文章信息
- 郭丽洁, 李富顺, 陈静静, 王齐晖, 褚云卓
- GUO Lijie, LI Fushun, CHEN Jingjing, WANG Qihui, CHU Yunzhuo
- 某医院近10年大肠埃希菌分离率和耐药率的变迁情况
- Changes in the isolation and drug resistance rate of Escherichia coli in a hospital over the past 10 years
- 中国医科大学学报, 2024, 53(3): 266-270
- Journal of China Medical University, 2024, 53(3): 266-270
-
文章历史
- 收稿日期:2023-04-21
- 网络出版时间:2024-03-04 21:27:15
大肠埃希菌是引起人类感染的重要革兰氏阴性菌,通常能引起泌尿系统、血液、腹腔等部位感染。国内监测数据显示,大肠埃希菌是革兰氏阴性菌的最主要病原菌[1-3]。近年来,多重耐药、泛耐药的大肠埃希菌不断出现,给临床治疗带来严峻挑战。本研究通过总结我院近10年大肠埃希菌分离率和耐药率的变迁情况,为临床抗感染经验治疗提供依据。
1 材料与方法 1.1 研究对象从2013年至2022年间中国医科大学附属第一医院就诊患者中分离大肠埃希菌,剔除同一患者相同部位的重复菌株,只保留第1株。
1.2 细菌鉴定和药物敏感性试验细菌鉴定采用法国梅里埃公司VITEK 2和VITEK MS细菌鉴定系统。药物敏感性试验采用法国梅里埃公司GN09、GN16和GN335共3种药敏卡,按照仪器制造商建议,使用KB法补充或确认药物敏感性结果。每周以ATCC 25922、ATCC 27853进行质量控制。
1.3 耐药菌超广谱β内酰胺酶(extended-spectrum β-lacta-mase,ESBL)是由质粒介导的能水解青霉素类、头孢菌素和单环酰胺类等β内酰胺类抗菌药物的β内酰胺酶。耐碳青霉烯大肠埃希菌指对亚胺培南、美罗培南或厄他培南中任一种药物耐药的大肠埃希菌。
1.4 数据分析使用WHONET 5.6软件进行统计分析。使用美国临床和实验室标准协会2022年药敏折点对结果进行解释;替加环素采用美国食品药品监督管理局折点[4];头孢哌酮/舒巴坦采用头孢哌酮折点;黏菌素采用专家共识推荐折点[5]。
2 结果 2.1 10年间分离的大肠埃希菌在医院的分布情况共分离6 845株大肠埃希菌,其中4 446株(65.0%)来自女性患者,2 399株(35.0%)来自男性患者;患者年龄最大100岁,最小1 d,平均60岁。
2.1.1 大肠埃希菌在不同科室的分布80.5%的大肠埃希菌分离自住院患者,主要有内科(33.6%)、外科(30.8%)和重症医学科(6.0%)。19.5%的大肠埃希菌分离自门诊和急诊患者。见表 1。
Year | n | Inpatient | Out | Eme | ||||||
Med | Sur | ICU | Obg | Ped | Inf | Other | ||||
2013 | 610 | 218 | 219 | 25 | 31 | 5 | 8 | 24 | 47 | 33 |
2014 | 707 | 255 | 239 | 35 | 36 | 4 | 8 | 33 | 67 | 30 |
2015 | 683 | 253 | 257 | 45 | 16 | 10 | 3 | 23 | 49 | 27 |
2016 | 713 | 222 | 259 | 40 | 16 | 17 | 9 | 25 | 82 | 43 |
2017 | 610 | 209 | 204 | 44 | 12 | 8 | 5 | 24 | 59 | 45 |
2018 | 658 | 225 | 219 | 32 | 12 | 17 | 8 | 27 | 77 | 41 |
2019 | 728 | 240 | 200 | 46 | 40 | 9 | 10 | 28 | 91 | 64 |
2020 | 584 | 191 | 135 | 39 | 39 | 6 | 2 | 14 | 88 | 70 |
2021 | 876 | 289 | 196 | 58 | 42 | 10 | 14 | 22 | 142 | 103 |
2022 | 676 | 199 | 181 | 48 | 33 | 1 | 11 | 25 | 99 | 79 |
Total | 6 845 | 2 301 | 2 109 | 412 | 277 | 87 | 78 | 245 | 801 | 535 |
