.2020.04.004      [本文引用: 3]

Committee Opinion No.

712 Summary: Intrapartum Management of Intraamniotic Infection

[J]. Obstet Gynecol, 2017, 130(2):490-492. doi: 10.1097/AOG.0000000000002230.

DOI:10.1097/AOG.0000000000002230      URL     [本文引用: 8]

中华医学会妇产科学分会产科学组.

胎膜早破的诊断与处理指南(2015)

[J]. 中华妇产科杂志, 2015, 50(1):3-8. doi: 10.3760/cma.j.issn.0529-567x.2015.01.002.

DOI:10.3760/cma.j.issn.0529-567x.2015.01.002      [本文引用: 5]

Higgins RD, Saade G, Polin RA, et al.

Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop

[J]. Obstet Gynecol, 2016, 127(3):426-436. doi: 10.1097/AOG.0000000000001246.

DOI:10.1097/AOG.0000000000001246      PMID:26855098      [本文引用: 3]

In January 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited an expert panel to a workshop to address numerous knowledge gaps and to provide evidence-based guidelines for the diagnosis and management of pregnant women with what had been commonly called chorioamnionitis and the neonates born to these women. The panel noted that the term chorioamnionitis has been used to label a heterogeneous array of conditions characterized by infection and inflammation or both with a consequent great variation in clinical practice for mothers and their newborns. Therefore, the panel proposed to replace the term chorioamnionitis with a more general, descriptive term: "intrauterine inflammation or infection or both," abbreviated as "Triple I." The panel proposed a classification for Triple I and recommended approaches to evaluation and management of pregnant women and their newborns with a diagnosis of Triple I. It is particularly important to recognize that an isolated maternal fever is not synonymous with chorioamnionitis. A research agenda was proposed to further refine the definition and management of this complex group of conditions. This article provides a summary of the workshop presentations and discussions.

Conde-Agudelo A, Romero R, Jung EJ, et al.

Management of clinical chorioamnionitis: an evidence-based approach

[J]. Am J Obstet Gynecol, 2020, 223(6):848-869. doi: 10.1016/j.ajog.2020.09.044.

DOI:10.1016/j.ajog.2020.09.044      PMID:33007269      [本文引用: 1]

This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.Published by Elsevier Inc.

余德玲.

某院2018年—2020年妇产科胎膜早破合并绒毛膜羊膜炎患者胎膜标本中病原菌的分布及耐药情况分析

[J]. 抗感染药学, 2021, 18(5):698-700. doi: 10.13493/j.issn.1672-7878.2021.05-020.

DOI:10.13493/j.issn.1672-7878.2021.05-020      [本文引用: 1]

目的: 分析医院 2018 年&#x02014;2020 年妇产科胎膜早破合并绒毛膜羊膜炎患者胎膜标本中病原菌的分布及耐药情况,为临床治疗提供参考。方法: 选取医院 2018 年 11 月&#x02014;2020 年 10 月妇产科收治胎膜早破合并绒毛膜羊膜炎患者 100 例资料,统计其胎膜标本的细菌培养及药敏试验结果,分析主要革兰阴性菌、革兰阳性菌的药敏试验结果。结果: 100 例胎膜早破合并绒毛膜羊膜炎患者标本共培育菌株 100 株,其中革兰阴性菌 71 株(占 71.00%,以大肠埃希菌为主)、革兰阳性菌 29 株(占 29.00%,以粪肠球菌为主);主要革兰阴性菌大肠埃希菌对庆大霉素、头孢哌酮-舒巴坦钠、哌拉西林-他唑巴坦钠、亚胺培南的耐药率较低,对哌拉西林、红霉素、头孢噻肟、头孢呋辛的耐药率较高;主要革兰阳性菌粪肠球菌对丁胺卡那、利奈唑胺、庆大霉素、万古霉素、替考拉宁、哌拉西林-他唑巴坦钠、亚胺培南的耐药率较低,对红霉素、克林霉素、青霉素、氨苄西林、复方磺胺甲噁唑、左氧氟沙星的耐药率较高。结论: 胎膜早破合并绒毛膜羊膜炎患者胎膜标本中检测出的主要病原菌为大肠埃希菌与粪肠球菌,临床应根据药敏试验结果及患者实际情况合理选用抗菌药物。

Siegler Y, Weiner Z, Solt I.

ACOG Practice Bulletin No. 217: Prelabor Rupture of Membranes

[J]. Obstet Gynecol, 2020, 136(5):1061. doi: 10.1097/AOG.0000000000004142.

DOI:10.1097/AOG.0000000000004142      PMID:33093409      [本文引用: 6]

Menon R, Richardson LS.

Preterm prelabor rupture of the membranes: A disease of the fetal membranes

[J]. Semin Perinatol, 2017, 41(7):409-419. doi: 10.1053/j.semperi.2017.07.012.

