杭州地区2012~2018年耐甲氧西林金黄色葡萄球菌的分子流行病学特征及其变化趋势

doi:10.16288/j.yczz.23-166

遗传 ›› 2023, Vol. 45 ›› Issue (11): 1074-1084.doi: 10.16288/j.yczz.23-166

• 研究报告 • 上一篇

杭州地区2012~2018年耐甲氧西林金黄色葡萄球菌的分子流行病学特征及其变化趋势

朱云颖(), 王媛, 肖婷婷, 嵇金如, 沈萍, 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:2023-09-09 出版日期:2023-11-20 发布日期:2023-09-20
通讯作者: 肖永红 E-mail:21818043@zju.edu.cn;xiao-yonghong@163.com
作者简介:朱云颖，硕士，医师，研究方向：传染病学。E-mail: 21818043@zju.edu.cn。
基金资助:
国家自然科学基金项目(81971984);浙江省重点研发计划(2021C03068);济南微生态生物医学山东省实验室研究项目(JNL-2022006B)

Molecular epidemiology and change trend of methicillin-resistant Staphylococcus aureus from invasive infections of a hospital in Hangzhou from 2012 to 2018

Yunying Zhu(), Yuan Wang, Tingting Xiao, Jinru Ji, Ping Shen, Yonghong Xiao()

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine，Hangzhou 310003, China

Received:2023-06-19 Revised:2023-09-09 Published:2023-11-20 Online:2023-09-20
Contact: Yonghong Xiao E-mail:21818043@zju.edu.cn;xiao-yonghong@163.com
Supported by:
National Natural Science Foundation of China(81971984);Key Research and Development program of Zhejiang province(2021C03068);Research Project of Jinan Microecological Biomedicine Shandong Laboratory(JNL-2022006B)

摘要/Abstract

摘要：

耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus，MRSA)是威胁全球的公共卫生问题，给社会和患者造成严重的安全威胁，因此明确MRSA耐药性和时空分布的多态性对于其感染的诊治和防控至关重要。本研究通过收集本院162株MRSA菌株，将所有菌株根据标准区分为社区获得性(community-associated) MRSA (CA-MRSA)和医院获得性(hospital-associated) MRSA (HA-MRSA)，利用聚合酶链式反应(polymerase chain reaction，PCR)测定MRSA菌株的多位点序列分型(multilocus sequence typing，MLST)，葡萄球菌盒式染色体序列(staphylococcal chromosome cassette mec，SCCmec)、葡萄球菌A蛋白(staphylococcal protein A，spa)基因多态性，以及杀白细胞毒素(Panton-Valentine leucocidin，PVL)，分析了杭州地区不同年份(2012~2018年) MRSA菌株的分子特征。结果共发现16种ST型和30种spa型。ST型以ST5型为主(96/162,59.3%)，spa分型以t311型为主(83/162,51.2%)。发现5种SCCmec分型，以SCCmec II型最为常见(101/162,61.7%)，ST5-II-t311是本地区的第一优势MRSA克隆。2014~2018年，ST5型MRSA的患病率逐渐下降，而ST59型MRSA的患病率上升。同时，本研究检出家畜相关耐甲氧西林金黄色葡萄球菌(livestock-associated methicillin-resistant Staphylococcus aureus，LA-MRSA) ST398和ST9。PVL基因阳性MRSA菌株共28株(28/162,17.3%)，最常见的PVL阳性克隆是ST59-IVa-t437。CA-MRSA与HA-MRSA相比，ST型为ST5的比例较低(9.1% vs 67.1%，P=0.000)，ST59的比例较高(63.6% vs 11.4%，P=0.000)，且CA-MRSA携带PVL阳性基因的可能性更高(36.4% vs 14.3%，P=0.028)。上述结果表明，MRSA的分子类型越来越多样化，ST5-II-t311是本地区MRSA的优势克隆，但在2014~ 2018年呈下降趋势，而社区相关性克隆菌株ST59型MRSA在2014~2018年呈逐年上升趋势。

关键词: 耐甲氧西林金黄色葡萄球菌, 社区获得性, 医院获得性, 分子流行病学

Abstract:

