感染性结石的致病菌菌谱及预防结石复发的经验

Pathogenic bacteria spectrum of infectious stones and experience of preventing stone recurrence

目的探讨感染性结石患者术前尿细菌培养的致病菌菌谱及应用抗菌药物预防结石复发的经验。方法回顾性分析2017年1月至2021年7月郑州大学第二附属医院收治的79例感染性结石患者的病例资料,男29例(36.7%),女50例(63.3%)。年龄17~75岁,中位年龄49.0(40,55)岁。15例(19.0%)合并高血压病,13例(16.5%)合并糖尿病,3例(3.8%)合并心脑血管疾病。51例(64.6%)诊断为铸型感染性结石。所有患者均行手术清石,术后复查泌尿系CT未见结石残留定义为完全清石,术后继续口服药物抗感染和预防结石复发。根据患者出院后依从情况分为高依从性组和低依从性组。患者出院后能够定期返院复查尿常规和尿细菌培养,遵医嘱规范应用抗菌药物治疗,服用尿素酶抑制剂治疗≥6个月定义为高依从性。尿素酶抑制剂用法:醋羟胺酸胶囊,初始剂量250 mg,2次/日,连用3~4周;若患者可耐受,将剂量增加至3次/日;若出现不良反应,减量至1~2次/日。未规律服用敏感抗菌药物和/或醋羟胺酸减量后仍因震颤、心悸、头痛、贫血、胃肠道不适等不良反应,无法坚持用药者为低依从性组。比较两组随访3、6、12个月时结石复发情况。结果本组79例,56例(70.9%)术后完全清石。33例(41.8%)术前尿细菌培养阳性,最常见的致病菌为奇异变形杆菌17例(21.5%),其次为大肠埃希菌8例(10.1%)、肺炎克雷伯菌3例(3.8%)。奇异变形杆菌阳性17例中超广谱β-内酰胺酶(ESBLs)阳性6例,对氨苄西林、头孢唑啉、复方新诺明耐药比例为6/6例,对阿米卡星、头孢西丁、替卡西林/棒酸耐药比例为1/6例,对亚胺培南、多黏菌素、氨曲南均不耐药(0/6例);ESBLs阴性11例,对氨苄西林耐药比例为10/11例,对头孢唑啉、左氧氟沙星、环丙沙星、复方新诺明耐药比例为8/11例,对头孢西丁、头孢克罗、呋喃妥因、阿米卡星、米诺环素耐药比例为1/11例,对亚胺培南、替卡西林/棒酸、氨曲南均不耐药(0/11例)。ESBLs阳性菌株对78.6%的药物(头孢克罗、头孢唑啉、头孢他啶、呋喃妥因、诺氟沙星、左氧氟沙星、环丙沙星、头孢西丁、阿莫西林/棒酸、替卡西林/棒酸、氨苄西林、头孢曲松、头孢噻肟、头孢呋辛、头孢吡肟、庆大霉素、复方新诺明、妥布霉素、阿米卡星、四环素、氯霉素、米诺环素)耐药率低于ESBLs阳性菌株。大肠埃希菌阳性8例中,ESBLs阳性7例,对氨苄西林、头孢唑啉、头孢噻肟、头孢呋辛、头孢吡肟耐药比例为7/7例,对头孢西丁和米诺环素耐药比例为1/7例,对亚胺培南、呋喃妥因、阿米卡星均不耐药(0/7例);ESBLs阴性1例,除对氨苄西林耐药外,对其他抗菌药物均敏感。高依从性组和低依从性组出院后3、6、12个月的结石复发率分别为9.1%(4/44)和31.4%(11/35)(P=0.012)、13.6%(6/44)和60.0%(21/35)(P<0.05)、36.4%(16/44)和71.4%(25/35)(P=0.002),差异均有统计学意义。结论感染性结石患者尿细菌培养最常见的致病菌为奇异变形杆菌、大肠埃希菌、肺炎克雷伯菌。ESBLs阳性菌株对抗菌药物的耐药率显著高于ESBL阴性菌株。β-内酰胺酶抑制剂、头孢西丁、阿米卡星、亚胺培南等抗菌药物的耐药率较低。规范应用敏感抗菌药物和尿素酶抑制剂联合治疗可显著降低患者的结石复发率。