Med,internal medicine;Sur,surgery;Out,outpatient;Eme,emergency;ICU,intensive care unit;Obs,obstetrics and gynecology;Ped,pediatrics;Inf,infectious diseases. |
2.1.2 大肠埃希菌在不同标本中的分布
大肠埃希菌主要分离自尿液(57.8%)、血液(15.0%)、分泌物(9.2%)、引流液(8.1%)等标本,其中一半以上来自尿液。在尿培养中,大肠埃希菌分离率最高,是泌尿系统感染的重要病原菌。见表 2。
Year | Urine | Blood | Secretion | Fluid | Bile | Sputum | Hydrothorax and ascites | Tissue | Catheter | Cerebrospinal fluid | Other |
2013 | 355 | 100 | 52 | 23 | 38 | 28 | 9 | 1 | 1 | 2 | 1 |
2014 | 427 | 106 | 68 | 38 | 25 | 29 | 8 | 1 | 0 | 1 | 4 |
2015 | 416 | 116 | 56 | 41 | 20 | 20 | 4 | 3 | 2 | 2 | 3 |
2016 | 430 | 102 | 52 | 65 | 31 | 24 | 6 | 1 | 1 | 0 | 1 |
2017 | 341 | 108 | 33 | 60 | 33 | 22 | 5 | 3 | 2 | 1 | 2 |
2018 | 403 | 102 | 51 | 42 | 26 | 23 | 3 | 4 | 1 | 2 | 1 |
2019 | 424 | 100 | 82 | 60 | 28 | 16 | 7 | 2 | 1 | 1 | 7 |
2020 | 332 | 79 | 59 | 61 | 16 | 19 | 5 | 3 | 1 | 0 | 9 |
2021 | 470 | 137 | 95 | 89 | 33 | 27 | 11 | 4 | 3 | 1 | 6 |
2022 | 360 | 80 | 83 | 76 | 30 | 30 | 8 | 0 | 1 | 1 | 7 |
Total | 3 958 | 1 030 | 631 | 555 | 280 | 238 | 66 | 22 | 13 | 11 | 41 |
2.2 10年间分离的大肠埃希菌耐药率的变迁情况
10年间大肠埃希菌的头孢唑啉平均耐药率为78.0%(58.4%~99.5%),且呈逐年下降趋势。虽然庆大霉素平均耐药率[44.8%(38.7%~53.8%)]高于阿米卡星[4.4%(2.2%~6.9%)]和妥布霉素[16.6%(14.8%~19.3%)],但呈逐年下降趋势。产ESBL大肠埃希菌平均分离率为57.2%(54.3%~61.5%),且10年间无明显差异。大肠埃希菌对替加环素、黏菌素和头孢他啶阿维巴坦有良好活性。见表 3。
Antibacterial drug | 2013(n = 610) | 2014(n = 707) | 2015(n = 683) | 2016(n = 713) | 2017(n = 610) | 2018(n = 658) | 2019(n = 728) | 2020(n = 584) | 2021(n = 876) | 2022(n = 676) | |||||||||||||||||||
R | S | R | S | R | S | R | S | R | S | R | S | R | S | R | S | R | S | R | S | ||||||||||
Ampicillin | 88.3 | 10.6 | 84.3 | 14.6 | 82.1 | 15.6 | 83.5 | 15.1 | 84.4 | 14.0 | 84.3 | 13.9 | 82.0 | 16.6 | 82.0 | 16.3 | 80.6 | 17.5 | 80.2 | 18.3 | |||||||||
Piperacillin | 66.8 | 23.1 | 59.4 | 29.3 | 53.3 | 34.4 | 59.6 | 29.3 | 60.5 | 27.8 | 58.9 | 26.6 | 57.9 | 30.5 | 55.8 | 32.5 | 54.2 | 35.6 | 55.3 | 33.2 | |||||||||
Cefoperazone-sulbactam | NA | NA | NA | NA | NA | NA | 2.8 | 87.6 | 6.8 | 85.6 | 4.4 | 83.0 | NA | NA | NA | NA | 7.8 | 86.5 | 4.3 | 88.1 | |||||||||
