优化抗生素管理对胎龄小于32周早产儿近期临床结局的影响

doi:10.3969/j.issn.1004-583X.2023.08.005

摘要/Abstract

摘要：

目的回顾性分析胎龄小于32周早产儿的临床资料,探讨优化抗生素管理对早产儿近期临床结局的影响。方法收集2017年1月1日至2018年6月30日、2019年1月1日至2020年12月31日于青岛大学附属医院新生儿监护室住院治疗的胎龄小于32周早产儿的临床资料。优化抗生素管理于2019年1月开始实施,将上述临床资料分为两组:优化前组158例(2017年1月1日至2018年6月30日);优化组156例(2019年1月1日至2020年12月31日),回顾性分析两组患儿的临床资料。结果与优化前组相比,优化组在早期抗生素使用时间(6 d比10 d)、抗生素使用总时间(11 d比16 d)、肠外营养时间(18 d比29.5 d)方面均明显缩短(P<0.01),早产儿视网膜病变(retinopathy of prematurity,ROP)的发生率明显降低(7.69% vs 15.82%,P<0.05);Logistic回归分析显示优化抗生素管理与近期不良结局无明显关联(P>0.05), 抗生素使用时间延长、血培养阳性及机械通气是近期不良结局的危险因素。结论优化抗生素管理,缩短早产儿不必要的抗生素暴露,可减少肠外营养时间,降低ROP发生率,且不增加近期临床不良结局。延长抗生素使用时间增加近期临床不良结局。

关键词: 婴儿, 早产, 抗生素管理, 不良结局

Abstract:

Objective To explore the effect of an optimized antibiotic management on the short-term clinical outcome of preterm infants born with gestational age of<32 weeks by retrospectively analyzing their clinical data. Methods Clinical data were retrospectively collected from preterm infants born with gestational age of <32 weeks who were admitted to the Neonatal Intensive Care Unit of the Affiliated Hospital of Qingdao University from January 1, 2017 to June 30, 2018 and from January 1, 2019 to December 31, 2020. The optimized antibiotic strategy was implemented since January 1, 2019. Included preterm infants were divided into two groups, including pre-optimization group (January 1, 2017 to June 30, 2018, n=158) and optimization group (January 1, 2019 to December 31, 2020, n=156). The clinical data of preterm infants were compared between groups.Results Compared with the pre-optimization group, the duration of antibiotic use in the early postnatal period (6 d vs 10 d), the total duration of antibiotic use during hospitalization (11 d vs 16 d), and the duration of parenteral nutrition (18 d vs 29.5 d) in the optimization group were significantly shortened (P<0.01). The incidence rate of retinopathy of prematurity (ROP) in the optimization group was significantly lower than that in the pre-optimization group (7.69% vs 15.82%, P<0.05). The multivariate logistic regression analysis revealed that optimized antibiotic management was not significantly correlated with short-term adverse outcomes (P>0.05). Prolonged antibiotic use, positive blood culture and mechanical ventilation were risk factors for short-term adverse clinical outcome.Conclusion Shortening unnecessary antibiotic exposure in preterm infants can reduce the duration of parenteral nutrition and the incidence of ROP without increasing short-term adverse clinical outcomes. Prolonged antibiotic use increases the risk of adverse clinical outcome.

Key words: infant, premature, optimized antibiotic management, adverse outcome

中图分类号:

R722

薛瑞瑞, 李向红, 李亮亮, 尹向云, 锡洪敏, 杨萍, 马丽丽. 优化抗生素管理对胎龄小于32周早产儿近期临床结局的影响[J]. 临床荟萃, 2023, 38(8): 706-713.

