糖尿病与非糖尿病患者社区获得性高毒肺炎克雷伯菌肝脓肿临床及病原学特征比较

doi:10.16288/j.yczz.23-167

遗传 ›› 2023, Vol. 45 ›› Issue (11): 1052-1061.doi: 10.16288/j.yczz.23-167

糖尿病与非糖尿病患者社区获得性高毒肺炎克雷伯菌肝脓肿临床及病原学特征比较

叶静(), 王媛, 熊璐颖, 肖永红()

浙江大学医学院附属第一医院传染病重症诊治全国重点实验室，杭州 310003

收稿日期:2023-06-19 修回日期:2023-09-18 出版日期:2023-11-20 发布日期:2023-09-29
通讯作者: 肖永红 E-mail:21918251@zju.edu.cn;xiao-yonghong@163.com
作者简介:叶静，硕士，医师，研究方向：传染病学。E-mail: 21918251@zju.edu.cn。
基金资助:
浙江省重点研发计划(2021C03068);国家自然科学基金(81971984);济南微生态生物医学山东实验室研究项目(JNL-2022006B)

Comparison of clinical and microbiological characteristics of community-acquired hypervirulent Klebsiella pneumoniae liver abscess in diabetic and non-diabetic patients

Jing Ye(), Yuan Wang, Luying Xiong, Yonghong Xiao()

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

Received:2023-06-19 Revised:2023-09-18 Published:2023-11-20 Online:2023-09-29
Contact: Yonghong Xiao E-mail:21918251@zju.edu.cn;xiao-yonghong@163.com
Supported by:
Key Research and Development Program of Zhejiang Province(2021C03068);National Natural Science Foundation of China(81971984);Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022006B)

摘要/Abstract

摘要：

高毒力肺炎克雷伯菌(hypervirulent Klebsiella pneumoniae，HvKP)造成侵袭性感染已在全球范围内被广泛报道，其感染者主要集中在患有糖尿病(diabetes mellitus，DM)、慢性肝病等基础疾病的社区人群，且容易发生全身迁徙性感染。本研究收集了本院2013年1月~2018年12月社区获得性肺炎克雷伯菌肝脓肿患者377名，男性占65.8%，其中49.6%有DM。DM患者易发生眼部及中枢神经系统(central nervous system，CNS)感染，治疗过程中更需要持续的局部脓肿引流，其中血糖控制差的患者继发血流感染(bloodstream infections，BSI)的比率更高。共获得HvKP菌株219株，K1/K2血清型占总数81.7%，K2型患者发生BSI的比率高于K1型。PCR检测结果表明，毒力基因(rmpA、areo、kfu、allS、iroN、magA、uge、wcaG)在K1/K2型菌株的携带率明显高于non-K1/K2型，ST23和ST65是最常见的多位点序列分型(multilocus sequence typing, MLST)，分别属于K1及K2血清型。另外收集35株经典肺炎克雷伯菌(classic Klebsiella pneumoniae，cKP)，其血清分型主要以非K1/K2型为主。HvKP的毒力基因携带率及黏性程度明显高于cKP，前者造成的原发性肝脓肿患者易出现多组织器官感染，但对除氨苄西林以外的临床常用抗菌药物表现出更高敏感性，经过有效的治疗，患者的总体预后较好。本研究对社区获得性高毒肺炎克雷伯菌的病原学特征进行分析，并结合患者临床特征进行阐述，可对临床及科研工作起到一定参考价值。

关键词: 肝脓肿, 高毒力肺炎克雷伯菌

Abstract:

