Effect of 13-valent pneumococcal conjugate vaccine on serotypes and antibiotic-resistance of streptococcus pneumoniae in children
-
摘要:
目的 了解就诊儿童肺炎链球菌(Streptococcus pneumoniae, Spn)血清型分布和耐药特征，探索接种13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine, PCV13)对Spn的影响。 方法 收集2017—2019年苏州大学附属儿童医院疫苗接种信息明确的就诊儿童的Spn菌株，根据疫苗接种情况进行分组，并采用荚膜肿胀法进行血清分型，E-test法检测菌株抗生素的耐药性，比较是否接种PCV13对Spn血清型和耐药性的差别。 结果 共收集692株Spn，其中20株分离自接种PCV13儿童。接种组中常见的血清型为19F、6B、19A、23F，对照组中常见的血清型为19F、6B、23F、19A、14，两组血清型分布差别无统计学意义(P=0.868)，PCV13血清型覆盖率分别为70.0% 和72.4%(P=0.491)。所有菌株对红霉素、四环素、克林霉素高度耐药，且多重耐药率达98.5%。接种组和对照组的Spn菌株对青霉素的不敏感率分别为5.0%和9.1%(P=0.804)。 结论 苏州大学附属儿童医院监测就诊儿童Spn血清型以PCV13覆盖的血清型为主，菌株对β-内酰胺类抗生素的耐药性有所下降，但对红霉素等其他常用抗菌药物的耐药性依旧严峻，并存在大量的多重耐药情况。尚未观察到接种PCV13对菌株血清型分布及降低抗生素耐药性的明显效果。 -
关键词:
- 肺炎链球菌 /
- 13价肺炎球菌结合疫苗 /
- 血清型 /
- 抗生素耐药性 /
- 儿童
Abstract:Objective To investigate the serotype distribution and antibiotic-resistance of Streptococcus pneumoniae (S. pneumoniae) isolated from medical-visiting children, and to explore the effect of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal isolates. Methods The strains of S. pneumoniae isolated from children with confirmed vaccination information in Soochow University Affiliated Children's Hospital (SCH) from 2017 to 2019 were collected. The strains were grouped according to the vaccination status, used quellung reactions to serotype and employed E-test method to determine the antibiotic resistance of strains, and compared the differences in serotypes and antibiotic-resistance between with and without PCV13 vaccination. Results A total of 692 strains of S. pneumoniae were collected, 20 of which were isolated from children vaccinated with PCV13. Serotypes 19F, 6B, 19A and 23F were prevalent in vaccinated children, while serotypes 19F, 6B, 23F, 19A and 14 were common in unvaccinated children. There was no significant difference between the two groups in serotype distribution (P=0.868), and the PCV13 serotype coverage was 70.0% and 72.4%, respectively (P=0.491). All strains were highly resistant to erythromycin, tetracycline and clindamycin, and the multi-antibiotic resistance rate was 98.5%. The unsusceptible rates of penicillin were 5.0% and 9.1% in the vaccinated and unvaccinated groups, respectively (P=0.804). Conclusions Most S. pneumoniae strains from children in SCH were covered by PCV13 serotypes. The resistance of S. pneumoniae to lactams antibiotics was decreased, but the resistance to other commonly used antibiotics such as erythromycin remained severe, and the multi-antibiotic resistance rate was high. No apparent effect of PCV13 on serotype distribution and antibiotic resistance was observed. -
图 1 接种组和对照组Spn菌株血清型分布
Figure 1. Serotype distribution of S.pneumoniae strains in the vaccinated group and the control group
