产科抗生素临床应用进展

doi:10.12280/gjfckx.20220546

摘要/Abstract

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.

Key words: Anti-bacterial agents, Reproductive tract infections, Bacterial infections, Puerperal infection, Pregnant women

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.

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.

图/表 7

参考文献 51

[1]	陶冶, 孙智晶, 朱兰, 等. 妊娠期及产后脓毒症68例临床分析[J]. 中华妇产科杂志, 2020, 55(11):770-777. doi: 10.3760/cma.j.cn112141-20200521-00430. doi: 10.3760/cma.j.cn112141-20200521-00430.
[2]	李婷, 黎欢, 李金灵, 等. 阴道微生态研究进展概述[J]. 中国妇幼保健, 2022, 37(3):574-576. doi: 10.19829/j.zgfybj.issn.1001-4411.2022.03.057. doi: 10.19829/j.zgfybj.issn.1001-4411.2022.03.057
[3]	Acosta CD, Harrison DA, Rowan K, et al. Maternal morbidity and mortality from severe sepsis: a national cohort study[J]. BMJ Open, 2016, 6(8):e012323. doi: 10.1136/bmjopen-2016-012323. doi: 10.1136/bmjopen-2016-012323
[4]	Anahtar MN, Gootenberg DB, Mitchell CM, et al. Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity[J]. Cell Host Microbe, 2018, 23(2):159-168. doi: 10.1016/j.chom.2018.01.013. doi: S1931-3128(18)30048-9 pmid: 29447695
[5]	中华医学会妇产科学分会感染性疾病协作组. 细菌性阴道病诊治指南(2021修订版)[J]. 中华妇产科杂志, 2021, 56(1):3-6. doi: 10.3760/cma.j.cn112141-20200717-00583. doi: 10.3760/cma.j.cn112141-20200717-00583.
[6]	Sherrard J, Wilson J, Donders G, et al. 2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation(WHO) guideline on the management of vaginal discharge[J]. Int J STD AIDS, 2018, 29(13):1258-1272. doi: 10.1177/0956462418785451. doi: 10.1177/0956462418785451 pmid: 30049258
[7]	US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement[J]. JAMA, 2020, 323(13):1286-1292. doi: 10.1001/jama.2020.2684. doi: 10.1001/jama.2020.2684 pmid: 32259236
[8]	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.
[9]	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
[10]	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
[11]	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
[12]	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
[13]	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
[14]	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.
[15]	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
[16]	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
[17]	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
[18]	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
[19]	Queensland Clinical Guidelines. Early onset group B[EB/OL]. (2020-04-01)[2021-07-01]. http://www.health.qld.gov.au/qcq.
[20]	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
[21]	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.
[22]	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.
[23]	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
[24]	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
[25]	金英, 张正银, 黄韵, 等. 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
[26]	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
[27]	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
[28]	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
[29]	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
[30]	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
[31]	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
[32]	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
[33]	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
[34]	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
[35]	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
[36]	刘敏雪, 黄丽英, 王双杰, 等. 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
[37]	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
[38]	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.
[39]	石慧峰, 陈练, 尹韶华, 等. 2016—2020年中国阴道分娩并发症发生现状调查[J]. 实用妇产科杂志, 2022, 38(1):13-17.
[40]	中华医学会妇产科学分会感染性疾病协作组. 妇产科抗生素使用指南[J]. 中华妇产科杂志, 2011, 46(3):230-233. doi: 10.3760/cma.j.issn.0529-567x.2011.03.018. doi: 10.3760/cma.j.issn.0529-567x.2011.03.018
[41]	Lewicky-Gaupp C, Leader-Cramer A, Johnson LL, et al. Wound complications after obstetric anal sphincter injuries[J]. Obstet Gynecol, 2015, 125(5):1088-1093. doi: 10.1097/AOG.0000000000000833. doi: 10.1097/AOG.0000000000000833 pmid: 25932836
[42]	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. 妇产科围手术期抗菌药物预防使用指导方案[J]. 中国药学杂志, 2021, 56(3):250-256. doi: 10.11669/cpj.2021.03.014. doi: 10.11669/cpj.2021.03.014
[43]	李洁萍. 甲硝唑联合头孢呋辛对剖宫产术后感染的预防效果[J]. 临床合理用药杂志, 2020, 13(21):122-124. doi:10.15887/j.cnki.13-1389/r.2020.21.051. doi: 10.15887/j.cnki.13-1389/r.2020.21.051
[44]	Jyothi MS, Kalra JK, Arora A, et al. Randomized controlled trial of cefazolin monotherapy versus cefazolin plus azithromycin single dose prophylaxis for cesarean deliveries: A developing country′s perspective[J]. J Family Med Prim Care, 2019, 8(9):3015-3021. doi: 10.4103/jfmpc.jfmpc_593_19. doi: 10.4103/jfmpc.jfmpc_593_19
[45]	杨慧霞, 漆洪波, 郑勤田. 威廉姆斯产科学[M]. 25版. 北京: 人民卫生出版社, 2020.
[46]	Abir G, Bauer ME. Maternal sepsis update[J]. Curr Opin Anaesthesiol, 2021, 34(3):254-259. doi: 10.1097/ACO.0000000000000997. doi: 10.1097/ACO.0000000000000997
[47]	胡必杰, 潘玉. 哈里森感染病学[M]. 上海: 上海科学技术出版社, 2019.
[48]	严少梅, 樊尚荣. 2019年美国母胎医学会“妊娠期及产褥期脓毒症诊断和治疗共识”解读[J]. 中华产科急救电子杂志, 2019, 8(2):108-115. doi: 10.3877/cma.j.issn.2095-3259.2019.02.010. doi: 10.3877/cma.j.issn.2095-3259.2019.02.010
[49]	樊尚荣. 产科重症感染的多学科防治[J]. 中华产科急救电子杂志, 2017, 6(3):129-132. doi: 10.3877/cma.j.issn.2095-3259.2017.03.001. doi: 10.3877/cma.j.issn.2095-3259.2017.03.001
[50]	肖云山, 林雪燕, 张雪芹. 产褥期重症感染的处理[J]. 中国实用妇科与产科杂志, 2021, 37(10):1016-1020. doi: 10.19538/j.fk2021100109. doi: 10.19538/j.fk2021100109
[51]	《抗菌药物临床应用指导原则》修订工作组. 抗菌药物临床应用指导原则(2015年版)[M]. 北京: 人民卫生出版社, 2015:1-15.

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

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

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

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

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