Invasive infection caused by hypervirulent Klebsiella pneumoniae (HvKP) has been reported worldwide. Most of the patients are community population, related to diabetes mellitus (DM), chronic liver disease and other basic diseases, which prone to systemic migratory infection. In this study, we collected 377 patients with community acquired Klebsiella pneumoniae liver abscess in our hospital from January 2013 to December 2018, 65.8% of whom were male, and 49.6% had DM. Patients with DM are prone to eye and central nervous system (CNS) infection, which need continuous local abscess drainage during treatment. Among them, patients with poor blood glucose control have a higher rate of blood stream infections (BSI). 219 strains of HvKP were obtained, with K1/K2 Serotype accounted for 81.7%. The incidence of BSI in K2 patients was higher than that in K1 patients. The PCR results indicate that the carrying rate of virulence genes (rmpA、areo、kfu、allS、iroN、magA、uge、wcaG) in K1/K2 type strains is significantly higher than that in non K1/K2 type strains. ST23 and ST65 are the most common multilocus sequence typing (MLST), which belong to K1 and K2 Serotype respectively. All of HvKP strains showed high sensitivity to commonly used clinical antibiotics other than ampicillin, with 54.3% of the strains exhibiting high viscosity characteristics. Meanwhile, 35 classic Klebsiella pneumoniae (cKP) strains were collected, and their serum typing is mainly non K1/K2. The carrying rate of virulence genes and viscosity degree in HvKP are significantly higher than those in cKP. Primary liver abscess caused by HvKP is prone to multiple tissue and organ infections, but it shows higher sensitivity to most commonly used antibiotics in clinical practice except for ampicillin. After effective treatment, the overall prognosis of patients is better. This study analyzes the pathogenic characteristics of HvKP and elaborates on the clinical characteristics of patients, which can provide reference for clinical and scientific research work.

Key words: liver abscess, hypervirulent Klebsiella pneumoniae

叶静, 王媛, 熊璐颖, 肖永红. 糖尿病与非糖尿病患者社区获得性高毒肺炎克雷伯菌肝脓肿临床及病原学特征比较[J]. 遗传, 2023, 45(11): 1052-1061.

Jing Ye, Yuan Wang, Luying Xiong, Yonghong Xiao. Comparison of clinical and microbiological characteristics of community-acquired hypervirulent Klebsiella pneumoniae liver abscess in diabetic and non-diabetic patients[J]. Hereditas(Beijing), 2023, 45(11): 1052-1061.

