ICU医院获得性MRSA肺炎患者的菌株耐药基因分析及利奈唑胺和万古霉素的治疗效果

Analysis of bacterial strain drug-resistant genes in ICU patients with hospital-acquired MRSA pneumonia and the therapeutic effects of linezolid and vancomycin

目的分析ICU医院获得性耐甲氧西林金黄色葡萄球菌(MRSA)肺炎患者的菌株的耐药和耐药基因检出情况,比较利奈唑胺和万古霉素的治疗效果。方法收集某三甲医院ICU收治的410例医院获得性MRSA肺炎患者的痰液,分离菌株,检测其对其他抗生素的敏感性及相关耐药基因。将所有患者随机分为对照组和观察组,各205例,对照组采用万古霉素治疗,观察组给予利奈唑胺。比较两组患者的临床疗效、病原菌清除率、治疗期间医院内病死率和不良反应发生情况。采用决策树模型分析利奈唑胺和万古霉素治疗MRSA肺炎的成本效果。结果(1)MRSA对青霉素、苯唑西林、头孢西丁、四环素、克林霉素、红霉素、环丙沙星及复方磺胺甲噁唑等药物均有不同程度的耐药,其中多重药物耐药率高达32.20%。但410株MRSA均未检出对利奈唑胺、万古霉素、替加环素耐药。(2)β-内酰胺类耐药基因mecA、氨基糖苷修饰酶基因aac(6′)/aph(2″)、大环内酯类23S rRNA甲基化酶基因ermA/C、四环素类核糖体保护蛋白基因tetM/K、喹诺酮类耐药基因qnrA/B的检出率分别为100.00%、38.29%、65.37%、57.56%、21.00%。(3)观察组患者的临床治疗总有效率和病菌清除率均高于对照组,不良反应发生率低于对照组(均P<0.05),但两组的医院病死率差异无统计学意义(P>0.05)。(4)决策树模型分析结果显示,相比于万古霉素治疗,采用利奈唑胺治疗MRSA重症肺炎的成本效果比较高,每提高一个单位总有效率利奈唑胺治疗需多花费31321.41元,但其相对于万古霉素的增量成本效果比低于2019年人均国内生产总值(>60000元),性价比仍较高。结论ICU医院获得性MRSA肺炎患者的菌株耐药情况严重,耐药基因检出率高。相比于万古霉素治疗,采用利奈唑胺治疗MRSA肺炎的病菌清除率高、不良反应少、临床疗效和成本效果更优,临床上可推荐首选利奈唑胺治疗MRSA肺炎。

Objective To analyze the detection condition of bacterial strain drug resistance and drug-resistant genes in ICU patients with hospital-acquired methicillin-resistant Staphylococcus aureus(MRSA)pneumonia,and to compare the therapeutic effects of linezolid and vancomycin.Methods Sputa of 410 patients with hospital-acquired MRSA pneumonia admitted to the ICU of a ClassⅢLevel A hospital were collected,and bacterial strains were isolated from the sputa so as to detect them on susceptibility of other antibiotics and related drug-resistant genes.All patients were randomly assigned to control group or observation group,with 205 cases in each group.The control group was treated with vancomycin,whereas the observation group was administrated linezolid.The clinical efficacy,clearance rate of pathogenic bacteria,hospital fatality rate during treatment,and occurrence conditions of adverse reactions in patients were compared between the two groups.The decision tree model was employed to analyze the cost-effectiveness of linezolid and vancomycin for treating MRSA pneumonia.Results(1)MRSA had different degrees of drug resistance to penicillin,oxacillin,cefoxitin,tetracycline,clindamycin,erythrocin,ciprofloxacin,and Compound Sulfamethoxazole,among which multiple drug-resistant rate reached up to 32.20%;however,no resistance to linezolid,vancomycin,and tigecycline was detected from 410 strains of MRSA.(2)The detection rates ofβ-lactams resistance gene mecA,aminoglycoside modification enzyme gene aac(6′)/aph(2"),macrolides 23S rRNA methylase gene ermA/C,tetracycline ribosomal protective protein gene tetM/K,quinolone resistance gene qnrA/B were 100.00%,38.29%,65.37%,57.56%,and 21.00%,respectively.(3)Patients in the observation group exhibited a higher total effective rate of clinical treatment,and a higher clearance rate of pathogenic bacteria,whereas a lower incidence rate of adverse reactions as compared with the control group(all P<0.05);however,no statistically significant difference was found in hospital fatality rate between the two groups(P>0.05).(4)The results of decision tree model analysis revealed that compared with the treatment of vancomycin,employing linezolid for treating MRSA severe pneumonia expressed relatively higher cost-effectiveness,each unit increase in the total effective rate of linezolid treatment would cost 31321.41 yuan more;however,its incremental cost-effectiveness ratio to vancomycin was lower than the national per capita Gross Domestic Product in 2019(>60000 yuan),and its cost-performance ratio was still high.Conclusion Bacterial strain drug-resistant condition in ICU patients with hospital-acquired MRSA pneumonia is severe,and the detection rate of drug-resistant genes is high.Compared with the treatment of vancomycin,employing linezolid for treating MRSA pneumonia exhibits a high clearance rate of pathogenic bacteria,fewer adverse reactions,superior clinical efficacy and cost-effectiveness.Linezolid is the first choice to be promoted for treating MRSA pneumonia in clinics.