Correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients

Correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients Yuanyuan Xiao, Juping Duan, Caixia Tan, Ju Zou, Siyao Chen, Ting Liu, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3869345/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose It is generally believed that Carbapenem-resistant Enterobacteriaceae (CRE) colonization is primarily responsible for subsequent systemic infection in humans. In China, the specific situation of CRE colonization and subsequent systemic infection in hospitalized patients necessitates further exploration. Methods We retrospectively analyzed data of intestinal CRE colonization inpatients at Xiangya Hospital, Central South University, regarding demography, clinical and pathogenic characteristics, treatment, and outcome. A risk prediction model for subsequent CRE infection was established and externally validated. Results In total, 839 intestinal CRE colonization samples from inpatients were included. Finally, 317 cases of intestinal CRE colonization were enrolled, 25.9% of whom developed systemic infections. The subsequent CRE infection rates of CRKP and CREC were 27.0% and 32.3%, respectively. The incidence of subsequent CRE infection in the respiratory medicine department, hematology department, and intensive care unit (ICU) was 26.7%, 21.8%, and 45.0%, respectively. Taking probiotics and the combined oral and intravenous administration of antibiotics were the protective factors for the subsequent infection of intestinal CRE colonization, while liver disease, agranulocytosis ≥ 7 days, hypoproteinemia, invasive respiratory assisted ventilation, history of surgery/trauma in the past 3 months, and use of antifungal drugs were the independent risk factors. Conclusions CRE infection after intestinal CRE colonization in inpatients can significantly prolong the length of hospital stay and increase total medical costs. The CRE infection group exhibited poor efficacy and high mortality. Thus, the established risk prediction model for intestinal infection after CRE colonization in hospitalized patients has a good prediction efficacy for high-risk departments. Carbapenem-resistant Enterobacteriaceae CRE colonization infection prediction model Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction The number of cases of infection caused by Carbapenem-resistant Enterobacteriaceae (CRE) continues to increase globally, causing a high rate of incidence in susceptible groups such as children, the elderly, transplant recipients, and immunosuppressive patients, especially when these patients are hospitalized[ 1 – 3 ]. In recent years, the treatment of CRE-infected patients has also faced considerable difficulties, and is associated with poor prognosis and high mortality. As early as 2013, due to the high hazards of CRE infection, the Centers for Disease Control and Prevention (CDC) listed CRE as the first “emergency” level of drug-resistant bacteria[ 4 ]. According to the European CDC’s 2022 report on bacterial resistance surveillance in 41 European countries, the resistance rate of Escherichia coli to carbapenems was low, and only six countries, namely Belarus, North Macedonia, Russia, Serbia, Turkey, and Ukraine, had a resistance rate higher than 1.0%. However, the resistance rate of Klebsiella pneumoniae to carbapenems rose from 6.2% in 2012 to 10.0% in 2020, with six countries or regions, namely Belarus, Georgia, Greece, Moldova, Russia, and Ukraine, showing resistance above 50.0%. Moreover, the isolation rate of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in Greece was the highest, reaching 66.3%[ 5 ]. The CDC estimates that as of 2017, approximately 13,100 hospitalized patients in the United States were infected with CRE, among which 1,100 died, leading to a case fatality rate of 8.4%[ 1 ]. Thus, this shows that CRE infection has gradually become a major global public health threat, causing an enormous economic burden of disease to society at large. Consequently, there are severe challenges to the prevention, control, and treatment of CRE nosocomial infections. It is generally believed that CRE colonization is primarily responsible for infection, and patients with CRE colonization have a significantly high risk of infection[ 6 ]. A previous study has shown that it takes a very long time for patients initially colonized with CRE to turn negative naturally, with an average of approximately 387 days[ 7 ]. This suggests that decolonization therapy of CRE is important to prevent the morbidity and mortality associated with these infections. However, relevant studies have shown that among 1806 patients with CRE colonization, the overall risk of infection with CRE was 16.5% (299/1806)[ 8 ]. Therefore, most CRE carriers will not be infected with CRE, and if excessive decolonization is performed in clinical practice, it may lead to a waste of medical resources and abuse of antibiotics. Thus, there is no general consensus among experts on the specific timing and the degree of decolonization therapy. However, the situation of subsequent infection in current CRE colonized patients in China is not yet fully clear. Hence, the population characteristics, clinical features, and related risk factors of subsequent systemic infection in CRE colonized patients need to be further explored. CRE colonization in the intestinal tract usually precedes or coexists with CRE infection[ 6 ]. Under normal circumstances, colonized CRE, gut microbiota, and the host interact in a dynamic equilibrium state. When the gut microbiota is disturbed due to causes such as diet, drugs, and diseases, the normal intestinal flora loses resistance to colonized CRE, thus increasing the risk of CRE infection[ 9 , 10 ]. Clinically, in high-risk groups such as patients with hematological tumor, hematopoietic stem cell transplantation, and organ transplantation, the proportion of intestinal CRE colonization increases significantly, and the intestinal CRE colonization rate in such hospitalized patients ranges from 6.8–45.4%[ 9 – 12 ]. The World Health Organization recommends that for asymptomatic CRE colonized patients, pathogenic surveillance should be guided by the epidemiology and risk assessment of each region/country[ 13 , 14 ]. In other words, early identification of patients with CRE colonization can further track and prevent the prevalence and spread of CRE in hospitals[ 15 ]. Currently, the preferred screening sites recommended by the American CDC and the European Society for Clinical Microbiology are intestinally derived samples (including feces and rectal swabs)[ 13 , 16 ]. Stool is the best screening specimen, and stool CRE detection is relatively convenient and easy to popularize clinically. Therefore, we conducted a retrospective study to understand the association between intestinal CRE colonization and subsequent CRE systemic infection in hospitalized patients. Our study focused on all CRE-positive specimens from January 1, 2013 to October 1, 2022, and the patients were from all clinical departments of Xiangya Hospital, Central South University. This provides a wide range of observation groups for this study and makes the research results valuable for clinical reference. The main objective of our study was to identify the population characteristics, clinical features, pathogenic characteristics, and risk factors of systemic infection after CRE colonization in inpatients, and to establish a risk prediction model for subsequent infection in CRE carriers. These need to be done to facilitate early identification of high-risk hospitalized patients, timely implementation of decolonization treatment interventions, and ultimately achieve the goal of prevention and control of CRE nosocomial infection. Materials and Methods Study subjects and design The subjects of the study were inpatients with positive stool CRE screening at Xiangya Hospital, Central South University, from January 1, 2013 to October 1, 2022. If the same patient was hospitalized for several times, the hospitalization data at the time of the first report was selected. If the samples from the same patient were positive multiple times, the first positive result was taken as the starting point of the research until the patient was discharged. All specimens used met the following inclusion criteria: (1) stool CRE screening results were positive, (2) no CRE infection was diagnosed prior to positive stool screening, (3) no CRE colonization of other sites before positive stool screening, and (4) hospitalization time ≥ 48 hours. In addition, the exclusion criteria were as follows: (1) pregnant patients, (2) patients discharged within 48 hours after a positive stool CRE screening, (3) contaminated or unqualified clinical specimens, and (4) missing clinical data. Study groups and definition The positive samples of stool CRE screening were monitored through the nosocomial infection real-time monitoring and management system. Samples were included or excluded according to the previously described criteria. Finally, hospitalized patients with intestinal CRE colonization were included in the study. The clinical data of the patients were collected retrospectively. Based on whether the patients subsequently developed CRE systemic infection, they were divided into the “CRE infection group” and the “non-CRE infection group.” Among them, CRE infection was diagnosed as positive CRE detection in the patient's blood culture or other sterile sites, which can be confirmed as infection. Otherwise, the samples from suspected contamination sources, such as urine, stool, sputum, and wound secretion, were judged according to the standards provided by the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN)[ 17 ]. In this study, systemic infection was defined as common infections in various systems of the organism, including bloodstream infection, pulmonary infection, abdominal infection, urinary tract infection, skin and soft tissue infection, surgical site infection, gastrointestinal system infection, and central nervous system infection. CRE colonization means that the samples from suspected contamination sources test positive for CRE, but if they do not meet the above diagnostic criteria for CRE infection, it is judged as CRE colonization. After admission, if the fecal CRE screening indicated positive and the patient did not meet the criteria for infection, then it was diagnosed as intestinal CRE colonization. Patient groups and clinical variables As shown in Fig. 1 , from January 2013 to October 2022, a total of 839 specimens from inpatients with positive stool CRE screening at Xiangya Hospital, Central South University, were retrospectively analyzed through the Lan Qing Ting Hospital Infection Real-time surveillance and Management Platform 7.0 version. Screening was conducted strictly in accordance with the inclusion and exclusion criteria, and the number of hospitalized patients with intestinal CRE colonization finally included in this study was 317. According to whether the patients subsequently developed systemic CRE infection, they were divided into a CRE infection group and a non-CRE infection group. Then, the population characteristics, clinical characteristics, incidence, and influencing factors of the two groups of patients were further explored. Meanwhile, data from 2013 to 2021 were used to develop the risk prediction model, and data from patients in 2022 were used to validate the model. The clinical variables evaluated comprised age, gender, length of hospital stay and cost, department, underlying diseases, comorbidities, clinically invasive procedures, colonization and infection strain type, infection site, therapy, and efficacy. The first relevant laboratory tests on admission were mainly routine blood, liver and kidney function, and inflammatory indicators. Comorbidities, underlying diseases, invasive procedures, special drugs, and antibiotic use before infection were collected. Statistical analysis Statistical analysis was performed using IBM SPSS software (version 26.0), and GraphPad Prism (version 9.5.1). Normally distributed measurement data was represented by mean ± standard deviation (‾x ± S), and skewed distribution measurement data was represented by median and interquartile range, namely M (P25, P75), and count data are expressed as absolute frequencies and percentages, such as N (%). The normally distributed quantitative variables were analyzed by Student-t test, the skewed distribution quantitative variables were analyzed by Wilcoxon rank sum test, and the qualitative variables were analyzed by chi-squared test or Fisher’s exact test. P < 0.05 was considered statistically significant. According to the results of univariate association analysis, factors with P < 0.05 were selected for multivariate analysis. Multivariate analysis was performed by logistic regression analysis, and odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The fitting effect of multivariate binary logistic regression analysis was evaluated by receiver operating curve (ROC). R was used to draw the nomogram and calibration curve of the risk prediction model of systemic infection after intestinal CRE colonization in hospitalized patients. Meanwhile, the external verification of the model proved that the model had good prediction efficiency. Results Baseline data comparison In all, 317 hospitalized patients with intestinal CRE colonization were included in this study, including 82 patients with subsequent CRE infection and 235 patients without CRE infection. Patients in the CRE infection group had a longer average hospital stay (Z = 3.606, P < 0.001) and a significantly higher total