Xue Ruirui, Li Xianghong, Li Liangliang, Yin Xiangyun, Xi Hongmin, Yang Ping, Ma Lili. Effect of an optimized antibiotic management on the short-term clinical outcome of preterm infants born with gestational age of<32 weeks[J]. Clinical Focus, 2023, 38(8): 706-713.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2023.08.005

https://huicui.hebmu.edu.cn/CN/Y2023/V38/I8/706

图/表 6

参考文献 37

[1]	Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, et al. The global burden of paediatric and neonatal sepsis: A systematic review[J]. Lancet Respir Med, 2018, 6(3): 223-230. doi: 10.1016/S2213-2600(18)30063-8 pmid: 29508706
[2]	Puopolo KM, Mukhopadhyay S, Hansen NI, et al. Identification of extremely premature infants at low risk for early-onset sepsis[J]. Pediatrics, 2017, 140(5):e20170925. doi: 10.1542/peds.2017-0925 URL
[3]	GBD 2015 Child Mortality Collaborators Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980-2015: A systematic analysis for the Global Burden of Disease Study 2015.[J]. Lancet, 2016, 388(10053): 1725-1774. doi: S0140-6736(16)31575-6 pmid: 27733285
[4]	Cailes B, Kortsalioudaki C, Buttery J, et al. Antimicrobial resistance in UK neonatal units: neonIN infection surveillance network[J]. Arch Dis Child Fetal Neonatal Ed, 2018, 103(5): F474-F478. doi: 10.1136/archdischild-2017-313238 URL
[5]	Li JY, Chen SQ, Yan YY, et al. Identification and antimicrobial resistance of pathogens in neonatal septicemia in China-A meta-analysis[J]. Int J Infect Dis, 2018, 71: 89-93. doi: 10.1016/j.ijid.2018.04.794 URL
[6]	Letouzey M, Lorthe E, Marchand-Martin L, et al. Early antibiotic exposure and adverse outcomes in very preterm infants at low risk of early-onset sepsis: The EPIPAGE-2 Cohort Study[J]. J Pediatr, 2022, 243: 91-98.e4. doi: 10.1016/j.jpeds.2021.11.075 URL
[7]	Ting JY, Roberts A, Sherlock R, et al. Duration of initial empirical antibiotic therapy and outcomes in very low birth weight infants[J]. Pediatrics, 2019, 143(3): e20182286. doi: 10.1542/peds.2018-2286 URL
[8]	Cantey JB, Pyle AK, Wozniak PS, et al. Early antibiotic exposure and adverse outcomes in preterm, very low birth weight infants[J]. J Pediatr, 2018, 203: 62-67. doi: 10.1016/j.jpeds.2018.07.036 URL
[9]	Slob EMA, Brew BK, Vijverberg SJH, et al. Early-life antibiotic use and risk of asthma and eczema: results of a discordant twin study[J]. Eur Respir J, 2020, 55(4): 1902021. doi: 10.1183/13993003.02021-2019 URL
[10]	Rasmussen SH, Shrestha S, Bjerregaard LG, et al. Antibiotic exposure in early life and childhood overweight and obesity: A systematic review and meta-analysis[J]. Diabetes Obes Metab, 2018, 20(6): 1508-1514. doi: 10.1111/dom.13230 pmid: 29359849
[11]	中华医学会儿科学分会新生儿学组, 中国医师协会新生儿科医师分会感染专业委员会. 新生儿败血症诊断及治疗专家共识(2019年版)[J]. 中华儿科杂志, 2019, 57(4): 252-257.
[12]	Ting JY, Synnes A, Roberts A, et al. Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis[J]. JAMA Pediatr, 2016, 170(12): 1181-1187. doi: 10.1001/jamapediatrics.2016.2132 pmid: 27775765
[13]	Dutta S, Singh B, Chessell L, et al. Guidelines for feeding very low birth weight infants[J]. Nutrients, 2015, 7(1): 423-442. doi: 10.3390/nu7010423 pmid: 25580815
[14]	No authors listed. 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 URL
[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 pmid: 30640366
[16]	Kim JH, Sampath V, Canvasser J. Challenges in diagnosing necrotizing enterocolitis[J]. Pediatr Res, 2020, 88(Suppl 1): 16-20. doi: 10.1038/s41390-020-1090-4 pmid: 32855507