表 1 Spn临床分离株的基本情况[n(%)]
Table 1. Characteristics of S.pneumoniae isolates [n(%)]
基本信息 接种组 对照组 合计 基本信息 接种组 对照组 合计 菌株数(株) 20(100.0) 672(100.0) 692(100.0) 菌株收集年份(年) 性别 2017 1(5.0) 70(10.4) 71(10.3) 男性 10(50.0) 444(66.1) 454(65.6) 2018 2(10.0) 351(52.2) 353(51.0) 女性 10(50.0) 228(33.9) 238(34.4) 2019 17(85.0) 251(37.4) 268(38.7) 年龄(岁) 入院第一诊断 0~ < 1 11(55.0) 371(55.2) 382(55.2) 社区获得性肺炎 18(90.0) 596(88.7) 614(88.7) 1~ < 2 8(40.0) 261(38.8) 269(38.9) 急性中耳炎 0(0.0) 8(1.2) 8(1.2) 2~ < 3 1(5.0) 40(6.0) 41(5.9) 下呼吸道感染 0(0.0) 7(1.0) 7(1.0) 菌株来源 脑膜炎 0(0.0) 2(0.3) 2(0.3) 侵袭性 0(0.0) 3(0.4) 3(0.4) 上呼吸道感染 0(0.0) 1(0.1) 1(0.1) 非侵袭性 20(100.0) 669(99.6) 689(99.6) 其他 2(10.0) 58(8.7) 60(8.7) 
下载: 导出CSV
表 2 接种组和对照组分离菌株的药敏结果[n(%)]
Table 2. Drug sensitivity of S.pneumoniae strains in the vaccinated group and the control group [n(%)]
抗生素 接种组(n=20) 对照组(n=672) 敏感 中介 耐药 敏感 中介 耐药 PEN 19(95.0) 1(5.0) 611(90.9) 57(8.5) 4(0.6) AMX 12(60.0) 6(30.0) 1(5.0) 472(70.2) 167(24.9) 32(4.8) CTX a 13(65.0) 6(30.0) 1(5.0) 506(75.3) 81(12.1) 85(12.6) LEV 19(100.0) 671(99.9) 1(0.1) MXF 20(100.0) 663(100.0) VCM 20(100.0) 672(100.0) C 20(100.0) 606(90.2) 66(9.8) RD 19(100.0) 669(99.6) 3(0.4) TEL 19(95.0) 1(5.0) 627(94.6) 36(5.4) EM 20(100.0) 2(0.3) 670(99.7) TC 1(5.0) 19(95.0) 52(7.7) 620(92.3) CLT 19(100.0) 16(2.4) 656(97.6) LZD 20(100.0) 672(100.0) SXT 3(15.0) 1(5.0) 16(80.0) 66(9.8) 83(12.4) 523(77.8) QD 2(10.5) 17(89.5) 200(29.8) 472(70.2) 注：PEN-青霉素G；AMX-阿莫西林；CTX-头孢噻肟；LEV-左氧氟沙星；MXF-莫西沙星；VCM-万古霉素；C-氯霉素；RD-利福平；TEL-泰利霉素；EM-红霉素；TC-四环素；CLT-克林霉素；LZD-利奈唑烷；SXT-复方新诺明；QD-喹奴普汀-达福普汀。其中对AMX、LEV、RD、CLT、QD均有1株分离株未进行相应的药敏检测，对MXF和TEL则有9株菌株未检测。a χ2=6.164, P=0.046。
下载: 导出CSV
表 3 接种组和对照组分离菌株对多种抗生素的耐药模式[n(%)]
Table 3. The resistance modes of S.pneumoniae strains to multiple antibiotics in the vaccinated group and the control group [n(%)]
多重耐药模式 接种组(n=20) 对照组(n=672) EM+CLT+TC+SXT+QD 7(35.0) 195(29.0) EM+CLT+TC+SXT+QD+β 6(30.0) 143(21.3) EM+TC+SXT 1(5.0) 98(14.6) EM+CLT+TC+SXT 1(5.0) 97(14.4) EM+CLT+TC+SXT+β 1(5.0) 27(4.0) EM+CLT+TC+QD 2(10.0) 25(3.7) EM+CLT+TC+SXT+QD+C 0(0.0) 25(3.7) EM+CLT+TC+SXT+C 0(0.0) 23(3.4) EM+CLT+SXT+QD 1(5.0) 12(1.8) EM+CLT+SXT 0(0.0) 11(1.6) EM+CLT+TC 0(0.0) 8(1.2) EM+TC+SXT+β 0(0.0) 6(0.9) EM+CLT+SXT+QD+β 0(0.0) 6(0.9) EM+CLT+QD 0(0.0) 5(0.7) EM+CLT+QD+β 0(0.0) 2(0.3) EM+CLT+QD+C 0(0.0) 2(0.3) EM+CLT+SXT+QD+C 0(0.0) 2(0.3) EM+CLT+TC+SXT+QD+β+C 0(0.0) 2(0.3) EM+CLT+TC+β 0(0.0) 1(0.1) EM+CLT+TC+C 0(0.0) 1(0.1) EM+CLT+SXT+C 0(0.0) 1(0.1) EM+TC+SXT+C 0(0.0) 1(0.1) 注：PEN-青霉素G；AMX-阿莫西林；CTX-头孢噻肟；LEV-左氧氟沙星；MXF-莫西沙星；VCM-万古霉素；C-氯霉素；RD-利福平；TEL-泰利霉素；EM-红霉素；TC-四环素；CLT-克林霉素；LZD-利奈唑烷；SXT-复方新诺明；QD-喹奴普汀-达福普汀。其中耐药模式包括中介和耐药。
下载: 导出CSV
-