hospital cost than patients in the non-CRE infection group (Z = 7.415, P < 0.001). Additionally, the antibiotic exposure time (Z = 2.647, P = 0.008) and cost (Z = 7.341, P < 0.001) greatly increased in the CRE infection group. There were no statistically significant differences in age and gender between the two groups. For the first laboratory examination after intestinal CRE colonization in hospitalized patients, combined with the comparative analysis of the two groups, we found that the white blood cell count (Z = 3.277, P = 0.001) and the procalcitonin index (Z = 5.152, P < 0.001) of the two groups of patients were significantly different. However, the albumin level of the CRE infection group was significantly lower than that of the non-CRE infection group (t = 8.341, P < 0.001). There was no significant difference in other blood routine indexes and biochemical indexes between the two groups. For details, see Table 1 . Table 1 Basic data of patients in the CRE infection and no CRE infection groups Variable No CRE infection group (n = 235, 74.13%) CRE infection group (n = 82, 25.87%) χ 2 /Z/t P Baseline information Male [n (%)] 169(71.9%) 62(75.6%) 0.420 0.517 Age[M(P 25 , P 75 )] 49.12 ± 22.66 53.7 ± 22.86 1.560 0.120 Total hospitalization time(days) 26(14, 41) 33(21.5, 57.5) 3.606 <0.001* Total hospitalization cost 144735.34(72240.34, 243762.98) 281852.34(210793.16, 445289.05) 7.415 <0.001* Antibacterial cost 11204.00(2666.40, 30188.91) 61881.80(23401.49, 91582.75) 7.341 <0.001* Total antibacterial exposure time(days) 23(12, 37) 29(17, 47.5) 2.647 0.008* laboratory examination WBC[M(P 25 , P 75 )] 6.40(4.00, 10.10) 10.30(2.95, 15.9) 3.277 0.001* HB[‾x ± S] 100.52 ± 27.41 93.31 ± 23.49 1.741 0.083 Plt[M(P25,P75)] 175(71.25, 260) 184(66, 349) 0.387 0.699 NE#[M(P 25 , P 75 )] 4.70(2.20, 9.00) 7.70(1.65, 12.80) 1.797 0.072 ALB[‾x ± S] 34.17 ± 7.39 28.31 ± 4.20 8.341 <0.001* TBIL[M(P25,P75)] 9.7(7.03, 14.48) 16.4(6.9, 30.8) 1.320 0.187 ALT[M(P25,P75)] 21.9(11.45, 41.18) 31.3(17.2, 64) 1.022 0.307 AST[M(P25,P75)] 32.65(21.4, 57.88) 43.3(29, 77.4) 1.186 0.236 BUN[M(P25,P75)] 6.85(4.78, 11.81) 7.86(4.69, 14.11) 0.961 0.336 CR[M(P25,P75)] 80.05(58, 127.53) 75.10(62, 123.20) 0.240 0.810 CRP[M(P25,P75)] 73.85(22.33, 120.67) 89.90(30.3, 130) 1.110 0.267 ESR [‾x ± S] 55.43 ± 35.53 56.13 ± 33.37 0.105 0.916 PCT[M(P 25 ,P 75 )] 0.27(0.10, 0.76) 1.30(0.25, 10.88) 5.152 <0.001* Classification of colonizing strains ** Klebsiella pneumoniae 149(63.40%) 58(69.88%) 1.440 0.230 Escherichia coli 42(17.87%) 14(16.87%) 0.030 0.863 Enterobacter cloacae 16(6.81%) 4(4.82%) 0.383 0.536 Klebsiella aerogenes 6(2.55%) 2(2.41%) <0.001 1.000 Klebsiella oxytoca 7(2.98%) 0(0.0%) 1.309 0.253 Citrobacter fraudii 1(0.43%) 2(2.41%) 2.629 0.165 Citrobacter cruzi 1(0.43%) 0(0.0%) 0.350 1.000 Serratia marcescens 0(0.0%) 1(1.20%) 2.875 0.259 unclassified CRE 13(5.53%) 2(2.41%) 0.695 0.404 * p < 0.05, indicating a statistically significant difference. Distribution of departments The details of the department distribution of patients in this study are shown in Fig. 2 . The samples of inpatients colonized with intestinal CRE came from 26 clinical departments of Xiangya Hospital, Central South University, mainly in the departments of respiratory medicine, hematology, intensive care unit (ICU), and pediatric hematology, with 100 cases (31.55%), 94 cases (29.65%), 42 cases (13.25%) and 21 cases (6.62%), respectively. Among them, the patients with subsequent CRE infection were mainly in the department of respiratory medicine (n = 27, 33.3%), the department of hematology (n = 17, 20.99%) and the department of critical care medicine (n = 21, 13.25%). At the same time, the incidence of subsequent infection of intestinal CRE colonization among patients in different departments was also different. The incidence of subsequent CRE infection in the ICU was 50.00%. It was 26.7% in the department of respiratory medicine, 18.09% in the department of hematology, and 28.57% in the department of ICU. Pathogens and infections Classification of colonizing strains As shown in Fig. 3 A, a total of 317 strains of patients with positive stool CRE screening were included in this study. There was no statistically significant difference in the classification of colonizing strains between the two groups. Among them, K. pneumoniae was the main pathogen (n = 149, 63.40% vs. n = 58, 69.88%), followed by E. coli (n = 42, 17.87% vs. n = 14, 16.87%) and Enterobacter cloacae (n = 16, 6.81% vs. n = 4, 4.82%). Of note, no specific strain was isolated in 15 patients and both E. coli and K. pneumoniae were isolated in one patient (Table 1 ). Types of CRE strains detected We analyzed the types of pathogens responsible for subsequent infections in hospitalized patients with intestinal CRE colonization. A total of 81 strains were detected, among which K. pneumoniae was the most common, accounting for 69.77%, followed by E. coli and E. cloacae , accounting for 16.28% and 5.81%, respectively. At the same time, we found that the infection rates of subsequent infections of different strains were also different. Among them, K. pneumoniae was 28.99% (60/207), E. coli was 25.00% (14/56), and E. cloacae was 25% (5/20) (Fig. 3 A). Sources of CRE strain detected As shown in Fig. 3 B, the analysis of the detected pathogenic bacteria sites after intestinal CRE colonization in hospitalized patients and subsequent infection revealed that the main specimen sources included lungs (n = 38), blood flow (n = 32), digestive tract (n = 17), urinary tract (n = 9), pleural ascites and postoperative drainage fluid (n = 6), catheter-related infection (n = 1), surgical site (n = 3), skin and soft tissue (n = 2) and cerebrospinal fluid (n = 38). Furthermore, the site of CRE infection was consistent with the source of the sample. The most common was pulmonary infection, accounting for 33.04%, followed by bloodstream infection at 27.83%, then followed by digestive tract infection and urinary tract infection which accounted for 14.78% and 7.83%, respectively. However, intracranial infection was rarest, and only one patient was detected to have pathogens from cerebrospinal fluid. Figure 3 A shows the classification of colonized and infection strains. Figure 3 B shows the subsequent infections of different CRE colonizing sites. No specific strain was isolated from 13 colonized samples from patients, and one of them was subsequently detected positive for Proteus mirabilis. Clinical characteristics of patients Underlying diseases and complications As shown in Table 2 , among the 214 inpatients from January 1, 2013 to September 31, 2021, patients in the two groups had numerous comorbidities and underlying diseases, usually involving multiple organs or systems, and almost all categories of diseases were included. In both the CRE infection group or the non-CRE infection group, the most common underlying clinical disorder was pulmonary lesion, with 115 cases in the non-CRE infection group (72.3%), and 41 cases in the CRE infection group (74.5%). Univariate analysis showed that underlying diseases including liver lesions and digestive tract lesions, combined with other infections, agranulocytosis ≥ 7 days, and hypoalbuminemia, were statistically different between the two groups, while there was no significant difference in other comorbidities. Furthermore, we found that the incidence of subsequent CRE infection varied with different underlying diseases and complications. Among the underlying diseases, liver disease was 43.4%, and digestive tract disease was 36.8%. The incidence of subsequent systemic CRE infection with other infections was 30.6%, agranulocytosis ≥ 7 days was 39.6%, and hypoproteinemia was 61.9%. Clinical invasive operation According to the analysis of the invasive operation of the two groups in hospitalized patients before CRE infection, we found that the most common invasive operation was arteriovenous catheterization (n = 157, 98.7% vs. n = 55, 100%), followed by indwelling catheter (n = 91, 57.2% vs. n = 39, 70.9). Among them, when the patients had an indwelling gastrojejunal tube or ostomy tube (χ 2 = 5.106, P = 0.024), invasive respiratory assisted ventilation (χ 2 = 6.431, P = 0.011), and a history of surgery or traumatism in the past 3 months (χ 2 = 9.393, P = 0.002), the difference between the two groups was statistically significant. For other invasive operations, there was no significant difference between the two groups (Table 2 ). Use of drugs and biological agents By analyzing the use of special drugs before the occurrence of CRE infection in the two inpatient groups, we found that the most common ones were the use of intestinal probiotics (n = 115, 72.3% vs. n = 30, 54.5%) and glucocorticoids (n = 93, 58.5% vs. n = 35, 63.6%). For example, when intestinal probiotics were used (χ2 = 5.914, P = 0.015), the difference between the two groups was statistically significant. As shown in Table 2 , there was no significant difference between other special drugs and measures used before infection, including immunosuppressants, biological agents, glucocorticoids, chemotherapeutic drugs, and targeted drugs). Antimicrobial agents and therapeutic effect Use of antimicrobial agents before infection To analyze the use of antibiotics before the diagnosis of CRE infection, we found that there were statistically significant differences in the use of four types of antibiotics between the two groups, namely tigecycline (χ 2 = 4.681, P = 0.031), polymyx prime (χ 2 = 11.315, P = 0.001), glycopeptides (χ 2 = 5.701, P = 0.017), and antifungal (χ 2 = 7.425, P = 0.007). However, there were no significant differences in the use of cephalosporins, β-lactamase inhibitors and compound preparations, quinolones, carbapenems, ceftazidime avibactam, TMP/SMX, and aminoglycosides before infection between the two groups. Furthermore, when both oral and intravenous antibiotics were administered compared to intravenous antibiotics alone, there was a statistically significant difference between the two groups (χ 2 = 9.125, P = 0.003) (Table 2 ). Table 2 Univariate analysis of risk factors for subsequent infection in CRE intestinal carriers Variable No CRE infection group (n = 159, 74.30%) CRE infection group (n = 55, 25.70%) χ 2 P Value The underlying diseases Hypertension 48(30.2%) 19(34.5%) 0.361 0.584 Diabetes 30(18.9%) 12(21.8%) 0.225 0.635 Coronary heart disease 35(22.0%) 12(21.8%) 0.001 0.976 Hematological neoplasms 54(34.0%) 19(34.5%) 0.006 0.937 Solid tumors 18(11.3%) 7(12.7%) 0.078 0.780 Cerebrovascular disease 49(30.8%) 22(40.0%) 1.554 0.213 Pulmonary lesions 115(72.3%) 41(74.5%) 0.102 0.750 Liver lesions 30(18.9%) 23(41.8%) 11.552 0.001* Urinary system disease 34(21.4%) 18(32.7%) 2.859 0.091 Digestive tract lesions 36(22.6%) 21(38.2%) 5.050 0.025* Tuberculosis infection 8(5.0%) 5(9.1%) 0.576 0.448 Connective tissue disease 13(8.2%) 1(1.8%) 1.786 0.181 combined with other infections 102(64.2%) 45(81.7%) 5.931 0.015* combined with agranulocytosis ≥ 7 days 29(18.2%) 19(34.5%) 6.245 0.012* combined with hypoalbuminemia 40(72.7%) 65(40.9%) 16.584 <0.001* Clinical invasive operation Arteriovenous catheterization 157(98.7%) 55(100%) - 1.000 Various thoracic and abdominal drainage tube 44(27.7%) 23(41.8%) 3.802 0.051 Bronchoscopy 66(41.5%) 27(49.1%) 0.956 0.328 Indwelling catheter 91(57.2%) 39(70.9%) 3.205 0.073 Indwelling gastrojejunal tube or ostomy tube 85(53.5%) 39(70.9%) 5.106 0.024* Blood purification therapy 24(15.1%) 11(20.0%) 0.719 0.397 Noninvasive respiratory assisted ventilation 42(26.4%) 10(18.2%) 1.506 0.220 Invasive respiratory assisted ventilation 64(40.3%) 33(60.0%) 6.431 0.011* History of surgery or traumatism 66(41.5%) 36(65.5%) 9.393 0.002* Use of drugs and biological agents Immunosuppressants 62(39.0%) 22(40.0%) 0.017 0.895 Biological agents 10(6.3%) 4(7.3%) <0.000 1.000 Intestinal probiotics 115(72.3%) 30(54.5%) 5.914 0.015* Glucocorticoids 93(58.5%) 35(63.6%) 0.450 0.502 Chemotherapeutic drugs 48(30.2%) 14(25.5%) 0.445 0.505 Targeted drugs 11(6.9%) 5(9.4%) 0.090 0.764 Antibacterial agents Cephalosporins 27(17.0%) 9(16.4%) 0.011 0.916 β-lactamase inhibitors and compound preparations 130(81.8%) 47(85.5%) 0.390 0.532 aminoglycosides 33(20.8%) 10(18.2%) 0.168 0.681 Quinolones 60(37.7%) 25(45.5%) 1.017 0.313 carbapenems 116(73.0%) 46(83.6%) 2.534 0.111 Tigecycline 32(20.1%) 19(34.5%) 4.681 0.031* polymyx prime 22(13.8%) 19(34.5%) 11.315 0.001* ceftazidime avibactam 4(2.5%) 2(3.6%) <0.001 1.000 TMP/SMX 81(50.9%) 25(45.5%) 0.493 0.483 glycopeptides 63(39.6%) 32(58.2%) 5.702 0.017* Antifungal 92(57.9%) 43(78.2%) 7.425 0.007* Use time ≥ 15 days 115(72.3%) 34(61.8%) 2.134 0.144 Oral combined with intravenous route 93(60.0%) 20(36.4%) 9.125 0.003* * p < 0.05, indicating a statistically significant difference. Curative effect and outcome Figure 4 shows the curative effect and outcome of the two groups. We found that the effective rate in the non-CRE infection group was significantly higher than that of the CRE infection group, which were 85.11% (200/235) and 52.24% (43/82), respectively. The inefficiency rate of the CRE infection group was 47.56%, which was significantly higher than that of the group without subsequent CRE infection. Furthermore, we found that inpatients who developed CRE infection after intestinal CRE colonization had relatively poor prognosis, as the mortality rate was 18.3%. (χ 2 value = 11.129, P = 0.001). Figure 4 Curative effect and outcome of patients in the two groups after treatment Establishing a risk prediction model Multivariate logistic regression analysis Based on the previous univariate analysis results of underlying diseases and comorbidities, invasive procedures, special