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Drug Resistance Mechanisms And Homology Study Of Carbapenem-Resistant Klebsiella Pneumonia

Posted on:2016-08-09Degree:MasterType:Thesis
Country:ChinaCandidate:Y P DingFull Text:PDF
GTID:2284330470457532Subject:Internal medicine
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Klebsiella pneumoniae is one of the most common pathogenic bacteria in hospital acquired infections, which can cause pneumonia, sepsis, urinary tract infection, liver abscess, peritonitis and so on. Because of improper use of antibiotics, Carbapenem-Resistant Klebsiella pneumoniae (CRKP) shows a trend of global spreading. In China, the isolation rate of CRKP increases in recent years, which has brought great challenges to the clinical treatment. The purpose of this study was to investigate the nosocomial infection associated risk factors and the antibiotic resistance mechanism of CRKP in our hospital, as well as to analyze the (molecular characteristics) homology and the current status of nosocomial infections, so as to provide a scientific basis for the prevention and control of CRKP.Thirty CRKP isolates were collected from8clinical departments in our hospital. Clinical data was collected and analyzed by the unified questionnaire. The K-B disk diffusion method was used for antimicrobial susceptibility test, and carbapenemases were screened by modified Hodge test. The homology of these isolates was analyzed by the two methods of pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Genetic relationship of some isolates was analyzed by whole genome sequencing (WGS).Clinical data showed that the mean age of30patients with infection was high (72±15). Various disease score indexes showed they were in severe disease conditions. Basic diseases of nervous system diseases, diabetes, and heart failure accounted for the top three in patients with underlying conditions. In the past three months, about90%of patients were treated with β-lactamases inhibitor compound preparations, more than 50%of the patients had tried carbapenem antibiotics. In recent three months, the vast majority of patients had indwelling catheter, such as catheters, deep venous catheter and the endotracheal tube, etc. In vitro antimicrobial susceptibility tests showed that all isolates were resistant to meropenem and ertapenem, and all were resistant to imipenem except one showing intermediate. For the third and fourth generation cephalosporins and P-lactamases inhibitor compounds, all isolates were resistant. The resistance rates of these isolates to ciprofloxacin, gentamicin and amikacin were90%,97%and87%, respectively. All isolates weren’t resistant to polymyxin E and tigecycline. Resistant enzyme gene detection results indicated that30isolates of Klebsiella pneumoniae carried both blaSHV and blaKPC-2. In addition, some isolates also carried blaCTX-M and blaTEM. All isolates were divided into8clone groups of A-H by PFGE, in which A and C clone group displayed nosocomial dissemination. MLST analysis acquired5sequence types (STs), of which23isolates belonged to ST11,3isolates belonged to ST437,2isolates belonged to ST290, and the other two isolates were ST133and ST15respectively.5isolates of A clone group (ST11) were submitted to whole genome sequencing (WGS) analysis, and were divided into three different groups (2isolates:2isolates:1isolate). Isolates in the same group showed close relationship as a cluster. While the single isolate formed an independent cluster which showed alienation, compared with the former two clusters. Therefore, WGS relative to the PFGE and MLST further revealed the genetic background of isolates, in favor of the trace for the isolates.To sum up, patients with CRKP had a variety of risk factors, the prognosis of patients is associated with multiple risk factors and treatment. The initial empirical anti-infection treatment should consider infection risk factors, analysze patients comprehensively in time, and combine with the result of antimicrobial susceptibilities tests for target treatment. Producing pneumonia KPC-2is an important cause of the CRKP in our hospital, and its jointly carried multidrug resistant genes have led to the multidrug resistant phenotype. ST11clone spread is an important cause of epidemic in the hospital which remind us to strengthen the nosocomial infection monitoring.
Keywords/Search Tags:carbapenems, Klebsiella pneumoniae, resistance, carbapenemase, pulsed field gel electrophoresis, multilocus sequence typing, whole genome sequencing
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