Piperacillin-tazobactam | 3.3 | 93.4 | 3.0 | 95.1 | 2.1 | 94.7 | 1.7 | 96.3 | 4.8 | 91.3 | 2.4 | 93.6 | 2.4 | 94.3 | 1.7 | 94.9 | 2.1 | 94.8 | 2.2 | 94.1 | |||||||||
Cefazolin | 91.2 | 8.8 | 99.1 | 0.7 | 99.2 | 0.8 | 99.3 | 0.7 | 99.5 | 0.5 | 99.5 | 0.5 | 61.6 | 37.9 | 58.4 | 41.6 | 58.8 | 41.1 | 60.2 | 39.3 | |||||||||
Cefotaxime | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 57.9 | 35.0 | 54.9 | 39.4 | 56.8 | 39.0 | 56.8 | 38.0 | 56.5 | 39.9 | |||||||||
Ceftazidime | 26.7 | 71.3 | 23.8 | 74.6 | 25.8 | 73.6 | 26.4 | 72.0 | 27.6 | 70.6 | 24.6 | 74.5 | 23.8 | 74.2 | 23.1 | 75.3 | 26.0 | 72.1 | 25.3 | 73.5 | |||||||||
Ceftriaxone | 59.7 | 40.3 | 54.2 | 45.7 | 53.7 | 46.2 | 56.9 | 43.0 | 56.2 | 42.8 | 57.3 | 42.7 | 53.8 | 45.7 | 56.2 | 43.6 | 55.5 | 44.4 | 54.6 | 45.4 | |||||||||
Cefepime | 30.8 | 60.1 | 22.0 | 67.2 | 19.2 | 71.0 | 19.4 | 72.0 | 22.3 | 65.6 | 17.5 | 73.2 | 20.5 | 69.5 | 17.9 | 74.3 | 19.9 | 72.3 | 19.2 | 73.4 | |||||||||
Cefotetan | 1.9 | 97.9 | 2.4 | 97.0 | 3.0 | 96.0 | 1.5 | 97.8 | 3.5 | 96.0 | 2.6 | 96.2 | 2.2 | 96.9 | 1.4 | 97.7 | 3.2 | 95.9 | 2.7 | 97.1 | |||||||||
Aztreonam | 41.8 | 56.1 | 38.7 | 60.2 | 35.6 | 64.3 | 39.4 | 60.0 | 40.1 | 58.9 | 38.8 | 61.0 | 37.4 | 62.1 | 34.1 | 65.2 | 35.4 | 63.9 | 36.6 | 63.0 | |||||||||
Imipenem | 0.2 | 99.6 | 0.1 | 99.6 | 0.4 | 99.5 | 0.7 | 99.2 | 2.1 | 97.6 | 1.4 | 97.8 | 1.3 | 98.2 | 1.0 | 98.8 | 1.6 | 98.4 | 1.6 | 98.3 | |||||||||
Meropenem | 0.2 | 99.6 | 0.3 | 99.7 | 0.4 | 99.5 | 0.6 | 99.4 | 2.2 | 97.6 | 1.1 | 98.6 | 1.3 | 98.7 | 1.0 | 98.8 | 1.5 | 98.4 | 1.8 | 97.9 | |||||||||
Amikacin | 6.9 | 92.1 | 5.8 | 93.7 | 5.3 | 93.9 | 5.1 | 94.2 | 8.3 | 90.7 | 4.7 | 94.8 | 3.3 | 96.2 | 2.6 | 96.9 | 2.9 | 96.9 | 2.2 | 97.5 | |||||||||
Gentamicin | 53.8 | 45.9 | 50.4 | 49.0 | 47.4 | 52.5 | 44.5 | 54.9 | 44.4 | 54.9 | 47.0 | 51.9 | 43.8 | 55.4 | 39.6 | 59.4 | 39.9 | 59.4 | 38.7 | 60.6 | |||||||||
Tobramycin | 18.1 | 47.8 | 14.8 | 49.6 | 16.7 | 51.8 | 16.5 | 53.6 | 19.3 | 53.3 | 17.1 | 51.5 | 16.8 | 53.5 | 15.7 | 57.9 | 15.5 | 57.5 | 16.1 | 59.2 | |||||||||