drugs and preparations, and the use of antibiotics, a total of 14 influencing factors with P value < 0.05 were selected and included in the multivariate logistic regression analysis. Then, a total of eight independent influencing factors of subsequent CRE system infection in patients with intestinal CRE colonization were obtained, it was found that taking probiotics, oral administration combined with intravenous use of antibiotics were protective factors of CRE infection after intestinal CRE colonization in hospitalized patient, while complicated with liver disease, combined with agranulocytosis ≥ 7 days, hypoproteinemia, invasive respiratory assisted ventilation, history of surgery/trauma in the past 3 months, and use of antifungal drugs were independent risk factors. This is shown in Table 3. Finally, we established a risk prediction model of systemic infection after intestinal CRE colonization in inpatients. The results were displayed using forest plots. Table 3 Multivariate logistic regression analysis of risk factors for subsequent infection in CRE intestinal carriers External evaluation and validation of the model We also evaluated the performance of the model in terms of discrimination, calibration, and clinical adaptability. The proposed prediction model was externally validated using data of inpatients from Xiangya Hospital Central South University in October 1, 2021 to October 1, 2022. Figure 5 shows the ROC curve to evaluate the fitting effect of the model. The area under the curve (AUC) for the model and validation data is 0.883 (95%CI:0.831–0.934) and 0.844 (95%CI:0.745–0.943), respectively. Furthermore, Fig. 6 A and B shows the calibration curves of the prediction model and validation sample respectively, indicating that the model has a good consistency between the predicted probability and the actual occurrence probability, which shows that it has a relatively accurate predictive value. As shown in Fig. 7 A and B, the decision curve of the prediction model for both modeling and validation cohorts yielded a higher net clinical benefit than the treat-all and treat-none strategies in the entire range of thresholds. These results demonstrate that the model has excellent prediction performance. Finally, the nomogram of the risk prediction model is shown in Fig. 8 . Discussion Of the 317 inpatients with CRE colonization in this study, 25.9% subsequently developed systemic CRE infection, which was relatively higher than previous research[ 8 , 18 ]. This is primarily because a large number of the patients were from the ICU, and systemic infection was included in this study. With respect to the types of colonized strains in the two groups, K. pneumoniae was the first, with 67.9% in the non-CRE infection group and 72.7% in the CRE infection group, which was generally consistent with the results of other studies[ 19 – 22 ]. Departing from previous studies, we focused on systemic infection in this study, and the sites of subsequent CRE infection were consistent with the source of samples. The most common one was respiratory system specimens, accounting for 35%, followed by bloodstream infection, digestive system infection, and urinary system infection, accounting for 21%, 18%, and 10% respectively. In contrast, the distribution of CRE infection specimens in our hospital is generally similar to related studies, while the proportion of the sources of digestive system specimens is significantly different[ 8 , 23 ], which may be due to the fact that the objects of this study are inpatients with intestinal CRE colonization. Of note, considering that pulmonary infections are the most common, aspiration of gastrointestinal contents may be a potential mechanism that links intestinal colonization with the occurrence of CRE infections in the critically ill cohort[ 24 ]. Therefore, special attention should be paid so as to avoid aspiration when performing related clinical operations such as tracheal intubation, gastric tube insertion, fiberoptic bronchoscopy, and gastroscopy. The incidence of CRE colonization and infection in clinical departments also varied. In this study, the colonization or infection of CRE mainly occurred in respiratory medicine, hematology, ICU, and other specialized ICU, which is consistent with relevant studies[ 8 , 24 ], and the incidence of subsequent CRE infection was 26.7%, 21.8%, and 45.0%, respectively. Often, most patients in these departments have poor immunity, complex conditions, long hospitalization time, and more frequent use of antibiotics, which lead to patients being more susceptible to the surrounding drug-resistant environment and greatly increase the risk of CRE colonization and subsequent CRE infection in hospitalized patients. In fact, most of the patients in the above high-risk departments had a history of invasive operations. We found that the most common was arteriovenous catheterization. Indwelling catheter, especially deep venous catheterization, may greatly increase the opportunistic infection of colonized bacteria into the blood, thus further increasing the risk of CRE bloodstream infection[ 25 ]. Other invasive operations included patients with indwelling gastrojejunal tube or ostomy tube, assisted ventilation with invasive breathing, and a history of surgery or trauma in the past 3 months, which may be the influencing factors of intestinal CRE colonization and subsequent development of CRE infection in hospitalized patients. This is roughly the same as the results of related studies[ 8 , 24 , 26 ]. Invasive operations can destroy the body’s natural barrier, and directly or indirectly place pathogens into the human body. This results in flora translocation, thus increasing the possibility of bacterial colonization or infection. Therefore, for the high-risk departments, unnecessary invasive operations must be minimized, and relevant measures should be taken to monitor, prevent and control CRE infection, so as to put an end to CRE infection from the source[ 13 , 27 ]. Clinically, many patients have comorbidities or multiple underlying diseases. Studies have shown that patients with CRE colonization combined with advanced liver cirrhosis can manifest increased intestinal permeability and impaired reticuloendothelial system function, while patients with organ transplantation and allogeneic hematopoietic cell transplantation often manifest a combination of neutropenia and intestinal rejection[ 28 – 30 ]. Thus, the risk of bacterial translocation and infection after intestinal CRE colonization in such patients is significantly increased. Our research found that, combined with liver disease (mainly including liver insufficiency, liver failure, liver cirrhosis, and liver transplantation), agranulocytosis ≥ 7 days and hypoalbuminemia were independent risk factors for subsequent infection of intestinal CRE colonization in hospitalized patients, which is consistent with the findings of relevant studies[ 28 , 31 ]. At the same time, laboratory examinations revealed that the CRE infection group had significantly lower levels of albumin, which was caused by factors such as albumin redistribution due to increased vascular permeability, reduced albumin synthesis under pathological conditions, and increased consumption in critically ill patients. Moreover, the plasma protein binding rate is significantly reduced in patients with hypoalbuminemia, and this makes some antibacterial drugs less effective, forming a vicious circle, and inducing CRE infection or leading to poor prognosis[ 32 , 33 ]. Therefore, to reduce the risk of infection in patients with CRE colonization, it is necessary to promptly correct hypoproteinemia and regularly monitor blood drug concentration. In addition, we found that probiotic administration was a protective factor against subsequent CRE infection (OR = 0.338). In the state of CRE colonization, when patients suffer from intestinal flora disorders caused by diet, inflammatory bowel disease, antibiotics, and more, intestinal flora translocation of colonizing bacteria will occur due to intestinal mucosal damage, which leads to further infection[ 6 , 9 , 10 ]. The use of probiotics may reduce this risk. Relevant studies have shown that probiotics may have anti-inflammatory, immunomodulatory, inhibiting abnormal cell proliferation, and antioxidant activities[ 34 ]. Therefore, for patients with intestinal CRE colonization, especially those with other infections and using antibiotics, we should regularly monitor the stool and timely add probiotics to regulate intestinal flora in order to reduce the occurrence of subsequent CRE infection. The use of antibiotics is closely related to infection. Considering colonization and infection, it is particularly important to clarify the use of antibacterial agents before CRE infection. Notably, we found that the use of tigecycline, polymyxin, glycopeptides, and antifungal agents may influence the subsequent development of CRE infection in hospitalized patients with intestinal CRE colonization, of which antifungal agents (OR = 7.764) was an independent risk factor. Another study also showed that tigecycline was an independent risk factor for subsequent infection after CRE colonization[ 26 ]. We considered the following reasons. First, the drugs may have been administered because of coexisting infections that did not respond well to treatment. Second, the clinical effect of monotherapy against CRE infection is not good, and most treatment schemes include a two-drug combination, a three-drug combination, or a carbapenem-containing combination[ 13 ]. Third, the whole CRE was analyzed instead of specific strains in our study, which may affect the results because of the differences in drug sensitivity of specific strains. Furthermore, we found that combined oral and intravenous antibiotics administration is a protective factor against subsequent infections in hospitalized patients with intestinal CRE colonization (OR = 0.152). In point of fact, many patients were given oral antibiotics due to severe intestinal microbiota imbalance caused by diarrhea, which would inevitably lead to intestinal mucosal damage if not treated in time. Studies have shown that the realization of intestinal barrier function chiefly includes the adhesion of tight junction proteins to epithelial cells, the secretion of mucus by intestinal immune cells, antibodies, and antibacterial effector molecules[ 35 , 36 ]. If this barrier function is impaired for any reason, the risk of infection by colonizing bacteria in the gut will significantly increase [ 36 , 37 ]. We found that the subsequent CRE infection in patients with intestinal CRE colonization significantly prolonged the length of hospital stay and the total hospitalization cost, and also greatly increased the cost and curative time of antibiotics. This is consistent with related studies[ 8 , 38 ]. It follows that the subsequent CRE infection in patients with intestinal CRE colonization increases the antibiotic exposure and economic burden of patients, and also increases the medical burden of the country. Moreover, hospitalized patients who subsequently develop CRE infection after intestinal CRE colonization have relatively poor efficacy (85.11% vs. 52.44%) and high mortality (6.0% vs. 18.3%). The relevant literature also reported that approximately 36% of patients who developed infection after CRE colonization died within 90 days[ 24 ]. The mortality rate for fatal CRE infection after colonization in liver transplant patients is 78%[ 28 ]. In patients with hematological malignancies complicated with bloodstream infection, the 30-day-related fatality rate caused by CRE is as high as 51%[ 39 ], while in patients receiving hematopoietic stem cell transplantation, the overall 90-day mortality rate of CRE-infected patients is even higher, approximately 58%[ 40 ]. In this study, we comprehensively analyzed the correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients from the aspects of population, clinical characteristics, incidence, risk factors and disease economics, and established a risk prediction model for systemic infection after intestinal CRE colonization in hospitalized patients, which is highly valuable. It is helpful to improve clinicians' understanding of intestinal CRE colonization and subsequent infection, assist them in making risk assessment before empirical treatment of intestinal CRE colonization, and then take corresponding intervention measures to prevent CRE infection. The study also provides a reference for the rational use of antibiotics, which has a good clinical guiding significance. However, the present study also has certain limitations. First, as a single-center retrospective study, there are selection bias and information bias. Second, the statistical significance of some variables in the multivariate analysis may have been obscured due to the uneven distribution of sample sizes between the two groups. Therefore, prospective case–control studies or cohort studies with a large scale and multiple centers could be conducted in the future. Moreover, whether CRE colonization should be treated and the timing of decolonization still need further exploration. The gut microbiota of CRE colonization and subsequent infection also deserves further study. This study has a prime reference value for early identification of high-risk patients and prediction of the possibility of infection, which is of great significance for the clinical prevention and control of CRE colonization, and the inhibition of subsequent systemic infection. Conclusions This study explored the correlation between intestinal CRE colonization and subsequent systemic infection in inpatients in a large teaching hospital. In total, 317 cases of intestinal CRE colonization were included, with an incidence of subsequent systemic CRE infection of 25.9%. It was found that CRKP and CREC were the main bacterial strains that followed intestinal CRE colonization in hospitalized patients. The main sites of infection were the lungs and blood stream. High-risk departments mainly included respiratory medicine, hematology, and ICU. CRE infection occurring after intestinal CRE colonization in inpatients can significantly prolong the length of staying at hospital and increased the total cost. Also, the CRE infection group had poor efficacy and high mortality. The established risk prediction model for intestinal infection after CRE colonization in hospitalized patients had a good prediction efficiency for high-risk departments. Declarations Author Contributions Conceptualization: Chunhui Li, Anhua Wu, Lina Zhang, Xin Chen, Yajing Xu and Yuanyuan Li. Methodology: Yuanyuan Xiao, Juping Duan, Caixia Tan and Ju Zou. Data collection: Yuanyuan Xiao, Siyao Chen and Ting Liu. Writing original draft: Yuanyuan Xiao. Manuscript revision and and editing: Chunhui Li and Anhua Wu. Funding acquisition: Chunhui Li, Anhua Wu and Juping Duan. All authors contributed to the article and reviewed the manuscript. Funding This research was supported by the National Key Research and Development Program of China (No. 2022YFC2009801, 2022YFC2009805), the Natural Science Foundation of Hunan Province (No. 2021JJ31071), Health Development Research Center of the National Health Commission, "Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions" (CNHDRC-KJ-L-2020-53-04375), and Changsha science and technology plan project (NO. kq2202059). Data Availability The datasets used during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare no conflicts of interest. 