图/表 6

表1

表2

图1

表3

图2

表4

参考文献 15

[1]	Chen YC, Lin CH, Chang SN, Shi ZY.Epidemiology and clinical outcome of pyogenic liver abscess: an analysis from the National Health Insurance Research Database of Taiwan, 2000-2011. J Microbiol Immunol Infect, 2016, 49(5): 646-665. doi: 10.1016/j.jmii.2014.08.028
[2]	Chang FY, Chou MY.Comparison of pyogenic liver abscesses caused by Klebsiella pneumoniae and non-K. pneumoniae pathogens. J Formos Med Assoc, 1995, 94(5): 232-237.
[3]	Russo TA, Marr CM. Hypervirulent Klebsiella pneumoniae. Clin Microbiol Rev, 2019, 32(3): e00001-e00019.
[4]	Lederman ER, Crum NF. Pyogenic liver abscess with a focus on Klebsiella pneumoniae as a primary pathogen: an emerging disease with unique clinical characteristics. Am J Gastroenterol, 2005, 100(2): 322-331. doi: 10.1111/j.1572-0241.2005.40310.x pmid: 15667489
[5]	Oh H, Heo ST, Kim M, Kang CH, Yoo JR. Devastating community-acquired bacterial meningitis caused by hypervirulent Klebsiella pneumoniae in an immunecompetent patient. J Clin Neurol, 2021, 17(3): 484-486. doi: 10.3988/jcn.2021.17.3.484
[6]	Russo TA, MacDonald U, Hassan S, Camanzo E, LeBreton F, Corey B, McGann P. An assessment of siderophore production, mucoviscosity, and mouse infection models for defining the virulence spectrum of Hypervirulent Klebsiella pneumoniae. mSphere, 2021, 6(2): e00045-21.
[7]	Russo TA, Olson R, Fang CT, Stoesser N, Miller M, MacDonald U, Hutson A, Barker JH, La Hoz RM, Johnson JR.Identification of Biomarkers for Differentiation of Hypervirulent Klebsiella pneumoniae from Classical K. pneumoniae. J Clin Microbiol, 2018, 56(9): e00776-18.
[8]	Fung CP, Lin YT, Lin JC, Chen TL, Yeh KM, Chang FY, Chuang HC, Wu HS, Tseng CP, Siu LK. Klebsiella pneumoniae in gastrointestinal tract and pyogenic liver abscess. Emerg Infect Dis, 2012, 18(8): 1322-1325. doi: 10.3201/eid1808.111053 pmid: 22840473
[9]	Yu WL, Ko WC, Cheng KC, Lee HC, Ke DS, Lee CC, Fung CP, Chuang YC. Association between rmpA and magA genes and clinical syndromes caused by Klebsiella pneumoniae in Taiwan. Clin Infect Dis, 2006, 42(10): 1351-1358. doi: 10.1086/503420
[10]	Li LJ, Yuan ZY, Chen DN, Xie XY, Zhang BS. clinical and microbiological characteristics of invasive and hypervirulent Klebsiella pneumoniae infections in a teaching hospital in China. Infect Drug Resist, 2020, 13: 4395-4403. doi: 10.2147/IDR.S282982
[11]	Lai YC, Peng HL, Chang HY. RmpA2, an activator of capsule biosynthesis in Klebsiella pneumoniae CG43, regulates K2 cps gene expression at the transcriptional level. J Bacteriol, 2003, 185(3): 788-800. doi: 10.1128/JB.185.3.788-800.2003
[12]	Lin CT, Chen YC, Jinn TR, Wu CC, Hong YM, Wu WH. Role of the cAMP-dependent carbon catabolite repression in capsular polysaccharide biosynthesis in Klebsiella pneumoniae. PLoS One, 2013, 8(2): e54430. doi: 10.1371/journal.pone.0054430
[13]	Yeh KM, Kurup A, Siu LK, Koh YL, Fung CP, Lin JC, Chen TL, Chang FY, Koh TH. Capsular serotype K1 or K2, rather than magA and rmpA, is a major virulence determinant for Klebsiella pneumoniae liver abscess in Singapore and Taiwan. J Clin Microbiol, 2007, 45(2): 466-471. doi: 10.1128/JCM.01150-06
[14]	Moranta D, Regueiro V, March C, Llobet E, Margareto J, Larrarte E, Garmendia J, Bengoechea JA. Klebsiella pneumoniae capsule polysaccharide impedes the expression of beta-defensins by airway epithelial cells. Infect Immun, 2010, 78(3): 1135-146. doi: 10.1128/IAI.00940-09 pmid: 20008534
[15]	Fang CT, Lai SY, Yi WC, Hsueh PR, Liu KL, Chang SC. Klebsiella pneumoniae genotype K1: an emerging pathogen that causes septic ocular or central nervous system complications from pyogenic liver abscess. Clin Infect Dis, 2007, 45(3): 284-293. doi: 10.1086/519262

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

血清分型与目的基因	序列(5′→3′)	退火温度(℃)	产物片段大小(bp)
K1	F：GGTGCTCTTTACATCATTGC R：GCAATGGCCATTTGCGTTAG	58	1047
K2	F：GACCCGATATTTCATACTTGACAGAG R：CCTGAAGTAAAATCGTAAATAGAT	50	641
K5	F：TGGTAGTGATGCTCGCGA R：CCTGAACCCACCCCAATC	58	280
K20	F：CCGATTCGGTCAACTAGCTT R：GCACCTCTATGAACTTTCAG	58	741
K54	F：CATTAGCTCAGTGGTTGGCT R：GCTTGACAAACACCATAGCAG	50	881
K57	F：CGACAAATCTCTCCTGACGA R：CGCGACAAACATAACACTCG	50	1037
rmpA	F：ACTGGGCTACCTCTGCTTCA R：CTTGCATGAGCCATCTTTCA	53	536
fimH	F：TGCTGCTGGGCTGGTCGATG R：GGGAGGGTGACGGTGACATC	57	506
areo	F：GCATAGGCGGATACGAACAT R：CACAGGGCAATTGCTTACCT	53	556
kfu	F：ATAGTAGGCGAGCACCGAGAF R：AGAACCTTCCTCGCTGAACA	59	520
allS	F：CCGAAACATTACGCACCTTT R：ATCACGAAGAGCCAGGTCAC	57	508
iroN	F：CCGCAAAGAGACGAACCGCCTT R：CGGGCAATCCCCGCTTTGACTT	57	546
magA	F：GGTGCTCTTTACATCATTGC R：GCAATGGCCATTTGCGTTAG	55	1280
wabG	F：ACCATCGGCCATTTGATAGA R：CGGACTGGCAGATCCATATC	55	578
uge	F：TCTTCACGCCTTCCTTCACT R：GATCATCCGGTCTCCCTGTA	57	534
mrkD	F：AAGCTATCGCTGTACTTCCGGCA R：GGCGTTGGCGCTCAGATAGG	57	340
wcaG	F：GGTTGGKTCAGCAATCGTA R：ACTATTCCGCCAACTTTTGC	50	169