[1] 郭莹, 乔莉娜. 儿童侵袭性与非侵袭性肺炎链球菌病临床特征及耐药性分析[J]. 中国当代儿科杂志, 2021, 23(5): 466-470. DOI: 10.7499/j.issn.1008-8830.2011125.Guo Y, Qiao LN. Clinical features and antibiotic sensitivity of invasive pneumococcal disease versus noninvasive pneumococcal disease in children[J]. Chin J Contemp Pediatr, 2021, 23(5): 466-470. DOI: 10.7499/j.issn.1008-8830.2011125. [2] Kyaw M H, Lynfield R, Schaffner W, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae[J]. N Engl J Med, 2006, 354(14): 1455-1463. DOI: 10.1056/NEJMoa051642. [3] Wahl B, O'Brien KL, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15[J]. Lancet Glob Health, 2018, 6(7): e744-e757. DOI: 10.1016/s2214-109x(18)30247-x. [4] 中华预防医学会, 中华预防医学会疫苗与免疫分会. 肺炎球菌性疾病免疫预防专家共识(2020版)[J]. 中华流行病学杂志2020, 41(12): 1945-1979. DOI: 10.3760/cma.j.cn112338-20201111-01322.Chinese Preventive Medicine Association, Vaccine and Immunology Branch of Chinese Preventive Medicine Association. Expert consensus on immunoprophylaxis of pneumococcal disease (2020 version)[J]. Chin J Epidemiol, 2020, 41(12): 1945-1979. DOI: 10.3760/cma.j.cn112338-20201111-01322. [5] Lyu S, Yao K H, Dong F, et al. Vaccine Serotypes of Streptococcus pneumoniae with High-level Antibiotic Resistance Isolated More Frequently Seven Years After the Licensure of PCV7 in Beijing[J]. Pediatr Infect Dis J, 2016, 35(3): 316-21. DOI: 10.1097/inf.0000000000001000. [6] 陈凯乐, 邵雪君, 张锡彦, 等. 2013-2015年苏州地区儿童肺炎链球菌血清型与耐药监测[J]. 中国初级卫生保健, 2019, 33(8): 106-109. DOI: 10.3969/j.issn.1001-568X.2019.08.0039.Chen KL, Shao XJ, Zhang XY, et al. Surveillance on serotype distribution and antimicrobial resistance patterns of streptococcus pneumonia in suzhou from 2013 to 2015[J]. Chin Primary Health Care, 2019, 33(8): 106-109. DOI: 10.3969/j.issn.1001-568X.2019.08.0039. [7] 徐妍娜, 叶璐, 方寅飞. 学龄前儿童肺炎链球菌感染的流行病学特征、血清型与耐药性分析[J]. 中国卫生检验杂志, 2020, 30(10): 1242-1245. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202010027.htmXu YN, Ye L, Fang YF. Analysis of epidemiological characteristics, serotypes and drug resistance of pre-school children with pneumococcal infection[J]. Chin J Health Lab Technol, 2020, 30(10): 1242-1245. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ202010027.htm [8] Chen K, Zhang X, Shan W, et al. Serotype distribution of Streptococcus pneumoniae and potential impact of pneumococcal conjugate vaccines in China: A systematic review and meta-analysis[J]. Hum Vaccin Immunother, 2018, 14(6): 1453-1463. DOI: 10.1080/21645515.2018.1435224. [9] 胡付品, 郭燕, 朱德妹, 等. 2018年CHINET中国细菌耐药性监测[J]. 中国感染与化疗杂志, 2020, 20(1): 1-10. DOI: 10.16718/j.1009-7708.2020.01.001.Hu FP, Guo Y, Zhu DM, et al. CHINET surveillance of bacterial resistance in China: 2018 report[J]. Chin J Infect Chemother, 2020, 20(1): 1-10. DOI: 10.16718/j.1009-7708.2020.01.001. [10] 陈巧君, 王婷. 儿童呼吸道肺炎链球菌的感染状况、血清学分型及耐药性研究[J]. 