Objective To investigate the pathogenic bacteria profiles in preoperative urine bacterial cultures of patients with infected kidney stones and use antibacterial drugs to prevent recurrence.Methods The data of 79 cases with infected kidney stones admitted to the Second Affiliated Hospital of Zhengzhou University from January 2017 to July 2021 were retrospectively analyzed,among whom 29(36.7%)were male and 50(63.3%)were female.The age ranged from 17-75 years,with a median age of 49.0(40,55)years.Fifteen cases(19.0%)combined hypertension,13 cases(16.5%)combined diabetes mellitus,and 3 cases(3.8%)combined with cardiovascular disease.Fifty-one cases(64.6%)were diagnosed with cast infectious stones.All patients underwent surgical lithotripsy,and postoperative review of the urological computerized tomography(CT)revealed no residual stones defined as complete lithotripsy,and postoperative oral medication was continued to control infection and prevent stone recurrence.According to post-hospitalization compliance,patients were divided into high and low compliance groups.The high compliance group consisted of patients who returned to the hospital regularly for routine urinalysis and urine bacterial culture after discharge,followed the doctor's prescription for standardized antibacterial drug therapy,and complied with urease inhibitor therapy for≥6 months.The low compliance group included patients who did not take sensitive antimicrobial drugs regularly and/or were unable to adhere to the medication even after the reduction of vinblastine due to adverse events such as tremor,palpitations,headache,anemia,or gastrointestinal discomfort.The recurrence of stones at 3,6 and 12 months of follow-up was compared between the two groups.Results Of the 79 cases in this group,56(70.9%)were completely clear of stone after surgery.Thirty-three cases(41.8%)presented positive in preoperative urine bacterial culture,and the most common causative organism was Aspergillus oddus in 17 cases(21.5%),followed by Escherichia coli in 8 cases(10.1%)and Klebsiella pneumoniae in 3 cases(3.8%).Among the 17 positive cases of A.oddis,six were positive for ultra broad spectrumβ-lactamases(ESBLs),6/6 were resistant to ampicillin,cefazolin,and cotrimoxazole,1/6 were resistant to amikacin,cefoxitin,and ticarcillin/stick acid,and none were resistant to imipenem,polymyxin,or aminotrans(0/6 cases).Of the cases,11 were negative for ESBLs.Ten out of eleven cases were resistant to ampicillin.Furthermore,8/11 cases were resistant to cefazolin,levofloxacin,ciprofloxacin,and cotrimoxazole and 1/11 were resistant to cefoxitin,cefaclor,furantoin,amikacin,and minocycline,and 0/11 were resistant to imipenem,ticarcillin/stick acid,aminotrans.ESBLs positive strains were resistant to 78.6%of the tested drugs(cefaclor,cefazolin,ceftazidime,furantoin,norfloxacin,levofloxacin,ciprofloxacin,cefoxitin,amoxicillin/rod acid,ticarcillin/rod acid,ampicillin,ceftriaxone,cefotaxime,cefuroxime,cefepime,gentamicin,cotrimoxazole,tobramycin,amikacin,tetracycline,chloramphenicol,and minocycline)at a lower rate of resistance than ESBLs positive strains.Of the eight positive cases of E.coli,seven were ESBLs positive,7/7 were resistant to ampicillin,cefazolin,cefotaxime,cefuroxime,and cefepime,1/7 were resistant to cefoxitin and minocycline,and 0/7 were resistant to imipenem,furantoin,or amikacin.One case was ESBLs negative and was resistant to all antimicrobial drugs except for ampicillin.Stone recurrence rates at 3,6,and 12 months after discharge were 9.1%(4/44)and 31.4%(11/35),13.6%(6/44),respectively,in the high compliance group,and 60.0%(21/35),36.4%(16/44),and 71.4%(25/35),respectively,in the low compliance group.All differences were statistically significant.Conclusion The most common pathogenic bacteria isolated from urine bacterial cultures of patients with infectious stones were A.chimaera,E.coli,and K.pneumoniae.The resistance rate of ESBLs-positive strains to antimicrobial drugs was significantly higher than that of ESBL-negative strains,and the resistance rate of antimicrobial drugs such asβ-lactamase inhibitors,cefoxitin,amikacin,and imipenem was low.Combination therapy with standardized sensitive antimicrobial drugs and urease inhibitors significantly reduced the recurrence rate of stones among patients.