并发症	全部患者感染数 (%，n=377)	糖尿病组感染数 (%，n=187)	非糖尿病组感染数 (%，n=190)	P值
肺部感染	183(48.5%)	100(53.5%)	83(43.7%)	0.064
血流感染	96(25.5%)	51(27.3%)	45(23.7%)	0.478
眼部感染	10(2.7%)	9(4.8%)	1(0.5%)	0.010
中枢神经系统感染	5(1.3%)	5(2.7%)	0	0.029
皮肤软组织感染	4(1.1%)	2(1.1%)	2(1.1%)	1.000
腹腔其他部位感染	8(2.1%)	6(3.2%)	2(1.1%)	0.137
泌尿系感染	7(1.9%)	3(1.6%)	4(2.1%)	1.000
感染性休克	11(2.9%)	7(3.7%)	4(2.1%)	0.377

类别	全部菌株数 (%，n=254)	HvKP组菌株数 (%，n=219)	cKP组菌株数 (%，n=35)	P值
K1/K2	187(73.6%)	179(81.7%)	8(22.9%)	0.000
拉丝实验	126(49.6%)	119(54.3%)	7(20.0%)	0.000
rmpA	228(89.8%)	215(98.2%)	13(37.1%)	0.000
fimH	252(99.2%)	218(99.5%)	34(97.1%)	0.136
areo	228(89.8%)	215(98.2%)	13(37.1%)	0.000
kfu	141(55.5%)	132(60.3%)	9(25.7%)	0.000
allS	124(48.8%)	119(54.3%)	5(14.3%)	0.000
iroN	228(89.8%)	215(98.2%)	13(37.1%)	0.000
magA	129(50.8%)	125(57.1%)	4(11.4%)	0.000
wabG	254(100%)	219(100%)	35(100%)	-
uge	235(92.5%)	203(92.7%)	32(91.4%)	0.792
mrkD	252(99.2%)	218(99.5%)	34(97.1%)	0.136
wcaG	136(53.5%)	132(60.3%)	4(11.4%)	0.000

类别	全部HvKP菌株数 (%，n=219)	糖尿病组菌株数 (%，n=115)	非糖尿病组菌株数 (%，n=104)	P值
K1/K2	179(81.7%)	92(80%)	87(83.7%)	0.485
拉丝实验	119(54.3%)	61(53.0%)	58(55.8%)	0.686
rmpA	215(98.2%)	114(99.1%)	101(97.1%)	0.266
fimH	218(99.5%)	114(99.1%)	104(100%)	0.341
areo	215(98.2%)	114(99.1%)	101(97.1%)	0.266
kfu	132(60.3%)	72(62.6%)	60(57.7%)	0.458
allS	119(54.3%)	62(53.9%)	57(54.8%)	0.894
iroN	215(98.2%)	114(99.1%)	101(97.1%)	0.266
magA	125(57.1%)	63(54.8%)	62(59.6%)	0.471
wabG	219(100%)	115(100%)	104(100%)	-
uge	203(92.7%)	107(93.0%)	96(92.3%)	0.834
mrkD	218(99.5%)	114(99.1%)	104(100%)	0.341
wcaG	132(60.3%)	66(57.4%)	66(63.5%)	0.359

糖尿病与非糖尿病患者社区获得性高毒肺炎克雷伯菌肝脓肿临床及病原学特征比较

Comparison of clinical and microbiological characteristics of community-acquired hypervirulent Klebsiella pneumoniae liver abscess in diabetic and non-diabetic patients

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 6

参考文献 15

相关文章 0

编辑推荐

Metrics