溃疡性结肠炎艰难梭菌耐药现状与代谢表型之间的关系

The relationship between drug resistance status and metabolic phenotype of Clostridium difficile in ulcerative colitis

目的探究溃疡性结肠炎(UC)艰难梭菌(CD)耐药现状与代谢表型之间的关系。方法选取2018年7月-2021年7月本院收治的286例UC患者为研究对象;根据是否合并艰难梭菌感染(CDI)分为CDI组100例和非CDI组186例,对比分析两组患者的临床资料、实验室指标、内镜下表现及用药情况。检测菌株的毒素基因及核糖体分型,分析CD对不同种类抗菌药物的敏感性及与型别的关系。多因素Logistic回归分析影响UC合并CDI发生的独立危险因素,建立列线图预测模型,并进行模型评价。结果100株产毒菌,其中TcdA+TcdB+型57株,TcdA-TcdB+型43株。核糖体共23个型别,主要包括:RT012、RT001、HB024、RT017以及HB025型。CD对环丙沙星(CIP)、克林霉素(CC)、红霉素(E)和四环素(TE)的耐药率均较高;对利福昔明(RFX)、左氧氟沙星(LVX)、头孢曲松(CRO)、替加环素(TGC)、利福平(RA)和氯霉素(C)的耐药率均较低。各型别CD对美罗培南(MEM)、甲硝唑(MTZ)、万古霉素(VA)和非达霉素(FDX)均较敏感,多重耐药率高达68.00%。与其他型别相比,RT017型对CRO、E、TE、LVX、RA及RFX的耐药率更高(均P<0.05),RT001型对TGC的耐药率更高(P<0.05)。HB024型和其他所有型别(5个主要型别除外)CD的多重耐药率相对较低,RT012,RT001,RT017及HB025型CD的多重耐药率均超过80%(P<0.05)。年龄≥65岁、有手术史、重度UC、内镜检查有伪膜、全身应用糖皮质激素、使用IFX,均为UC合并CDI发生的独立危险因素(P<0.05)。列线图预测模型结果显示,各危险因素总计374分。受试者工作特征曲线(ROC)、校准曲线以及临床决策曲线(DCA)的评价结果显示,该预测模型的区分度、准确度以及有效性均较高。结论CD对CIP、CC、E和TE的耐药性较高,应当引起重视,对FDX、MTZ和VA敏感性较高。年龄≥65岁、有手术史、重度UC、内镜检查有伪膜、全身应用糖皮质激素、使用IFX,均为UC合并CDI发生的独立危险因素。

Objective To explore the relationship between the drug resistance status and metabolic phenotype of Clostridium difficile(CD)in ulcerative colitis(UC).Methods A total of 286 UC patients admitted to our hospital from July 2018 to July 2021 were selected as the study objects.The patients were divided into CDI group(100 cases)and non-CDI group(186 cases)according to whether Clostridium difficile infection(CDI)was present.The clinical data,laboratory indexes,endoscopic manifestations and drug use of the two groups were compared and analyzed.Toxin genes and ribosome typing were detected.The sensitivity of CD to different antimicrobial agents and its relationship with the type were analyzed.Multivariate Logistic regression analysis was performed to analyze the independent risk factors of UC combined with CDI.The prediction model of nomogram was established and evaluated.Results There were 100 strains of toxin-producing bacteria,including 57 strains of TcdA+TcdB+type and 43 strains of TcdA-TcdB+type.There were 23 types of ribosomes,including RT012(16 strains,16.00%),RT001(13 strains),HB024(11 strains),RT017(8 strains)and HB025(7 strains).The resistance rates of CD to ciprofloxacin(CIP),clindamycin(CC),erythromycin(E)and tetracycline(TE)were all high.The resistance rates of CD to rifaximin(RFX),levofloxacin(LVX),ceftriaxone(CRO),tigecycline(TGC),rifampin(RA)and chloramphenicol(C)were all low.All types of CD were sensitive to meropenem(MEM),metronidazole(MTZ),vancomycin(VA)and fidaxomicin(FDX),and the multidrug resistance rate was as high as 68.00%.Compared with other types,RT017 was more resistant to CRO,E,TE,LVX,RA and RFX(P<0.05),and RT001 was more resistant to TGC(P<0.05).The multidrug resistance rate of CD in HB024 and all other types(except the 5 main types)is relatively low,and the multidrug resistance rate of CD in RT012,RT001,RT017 and HB025 is more than 80%(P<0.05).Age≥65 years,history of surgery,severe UC,endoscopic examination with pseudomembrane,systemic glucocorticoid use,and use of IFX were all independent risk factors for UC complicated with CDI(P<0.05).The results of the nomogram prediction model showed that each risk factor totaled 374 points.The evaluation results of receiver operating characteristic curve(ROC),calibration curve and decision curve analysis(DCA)showed that the prediction model had high discrimination,accuracy and validity.Conclusion CD has high resistance to CIP,CC,E and TE,which should be paid attention to.It is highly sensitive to FDX,MTZ and VA.Age≥65 years old,history of surgery,severe UC,pseudomembrane on endoscopy,systemic glucocorticoid use,and use of IFX were all independent risk factors for UC complicated with CDI.