Ciprofloxacin | 76.8 | 22.7 | 74.8 | 21.7 | 76.0 | 20.2 | 71.9 | 24.9 | 76.7 | 20.0 | 76.1 | 20.7 | 75.6 | 20.2 | 75.2 | 22.2 | 75.6 | 20.6 | 71.3 | 23.5 | |||||||||
Levofloxacin | 71.8 | 15.6 | 68.9 | 10.9 | 70.1 | 10.1 | 65.8 | 13.4 | 71.1 | 8.5 | 68.1 | 9.6 | 66.9 | 10.0 | 69.9 | 9.9 | 69.1 | 9.4 | 65.6 | 12.6 | |||||||||
Tmp-smz | 67.9 | 32.1 | 63.1 | 36.9 | 65.1 | 34.9 | 61.0 | 39.0 | 56.4 | 43.6 | 60.3 | 39.5 | 57.2 | 42.8 | 59.5 | 40.5 | 60.1 | 39.9 | 57.5 | 42.5 | |||||||||
Nitrofurantoin | 5.1 | 83.3 | 7.0 | 78.3 | 5.1 | 79.8 | 5.7 | 86.9 | 3.2 | 88.8 | 3.5 | 89.1 | 3.3 | 86.6 | 2.7 | 86.7 | 2.3 | 91.3 | 2.3 | 92.2 | |||||||||
R,resistance rate;S,sensitive rate;NA,not available. |
2.3 不同标本来源的大肠埃希菌耐药率
不同标本来源的大肠埃希菌耐药率有明显差异,对不同抗菌药物的耐药率往往痰液来源的大肠埃希菌最高,分泌物来源的大肠埃希菌最低,尿液和血液来源的大肠埃希菌居中。见表 4。
Antibacterial drug | Urine(n = 3 958) | Blood(n = 1 030) | Secretion(n = 631) | Body fluid(n = 555) | Bile(n = 280) | Sputum(n = 238) | |||||||||||
R | S | R | S | R | S | R | S | R | S | R | S | ||||||
Ampicillin | 83.6 | 14.5 | 85.7 | 13.4 | 76.7 | 21.9 | 87.8 | 11.2 | 73.0 | 25.4 | 90.9 | 7.9 | |||||
Piperacillin | 57.5 | 30.9 | 61.2 | 27.4 | 48.9 | 39.9 | 67.4 | 21.8 | 55.7 | 33.9 | 76.1 | 13.5 | |||||
Cefoperazone-sulbactam | 4.0 | 87.3 | 4.7 | 89.8 | 2.0 | 90.6 | 14.7 | 74.7 | 8.4 | 77.9 | 10.1 | 77.2 | |||||
Piperacillin-tazobactam | 2.2 | 94.9 | 2.6 | 94.9 | 1.3 | 95.3 | 4.5 | 89.9 | 5.2 | 92.5 | 4.7 | 91.0 | |||||
Cefazolin | 78.7 | 21.1 | 80.8 | 19.0 | 64.1 | 35.7 | 82.8 | 17.2 | 78.6 | 21.4 | 89.9 | 10.1 | |||||
Cefotaxime | 57.0 | 37.4 | 56.4 | 40.4 | 45.3 | 51.2 | 67.0 | 31.5 | 51.9 | 38.9 | 77.1 | 20.0 | |||||
Ceftazidime | 25.2 | 73.4 | 26.4 | 71.6 | 17.5 | 81.3 | 33.4 | 64.8 | 29.9 | 68.8 | 35.4 | 61.1 | |||||
ceftriaxone | 54.4 | 45.4 | 60.8 | 39.1 | 45.7 | 53.8 | 66.9 | 33.1 | 52.9 | 46.4 | 76.4 | 23.6 | |||||
Cefepime | 20.7 | 70.0 | 20.0 | 68.3 | 14.2 | 79.2 | 27.3 | 62.5 | 24.1 | 67.1 | 33.5 | 56.8 | |||||
