肺部感染患者多重耐药铜绿假单胞菌的耐药谱与特征

周俊立; 张文萃; 王莹莹; 郑惠结; 刘宁; 李荧; 何穗平; 贡梓军; 姚振江

doi:10.16462/j.cnki.zhjbkz.2020.09.011

肺部感染患者多重耐药铜绿假单胞菌的耐药谱与特征

doi: 10.16462/j.cnki.zhjbkz.2020.09.011

510310 广州, 广东药科大学公共卫生学院流行病与卫生统计学系

基金项目:

广东省科技厅计划项目 2008B030301034

详细信息

通讯作者:
姚振江, E-mail:zhjyao2001@yahoo.com

中图分类号: R446.5
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出版历程
- 收稿日期: 2019-12-17
- 修回日期: 2020-04-08
- 刊出日期: 2020-09-10

Drug resistance spectrum and characteristics of multi-drug resistant Pseudomonas aeruginosa in patients with pulmonary infection

Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China

Funds:

Guangdong Science and Technology Planning Projet 2008B030301034

More Information

Corresponding author: YAO Zhen-jiang ,E-mail:zhjyao2001@yahoo.com

摘要

摘要: 目的了解广州市肺部感染患者分离的多重耐药铜绿假单胞菌（multi-drug resistant Pseudomonas aeruginosa，MDRPA）的耐药谱、产酶情况、耐药基因及其整合子基因的分布情况。方法对2008年-2012年在广州市某5所医院肺部感染患者中收集分离的MDRPA菌株，进行药敏试验和基因检测。结果共收集248株铜绿假单胞菌，分离MDRPA145株，多重耐药率为58.47%；对所测抗生素的耐药率均超过50.00%。MDRPA菌株产超广谱β-内酰胺酶（extended spectrum β-lactamases，ESBLs）、金属β内酰胺酶（metallo β lactamases，MBL）、C类头孢菌素酶（class C cephalosporinases，AmpC）的检出率分别为17.93%、21.38%和17.24%；ESBLs编码基因TEM、PER、OXA-10的检出率分别为54.48%、25.52%和33.79%，MBL编码基因IMP、VIM检出率分别为21.38%、9.66%，OprD2基因缺失率为32.41%，氨基糖苷类耐药基因ant（3″）-Ⅰ和aac（6'）-Ⅱ检出率分别为43.45%和40.69%，Ⅰ类整合子基因检出率为62.07%。结论广州市肺部感染患者铜绿假单胞菌的多重耐药现象严重，同时β-内酰胺酶及其编码基因、Ⅰ类整合子基因和多种耐药基因广泛存在于MDRPA中，应引起高度重视。
- 铜绿假单胞菌 /
- 肺部感染 /
- 多重耐药 /
- β-内酰胺酶 /
- 基因
Abstract: Objective To analyze drug resistance spectrum, production of beta-lactamases, distribution of drug-resistant genes and integrons genes in multi-drug resistant Pseudomonas aeruginosa (MDRPA) isolated from patients with pulmonary infection in Guangzhou City. Methods Antimicrobial susceptibility testing and genetic testing were performed for MDRPA isolates, which were collected from patients with pulmonary infection in five hospitals in Guangzhou from 2008 to 2012. Results Of the 248 Pseudomonas aeruginosa isolates, the prevalance of MDRPA was 58.47%. The resistance rates to antibiotics used were over 50.00%. Among 145 MDRPA strains, the detection rate of production of extended spectrum β-lactamases (ESBLs), metallo β lactamases (MBL) and class C cephalosporinases (AmpC) was 17.93%, 21.38%, 17.24%, respectively. The detection rate of encoding genes was TEM (54.48%), PER (25.52%), OXA-10 (33.79%), IMP (21.38%) and VIM (9.66%), respectively, and the lacking rate of OprD2 gene was 32.41%. The detection rate of aminoglycoside modifying enzyme genes ant(3″)-Ⅰ and aac(6')-Ⅱ was 43.45% and 40.69%, respectively, and class Ⅰ integron gene was 62.07%. Conclusion The multi-drug resistance situation of Pseudomonas aeruginosa in patients with pulmonary infection in Guangzhou is serious. Meanwhile, β-lactamase and its coding genes, class Ⅰ integron genes and a variety of drug resistance genes are widely found in MDRPA, which should be paid more attention to.
- Pseudomonas aeruginosa /
- Pulmonary infection /
- Multi-drug resistance /
- β-lactamase /
- Gene

