社区获得性尿路感染患者尿路病原菌分布及其对奈诺沙星和左氧氟沙星的敏感性

Distribution of urinary tract pathogens and susceptibility to nenofloxacin and levofolxacin in patients with community-acquired urinary tractinfection

目的探讨社区获得性尿路感染患者的尿路病原菌分布特点,及其对奈诺沙星和左氧氟沙星的敏感情况。方法本研究为前瞻性、多中心临床试验。纳入2021年11月至2022年8月于国内9家临床研究中心泌尿外科门诊就诊的患者。纳入标准:年龄18~70岁的社区获得性急性非复杂性膀胱炎(AUC)、反复发作尿路感染(rUTI)急性发作和非发热性复杂性尿路感染(cUTI)患者;具有尿路刺激征且尿常规白细胞异常升高。排除标准:人组前72h内接受有效的抗菌药物治疗,持续时间超过24h者;发热(>37.3℃)或存在上尿路感染症状如腰痛、肾区叩痛等;留置尿路导管者。初次就诊时留取清洁中段尿标本做细菌培养,分析不同类型尿路感染的尿路病原菌分布特点,并对革兰阴性菌进行超广谱β-内酰胺酶(ESBLs)测定。使用纸片扩散法测定尿路病原菌对奈诺沙星和左氧氟沙星的敏感性。比较不同病种病原菌对抗菌药物的敏感率和耐药率的差异。结果本研究共纳人9家医院的404例患者,男40例(9.9%),女364例(90.1%);6例细菌学结果缺失,最终398例纳入分析。398例中AUC243例,cUTI46例,rUTI109例。398例中,170例尿细菌培养阳性(共分离出177株病原菌),总体阳性率为42.7%(170/398)。177株病原菌中,大肠埃希菌比例最高为66.1%(117/177),其次为肺炎克雷伯杆菌6.8%(12/177)、无乳链球菌5.1%(9/177)。AUC和rUTI患者中大肠埃希菌比例分别为70.6%(85/119)和65.9%(29/44);cUTI患者中大肠埃希菌比例为28.6%(4/14),粪肠球菌比例为7.1%(1/14)。行ESBLs检测的革兰阴性菌中ESBLs总体检出率为30.9%(43/139)。药敏试验结果显示,总体对奈诺沙星的敏感率为74.6%(91/122),耐药率为25.4%(31/122);总体对左氧氟沙星敏感率为44.9%(70/156),耐药率为36.5%(57/156)。既往有尿路感染病史和无尿路感染病史患者中,尿路病原菌对左氧氟沙星耐药率分别为48.2%(27/56)和30.0%(30/100),二者差异有统计学意义(P=0.023)。革兰阴性菌对奈诺沙星的敏感率为70.7%(65/92),对左氧氟沙星的敏感率为50.0%(46/92),差异有统计学意义(P<0.001);革兰阳性菌对奈诺沙星的敏感率为80.0%(16/20),对左氧氟沙星的敏感率为70.0%(14/20),差异有统计学意义(P=0.009)。结论门诊社区获得性尿路感染患者的细菌谱依病种不同有很大差别,AUC和rUTI患者大肠埃希菌比例高于cUTI患者。总体革兰阴性菌中ESBLs检出率低于国内平均水平。既往有尿路感染病史者应用左氧氟沙星治疗失败的风险高。常见尿路病原菌对奈诺沙星敏感性好,高于左氧氟沙星。

Objective To investigate the distribution characteristics of urinary tract pathogens in patients with community-acquired urinary tract infection and their sensitivity to nenoxacin and levofloxacin.Methods This prospective,multicenter clinical trial included patients with community-acquired urinary tract infection who were admitted to urological clinics at 9 clinical research centers from November 2021 to August 2022.Inclusion criteria:Patients aged 18-70 years with community-acquired acute uncomplicated cystitis(AUC),recurrent acute episodes of urinary tract infection(rUTI),and non-febrile complicated urinary tract infection(cUTI)with signs of urinary tract irritation and abnormal elevation of routine white blood cells in urine.Exclusion criteria:①Patients who received effective antimicrobial therapy within 72 h before enrollment and lasted for more than 24 h.②Fever(>37.3℃)or symptoms of upper urinary tract infection such as low back pain,tapping pain in the kidney area,etc.③Indwelling urinary catheter.At the first visit,clean midstream urine samples were taken for bacterial culture,and the distribution characteristics of urinary pathogens of different types of urinary tract infections were analyzed.Extended spectrum β-lactamases(ESBLs)were measured for Gram-negative bacteria.The susceptibility of nenoxacin and levofloxacin to urinary tract pathogens was determined by disk diffusion method.Drug resistance rate,sensitivity rate were analyzed between different disease groups.Results There were 404 enrolled patients from 9 hospitals,including 364(90.1%)females and 40(9.9%)males.A total of 177 strains of pathogenic bacteria were isolated,among which the highest proportion of Escherichia coli was 66.1%(117/177).Klebsiella pneumoniae was followed by 6.8%(12/177)and Streptococcus agalactis 5.1%(9/177).The bacterial spectrum distribution of AUC and rUTI were similar,and the proportions of Escherichia coli were 70.6%(85/119)and 65.9%(29/44),respectively.However,the proportions of Escherichia coli isolated from cUTI patients were only 28.6%(4/14)and Enterococcus faecalis 7.1%(1/14).The overall detection rate of ESBLs in Gram-negative bacteria was 30.9%(43/139).The sensitivity rate of nenoxacin was 74.6%(91/122),and the resistance rate was 25.4%(31/122).The overall sensitivity rate of levofloxacin was 44.9%(70/156)and the resistance rate was 36.5%(57/156).The rate of resistance of urinary tract pathogens to levofloxacin was 48.2%(27/56)in patients with previous urinary tract infection history,and 30.0%(30/100)in patients with no previous urinary tract infection history,the difference was statistically significant(P=0.023).The sensitivity rate of Gram-negative bacteria to nenofloxacin was 70.7%(65/92)and that to levofloxacin was 50.0%(46/92,P<0.001).The sensitivity of Gram-positive bacteria to nenofloxacin was 80.0%(16/20),and that to levofloxacin was 70.0%(14/20,P=0.009).Conclusions The bacterial profile of out-patient community acquired urinary tract infection varies greatly according to different diseases.The proportion of Escherichia coli in AUC and rUTI patients is higher than that in cUTI.The detection rate of ESBLs in Gram-negative bacteria was lower than the domestic average.Patients with a history of urinary tract infection had a high risk of treatment failure with levofloxacin.The sensitivity of common urinary tract pathogens to nenofloxacin was higher than levofloxacin.