[17]	Higgins RD, Jobe AH, Koso-Thomas M, et al. Bronchopulmonary dysplasia: executive summary of a workshop[J]. J Pediatr, 2018, 197: 300-308. doi: 10.1016/j.jpeds.2018.01.043 URL
[18]	《实用新生儿学》第4版出版[J]. 中国循证儿科杂志, 2013, 8(6): 457.
[19]	Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances[J]. Lancet Neurol, 2009, 8(1): 110-124. doi: 10.1016/S1474-4422(08)70294-1 pmid: 19081519
[20]	Harriman TL, Carter B, Dail RB, et al. Golden hour protocol for preterm infants: A quality improvement project[J]. Adv Neonatal Care, 2018, 18(6): 462-470. doi: 10.1097/ANC.0000000000000554 pmid: 30212389
[21]	余加林. 重视早产儿早发型败血症的抗生素准确使用[J]. 中国当代儿科杂志, 2020, 22(1): 7-8.
[22]	Flannery DD, Ross RK, Mukhopadhyay S, et al. Temporal trends and center variation in early antibiotic use among premature infants[J]. JAMA Netw Open, 2018, 1(1): e180164. doi: 10.1001/jamanetworkopen.2018.0164 URL
[23]	王铭杰, 岳少杰, 林锦, 等湖南省极低/超低出生体重儿抗生素使用多中心调查报告[J]. 中国当代儿科杂志, 2020, 22(6): 561-566.
[24]	赵娟娟, 韩树萍, 余章斌, 等. 江苏省15家医院极低/超低出生体重儿抗生素使用现状调查[J]. 中国当代儿科杂志, 2022, 24(9): 988-93.
[25]	Mukhopadhyay S, Sengupta S, Puopolo KM. Challenges and opportunities for antibiotic stewardship among preterm infants[J]. Arch Dis Child Fetal Neonatal Ed, 2019, 104(3): F327-F332. doi: 10.1136/archdischild-2018-315412 URL
[26]	Kuzniewicz MW, Mukhopadhyay S, Li S, et al. Time to positivity of neonatal blood cultures for early-onset sepsis[J]. Pediatr Infect Dis J, 2020, 39(7): 634-640. doi: 10.1097/INF.0000000000002632 pmid: 32379197
[27]	Benitz WE. Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis[J]. Clin Perinatol, 2010, 37(2): 421-438. doi: 10.1016/j.clp.2009.12.001 pmid: 20569816
[28]	Puopolo KM, Benitz WE, Zaoutis TE. Management of neonates born at ≤34 6/7 weeks' gestation with suspected or proven early-onset bacterial sepsis[J]. Pediatrics, 2018, 142(6):e20182896. doi: 10.1542/peds.2018-2896 URL
[29]	National Institute for Heath and Care Excellence(NICE). Neonatal infection: antibiotics for prevention and treatment[EB/OL]. https://www.nice.org.uk/guidance/ng195, 2021[2021-09-01].
[30]	Zou ZH, Liu D, Li HD, et al. Prenatal and postnatal antibiotic exposure influences the gut microbiota of preterm infants in neonatal intensive care units[J]. Ann Clin Microbiol Antimicrob, 2018, 17(1): 9. doi: 10.1186/s12941-018-0264-y
[31]	Gasparrini AJ, Crofts TS, Gibson MK, et al. Antibiotic perturbation of the preterm infant gut microbiome and resistome[J]. Gut Microbes, 2016, 7(5): 443-449. doi: 10.1080/19490976.2016.1218584 pmid: 27472377
[32]	Martinez FE, Ferri WAG, Leone CR, et al. Early empiric antibiotic use is associated with delayed feeding tolerance in preterm infants: A retrospective analysis[J]. J Pediatr Gastroenterol Nutr, 2017, 65(1): 107-110. doi: 10.1097/MPG.0000000000001490 URL
[33]	褚梅艳, 王铭杰, 林锦, 等. 抗生素使用策略改进对胎龄<35周早产儿近期临床结局的影响[J]. 中国当代儿科杂志, 2022, 24(5): 521-529.
[34]	高宏程, 陈晨, 张迎秋, 等. 早产儿视网膜病变的危险因素研究进展[J]. 国际眼科杂志, 2018, 18(1): 80-83.
[35]	沈美丽, 何必子. 早产儿视网膜病37例相关因素分析[J]. 福建医药杂志, 2016, 38(2): 20-23.
[36]	Park SH, Yum HR, Kim S, et al. Retinopathy of prematurity in Korean infants with birthweight greater than 1500 g[J]. Br J Ophthalmol, 2016, 100(6): 834-838. doi: 10.1136/bjophthalmol-2015-306960 URL
[37]	Rina P, Zeng Y, Ying J, et al. Association of initial empirical antibiotic therapy with increased risk of necrotizing enterocolitis[J]. Eur J Pediatr, 2020, 179(7): 1047-1056. doi: 10.1007/s00431-020-03679-4 pmid: 32424744