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图 1 MDRPA在抗生素种类耐药数量的分布

Figure 1. Distribution of numbers of drug resistance in MDRPA

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表 1 2008—2012年MDRPA对13种抗生素的耐药情况[n(%)]

Table 1. Antimicrobial resistance rates of MDRPA to 13 kinds of antibiotics from 2008 to 2012 [n(%)]

抗生素	2008年(n=16)	2009年(n=35)	2010年(n=21)	2011年(n=34)	2012年(n=39)	合计(n=145)
头孢菌素类
头孢他啶^a	12(75.00)	26(74.29)	16(76.19)	21(61.76)	34(87.18)	109(75.17)
头孢吡肟^a	12(75.00)	19(54.29)	16(76.19)	28(82.35)	34(87.18)	109(75.17)
单环内酰胺类
氨曲南	13(81.25)	33(94.29)	19(90.48)	28(82.35)	28(71.79)	121(83.45)
青霉素类
哌拉西林^a	10(62.50)	22(62.86)	16(76.19)	28(82.35)	31(79.49)	107(73.79)
替卡西林^a	13(81.25)	26(74.29)	16(76.19)	25(73.53)	36(92.31)	116(80.00)
β-内酰胺酶抑制复合剂
哌拉西林/他唑巴坦^a	8(50.00)	18(51.43)	14(66.67)	26(76.47)	25(64.10)	91(62.76)
碳青霉烯类
美洛培南^a	6(37.50)	16(45.71)	15(71.43)	21(61.76)	18(46.15)	76(52.41)
亚胺培南	7(43.75)	20(57.14)	15(71.43)	27(79.41)	15(38.46)	84(57.93)
喹诺酮类
环丙沙星	14(87.50)	23(65.71)	19(90.48)	23(67.65)	23(58.97)	102(70.34)
左氧氟沙星	14(87.50)	22(62.86)	20(95.24)	24(70.59)	19(48.72)	99(68.28)
氨基糖苷类
庆大霉素^a	9(56.25)	18(51.43)	14(66.67)	25(73.53)	32(82.05)	98(67.59)
妥布霉素^a	10(62.50)	17(48.57)	12(57.14)	23(67.65)	28(71.79)	90(62.07)
阿米卡星^a	7(43.75)	15(42.86)	10(47.62)	20(58.82)	23(58.97)	75(51.72)
注：^a表示使用趋势性χ²检验，P < 0.05。

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表 2 MDRPA和NMDRPA的β-内酰胺酶检测情况[n(%)]

Table 2. Isolates rate of beta-lactamases in MDRPA and NMDRPA[n(%)]

酶	MDRPA (n=145)	NMDRPA (n=103)	合计(n=248)	χ²值	P值
ESBLs	26(17.93)	6(5.83)	32(12.90)	7.85	0.005
MBL	31(21.38)	2(1.94)	33(13.31)	19.72	< 0.001
AmpC	25(17.24)	11(10.68)	36(14.52)	2.09	0.148

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表 3 MDRPA和NMDRPA的基因检测情况[n(%)]

Table 3. Detection rate of genes in MDRPA and NMDRPA[n(%)]

基因	MDRPA (n=145)	NMDRPA (n=103)	合计(n=248)	χ²值	P值
β-内酰胺酶相关基因
TEM	79(54.48)	37(35.92)	116(46.77)	8.33	0.004
PER	37(25.52)	23(22.33)	60(24.19)	0.33	0.564
OXA-10	49(33.79)	12(11.65)	61(24.60)	15.92	< 0.001
IMP	31(21.38)	11(10.68)	42(16.94)	4.90	0.027
VIM	14(9.66)	0 (0.00)	14(5.65)	10.54	0.001
外膜孔蛋白基因
OprD2	98(67.59)	95(92.23)	193(77.82)	21.20	< 0.001
氨基糖苷类耐药基因
ant(3″)-Ⅰ	63(43.45)	23(22.33)	86(34.68)	11.86	0.001
aac(6′)-Ⅱ	59(40.69)	9(8.74)	68(27.42)	30.89	< 0.001
整合子基因
Ⅰ类	90(62.07)	40(38.83)	130(52.42)	13.03	< 0.001