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J Infect 2016, 73(4):336-345. doi: 10.1016/j.jinf.2016.07.002. Girmenia C, Rossolini GM, Piciocchi A, et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant 2015, 50(2):282-288. doi: 10.1038/bmt.2014.231. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3869345","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":267508044,"identity":"7f875e90-8183-48c2-9ec4-86265ea62819","order_by":0,"name":"Yuanyuan Xiao","email":"","orcid":"","institution":"Department of Infection Control Center of Xiangya Hospital, Central South University","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Xiao","suffix":""},{"id":267508045,"identity":"1b826e15-366a-49b4-be73-b1edb222ffca","order_by":1,"name":"Juping 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B ROC curve of the validation sample for infection after CRE colonization.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3869345/v1/2f01e574e74ff6ac25f937e1.png"},{"id":49827038,"identity":"a115c784-2094-43be-8c88-5a4119c3fba1","added_by":"auto","created_at":"2024-01-18 15:55:45","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":194372,"visible":true,"origin":"","legend":"\u003cp\u003eA Calibration curves of the risk prediction model for infection after CRE colonization. B Calibration curves of the validation sample for infection after CRE colonization.\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3869345/v1/1c39d6814a796924ec7eb0f1.png"},{"id":49827039,"identity":"0969acaa-e899-4716-a4b7-38a83d256317","added_by":"auto","created_at":"2024-01-18 15:55:46","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":105075,"visible":true,"origin":"","legend":"\u003cp\u003eDecision curve analysis of the prediction model for infection after CRE colonization. B Decision curve analysis of the validation cohorts for infection after CRE colonization.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-3869345/v1/f843fe20bf432f7962bb0e7f.png"},{"id":49827035,"identity":"a67f4568-397a-411a-a135-31808a26320f","added_by":"auto","created_at":"2024-01-18 15:55:45","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":244553,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram for the occurrence of infection after CRE colonization. The figure illustrates the data of patient number 142.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-3869345/v1/fc4b854124a18a51484e6e61.png"},{"id":49912168,"identity":"8061fc9f-6d89-4dd2-924e-60340aede4b2","added_by":"auto","created_at":"2024-01-20 12:22:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1643562,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3869345/v1/ddca37e5-c3e7-4e18-8ad2-afa1fe3d0afe.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe number of cases of infection caused by Carbapenem-resistant Enterobacteriaceae (CRE) continues to increase globally, causing a high rate of incidence in susceptible groups such as children, the elderly, transplant recipients, and immunosuppressive patients, especially when these patients are hospitalized[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In recent years, the treatment of CRE-infected patients has also faced considerable difficulties, and is associated with poor prognosis and high mortality. As early as 2013, due to the high hazards of CRE infection, the Centers for Disease Control and Prevention (CDC) listed CRE as the first \u0026ldquo;emergency\u0026rdquo; level of drug-resistant bacteria[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. According to the European CDC\u0026rsquo;s 2022 report on bacterial resistance surveillance in 41 European countries, the resistance rate of \u003cem\u003eEscherichia coli\u003c/em\u003e to carbapenems was low, and only six countries, namely Belarus, North Macedonia, Russia, Serbia, Turkey, and Ukraine, had a resistance rate higher than 1.0%. However, the resistance rate of \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e to carbapenems rose from 6.2% in 2012 to 10.0% in 2020, with six countries or regions, namely Belarus, Georgia, Greece, Moldova, Russia, and Ukraine, showing resistance above 50.0%. Moreover, the isolation rate of Carbapenem-resistant \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (CRKP) in Greece was the highest, reaching 66.3%[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The CDC estimates that as of 2017, approximately 13,100 hospitalized patients in the United States were infected with CRE, among which 1,100 died, leading to a case fatality rate of 8.4%[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Thus, this shows that CRE infection has gradually become a major global public health threat, causing an enormous economic burden of disease to society at large. Consequently, there are severe challenges to the prevention, control, and treatment of CRE nosocomial infections.\u003c/p\u003e \u003cp\u003eIt is generally believed that CRE colonization is primarily responsible for infection, and patients with CRE colonization have a significantly high risk of infection[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A previous study has shown that it takes a very long time for patients initially colonized with CRE to turn negative naturally, with an average of approximately 387 days[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This suggests that decolonization therapy of CRE is important to prevent the morbidity and mortality associated with these infections. However, relevant studies have shown that among 1806 patients with CRE colonization, the overall risk of infection with CRE was 16.5% (299/1806)[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, most CRE carriers will not be infected with CRE, and if excessive decolonization is performed in clinical practice, it may lead to a waste of medical resources and abuse of antibiotics. Thus, there is no general consensus among experts on the specific timing and the degree of decolonization therapy. However, the situation of subsequent infection in current CRE colonized patients in China is not yet fully clear. Hence, the population characteristics, clinical features, and related risk factors of subsequent systemic infection in CRE colonized patients need to be further explored.\u003c/p\u003e \u003cp\u003eCRE colonization in the intestinal tract usually precedes or coexists with CRE infection[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Under normal circumstances, colonized CRE, gut microbiota, and the host interact in a dynamic equilibrium state. When the gut microbiota is disturbed due to causes such as diet, drugs, and diseases, the normal intestinal flora loses resistance to colonized CRE, thus increasing the risk of CRE infection[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Clinically, in high-risk groups such as patients with hematological tumor, hematopoietic stem cell transplantation, and organ transplantation, the proportion of intestinal CRE colonization increases significantly, and the intestinal CRE colonization rate in such hospitalized patients ranges from 6.8\u0026ndash;45.4%[\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The World Health Organization recommends that for asymptomatic CRE colonized patients, pathogenic surveillance should be guided by the epidemiology and risk assessment of each region/country[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In other words, early identification of patients with CRE colonization can further track and prevent the prevalence and spread of CRE in hospitals[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Currently, the preferred screening sites recommended by the American CDC and the European Society for Clinical Microbiology are intestinally derived samples (including feces and rectal swabs)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Stool is the best screening specimen, and stool CRE detection is relatively convenient and easy to popularize clinically. Therefore, we conducted a retrospective study to understand the association between intestinal CRE colonization and subsequent CRE systemic infection in hospitalized patients. Our study focused on all CRE-positive specimens from January 1, 2013 to October 1, 2022, and the patients were from all clinical departments of Xiangya Hospital, Central South University. This provides a wide range of observation groups for this study and makes the research results valuable for clinical reference. The main objective of our study was to identify the population characteristics, clinical features, pathogenic characteristics, and risk factors of systemic infection after CRE colonization in inpatients, and to establish a risk prediction model for subsequent infection in CRE carriers. These need to be done to facilitate early identification of high-risk hospitalized patients, timely implementation of decolonization treatment interventions, and ultimately achieve the goal of prevention and control of CRE nosocomial infection.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy subjects and design\u003c/h2\u003e \u003cp\u003eThe subjects of the study were inpatients with positive stool CRE screening at Xiangya Hospital, Central South University, from January 1, 2013 to October 1, 2022. If the same patient was hospitalized for several times, the hospitalization data at the time of the first report was selected. If the samples from the same patient were positive multiple times, the first positive result was taken as the starting point of the research until the patient was discharged. All specimens used met the following inclusion criteria: (1) stool CRE screening results were positive, (2) no CRE infection was diagnosed prior to positive stool screening, (3) no CRE colonization of other sites before positive stool screening, and (4) hospitalization time\u0026thinsp;\u0026ge;\u0026thinsp;48 hours. In addition, the exclusion criteria were as follows: (1) pregnant patients, (2) patients discharged within 48 hours after a positive stool CRE screening, (3) contaminated or unqualified clinical specimens, and (4) missing clinical data.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy groups and definition\u003c/h2\u003e \u003cp\u003eThe positive samples of stool CRE screening were monitored through the nosocomial infection real-time monitoring and management system. Samples were included or excluded according to the previously described criteria. Finally, hospitalized patients with intestinal CRE colonization were included in the study. The clinical data of the patients were collected retrospectively. Based on whether the patients subsequently developed CRE systemic infection, they were divided into the \u0026ldquo;CRE infection group\u0026rdquo; and the \u0026ldquo;non-CRE infection group.\u0026rdquo; Among them, CRE infection was diagnosed as positive CRE detection in the patient's blood culture or other sterile sites, which can be confirmed as infection. Otherwise, the samples from suspected contamination sources, such as urine, stool, sputum, and wound secretion, were judged according to the standards provided by the Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this study, systemic infection was defined as common infections in various systems of the organism, including bloodstream infection, pulmonary infection, abdominal infection, urinary tract infection, skin and soft tissue infection, surgical site infection, gastrointestinal system infection, and central nervous system infection. CRE colonization means that the samples from suspected contamination sources test positive for CRE, but if they do not meet the above diagnostic criteria for CRE infection, it is judged as CRE colonization. After admission, if the fecal CRE screening indicated positive and the patient did not meet the criteria for infection, then it was diagnosed as intestinal CRE colonization.