人工气道患者碳青霉烯类抗菌药物耐药肺炎克雷伯菌感染的相关因素分析

Analysis of related factors of carbapenem resistant Klebsiella pneumoniae infection in patients with artificial airway

目的分析重症监护病房(ICU)建立人工气道机械通气患者肺部感染碳青霉烯类抗菌药物耐药肺炎克雷伯菌(CRKP)的临床特征及相关影响因素,为临床防止肺炎克雷伯菌感染提供理论依据。方法收集2016年1月至2019年12月首都医科大学附属北京世纪坛医院ICU收治的肺部感染肺炎克雷伯菌的建立人工气道患者的临床资料,分析CRKP肺炎患者(研究组)及碳青霉烯类抗菌药物敏感肺炎克雷伯菌(CSKP)肺炎患者(对照组)的临床特征〔包括性别、年龄、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、机械通气时间、机械通气>10 d患者比例、肺炎克雷伯菌检出前抗菌药物使用情况、白细胞计数(WBC)、C-反应蛋白(CRP)、降钙素原(PCT)、白蛋白、入院前卧床>1个月患者比例、28 d病死率〕、基础疾病及器官功能衰竭情况等;比较两组菌株对常见抗菌药物的耐药率和2016至2019年4年间肺炎克雷伯菌对不同抗菌药物耐药率的差异;采用多因素Logistic回归分析影响肺部感染CRKP的危险因素,并检测相关耐药基因。结果与对照组比较,研究组年龄更大〔岁:81.5(72.0,86.0)比78.0(71.0,80.5)〕,APACHEⅡ〔分:25.00(20.00,34.00)比19.00(14.00,23.25)〕和机械通气>10 d〔63.2%(182/288)比12.8%(10/78)〕、肺炎克雷伯菌检出前使用β-内酰胺酶抑制剂类抗菌药物〔75.69%(218/288)比30.77%(24/78)〕、使用碳青霉烯类抗菌药物〔79.86%(230/288)比41.03%(32/78)〕、使用≥2种抗菌药物〔80.90%(233/288)比29.49%(23/78)〕、入院前卧床>1个月〔40.97%(118/288)比11.54%(9/78)〕的比例及WBC〔×10^(9)/L:9.72(6.41,14.69)比7.57(5.84,12.61)〕、CRP〔mg/L:74.45(36.30,158.88)比39.22(13.68,92.51)〕、PCT〔μg/L:3.87(0.82,19.24)比0.51(0.25,5.71)〕和28 d病死率〔21.5%(62/288)比10.3%(8/78)〕更高,白蛋白〔g/L:24.1(18.3,28.6)比30.1(23.8,35.1)〕水平更低,机械通气时间更长〔d:16.5(9.0,19.0)比7.0(5.0,10.0)〕,合并慢性阻塞性肺疾病〔COPD:35.76%(103/288)比11.54%(9/78)〕、恶性肿瘤〔18.06%(52/288)比5.13%(4/78)〕及伴有肾衰竭〔31.94%(92/288)比11.54%(9/78)〕、休克〔51.74%(149/288)比19.23%(15/78)〕的比例更高,差异均有统计学意义(均P<0.05)。2016至2019年4年间肺炎克雷伯菌对氨曲南、哌拉西林/他唑巴坦、亚胺培南、环丙沙星的耐药率比较差异均有统计学意义(均P<0.05);对氨曲南、哌拉西林/他唑巴坦的耐药率以2019年最高(分别为88.17%、86.02%),均以2016年最低(分别为70.65%、57.61%);对亚胺培南的耐药率以2018年最高(86.32%),以2016年最低(59.78%);对环丙沙星的耐药率以2016年最高(76.09%),以2018年最低(53.68%)。研究组耐药株对头孢替坦、阿米卡星、哌拉西林/他唑巴坦、头孢他啶、头孢曲松、庆大霉素的耐药率均明显高于对照组(82.99%比62.82%、49.31%比17.95%、75.69%比60.26%、81.25%比64.10%、80.21%比58.97%、91.32%比60.26%,均P<0.05)。Logistic回归分析显示,合并COPD、严重低蛋白血症、机械通气时间>10 d及肺炎克雷伯菌检出前使用碳青霉烯类抗菌药物是CRKP感染的独立危险因素。基因检测显示:CRKP中含有TEM、KPC、AmpC、aac(3)-Ⅱ、ant(3")-Ⅰ、qnrS等多种耐药基因。TEM的检出率最高(为74.00%),qnrA检出率最低(为6.67%)。结论ICU建立人工气道机械通气患者出现CRKP与多种因素相关,应缩短机械通气时间,避免碳青霉烯类抗菌药物不规范的使用,提高血白蛋白水平,以减少CRKP肺炎的发生,改善患者预后。