项目	优化前组(n=158)	优化组(n=156)	χ²/t值	P值
患儿性别[例(%)]
女性男性	68(43.04) 90(56.96)	68(43.59) 88(56.41)	0.010	0.921
胎龄(w)	30.23±1.23	29.79±1.56	2.81	0.005
出生体重(g)	1382.71±279.28	1311.96±331.63	2.044	0.042
1 min评分[例(%)]
>7 ≤7	112(70.89) 46(29.11)	102(65.38) 54(34.62)	1.095	0.295
5 min评分[例(%)]
>7 ≤7	140(88.61) 18(11.39)	134(85.90) 22(14.10)	0.519	0.471
SGA[例(%)]
否是	123(77.85) 35(22.15)	145(92.95) 11(7.05)	14.316	<0.01
分娩方式[例(%)]
顺产剖宫产	48(30.38) 110(69.62)	36(23.08) 120(76.92)	2.136	0.144
单多胎分组[例(%)]
单胎	102(64.56)	120(76.92)
双胎	44(27.85)	33(21.15)	8.418	0.015
三胎	12(7.59)	3(1.92)
试管婴儿[例(%)]
否是	128(81.01) 30(18.99)	129(82.69) 27(17.31)	0.149	0.699
窒息[例(%)]
否是	108(68.35) 50(31.65)	105(67.31) 51(32.69)	0.039	0.843
窒息抢救情况[例(%)]
否是	119(75.32) 39(24.68)	115(73.72) 14(8.97)	0.106	0.745
白细胞计数异常(生后24 h内)[例(%)]
否是	141(89.24) 17(10.76)	125(80.13) 31(19.87)	5.033	0.025
C反应蛋白升高[例(%)]
否是	151(95.57) 7(4.43)	153(98.08) 3(1.92)	0.891	0.345
血小板减少[例(%)]
否是	153(96.84) 5(3.16)	154(98.72) 2(1.28)	0.559	0.455
血培养阳性[例(%)]
否是	155(98.10) 3(1.90)	141(90.38) 15(9.62)	8.650	0.003
EOS(临床诊断)[例(%)]
否是	141(89.24) 17(10.76)	148(94.87) 8(5.13)	3.397	0.065
PICC应用[例(%)]
否是	96(60.76) 62(39.24)	61(39.10) 95(60.90)	14.727	<0.001
PS应用[例(%)]
否是	97(61.39) 61(38.61)	102(65.38) 54(34.62)	0.539	0.463
机械通气[例(%)]
否是	121(76.58) 37(23.42)	134(85.90) 22(14.10)	4.464	0.035
孕母年龄(岁)	30.72±4.67	32.65±4.72	3.656	<0.01
产前发热[例(%)]
否	150(94.94)	147(94.23)
是	3(1.90)	8(5.13)	-	0.102
不详	5(3.16)	1(0.64)
产前抗生素[例(%)]
否	119(75.32)	97(62.18)
是	33(20.89)	58(37.18)	-	0.001
不详	6(3.80)	1(0.64)
产前激素[例(%)]
否	36(22.78)	41(26.28)
是	116(73.42)	115(73.72)	-	0.042
不详	6(3.80)	0(0.00)
胎膜早破(≥18 h)[例(%)]
否是	140(88.61) 18(11.39)	127(81.41) 29(18.59)	3.195	0.074
宫内窘迫[例(%)]
否是	140(88.61) 18(11.39)	129(82.69) 27(17.31)	2.237	0.149