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePatient groups and clinical variables\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, from January 2013 to October 2022, a total of 839 specimens from inpatients with positive stool CRE screening at Xiangya Hospital, Central South University, were retrospectively analyzed through the Lan Qing Ting Hospital Infection Real-time surveillance and Management Platform 7.0 version. Screening was conducted strictly in accordance with the inclusion and exclusion criteria, and the number of hospitalized patients with intestinal CRE colonization finally included in this study was 317. According to whether the patients subsequently developed systemic CRE infection, they were divided into a CRE infection group and a non-CRE infection group. Then, the population characteristics, clinical characteristics, incidence, and influencing factors of the two groups of patients were further explored. Meanwhile, data from 2013 to 2021 were used to develop the risk prediction model, and data from patients in 2022 were used to validate the model.\u003c/p\u003e \u003cp\u003eThe clinical variables evaluated comprised age, gender, length of hospital stay and cost, department, underlying diseases, comorbidities, clinically invasive procedures, colonization and infection strain type, infection site, therapy, and efficacy. The first relevant laboratory tests on admission were mainly routine blood, liver and kidney function, and inflammatory indicators. Comorbidities, underlying diseases, invasive procedures, special drugs, and antibiotic use before infection were collected.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using IBM SPSS software (version 26.0), and GraphPad Prism (version 9.5.1). Normally distributed measurement data was represented by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (\u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;S), and skewed distribution measurement data was represented by median and interquartile range, namely M (P25, P75), and count data are expressed as absolute frequencies and percentages, such as N (%). The normally distributed quantitative variables were analyzed by Student-t test, the skewed distribution quantitative variables were analyzed by Wilcoxon rank sum test, and the qualitative variables were analyzed by chi-squared test or Fisher\u0026rsquo;s exact test. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. According to the results of univariate association analysis, factors with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were selected for multivariate analysis. Multivariate analysis was performed by logistic regression analysis, and odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The fitting effect of multivariate binary logistic regression analysis was evaluated by receiver operating curve (ROC). R was used to draw the nomogram and calibration curve of the risk prediction model of systemic infection after intestinal CRE colonization in hospitalized patients. Meanwhile, the external verification of the model proved that the model had good prediction efficiency.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eBaseline data comparison\u003c/h2\u003e \u003cp\u003eIn all, 317 hospitalized patients with intestinal CRE colonization were included in this study, including 82 patients with subsequent CRE infection and 235 patients without CRE infection. Patients in the CRE infection group had a longer average hospital stay (Z\u0026thinsp;=\u0026thinsp;3.606, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and a significantly higher total hospital cost than patients in the non-CRE infection group (Z\u0026thinsp;=\u0026thinsp;7.415, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, the antibiotic exposure time (Z\u0026thinsp;=\u0026thinsp;2.647, P\u0026thinsp;=\u0026thinsp;0.008) and cost (Z\u0026thinsp;=\u0026thinsp;7.341, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) greatly increased in the CRE infection group. There were no statistically significant differences in age and gender between the two groups. For the first laboratory examination after intestinal CRE colonization in hospitalized patients, combined with the comparative analysis of the two groups, we found that the white blood cell count (Z\u0026thinsp;=\u0026thinsp;3.277, P\u0026thinsp;=\u0026thinsp;0.001) and the procalcitonin index (Z\u0026thinsp;=\u0026thinsp;5.152, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of the two groups of patients were significantly different. However, the albumin level of the CRE infection group was significantly lower than that of the non-CRE infection group (t\u0026thinsp;=\u0026thinsp;8.341, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There was no significant difference in other blood routine indexes and biochemical indexes between the two groups. For details, see Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBasic data of patients in the CRE infection and no CRE infection groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNo CRE infection group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;235, 74.13%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCRE infection group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;82, 25.87%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e/Z/t\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBaseline information\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMale [n (%)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e169(71.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62(75.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAge[M(P\u003csub\u003e25\u003c/sub\u003e, P\u003csub\u003e75\u003c/sub\u003e)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e49.12\u0026thinsp;\u0026plusmn;\u0026thinsp;22.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.560\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal hospitalization time(days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e26(14, 41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33(21.5, 57.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e3.606\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal hospitalization cost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e144735.34(72240.34, 243762.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e281852.34(210793.16, 445289.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e7.415\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAntibacterial cost\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e11204.00(2666.40, 30188.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61881.80(23401.49, 91582.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e7.341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal antibacterial exposure time(days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e23(12, 37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29(17, 47.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e2.647\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.008*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003elaboratory examination\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eWBC[M(P\u003csub\u003e25\u003c/sub\u003e, P\u003csub\u003e75\u003c/sub\u003e)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6.40(4.00, 10.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.30(2.95, 15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e3.277\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHB[\u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;S]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e100.52\u0026thinsp;\u0026plusmn;\u0026thinsp;27.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e93.31\u0026thinsp;\u0026plusmn;\u0026thinsp;23.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.741\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePlt[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e175(71.25, 260)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e184(66, 349)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.387\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.699\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNE#[M(P\u003csub\u003e25\u003c/sub\u003e, P\u003csub\u003e75\u003c/sub\u003e)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e4.70(2.20, 9.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.70(1.65, 12.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.797\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eALB[\u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;S]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e34.17\u0026thinsp;\u0026plusmn;\u0026thinsp;7.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.31\u0026thinsp;\u0026plusmn;\u0026thinsp;4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e8.341\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTBIL[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e9.7(7.03, 14.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.4(6.9, 30.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eALT[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e21.9(11.45, 41.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.3(17.2, 64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eAST[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e32.65(21.4, 57.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.3(29, 77.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.186\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBUN[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e6.85(4.78, 11.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.86(4.69, 14.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.961\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.336\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCR[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e80.05(58, 127.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.10(62, 123.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCRP[M(P25,P75)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e73.85(22.33, 120.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e89.90(30.3, 130)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e1.110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.267\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eESR [\u0026oline;x\u0026thinsp;\u0026plusmn;\u0026thinsp;S]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e55.43\u0026thinsp;\u0026plusmn;\u0026thinsp;35.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.13\u0026thinsp;\u0026plusmn;\u0026thinsp;33.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.916\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePCT[M(P\u003csub\u003e25\u003c/sub\u003e,P\u003csub\u003e75\u003c/sub\u003e)]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0.27(0.10, 0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e1.30(0.25, 10.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.152\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClassification of colonizing strains\u003c/b\u003e**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella pneumoniae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e149(63.40%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e58(69.88%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.440\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEscherichia coli\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e42(17.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e14(16.87%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnterobacter cloacae\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e16(6.81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e4(4.82%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.383\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.536\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella aerogenes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e6(2.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e2(2.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKlebsiella oxytoca\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e7(2.98%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.309\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.253\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCitrobacter fraudii\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1(0.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e2(2.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCitrobacter cruzi\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1(0.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerratia marcescens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e0(0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e1(1.20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.259\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunclassified CRE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e13(5.53%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003e2(2.41%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.695\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.404\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, indicating a statistically significant difference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDistribution of departments\u003c/h2\u003e \u003cp\u003eThe details of the department distribution of patients in this study are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The samples of inpatients colonized with intestinal CRE came from 26 clinical departments of Xiangya Hospital, Central South University, mainly in the departments of respiratory medicine, hematology, intensive care unit (ICU), and pediatric hematology, with 100 cases (31.55%), 94 cases (29.65%), 42 cases (13.25%) and 21 cases (6.62%), respectively. Among them, the patients with subsequent CRE infection were mainly in the department of respiratory medicine (n\u0026thinsp;=\u0026thinsp;27, 33.3%), the department of hematology (n\u0026thinsp;=\u0026thinsp;17, 20.99%) and the department of critical care medicine (n\u0026thinsp;=\u0026thinsp;21, 13.25%). At the same time, the incidence of subsequent infection of intestinal CRE colonization among patients in different departments was also different. The incidence of subsequent CRE infection in the ICU was 50.00%. It was 26.7% in the department of respiratory medicine, 18.09% in the department of hematology, and 28.57% in the department of ICU.