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参考文献(24)

[1]	Feng W, Sun F, Wang Q, et al. Epidemiology and resistance characteristics of Pseudomonas aeruginosa isolates from the respiratory department of a hospital in China[J]. J Glob Antimicrob Resist, 2017, 8:142-147. DOI: 10.1016/j.jgar.2016.11.012.
[2]	张祎博, 孙景勇, 倪语星, 等. 2005-2014年CHINET铜绿假单胞菌耐药性监测[J].中国感染与化疗杂志, 2016, 16(2):141-145. DOI: 10.16718/j.1009-7708.2016.02.005. Zhang YB, Sun JY, Ni YX, et al. Resistance profile of Pseudomonas aeruginosa in hospitals across China:the results from the CHINET antimicrobial resistance surveillance program, 2005-2014[J]. Chin J Infect Chemother, 2016, 16(2):141-145. DOI: 10.16718/j.1009-7708.2016.02.005.
[3]	Zilberberg MD, Shorr AF. Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens from hospitalized patients with pneumonia and bloodstream infections in the United States from 2000 to 2009[J]. J Hosp Med, 2013, 8(10):559-563. DOI: 10.1002/jhm.2080.
[4]	中华人民共和国卫生部.医院感染诊断标准(试行)[J].中华医学杂志, 2001, 81(5):314-320. DOI: 10.3760/j:issn:0376-2491.2001.05.027. Ministry of Health of the People's Republic of China. Nosocomial infection diagnostic standard (Trial)[J]. Natl Med J China, 2001, 81(5):314-320. DOI: 10.3760/j:issn:0376-2491.2001.05.027.
[5]	de Almeida Silva KCF, Calomino MA, Deutsch G, et al. Molecular characterization of multidrug-resistant (MDR) Pseudomonas aeruginosa isolated in a burn center[J]. Burns, 2017, 43(1):137-143. DOI: 10.1016/j.burns.2016.07.002.
[6]	张传飞.多重耐药铜绿假单胞菌产ESBLs酶与高产AmpC酶情况及药物敏感性研究[J].中国微生态学杂志, 2015, 27(1):76-79. DOI: 10.13381/j.cnki.cjm.201501020. Zhang CF. Research on ESBLs and AmpC from multi drug resistant Pseudomonas aeruginosa and their drug sensitivity[J]. Chin J Microecol, 2015, 27(1):76-79. DOI: 10.13381/j.cnki.cjm.201501020.
[7]	John S, Balagurunathan R. Metallo beta lactamase producing Pseudomonas aeruginosa and Acinetobacter baumannii[J]. Indian J Med Microbiol, 2011, 29(3):302-304. DOI: 10.4103/0255-0857.83918.
[8]	凌寿坚, 陈日荣, 周美容, 等.三种检测铜绿假单胞菌AmpC酶方法的评价[J].热带医学杂志, 2007, 7(5):470-472. DOI: 10.3969/j.issn.1672-3619.2007.05.023. Ling SJ, Chen RR, Zhou MR, et al. To evaluate the three methods used in the examination of Ampc enzyme of Pseudomonas aeruginosa[J]. J Trop Med, 2007, 7(5):470-472. DOI: 10.3969/j.issn.1672-3619.2007.05.023.
[9]	吕军, 杨宏伟, 曹峰, 等.铜绿假单胞菌β-内酰胺类抗菌药物耐药相关基因研究[J].湖北医药学院学报, 2011, 30(6):577-580. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=yyyxyxb201106007 Lyu J, Yang HW, Cao F, et al. Study on β-lactam antibiotic resistant genes in Pseudomonas aeruginosa strain[J]. J HBUM, 2011, 30(6):577-580. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=yyyxyxb201106007