Cefotetan | 2.2 | 96.9 | 1.9 | 97.4 | 2.1 | 97.3 | 5.3 | 93.9 | 3.8 | 94.8 | 4.1 | 95.5 | |||||
Aztreonam | 37.0 | 62.4 | 39.9 | 59.3 | 28.6 | 71.0 | 48.9 | 50.5 | 40.7 | 58.3 | 53.5 | 45.7 | |||||
Imipenem | 0.9 | 99.0 | 0.9 | 98.7 | 0.6 | 99.3 | 2.4 | 96.8 | 2.0 | 97.7 | 1.9 | 97.3 | |||||
Meropenem | 0.8 | 99.1 | 0.8 | 98.8 | 0.4 | 99.5 | 2.6 | 97.1 | 2.0 | 97.3 | 2.7 | 96.9 | |||||
Amikacin | 4.5 | 95.0 | 3.6 | 95.8 | 3.4 | 96.2 | 4.8 | 94.5 | 4.5 | 95.1 | 7.8 | 91.6 | |||||
Gentamicin | 45.0 | 54.1 | 47.1 | 52.5 | 41.8 | 57.9 | 48.1 | 51.9 | 32.2 | 67.1 | 50.0 | 48.0 | |||||
Tobramycin | 16.5 | 53.8 | 16.7 | 52.6 | 12.3 | 57.2 | 21.7 | 50.9 | 13.4 | 66.7 | 24.6 | 43.1 | |||||
Ciprofloxacin | 79.0 | 18.3 | 72.4 | 23.6 | 62.0 | 33.3 | 74.7 | 21.5 | 66.1 | 29.7 | 81.8 | 15.1 | |||||
Levofloxacin | 73.8 | 8.8 | 63.2 | 11.5 | 55.4 | 16.3 | 68.1 | 10.0 | 58.3 | 24.1 | 75.2 | 10.5 | |||||
TMP-SMZ | 60.2 | 39.8 | 64.9 | 35.0 | 59.6 | 40.4 | 65.3 | 34.7 | 48.5 | 51.5 | 72.5 | 27.5 | |||||
Nitrofurantoin | 5.2 | 85.3 | 1.8 | 89.8 | 1.9 | 88.9 | 3.3 | 87.5 | 2.7 | 86.3 | 2.9 | 82.7 | |||||
Tegacyclin | 0.2 | 98.3 | 0.0 | 99.1 | 0.0 | 99.2 | 0.6 | 97.5 | 0.0 | 98.6 | 0.0 | 96.8 | |||||
R,resistance rate;S,sensitive rate. |
2.4 不同科室来源的大肠埃希菌耐药率
不同科室来源的大肠埃希菌耐药率不同,重症医学科来源的大肠埃希菌耐药率最高。大肠埃希菌对碳青霉素烯类抗菌药物的耐药率较低,仅为1.2%(0.2%~2.6%),且碳青霉烯耐药大肠埃希菌分离率重症医学科远高于内科、外科以及门诊和急诊。见表 5。
Antibacterial drug | Sur(n = 2 109) | Med(n = 2 301) | ICU(n = 412) | Out & Eme(n = 1 336) | |||||||
R | S | R | S | R | S | R | S | ||||
Ampicillin | 85.7 | 12.8 | 80.5 | 17.5 | 88.7 | 10.3 | 86.2 | 12.6 | |||
Piperacillin | 63.2 | 25.1 | 52.5 | 35.3 | 64.9 | 23.1 | 61.7 | 26.8 | |||
Cefoperazone-sulbactam | 6.8 | 83.0 | 3.4 | 89.4 | 14.2 | 75.4 | 3.5 | 88.3 | |||
Piperacillin-tazobactam | 3.0 | 93.2 | 2.2 | 95.2 | 5.4 | 88.5 | 1.6 | 95.6 | |||
Cefazolin | 85.2 | 14.8 | 75.8 | 24.0 | 84.3 | 15.7 | 77.1 | 22.5 | |||
Cefotaxime | 62.0 | 33.4 | 53.1 | 40.8 | 62.9 | 33.7 | 61.5 | 35.1 | |||
Ceftazidime | 29.0 | 69.7 | 22.8 | 75.7 | 34.3 | 63.2 | 27.5 | 70.9 | |||
