Study On The Molecular Epidemiological Characteristics Of Intestinal Colonization CRE And Displaced Pulmonary Infection In ICU Patients

Objective:Carbapenem-Resistant Enterobacteriaceaes are resistant to any of the Carbapenem antimicrobials(such as Ertapenem,Donipenem,Imipenem,Meropenem)or those carbapenemases-producing Enterobacteriaceae[1].CRE infection has highly epidemic,drug resistance and mortality,and the absence of useful drugs poses a great challenge to clinical anti-infection treatment.CRE is mainly popular in Intensive Care Units(ICU)where there are a large number of susceptible people[2],and it mainly colonizes in the human intestine.Studies have shown that CRE colonization is an independent risk factor for the infection[3].Meanwhile,CRE colonization is an important factor and source of infection caused by migration to other sites[4],as well as displaces and leads to pulmonary infectio1 csi.However,there are few reports about the risk of displaced pulmonary infection by intestinal colonization.To explore the phenotype and drug resistance genotype of CRE colonized by intestinal colonization in ICU patients in our hospital,By studying on the incidence,risk factors and displacement time of pulmonary infection in patients with CRE intestinal colonization,we can predict and reduce the risk of CRE colonization developing into infection,and provide a basis for clinically effective prevention of CRE infection and empirical treatment against infection.Methods:1.The author collected fecal,rectal or perianal swab samples from the Fourth Affiliated Hospital of Kunming Medical University ICU admitted patients from december 1,2018 to december 31,2019,these samples were inoculated on the screening plate for primary screening.The strain was identified by VITEK2 automatic system and drug sensitivity test.The carbapenemase phenotype was confirmed by mCIM combined with eCIM test.Sputum samples from patients with intestinal colonization and development as pulmonary infection were collected and repeated above identification,drug sensitivity and phenotype confirmation test.2.The author used Polymerase Chain Reaction(PCR)method to detect drug resistance genes(KPC-2?NDM-1?VIM-2?IMP?OXA-48)and sequenced the positive products to understand the CRE drug resistance genotypes;Multilocus Sequence Typing(MLST)was used to obtain the main sequence type(ST)of the strain.3.To understand the risk factors of intestinal colonization CRE:patients with intestinal colonization were chose in the experimental group,patients with intestinal colonization without CRE and complete data were chose in the control group,and the clinical data of the experimental group and the control group were collected,including sex,age,history of hospitalization in the last 6 months,basic disease,APACHE II score,invasive manipulation,use of antibiotics,proton pump inhibitors,hormones,antifungal drugs,carrying other multi-drug resistant bacteria during this hospitalization,experimental examination(including procalcitonin,blood routine,liver function,renal function,coagulation function),and so on.The clinical data of the two groups were analyzed statistically by single factor and multiple factors on SPSS 22,and the result of p<0.05 having statistical significance.4.To understand the risk factors for developing from intestinal colonization to pulmonary infection:taking these patients with intestinal colonization CRE and become pulmonary CRE infection into the experimental group;The patients who had no lung infections until the end of the follow-up period of intestinal colonization CRE were took into the control group.COX regression model analysis was used to analyze the clinical data of the two groups,including sex,age,invasive manipulation,use of antibiotics,proton pump inhibitors,hormones,antifungal drugs,experimental examination(including procalcitonin,blood routine,liver function,renal function,coagulation function),to explore the risk factors of developing intestinal colonization into pulmonary infection.Results:1.There were 54 cases of intestinal colonization CRE in ICU who are just in the hospital,the rate of intestinal colonization CRE was 7.93%(54/681).In all,49 strains of Klebsiella Pneumoniae,3 strains of Escherichia Coli and 2 strains of Enterobacter Cloacae were isolated.2.The results of mCIM combined with eCIM test showed that 50(92.59%)mCIM test were positive,suggesting carbapenemase production,44(88.0%)mCIM were positive and eCIM test were negative,suggesting that serine carbapenemase production and 6(12.0%)mCIM?eCIM test were all positive,suggesting metal ?-lactamase production.3.The results of drug resistance genes showed that 48 strains detected carbapenem resistance genes,and the positive rates of drug resistance genes OXA-48,KPC-2 and NDM-1 were 47.92%,43.75%and 8.33%,respectively VIM-2 and IMP were not detected,and the sequencing results were 99%consistent.4.MLST results showed that among 49 strains of Carbapenem-resistant Klebsiella Pneumoniae,23 strains were ST231 type,19 strains were ST 11 type,1 strain was ST258 type,1 strain was ST609 type,1 strain was ST1 type,and the results of 4 strains are unknown;3 strains of Carbapenem-resistant Escherichia Coli are all ST88 type;2 strains of Carbapenem-resistant Enterobacter Cloacae are ST509 type and ST131 type.5.Single-factor analysis of clinical data revealed that patients'age?80,? three basic diseases,APACHE ? score greater than 21 points,carrying other multi-drug resistant bacteria,carbapenem antibiotics,antifungal drug use,D-dimer,fibrin degradation products,antithrombin ? and albumin may be risk factors for intestinal colonization CRE;Multi-factor analysis which is using binary unconditional logistic regression,the results showed that APACHE ? score>21 and carrying other multi-drug resistant bacteria were independent risk factors for intestinal colonization CRE patients,and albumin was a protective factor.6.There were 27 cases(50%)of lung infections developed from intestinal colonization CRE,and the results of CRE strains,resistance genes and ST type isolated from swab and sputum samples were consistent in each patient.7.The median time from intestinal colonization to pulmonary infection was 4 days.8.By COX regression analysis,the risk factor for colonization of CRE from the intestine to the displacement of lung infection is the use of carbapenem antibiotics.Conclusion:CRKP of producing OXA-48 enzyme are the most common intestinal colonization CRE in some ICU patients of our hospital,and the results of sequence typing were all ST231.The presence of intestinal colonization is mainly related to the severity of the disease,carrying multi-drug resistant bacteria and nutritional status.Intestinal colonization CRE is closely correlated with the subsequent development of lung infection.The lung CRE strain may be displaced from intestinal colonization CRE,and the risk factor for the occurrence of displaced infections is the use of carbapenem antibiotics.