The disease caused by methicillin-resistant Staphylococcus aureus (MRSA) is a global public health challenge that threatens society and patients seriously. Therefore, the molecular epidemiology and change trend of MRSA is essential for the control and treatment of diseases caused by the pathogen in their regions. To explore molecular epidemiology of MRSA in Hangzhou, we collected 162 MRSA isolates from 2012 to 2018, conducted the antimicrobial susceptibility and used polymerase chain reaction(PCR) to test the molecular typing including multilocus sequence typing (MLST), staphylococcal chromosome cassette mec (SCCmec), staphylococcal protein A (spa A) and Panton-Valentine leucocidin (PVL). All the strains was divided into community-associated MRSA (CA-MRSA) or hospital-associated MRSA (HA-MRSA). 162 MRSA isolates were divided into 16 STs and 30 spa types. The major ST type was ST5 (96/162, 59.3%) and the predominant spa type was t311 (83/162, 51.2%). Five SCCmec types were found and the most common SCCmec type was type II (101/162, 61.7%). ST5-II-t311 was the predominant MRSA clone. And the prevalence of ST5 MRSA gradually declined from 2014 to 2018 but the prevalence of ST59 MRSA significantly increased. At the same time, livestock-associated methicillin-resistant Staphylococcus aureus(LA-MRSA) ST398 and ST9 were detected. Twenty-eight isolates were PVL gene positive (28/162, 17.3%). The most prevalent PVL-positive clone was ST59-IVa-t437. Comparing with HA-MRSA, CA-MRSA had a lower probability of ST5 (9.1% vs 67.1%, P=0.000) but a higher probability of ST59 (63.6% vs 11.4%, P=0.000), not only that, it was more likely to carrying PVL-positive gene (36.4% vs 14.3%, P=0.028). In summary, the molecular types of MRSA were getting complex over time. ST5-II-t311 was the predominant clone of MRSA isolate with a downward incidence from 2014 to 2018. ST59 MRSA strains, which is thought community related strain are spreading into hospitals and has an upward incidence from 2014 to 2018.

Key words: methicillin-resistant Staphylococcus aureus, molecular characterization, community-associated, hospital-associated

朱云颖, 王媛, 肖婷婷, 嵇金如, 沈萍, 肖永红. 杭州地区2012~2018年耐甲氧西林金黄色葡萄球菌的分子流行病学特征及其变化趋势[J]. 遗传, 2023, 45(11): 1074-1084.

Yunying Zhu, Yuan Wang, Tingting Xiao, Jinru Ji, Ping Shen, Yonghong Xiao. Molecular epidemiology and change trend of methicillin-resistant Staphylococcus aureus from invasive infections of a hospital in Hangzhou from 2012 to 2018[J]. Hereditas(Beijing), 2023, 45(11): 1074-1084.

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ST分型	SCCmec	spa	菌株数(n)	百分比(%)	ST分型	SCCmec	spa	菌株数(n)	百分比(%)
ST5	II	t311	81	50.0	ST88	III	t7637	1	0.6
ST5	II	t002	5	3.1	ST88	V	t2526	1	0.6
ST5	II	t2460	3	1.9	ST630	II	t4549	4	2.5
ST5	II	t494	1	0.6	ST630	V	t4549	1	0.6
ST5	II	t2731	1	0.6	ST965	NT	t062	2	1.2
ST5	II	t3235	1	0.6	ST965	IVa	t062	1	1.2
ST5	NT	t311	2	1.2	ST965	II	t062	1	0.6
ST5	IVa	t693	1	0.6	ST239	III	t030	2	1.2
ST5	V	t319	1	0.6	ST239	NT	t421	1	0.6
ST59	IVa	t437	18	11.1	ST1	IVa	t127	1	0.6
ST59	IVa	t172	4	2.5	ST1	NT	t127	1	0.6
ST59	IVa	t441	2	1.2	ST188	I	t189	1	0.6
ST59	IVa	t163	1	0.6	ST188	IVa	t3887	1	0.6
ST59	NT	t437	3	1.8	ST6	NT	t701	1	0.6
ST59	V	t437	1	0.6	ST7	IVa	t091	1	0.6
ST59	V	t4135	1	0.6	ST9	NT	t899	1	0.6
ST398	NT	t034	7	4.3	ST22	NT	t309	1	0.6
ST398	II	t034	1	0.6	ST573	IVa	t127	1	0.6
ST88	NT	t2310	1	0.6	ST764	II	t045	1	0.6
ST88	NT	t7637	1	0.6	ST3193	IVa	t172	1	0.6
ST88	II	t15047	1	0.6