Ceftriaxone | 61.3 | 38.5 | 50.3 | 49.6 | 64.5 | 34.7 | 60.3 | 39.6 | |||
Cefepime | 24.7 | 65.3 | 17.9 | 73.8 | 30.3 | 60.2 | 20.0 | 69.0 | |||
Cefotetan | 3.2 | 96.0 | 2.3 | 96.8 | 6.1 | 93.4 | 2.0 | 97.4 | |||
Aztreonam | 43.4 | 55.7 | 32.7 | 66.7 | 47.4 | 51.1 | 39.2 | 59.7 | |||
Imipenem | 0.9 | 98.8 | 1.0 | 98.8 | 3.2 | 96.8 | 1.0 | 99.0 | |||
Meropenem | 1.0 | 99.0 | 1.0 | 98.8 | 2.9 | 96.9 | 0.7 | 99.1 | |||
Amikacin | 6.4 | 92.8 | 3.4 | 96.3 | 6.8 | 92.5 | 4.0 | 95.3 | |||
Gentamicin | 45.8 | 53.0 | 43.5 | 56.1 | 53.1 | 46.7 | 45.9 | 53.5 | |||
Tobramycin | 19.8 | 51.9 | 14.2 | 56.5 | 20.7 | 45.6 | 17.8 | 51.9 | |||
Ciprofloxacin | 77.4 | 19.4 | 75.1 | 22.2 | 77.9 | 18.2 | 79.4 | 17.1 | |||
Levofloxacin | 71.3 | 9.9 | 68.5 | 11.6 | 71.6 | 9.8 | 73.6 | 8.2 | |||
Tmp-smz | 62.2 | 37.8 | 59.3 | 40.7 | 67.0 | 33.0 | 64.5 | 35.4 | |||
Nitrofurantoin | 5.3 | 84.3 | 4.0 | 86.7 | 3.7 | 82.8 | 2.9 | 90.5 | |||
Tegacyclin | 0.0 | 98.3 | 0.2 | 98.5 | 1.0 | 98.0 | 0.3 | 97.7 | |||
Sur,surgery;Med,internal medicine;ICU,intensive care unit;Out,outpatient;Eme,emergency;R,resistance rate;S,sensitive rate. |
3 讨论
本研究显示,虽然我院2020年至2022年就诊患者明显减少,但大肠埃希菌分离数量仍与前几年基本持平,大肠埃希菌仍是院内感染的重要病原菌;大肠埃希菌主要分离自住院患者(80.5%),其次为门诊患者(11.7%)和急诊患者(7.8%);大肠埃希菌主要分离自尿液(57.8%)、血液(15.0%)、分泌物(9.2%)、引流液(8.1%)。本研究中大肠埃希菌各标本类型分布与国内研究[6]基本一致。
本研究显示,大肠埃希菌对氨苄西林耐药率高于80%,对哌拉西林耐药率高于60%,但对β内酰胺复合制剂敏感性高于80%,具有良好活性。头孢唑啉常用于手术的预防用药,2019年至今头孢唑啉耐药率明显降低,可能与2020年至2023年医院手术量减少从而头孢唑啉使用量减少有关。本研究中,大肠埃希菌ESBL阳性占57.2%(54.3%~61.5%),与既往研究[1, 7]结果基本一致。产ESBL大肠埃希菌常呈多重耐药,同时携带质粒介导喹诺酮耐药基因,如qnrB和qnrS等[8]。
碳青霉烯类抗菌药物耐药率<2%,10年间以及不同标本来源的大肠埃希菌间无明显差异,仍可作为治疗产ESBL菌株的首选药物。研究[9]发现,大肠埃希菌最流行的碳青霉烯酶基因是blaNDM。替加环素、黏菌素和头孢他啶阿维巴坦作为治疗碳青霉烯耐药大肠埃希菌为数不多的选择,都有不同程度耐药,特别是重症医学科患者。质粒介导黏菌素耐药基因mcr-1[10]以及新发现的质粒编码的RND型外排泵基因簇导致替加环素耐药[11],这种质粒介导的耐药基因可在革兰氏阴性菌间快速传播。
综上所述,大肠埃希菌对抗菌药物存在不同程度耐药,不同标本来源的大肠埃希菌耐药率也不尽相同。尽管碳青霉烯类抗菌药物仍可作为治疗产ESBL菌株的优先选择,但替加环素、黏菌素和头孢他啶阿维巴坦治疗耐碳青霉烯大肠埃希菌时都有不同程度的耐药,提示应合理使用抗菌药物,以避免最终无药可用。
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