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003ePathogens and infections\u003c/h2\u003e \u003cp\u003eClassification of colonizing strains\u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, a total of 317 strains of patients with positive stool CRE screening were included in this study. There was no statistically significant difference in the classification of colonizing strains between the two groups. Among them, \u003cem\u003eK. pneumoniae\u003c/em\u003e was the main pathogen (n\u0026thinsp;=\u0026thinsp;149, 63.40% vs. n\u0026thinsp;=\u0026thinsp;58, 69.88%), followed by \u003cem\u003eE. coli\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;42, 17.87% vs. n\u0026thinsp;=\u0026thinsp;14, 16.87%) and \u003cem\u003eEnterobacter cloacae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;16, 6.81% vs. n\u0026thinsp;=\u0026thinsp;4, 4.82%). Of note, no specific strain was isolated in 15 patients and both \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eK. pneumoniae\u003c/em\u003e were isolated in one patient (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTypes of CRE strains detected\u003c/p\u003e \u003cp\u003eWe analyzed the types of pathogens responsible for subsequent infections in hospitalized patients with intestinal CRE colonization. A total of 81 strains were detected, among which \u003cem\u003eK. pneumoniae\u003c/em\u003e was the most common, accounting for 69.77%, followed by \u003cem\u003eE. coli\u003c/em\u003e and \u003cem\u003eE. cloacae\u003c/em\u003e, accounting for 16.28% and 5.81%, respectively. At the same time, we found that the infection rates of subsequent infections of different strains were also different. Among them, \u003cem\u003eK. pneumoniae\u003c/em\u003e was 28.99% (60/207), \u003cem\u003eE. coli\u003c/em\u003e was 25.00% (14/56), and \u003cem\u003eE. cloacae\u003c/em\u003e was 25% (5/20) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA).\u003c/p\u003e \u003cp\u003eSources of CRE strain detected\u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB, the analysis of the detected pathogenic bacteria sites after intestinal CRE colonization in hospitalized patients and subsequent infection revealed that the main specimen sources included lungs (n\u0026thinsp;=\u0026thinsp;38), blood flow (n\u0026thinsp;=\u0026thinsp;32), digestive tract (n\u0026thinsp;=\u0026thinsp;17), urinary tract (n\u0026thinsp;=\u0026thinsp;9), pleural ascites and postoperative drainage fluid (n\u0026thinsp;=\u0026thinsp;6), catheter-related infection (n\u0026thinsp;=\u0026thinsp;1), surgical site (n\u0026thinsp;=\u0026thinsp;3), skin and soft tissue (n\u0026thinsp;=\u0026thinsp;2) and cerebrospinal fluid (n\u0026thinsp;=\u0026thinsp;38). Furthermore, the site of CRE infection was consistent with the source of the sample. The most common was pulmonary infection, accounting for 33.04%, followed by bloodstream infection at 27.83%, then followed by digestive tract infection and urinary tract infection which accounted for 14.78% and 7.83%, respectively. However, intracranial infection was rarest, and only one patient was detected to have pathogens from cerebrospinal fluid.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA shows the classification of colonized and infection strains. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB shows the subsequent infections of different CRE colonizing sites. No specific strain was isolated from 13 colonized samples from patients, and one of them was subsequently detected positive for Proteus mirabilis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics of patients\u003c/h2\u003e \u003cp\u003eUnderlying diseases and complications\u003c/p\u003e \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, among the 214 inpatients from January 1, 2013 to September 31, 2021, patients in the two groups had numerous comorbidities and underlying diseases, usually involving multiple organs or systems, and almost all categories of diseases were included. In both the CRE infection group or the non-CRE infection group, the most common underlying clinical disorder was pulmonary lesion, with 115 cases in the non-CRE infection group (72.3%), and 41 cases in the CRE infection group (74.5%). Univariate analysis showed that underlying diseases including liver lesions and digestive tract lesions, combined with other infections, agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days, and hypoalbuminemia, were statistically different between the two groups, while there was no significant difference in other comorbidities. Furthermore, we found that the incidence of subsequent CRE infection varied with different underlying diseases and complications. Among the underlying diseases, liver disease was 43.4%, and digestive tract disease was 36.8%. The incidence of subsequent systemic CRE infection with other infections was 30.6%, agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days was 39.6%, and hypoproteinemia was 61.9%.\u003c/p\u003e \u003cp\u003eClinical invasive operation\u003c/p\u003e \u003cp\u003eAccording to the analysis of the invasive operation of the two groups in hospitalized patients before CRE infection, we found that the most common invasive operation was arteriovenous catheterization (n\u0026thinsp;=\u0026thinsp;157, 98.7% vs. n\u0026thinsp;=\u0026thinsp;55, 100%), followed by indwelling catheter (n\u0026thinsp;=\u0026thinsp;91, 57.2% vs. n\u0026thinsp;=\u0026thinsp;39, 70.9). Among them, when the patients had an indwelling gastrojejunal tube or ostomy tube (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.106, P\u0026thinsp;=\u0026thinsp;0.024), invasive respiratory assisted ventilation (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;6.431, P\u0026thinsp;=\u0026thinsp;0.011), and a history of surgery or traumatism in the past 3 months (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;9.393, P\u0026thinsp;=\u0026thinsp;0.002), the difference between the two groups was statistically significant. For other invasive operations, there was no significant difference between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eUse of drugs and biological agents\u003c/p\u003e \u003cp\u003eBy analyzing the use of special drugs before the occurrence of CRE infection in the two inpatient groups, we found that the most common ones were the use of intestinal probiotics (n\u0026thinsp;=\u0026thinsp;115, 72.3% vs. n\u0026thinsp;=\u0026thinsp;30, 54.5%) and glucocorticoids (n\u0026thinsp;=\u0026thinsp;93, 58.5% vs. n\u0026thinsp;=\u0026thinsp;35, 63.6%). For example, when intestinal probiotics were used (χ2\u0026thinsp;=\u0026thinsp;5.914, P\u0026thinsp;=\u0026thinsp;0.015), the difference between the two groups was statistically significant. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, there was no significant difference between other special drugs and measures used before infection, including immunosuppressants, biological agents, glucocorticoids, chemotherapeutic drugs, and targeted drugs).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAntimicrobial agents and therapeutic effect\u003c/h2\u003e \u003cp\u003eUse of antimicrobial agents before infection\u003c/p\u003e \u003cp\u003eTo analyze the use of antibiotics before the diagnosis of CRE infection, we found that there were statistically significant differences in the use of four types of antibiotics between the two groups, namely tigecycline (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;4.681, P\u0026thinsp;=\u0026thinsp;0.031), polymyx prime (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;11.315, P\u0026thinsp;=\u0026thinsp;0.001), glycopeptides (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;5.701, P\u0026thinsp;=\u0026thinsp;0.017), and antifungal (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;7.425, P\u0026thinsp;=\u0026thinsp;0.007). However, there were no significant differences in the use of cephalosporins, β-lactamase inhibitors and compound preparations, quinolones, carbapenems, ceftazidime avibactam, TMP/SMX, and aminoglycosides before infection between the two groups. Furthermore, when both oral and intravenous antibiotics were administered compared to intravenous antibiotics alone, there was a statistically significant difference between the two groups (χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;9.125, P\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate analysis of risk factors for subsequent infection in CRE intestinal carriers\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo CRE infection group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;159, 74.30%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCRE infection group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;55, 25.70%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eThe underlying diseases\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48(30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.361\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.584\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.635\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.976\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological neoplasms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54(34.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.937\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid tumors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18(11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.780\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49(30.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.554\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115(72.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(74.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.750\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLiver lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30(18.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.552\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrinary system disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(32.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.859\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDigestive tract lesions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.050\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.025*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTuberculosis infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8(5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.448\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConnective tissue disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13(8.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.786\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.181\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecombined with other infections\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102(64.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(81.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.931\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecombined with agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.245\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.012*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecombined with hypoalbuminemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40(72.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65(40.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.584\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical invasive operation\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArteriovenous catheterization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e157(98.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55(100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVarious thoracic and abdominal drainage tube\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44(27.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23(41.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.802\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchoscopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66(41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(49.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.956\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndwelling catheter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91(57.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(70.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndwelling gastrojejunal tube or ostomy tube\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85(53.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(70.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.106\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.024*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood purification therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24(15.