PVL阳性的分子分型	菌株数(n)	百分比(%)
ST59-IVa-t437	8	28.6
ST5-II-t311	4	14.3
ST59-NT-t437	2	7.1
ST5-II-t2460	1	3.6
ST59-IVa-t172	1	3.6
ST59-IVa-t441	1	3.6
ST59-V-437	1	3.6
ST59-V-t4135	1	3.6
ST398-II-t034	1	3.6
ST88-NT-t2310	1	3.6
ST88-NT-t7637	1	3.6
ST88-III-t7637	1	3.6
ST88-V-2526	1	3.6
ST965-IVa-t062	1	3.6
ST6-NT-t701	1	3.6
ST22-NT-t309	1	3.6
ST3193-IVa-t172	1	3.6

抗菌药物	耐药株数(%)	中介株数(%)	敏感株数(%)
克林霉素(CLI)	50(30.9)	1(0.6)	111(68.5)
红霉素(ERY)	138(85.2)	5(3.1)	19(11.7)
庆大霉素(GEN)	9(5.6)	14(8.6)	139(85.8)
环丙沙星(CIP)	107(66.0)	6(3.7)	49(30.2)
左氧氟沙星(LVX)	104(64.2)	3(1.9)	55(34.0)
莫西沙星(MXF)	102(63.0)	6(3.7)	54(33.3)
利福平(RIF)	5(3.1)	1(0.6)	156(96.3)
四环素(TCY)	69(42.6)	-	93(57.4)
复方新诺明(SXT)	5(3.1)	-	157(96.9)
利奈唑胺(LZD)	-	-	162(100)
替加环素(TGC)	-	-	162(100)
万古霉素(VAN)	-	-	162(100)

ST分型	菌株数	耐药率(%)
ST分型	菌株数	克林霉素(CLI)	红霉素(ERY)	庆大霉素(GEN)	环丙沙星(CIP)	左氧氟沙星(LVX)	莫西沙星(MFX)	利福平(RIF)	四环素(TCY)	复方新诺明(SXT)
ST5	96	20.8	100.0	16.7	99.0	99.0	99.0	3.1	54.2	0.0
ST59	30	73.3	76.7	0.0	20.0	6.7	6.7	0.0	30.0	0.0
ST398	8	25.0	50.0	0.0	12.5	12.5	12.5	12.5	12.5	0.0
ST630	5	0.0	40.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ST965	4	25.0	100.0	25.0	50.0	25.0	50.0	0.0	25.0	25.0
ST239	3	66.7	100.0	66.7	66.7	66.7	66.7	66.7	66.7	33.3
ST1	2	0.0	100.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ST188	2	50.0	100.0	50.0	100.0	100.0	100.0	0.0	50.0	50.0
ST6	1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ST7	1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	100.0	0.0
ST9	1	100.0	100.0	100.0	100.0	100.0	100.0	0.0	100.0	100.0
ST22	1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
ST573	1	0.0	100.0	0.0	100.0	100.0	100.0	0.0	0.0	0.0
ST764	1	100.0	100.0	100.0	100.0	100.0	100.0	0.0	100.0	0.0
ST3193	1	100.0	100.0	0.0	100.0	0.0	0.0	0.0	0.0	0.0
Total	162	31.5	88.3	14.2	69.8	66.0	66.7	3.7	42.6	3.1

类型	菌株数	耐药比例(%)
类型	菌株数	克林霉素(CLI)	红霉素(ERY)	庆大霉素(GEN)	环丙沙星(CIP)	左氧氟沙星(LVX)	莫西沙星(MFX)	利福平(RIF)	四环素(TCY)	复方新诺明(SXT)
CA-MRSA	22	63.6	72.7	4.5	13.6	13.6	13.6	0	27.3	9.1
HA-MRSA	140	25.7	87.1	5.7	74.3	72.1	70.7	3.6	45	2.1

杭州地区2012~2018年耐甲氧西林金黄色葡萄球菌的分子流行病学特征及其变化趋势

Molecular epidemiology and change trend of methicillin-resistant Staphylococcus aureus from invasive infections of a hospital in Hangzhou from 2012 to 2018

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Metrics

菌株	HA-MRSA (n=140)	CA-MRSA (n=22)	P-值
ST5 MRSA(%)	94(67.1)	2(9.1)	0.000
ST59 MRSA(%)	16 (11.4)	14 (63.6)	0.000
PVL-阳性MRSA(%)	20 (14.3)	8 (36.4)	0.028
血流感染MRSA(%)	93 (66.4)	18 (81.8)	0.217