中国卫生检验杂志, 2018, 28(7): 809-812. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201807013.htmChen QJ, Wang T. Infection status, serological typing and drug resistance of Streptococcus pneumoniae in children with respiratory tract[J]. Chin J Health Lab Technol, 2018, 28(7): 809-812. https://www.cnki.com.cn/Article/CJFDTOTAL-ZWJZ201807013.htm [11] 姚开虎, 史伟. 儿童肺炎链球菌耐药现状[J]. 中华实用儿科临床杂志, 2016, (4): 252-255, 256. DOI: 10.3760/cma.j.issn.2095-428X.2016.04.004.Yao KH, Shi W. Current status of antibiotic resistance of streptococcus pneumoniae in children[J]. Chinese Journal of Applied Clinical Pediatrics, 2016, (4): 252-255, 256. DOI: 10.3760/cma.j.issn.2095-428X.2016.04.004. [12] Kim SH, Song JH, Chung DR, et al. Changing trends in antimicrobial resistance and serotypes of Streptococcus pneumoniae isolates in Asian countries: an Asian Network for Surveillance of Resistant Pathogens (ANSORP) study[J]. Antimicrob Agents Chemother, 2012, 56(3): 1418-1426. DOI: 10.1128/AAC.05658-11. [13] 龚松迪, 华春珍, 李建平, 等. 2006-2014年我院1109例肺炎链球菌感染及其耐药模式分析[J]. 中国抗生素杂志, 2015, 40(11): 859-864, 880. DOI: 10.3969/j.issn.1001-8689.2015.11.013.Gong SD, Hua CZ, Li JP, et al. Analysis on 1, 109 cases caused by Streptococcus pneumoniae and the antibiotic resistance of all strains during 2006-2014[J]. J Chin Antibiotics, 2015, 40(11): 859-864, 880. DOI: 10.3969/j.issn.1001-8689.2015.11.013. [14] Wang L M, Cravo Oliveira Hashiguchi T, Cecchini M. Impact of vaccination on carriage of and infection by antibiotic-resistant bacteria: a systematic review and meta-analysis[J]. Clin Exp Vaccine Res, 2021, 10(2): 81-92. DOI: 10.7774/cevr.2021.10.2.81. [15] Lochen A, Croucher N J, Erson R M. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency[J]. Sci Rep, 2020, 10(1): 18977. DOI: 10.1038/s41598-020-75691-5. [16] Lewnard J A, Hanage W P. Making sense of differences in pneumococcal serotype replacement[J]. Lancet Infect Dis, 2019, 19(6): e213-e220. DOI: 10.1016/s1473-3099(18)30660-1. [17] Klugman K P, Black S. Impact of existing vaccines in reducing antibiotic resistance: Primary and secondary effects[J]. Proc Natl Acad Sci U S A, 2018, 115(51): 12896-12901. DOI: 10.1073/pnas.1721095115. [18] Principi N, Di Cara G, Bizzarri I, et al. Prevention of invasive pneumococcal disease: problems emerged after some years of the 13-valent pneumococcal conjugate vaccine use[J]. Curr Infect Dis Rep, 2018, 20(1): 1. DOI: 10.1007/s11908-018-0607-z. [19] Scelfo C, Menzella F, Fontana M, et al. Pneumonia and invasive pneumococcal diseases: the role of pneumococcal conjugate vaccine in the era of multi-drug resistance[J]. Vaccines, 2021, 9(5): 420. DOI: 10.3390/vaccines9050420. -
点击查看大图
图(1) / 表(3)
计量
- 文章访问数: 528
- HTML全文浏览量: 188
- PDF下载量: 62
- 被引次数: 0