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.719\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNoninvasive respiratory assisted ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42(26.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.220\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive respiratory assisted ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64(40.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33(60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.431\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.011*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistory of surgery or traumatism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66(41.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36(65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUse of drugs and biological agents\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62(39.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22(40.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.895\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiological agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4(7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntestinal probiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115(72.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(54.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucocorticoids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(58.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.450\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.502\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapeutic drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48(30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.445\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.505\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTargeted drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11(6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.090\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.764\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntibacterial agents\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCephalosporins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27(17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(16.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.916\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-lactamase inhibitors and compound preparations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e130(81.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47(85.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.390\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.532\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaminoglycosides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(20.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuinolones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(37.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.313\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecarbapenems\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116(73.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46(83.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTigecycline\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32(20.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.681\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.031*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epolymyx prime\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22(13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.315\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eceftazidime avibactam\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(3.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTMP/SMX\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81(50.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25(45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.483\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eglycopeptides\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63(39.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(58.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.702\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.017*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntifungal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e92(57.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(78.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.007*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUse time\u0026thinsp;\u0026ge;\u0026thinsp;15 days\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115(72.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34(61.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral combined with intravenous route\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93(60.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(36.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e* p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, indicating a statistically significant difference.\u003c/p\u003e \u003cp\u003eCurative effect and outcome\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure 4 shows the curative effect and outcome of the two groups. We found that the effective rate in the non-CRE infection group was significantly higher than that of the CRE infection group, which were 85.11% (200/235) and 52.24% (43/82), respectively. The inefficiency rate of the CRE infection group was 47.56%, which was significantly higher than that of the group without subsequent CRE infection. Furthermore, we found that inpatients who developed CRE infection after intestinal CRE colonization had relatively poor prognosis, as the mortality rate was 18.3%. (χ\u003csup\u003e2\u003c/sup\u003e value\u0026thinsp;=\u0026thinsp;11.129, P\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;4 Curative effect and outcome of patients in the two groups after treatment\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eEstablishing a risk prediction model\u003c/h2\u003e \u003cp\u003eMultivariate logistic regression analysis\u003c/p\u003e \u003cp\u003eBased on the previous univariate analysis results of underlying diseases and comorbidities, invasive procedures, special drugs and preparations, and the use of antibiotics, a total of 14 influencing factors with P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were selected and included in the multivariate logistic regression analysis. Then, a total of eight independent influencing factors of subsequent CRE system infection in patients with intestinal CRE colonization were obtained, it was found that taking probiotics, oral administration combined with intravenous use of antibiotics were protective factors of CRE infection after intestinal CRE colonization in hospitalized patient, while complicated with liver disease, combined with agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days, hypoproteinemia, invasive respiratory assisted ventilation, history of surgery/trauma in the past 3 months, and use of antifungal drugs were independent risk factors. This is shown in Table\u0026nbsp;3. Finally, we established a risk prediction model of systemic infection after intestinal CRE colonization in inpatients. The results were displayed using forest plots.\u003c/p\u003e \u003cp\u003e Table 3 Multivariate logistic regression analysis of risk factors for subsequent infection in CRE intestinal carriers\u003c/p\u003e\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1705575216.png\"\u003e\u003cbr\u003e\u003c/p\u003e \u003cp\u003eExternal evaluation and validation of the model\u003c/p\u003e \u003cp\u003eWe also evaluated the performance of the model in terms of discrimination, calibration, and clinical adaptability. The proposed prediction model was externally validated using data of inpatients from Xiangya Hospital Central South University in October 1, 2021 to October 1, 2022. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the ROC curve to evaluate the fitting effect of the model. The area under the curve (AUC) for the model and validation data is 0.883 (95%CI:0.831\u0026ndash;0.934) and 0.844 (95%CI:0.745\u0026ndash;0.943), respectively. Furthermore, Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e6\u003c/span\u003eA and B shows the calibration curves of the prediction model and validation sample respectively, indicating that the model has a good consistency between the predicted probability and the actual occurrence probability, which shows that it has a relatively accurate predictive value. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e7\u003c/span\u003eA and B, the decision curve of the prediction model for both modeling and validation cohorts yielded a higher net clinical benefit than the treat-all and treat-none strategies in the entire range of thresholds. These results demonstrate that the model has excellent prediction performance. Finally, the nomogram of the risk prediction model is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e8\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOf the 317 inpatients with CRE colonization in this study, 25.9% subsequently developed systemic CRE infection, which was relatively higher than previous research[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This is primarily because a large number of the patients were from the ICU, and systemic infection was included in this study. With respect to the types of colonized strains in the two groups, \u003cem\u003eK. pneumoniae\u003c/em\u003e was the first, with 67.9% in the non-CRE infection group and 72.7% in the CRE infection group, which was generally consistent with the results of other studies[\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Departing from previous studies, we focused on systemic infection in this study, and the sites of subsequent CRE infection were consistent with the source of samples. The most common one was respiratory system specimens, accounting for 35%, followed by bloodstream infection, digestive system infection, and urinary system infection, accounting for 21%, 18%, and 10% respectively. In contrast, the distribution of CRE infection specimens in our hospital is generally similar to related studies, while the proportion of the sources of digestive system specimens is significantly different[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], which may be due to the fact that the objects of this study are inpatients with intestinal CRE colonization. Of note, considering that pulmonary infections are the most common, aspiration of gastrointestinal contents may be a potential mechanism that links intestinal colonization with the occurrence of CRE infections in the critically ill cohort[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Therefore, special attention should be paid so as to avoid aspiration when performing related clinical operations such as tracheal intubation, gastric tube insertion, fiberoptic bronchoscopy, and gastroscopy.\u003c/p\u003e \u003cp\u003eThe incidence of CRE colonization and infection in clinical departments also varied. In this study, the colonization or infection of CRE mainly occurred in respiratory medicine, hematology, ICU, and other specialized ICU, which is consistent with relevant studies[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], and the incidence of subsequent CRE infection was 26.7%, 21.8%, and 45.0%, respectively. Often, most patients in these departments have poor immunity, complex conditions, long hospitalization time, and more frequent use of antibiotics, which lead to patients being more susceptible to the surrounding drug-resistant environment and greatly increase the risk of CRE colonization and subsequent CRE infection in hospitalized patients. In fact, most of the patients in the above high-risk departments had a history of invasive operations. We found that the most common was arteriovenous catheterization. Indwelling catheter, especially deep venous catheterization, may greatly increase the opportunistic infection of colonized bacteria into the blood, thus further increasing the risk of CRE bloodstream infection[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Other invasive operations included patients with indwelling gastrojejunal tube or ostomy tube, assisted ventilation with invasive breathing, and a history of surgery or trauma in the past 3 months, which may be the influencing factors of intestinal CRE colonization and subsequent development of CRE infection in hospitalized patients. This is roughly the same as the results of related studies[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Invasive operations can destroy the body\u0026rsquo;s natural barrier, and directly or indirectly place pathogens into the human body. This results in flora translocation, thus increasing the possibility of bacterial colonization or infection. Therefore, for the high-risk departments, unnecessary invasive operations must be minimized, and relevant measures should be taken to monitor, prevent and control CRE infection, so as to put an end to CRE infection from the source[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinically, many patients have comorbidities or multiple underlying diseases. Studies have shown that patients with CRE colonization combined with advanced liver cirrhosis can manifest increased intestinal permeability and impaired reticuloendothelial system function, while patients with organ transplantation and allogeneic hematopoietic cell transplantation often manifest a combination of neutropenia and intestinal rejection[\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Thus, the risk of bacterial translocation and infection after