[10]	叶惠芬, 陈惠玲, 刘平, 等.广州地区多重耐药铜绿假单胞菌相关耐药基因的研究[J].检验医学, 2010, 25(4):288-291. DOI: 10.3969/j.issn.1673-8640.2010.04.011. Ye HF, Chen HL, Liu P, et al. Research on the resistant genes of multidrug-resistant Pseudomonas aeruginosa from Guangzhou[J]. Laboratory Medicine, 2010, 25(4):288-291. DOI: 10.3969/j.issn.1673-8640.2010.04.011.
[11]	李艳华, 刘文恩, 简子娟, 等.铜绿假单胞菌耐药性分析及金属酶基因检测[J].中国感染与化疗杂志, 2013, 13(1):43-47. DOI: 10.16718/j.1009-7708.2013.01.002 Li YH, Liu WE, Jian ZJ, et al. Analysis of antimicrobial resistance and metallo-β-lactamase genes in Pseudomonas aeruginosa isolates[J]. Chin J Infect Chemother, 2013, 13(1):43-47. DOI: 10.16718/j.1009-7708.2013.01.002
[12]	Japoni A, Gudarzi M, Farshad S, et al. Assay for integrons and pattern of antibiotic resistance in clinical Escherichia coli strains by PCR-RFLP in Southern Iran[J]. Jpn J Infect Dis, 2008, 61(1):85-88. http://www.ncbi.nlm.nih.gov/pubmed/18219144
[13]	林海, 余跃天, 朱琤, 等.重症医学科多重耐药铜绿假单胞菌致肺部感染的流行病学特征及危险因素[J].临床与病理杂志, 2017, 37(10):2078-2084. DOI: 10.3978/j.issn.2095-6959.2017.10.010. Lin H, Yu YT, Zhu C, et al. Prevalence and risk factors of multidrug-resistant Pseudomonas aeruginosa pneumonia in intensive care unit[J]. J Clin Pathol Res, 2017, 37(10):2078-2084. DOI: 10.3978/j.issn.2095-6959.2017.10.010.
[14]	高春波, 苏丽菊, 柴淼, 等.哈尔滨地区铜绿假单胞菌β-内酰胺酶耐药基因的研究[J].中国卫生检验杂志, 2017, 27(13):1965-1976. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgwsjyzz201713045 Gao CB, Su LJ, Chai M, et al. Study on the β-lactamases resistant genes of Pseudomonas aeruginosa in four hospitals of Harbin[J]. Chin J Health Lab Tec, 2017, 27(13):1965-1976. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgwsjyzz201713045
[15]	王晓红, 张晓丽, 王勇, 等.多重耐药铜绿假单胞菌的临床感染分布及耐药性分析[J].中国全科医学, 2012, 15(22):2583-2585. DOI: 10.3969/j.issn.1007-9572.2012.08.031. Wang XH, Zhang XL, Wang Y, et al. Distribution of clinical infection and drug resistance analysis of multi-drug resistant Pseudomonas aeruginosa[J]. Chin Gen Pract, 2012, 15(22):2583-2585. DOI: 10.3969/j.issn.1007-9572.2012.08.031.
[16]	曾为伦, 吴海鸥, 章如玲, 等.多重耐药铜绿假单胞菌的相关耐药机制研究[J].中国抗生素杂志, 2016, 41(5):377-381. DOI: 10.13461/j.cnki.cja.005728. Zeng WL, Wu HO, Zhang RL, et al. The research of resistance mechanism on the multi-drug resistant P. aeruginosa[J]. J Chin Antibiotics, 2016, 41(5):377-381. DOI: 10.13461/j.cnki.cja.005728.