Objective To analyze the clinical characteristics and related influencing factors of carbapenem resistant Klebsiella pneumoniae(CRKP)in patients with artificial airway and mechanical ventilation in intensive care unit(ICU),and provide theoretical basis for clinical prevention of Klebsiella pneumoniae infection.Methods The clinical data of patients with pulmonary infection of Klebsiella pneumoniae in ICU of Beijing Shijitan Hospital Affiliated to Capital Medical University from January 2016 to December 2019 were collected.Compared CRKP pneumonia patients(study group)with carbapenem antibiotic sensitive Klebsiella pneumoniae(CSKP)pneumonia patients(control group),the clinical characteristics[gender,age,acute physiology and chronic health evaluationⅡ(APACHEⅡ),duration of mechanical ventilation,proportion of patients with mechanical ventilation>10 days,use of antibiotics before detection of Klebsiella pneumoniae,white blood cell count(WBC),C-reactive protein(CRP),procalcitonin(PCT),albumin,bedridden for more than 1 month before admission,28-day mortality]were analyzed.The drug resistance rates of Klebsiella pneumoniae in both groups and difference of drug resistance rate of Klebsiella pneumoniae to different antibiotics from 2016 to 2019 were compared.The risk factors of CRKP infection were analyzed by multivariate Logistic regression,and the related drug resistance genes were detected.Results Compared with the control group,the study group was older[years old:81.5(72.0,86.0)vs.78.0(71.0,80.5)],APACHEⅡ[point:25.00(20.00,34.00)vs.19.00(14.00,23.25)]and proportion of patients with mechanical ventilation>10 days[63.2%(182/288)vs.12.8%(10/78)],the use ofβ-lactamase inhibitor antibiotics before detection of Klebsiella pneumoniae[75.69%(218/288)vs.30.77%(24/78)],the use of carbapenems[79.86%(230/288)vs.41.03%(32/78)],the use of more than two kinds of antibiotics[80.90%(233/288)vs.29.49%(23/78)],proportion of patients staying in bed for more than 1 month before admission[40.97%(118/288)vs.11.54%(9/78)]and WBC[×10^(9)/L:9.72(6.41,14.69)vs.7.57(5.84,12.61)],CRP[mg/L:74.45(36.30,158.88)vs.39.22(13.68,92.51)],PCT[μg/L:3.87(0.82,19.24)vs.0.51(0.25,5.71)],28-day mortality[21.5%(62/288)vs.10.3%(8/78)]were higher,albumin[g/L:24.1(18.3,28.6)vs.30.1(23.8,35.1)]was lower,duration of mechanical ventilation[days:16.5(9.0,19.0)vs.7.0(5.0,10.0)]was longer,the proportion of patients with chronic obstructive pulmonary disease[COPD:35.76%(103/288)vs.11.54%(9/78)],malignant tumor[18.06%(52/288)vs.5.13%(4/78)],renal failure[31.94%(92/288)vs.11.54%(9/78)],shock[51.74%(149/288)vs.19.23%(15/78)]were higher,and the differences were statistically significant(all P<0.05).The drug resistance rates of Klebsiella pneumoniae to aztreonam,piperacillin/tazobactam,imipenem and ciprofloxacin were statistically significant(all P<0.05);the drug resistance rates of Klebsiella pneumoniae to aztreonam and piperacillin/tazobactam were the highest in 2019(88.17%and 86.02%,respectively),and the lowest in 2016(70.65%and 57.61%,respectively).The drug resistance rate to imipenem was the highest in 2018(86.32%),the lowest in 2016(59.78%);the resistance rate to ciprofloxacin was the highest in 2016(76.09%),and the lowest in 2018(53.68%).The resistance rates of ceftetan,amikacin,piperacillin/tazobactam,ceftazidime,ceftriaxone and gentamicin in the study group were significantly higher than those in the control group(82.99%vs.62.82%,49.31%vs.17.95%,75.69%vs.60.26%,81.25%vs.64.10%,80.21%vs.58.97%,91.32%vs.60.26%,all P<0.05).Logistic regression analysis showed that COPD,severe hypoproteinemia,mechanical ventilation time>10 days and the use of carbapenem antibiotics before detection of Klebsiella pneumoniae were independent risk factors of CRKP infection.Gene detection showed that there were TEM,KPC,AmpC,AAC(3)-Ⅱ,ant(3")-Ⅰ,qnrS and other drug resistance genes in CRKP.The detection rate of TEM was the highest(74.00%),and qnrA was the lowest(6.67%).Conclusions The occurrence of CRKP in ICU patients with artificial airway and mechanical ventilation is related to many factors.It is necessary to shorten the mechanical ventilation time,avoid the nonstandard use of carbapenem antibiotics,and improve the serum albumin level,so as to reduce the incidence of CRKP pneumonia and improve the prognosis of patients.