DOI:S0146-0005(17)30084-8      PMID:28807394      [本文引用: 1]

Preterm prelabor rupture of the membranes (pPROM) remains a significant obstetric problem that affects 3-4% of all pregnancies and precedes 40-50% of all preterm births. pPROM arises from complex, multifaceted pathways. In this review, we summarize some old concepts and introduce some novel theories related to pPROM pathophysiology. Specifically, we introduce the concept that pPROM is a disease of the fetal membranes where inflammation-oxidative stress axis plays a major role in producing pathways that can lead to membrane weakening through a variety of processes. In addition, we report microfractures in fetal membranes that are likely sites of tissue remodeling during gestation; however, increase in number and morphometry (width and depth) of these microfractures in pPROM membranes suggests reduced remodeling capacity of membranes. Microfractures can act as channels for amniotic fluid leak, and inflammatory cell and microbial migration. Further studies on senescence activation and microfracture formation and their role in maintaining membrane homeostasis are needed to fill the knowledge gaps in our understanding of pPROM as well as provide better screening (biomarker and imaging based) tools for predicting women at high risk for pPROM and subsequent preterm birth.Copyright © 2017 Elsevier Inc. All rights reserved.

刘婧, 彭婷.

34-36+6孕周胎膜早破期待治疗的研究进展

[J]. 中国实用妇科与产科杂志, 2022, 38(2):235-238. doi: 10.19538/j.fk2022020125.

DOI:10.19538/j.fk2022020125      [本文引用: 1]

Seaman RD, Kopkin RH, Turrentine MA.

Erythromycin vs azithromycin for treatment of preterm prelabor rupture of membranes: a systematic review and meta-analysis

[J]. Am J Obstet Gynecol, 2022, 226(6):794-801.e1. doi: 10.1016/j.ajog.2021.12.262.

DOI:10.1016/j.ajog.2021.12.262      URL     [本文引用: 1]

刘敏雪, 黄丽英, 王双杰, .

胎膜早破与正常胎膜破裂患者羊水病原菌分布及药敏分析

[J]. 重庆医学, 2022, 51(7):1147-1151. doi: 10.3969/j.issn.1671-8348.2022.07.013.

DOI:10.3969/j.issn.1671-8348.2022.07.013      [本文引用: 1]

胡娅莉.

早产临床诊断与治疗指南(2014)

[J]. 中华妇产科杂志, 2014, 49(7):481-485. doi: 10.3760/cma.j.issn.0529-567x.2014.07.001.

DOI:10.3760/cma.j.issn.0529-567x.2014.07.001      [本文引用: 2]

Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No.

199: Use of Prophylactic Antibiotics in Labor and Delivery

[J]. Obstet Gynecol, 2018, 132(3):e103-e119. doi: 10.1097/AOG.0000000000002833.

DOI:10.1097/AOG.0000000000002833.      URL     [本文引用: 8]

石慧峰, 陈练, 尹韶华, .

2016—2020年中国阴道分娩并发症发生现状调查

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To estimate the incidence of and risk factors for wound complications in women who sustain obstetric anal sphincter injuries.This was a prospective cohort study of women who sustained obstetric anal sphincter injuries during delivery of a full-term neonate between September 2011 and August 2013. Women were seen in the urogynecology clinic within 1 week of delivery and at 2, 6, and 12 weeks postpartum for perineal wound assessment. A visual analog scale for pain was administered at each visit.Five hundred two women met inclusion criteria for the study, and, ultimately, 268 women (54%) were enrolled. Eighty-seven percent of the cohort was nulliparous and 81% had a third-degree laceration. The majority (n=194) underwent an operative vaginal delivery (66.0% forceps and 6.0% vacuum). The overall risk was 19.8% (95% confidence interval [CI] 15.2-25.1%) for wound infection (n=53) and 24.6% (95% CI 19.6-30.2%) for wound breakdown (n=66). Operative vaginal delivery was associated with wound complications (infection, breakdown, or both) (adjusted odds ratio [OR] 2.54, 95% CI 1.32-4.87, P=.008). Intrapartum antibiotic therapy for obstetric indications was associated with a decreased risk of wound complications (adjusted OR 0.50, 95% CI 0.27-0.94, P=.03). Women with a wound complication reported significantly more pain within 1 week of delivery than women with a normally healing perineum (visual analog scale: 40.1±25.6 compared with 31.0±23, P=.002); this persisted at 12 weeks postpartum (6.6±7.5 compared with 3.4±7.1, P=.005).Women who sustain obstetric anal sphincter injuries are at high risk for the development of wound complications in the early postpartum period, warranting immediate and consistent follow-up.II.

中国药学会医院药学专业委员会妇产科药学学组, 中国妇幼保健协会药事管理专业委员会, 浙江省药学会医院药学专业委员会妇儿药学学组.

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产科重症感染的多学科防治

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