[17]	梁宏洁, 闫玉兰.铜绿假单胞菌耐药机制的研究进展[J].微创医学, 2014, 9(2):200-203. DOI: 10.11864/j.issn.1673.2014.02.25. Liang HJ, Yan YL. Research advance in antimicrobial resistance mechanisms of Pseudomonas aeruginosa[J]. Journal of Minimally Invasive Medicine, 2014, 9(2):200-203. DOI: 10.11864/j.issn.1673.2014.02.25.
[18]	姚蕾, 刘伟, 徐元宏.安徽省某三级综合医院多重耐药菌临床分布及耐药分析[J].中华疾病控制杂志, 2015, 19(8):857-859. DOI: 10.16462/j.cnki.zhjbkz.2015.08.027. Yao L, Liu W, Xu YH. Clinical distribution and drug resistance analysis of multidrug-resistant bacteria in a comprehensive tertiary hospital in Anhui Province[J]. Chin J Dis Control Prev, 2015, 19(8):857-859. DOI: 10.16462/j.cnki.zhjbkz.2015.08.027.
[19]	汪加朋, 徐化强, 汪文国.肺部感染患者多重耐药菌的耐药性分析[J].中国卫生标准管理, 2019, 10(3):44-46. DOI: 10.3969/j.issn.1674-9316.2019.03.020. Wang JP, Xu HQ, Wang WG. Drug resistance of multidrug-resistant bacteria in patients with pulmonary infection[J]. China Health Standard Management, 2019, 10(3):44-46. DOI: 10.3969/j.issn.1674-9316.2019.03.020.
[20]	刘丹丹, 沈纪录, 戴梦, 等.下呼吸道感染细菌菌谱及耐药性5年动态变化分析[J].中华疾病控制杂志, 2016, 20(1):63-66. DOI:10.16462/j.cnki. zhjbkz.2016.01. 016. Liu DD, Shen JL, Dai M, et al. Dynamic analysis on bacterium spectrum and drug resistance of lower respiratory tract infections for consecutive 5 years[J]. Chin J Dis Control Prev, 2016, 20(1):63-66. DOI: 10.16462/j.cnki.zhjbkz.2016.01.016.
[21]	闫玉兰, 郭世辉, 李萌, 等.铜绿假单胞菌外膜蛋白D2与亚胺培南耐药关系的研究[J].检验医学与临床, 2014, 11(1):13-14. DOI: 10.3969/j.issn.1672-9455.2014.01.006. Yan YL, Guo SH, Li M, et al. Study on relationship between outer membrane protein D2 of Pseudomonas aeruginosa and imipenem-resistance[J]. Lab Med Clin, 2014, 11(1):13-14. DOI: 10.3969/j.issn.1672-9455.2014.01.006.
[22]	张艳, 李静, 赵淑珍.多重耐药铜绿假单胞菌耐药基因的检测与分析[J].临床合理用药杂志, 2018, 11(29):172-173. DOI: 10.15887/j.cnki.13-1389/r.2018.29.114. Zhang Y, Li J, Zhao SZ. Genic analysis of multidrug-resistant Pseudomonas aeruginosa[J]. Chin J of Clinical Rational Drug Use, 2018, 11(29):172-173. DOI: 10.15887/j.cnki.13-1389/r.2018.29.114.
[23]	姜习新.多重耐药的铜绿假单胞菌Ⅰ类整合子与其多重耐药基因的相关性分析[J].检验医学与临床, 2012, 9(3):300-302. DOI: 10.3969/j.issn.1672-9455.2012.03.022. Jiang XX. Correlation analysis of Ⅰ integrons and multidrug resistant gene of multidrug-resistant Pseudomonas aeruginosa[J]. Lab Med Clin, 2012, 9(3):300-302. DOI: 10.3969/j.issn.1672-9455.2012.03.022.
[24]	黄震, 陈文胜, 余治健, 等. Ⅰ类整合子与铜绿假单胞菌多重耐药相关性研究[J].中国感染控制杂志, 2012, 11(3):165-168. DOI: 10.3969/j.issn.1671-9638.2012.03.002. Huang Z, Chen WS, Yu ZJ, et al. Relationship between class Ⅰ integron and multidrug resistance of Pseudomonas aeruginosa[J]. Chin J Infect Control, 2012, 11(3):165-168. DOI: 10.3969/j.issn.1671-9638.2012.03.002.