项目	优化前组(n=158)	优化组(n=156)	χ²/t值	P值
患儿性别[例(%)]
女性男性	68(43.04) 90(56.96)	68(43.59) 88(56.41)	0.010	0.921
胎龄(w)	30.23±1.23	29.79±1.56	2.81	0.005
出生体重(g)	1382.71±279.28	1311.96±331.63	2.044	0.042
1 min评分[例(%)]
>7 ≤7	112(70.89) 46(29.11)	102(65.38) 54(34.62)	1.095	0.295
5 min评分[例(%)]
>7 ≤7	140(88.61) 18(11.39)	134(85.90) 22(14.10)	0.519	0.471
SGA[例(%)]
否是	123(77.85) 35(22.15)	145(92.95) 11(7.05)	14.316	<0.01
分娩方式[例(%)]
顺产剖宫产	48(30.38) 110(69.62)	36(23.08) 120(76.92)	2.136	0.144
单多胎分组[例(%)]
单胎	102(64.56)	120(76.92)
双胎	44(27.85)	33(21.15)	8.418	0.015
三胎	12(7.59)	3(1.92)
试管婴儿[例(%)]
否是	128(81.01) 30(18.99)	129(82.69) 27(17.31)	0.149	0.699
窒息[例(%)]
否是	108(68.35) 50(31.65)	105(67.31) 51(32.69)	0.039	0.843
窒息抢救情况[例(%)]
否是	119(75.32) 39(24.68)	115(73.72) 14(8.97)	0.106	0.745
白细胞计数异常(生后24 h内)[例(%)]
否是	141(89.24) 17(10.76)	125(80.13) 31(19.87)	5.033	0.025
C反应蛋白升高[例(%)]
否是	151(95.57) 7(4.43)	153(98.08) 3(1.92)	0.891	0.345
血小板减少[例(%)]
否是	153(96.84) 5(3.16)	154(98.72) 2(1.28)	0.559	0.455
血培养阳性[例(%)]
否是	155(98.10) 3(1.90)	141(90.38) 15(9.62)	8.650	0.003
EOS(临床诊断)[例(%)]
否是	141(89.24) 17(10.76)	148(94.87) 8(5.13)	3.397	0.065
PICC应用[例(%)]
否是	96(60.76) 62(39.24)	61(39.10) 95(60.90)	14.727	<0.001
PS应用[例(%)]
否是	97(61.39) 61(38.61)	102(65.38) 54(34.62)	0.539	0.463
机械通气[例(%)]
否是	121(76.58) 37(23.42)	134(85.90) 22(14.10)	4.464	0.035
孕母年龄(岁)	30.72±4.67	32.65±4.72	3.656	<0.01
产前发热[例(%)]
否	150(94.94)	147(94.23)
是	3(1.90)	8(5.13)	-	0.102
不详	5(3.16)	1(0.64)
产前抗生素[例(%)]
否	119(75.32)	97(62.18)
是	33(20.89)	58(37.18)	-	0.001
不详	6(3.80)	1(0.64)
产前激素[例(%)]
否	36(22.78)	41(26.28)
是	116(73.42)	115(73.72)	-	0.042
不详	6(3.80)	0(0.00)
胎膜早破(≥18 h)[例(%)]
否是	140(88.61) 18(11.39)	127(81.41) 29(18.59)	3.195	0.074
宫内窘迫[例(%)]
否是	140(88.61) 18(11.39)	129(82.69) 27(17.31)	2.237	0.149

组别	例数	早期抗生素使用时间	抗生素使用总时间
优化前组	158	10.00(7.00~14.00)	16.00(8.00~28.00)
优化组	156	6.00(4.00~9.00)	11.00(6.00~22.00)
Z值		7.128	3.503
P值		<0.01	<0.01

组别	例数	早期抗生素使用时间	抗生素使用总时间
优化前组	158	10.00(7.00~14.00)	16.00(8.00~28.00)
优化组	156	6.00(4.00~9.00)	11.00(6.00~22.00)
Z值		7.128	3.503
P值		<0.01	<0.01

组别	例数	≤3 d	4~7 d	>7 d
优化前组	158	12(7.59)	12(7.59)	134(84.81)
优化组	156	22(14.10)	34(21.79)	100(64.1)
χ²值		18.391
P值		<0.01