intestinal CRE colonization in such patients is significantly increased. Our research found that, combined with liver disease (mainly including liver insufficiency, liver failure, liver cirrhosis, and liver transplantation), agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days and hypoalbuminemia were independent risk factors for subsequent infection of intestinal CRE colonization in hospitalized patients, which is consistent with the findings of relevant studies[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. At the same time, laboratory examinations revealed that the CRE infection group had significantly lower levels of albumin, which was caused by factors such as albumin redistribution due to increased vascular permeability, reduced albumin synthesis under pathological conditions, and increased consumption in critically ill patients. Moreover, the plasma protein binding rate is significantly reduced in patients with hypoalbuminemia, and this makes some antibacterial drugs less effective, forming a vicious circle, and inducing CRE infection or leading to poor prognosis[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Therefore, to reduce the risk of infection in patients with CRE colonization, it is necessary to promptly correct hypoproteinemia and regularly monitor blood drug concentration. In addition, we found that probiotic administration was a protective factor against subsequent CRE infection (OR\u0026thinsp;=\u0026thinsp;0.338). In the state of CRE colonization, when patients suffer from intestinal flora disorders caused by diet, inflammatory bowel disease, antibiotics, and more, intestinal flora translocation of colonizing bacteria will occur due to intestinal mucosal damage, which leads to further infection[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The use of probiotics may reduce this risk. Relevant studies have shown that probiotics may have anti-inflammatory, immunomodulatory, inhibiting abnormal cell proliferation, and antioxidant activities[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Therefore, for patients with intestinal CRE colonization, especially those with other infections and using antibiotics, we should regularly monitor the stool and timely add probiotics to regulate intestinal flora in order to reduce the occurrence of subsequent CRE infection.\u003c/p\u003e \u003cp\u003eThe use of antibiotics is closely related to infection. Considering colonization and infection, it is particularly important to clarify the use of antibacterial agents before CRE infection. Notably, we found that the use of tigecycline, polymyxin, glycopeptides, and antifungal agents may influence the subsequent development of CRE infection in hospitalized patients with intestinal CRE colonization, of which antifungal agents (OR\u0026thinsp;=\u0026thinsp;7.764) was an independent risk factor. Another study also showed that tigecycline was an independent risk factor for subsequent infection after CRE colonization[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. We considered the following reasons. First, the drugs may have been administered because of coexisting infections that did not respond well to treatment. Second, the clinical effect of monotherapy against CRE infection is not good, and most treatment schemes include a two-drug combination, a three-drug combination, or a carbapenem-containing combination[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Third, the whole CRE was analyzed instead of specific strains in our study, which may affect the results because of the differences in drug sensitivity of specific strains. Furthermore, we found that combined oral and intravenous antibiotics administration is a protective factor against subsequent infections in hospitalized patients with intestinal CRE colonization (OR\u0026thinsp;=\u0026thinsp;0.152). In point of fact, many patients were given oral antibiotics due to severe intestinal microbiota imbalance caused by diarrhea, which would inevitably lead to intestinal mucosal damage if not treated in time. Studies have shown that the realization of intestinal barrier function chiefly includes the adhesion of tight junction proteins to epithelial cells, the secretion of mucus by intestinal immune cells, antibodies, and antibacterial effector molecules[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. If this barrier function is impaired for any reason, the risk of infection by colonizing bacteria in the gut will significantly increase [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found that the subsequent CRE infection in patients with intestinal CRE colonization significantly prolonged the length of hospital stay and the total hospitalization cost, and also greatly increased the cost and curative time of antibiotics. This is consistent with related studies[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. It follows that the subsequent CRE infection in patients with intestinal CRE colonization increases the antibiotic exposure and economic burden of patients, and also increases the medical burden of the country. Moreover, hospitalized patients who subsequently develop CRE infection after intestinal CRE colonization have relatively poor efficacy (85.11% vs. 52.44%) and high mortality (6.0% vs. 18.3%). The relevant literature also reported that approximately 36% of patients who developed infection after CRE colonization died within 90 days[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The mortality rate for fatal CRE infection after colonization in liver transplant patients is 78%[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In patients with hematological malignancies complicated with bloodstream infection, the 30-day-related fatality rate caused by CRE is as high as 51%[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], while in patients receiving hematopoietic stem cell transplantation, the overall 90-day mortality rate of CRE-infected patients is even higher, approximately 58%[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, we comprehensively analyzed the correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients from the aspects of population, clinical characteristics, incidence, risk factors and disease economics, and established a risk prediction model for systemic infection after intestinal CRE colonization in hospitalized patients, which is highly valuable. It is helpful to improve clinicians' understanding of intestinal CRE colonization and subsequent infection, assist them in making risk assessment before empirical treatment of intestinal CRE colonization, and then take corresponding intervention measures to prevent CRE infection. The study also provides a reference for the rational use of antibiotics, which has a good clinical guiding significance. However, the present study also has certain limitations. First, as a single-center retrospective study, there are selection bias and information bias. Second, the statistical significance of some variables in the multivariate analysis may have been obscured due to the uneven distribution of sample sizes between the two groups. Therefore, prospective case\u0026ndash;control studies or cohort studies with a large scale and multiple centers could be conducted in the future. Moreover, whether CRE colonization should be treated and the timing of decolonization still need further exploration. The gut microbiota of CRE colonization and subsequent infection also deserves further study. This study has a prime reference value for early identification of high-risk patients and prediction of the possibility of infection, which is of great significance for the clinical prevention and control of CRE colonization, and the inhibition of subsequent systemic infection.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study explored the correlation between intestinal CRE colonization and subsequent systemic infection in inpatients in a large teaching hospital. In total, 317 cases of intestinal CRE colonization were included, with an incidence of subsequent systemic CRE infection of 25.9%. It was found that CRKP and CREC were the main bacterial strains that followed intestinal CRE colonization in hospitalized patients. The main sites of infection were the lungs and blood stream. High-risk departments mainly included respiratory medicine, hematology, and ICU. CRE infection occurring after intestinal CRE colonization in inpatients can significantly prolong the length of staying at hospital and increased the total cost. Also, the CRE infection group had poor efficacy and high mortality. The established risk prediction model for intestinal infection after CRE colonization in hospitalized patients had a good prediction efficiency for high-risk departments.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Chunhui Li, Anhua Wu, Lina Zhang, Xin Chen, Yajing Xu and Yuanyuan Li. Methodology: Yuanyuan Xiao, Juping Duan, Caixia Tan and Ju Zou. Data collection: Yuanyuan Xiao, Siyao Chen and Ting Liu. Writing original draft: Yuanyuan Xiao. Manuscript revision and and editing: Chunhui Li and Anhua Wu. Funding acquisition: Chunhui Li, Anhua Wu and Juping Duan. All authors contributed to the article and reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the National Key Research and Development Program of China (No. 2022YFC2009801, 2022YFC2009805), the Natural Science Foundation of Hunan Province (No. 2021JJ31071), Health Development Research Center of the National Health Commission, \u0026quot;Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions\u0026quot; (CNHDRC-KJ-L-2020-53-04375), and Changsha science and technology plan project (NO. kq2202059).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll methods were carried out in accordance with relevant guidelines and regulations. All experimental protocols were approved by the Ethics Committee of Xiangya Hospital, Central South University. Informed consent was obtained from all patients and/or their legal guardian.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCenters for Disease Control and Prevention, USA. Antibiotic resistance threats in the United States, 2019; 2019. Available at: https://stacks.cdc.gov/view/cdc/82532. Accessed 5 Jan 2024.\u003c/li\u003e\n\u003cli\u003eLogan LK, Weinstein RA. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J Infect Dis 2017, 215(suppl_1):S28-s36 ; https:// doi: 10.1093/infdis/jiw282.\u003c/li\u003e\n\u003cli\u003eJean SS, Harnod D, Hsueh PR. Global Threat of Carbapenem-Resistant Gram-Negative Bacteria. Front Cell Infect Microbiol. 2022;12:823684; https://doi:10.3389/fcimb.2022.823684.\u003c/li\u003e\n\u003cli\u003eCenters for Disease Control and Prevention (U.S.). 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Science 2018, 359(6382):1376-1383. doi: 10.1126/science.aar3318.\u003c/li\u003e\n\u003cli\u003eVargas-Alzate CA, Higuita-Guti\u0026eacute;rrez LF, L\u0026oacute;pez-L\u0026oacute;pez L, et al. High excess costs of infections caused by carbapenem-resistant Gram-negative bacilli in an endemic region. Int J Antimicrob Agents 2018, 51(4):601-607. doi: 10.1016/j.ijantimicag.2017.12.012.\u003c/li\u003e\n\u003cli\u003eSatlin MJ, Cohen N, Ma KC, et al. Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies. J Infect 2016, 73(4):336-345. doi: 10.1016/j.jinf.2016.07.002.\u003c/li\u003e\n\u003cli\u003eGirmenia C, Rossolini GM, Piciocchi A, et al. Infections by carbapenem-resistant Klebsiella pneumoniae in SCT recipients: a nationwide retrospective survey from Italy. Bone Marrow Transplant 2015, 50(2):282-288. doi: 10.1038/bmt.2014.231.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Carbapenem-resistant Enterobacteriaceae, CRE, colonization, infection, prediction model","lastPublishedDoi":"10.21203/rs.3.rs-3869345/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3869345/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eIt is generally believed that Carbapenem-resistant Enterobacteriaceae (CRE) colonization is primarily responsible for subsequent systemic infection in humans. In China, the specific situation of CRE colonization and subsequent systemic infection in hospitalized patients necessitates further exploration.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed data of intestinal CRE colonization inpatients at Xiangya Hospital, Central South University, regarding demography, clinical and pathogenic characteristics, treatment, and outcome. A risk prediction model for subsequent CRE infection was established and externally validated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eIn total, 839 intestinal CRE colonization samples from inpatients were included. Finally, 317 cases of intestinal CRE colonization were enrolled, 25.9% of whom developed systemic infections. The subsequent CRE infection rates of CRKP and CREC were 27.0% and 32.3%, respectively. The incidence of subsequent CRE infection in the respiratory medicine department, hematology department, and intensive care unit (ICU) was 26.7%, 21.8%, and 45.0%, respectively. Taking probiotics and the combined oral and intravenous administration of antibiotics were the protective factors for the subsequent infection of intestinal CRE colonization, while liver disease, agranulocytosis\u0026thinsp;\u0026ge;\u0026thinsp;7 days, hypoproteinemia, invasive respiratory assisted ventilation, history of surgery/trauma in the past 3 months, and use of antifungal drugs were the independent risk factors.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eCRE infection after intestinal CRE colonization in inpatients can significantly prolong the length of hospital stay and increase total medical costs. The CRE infection group exhibited poor efficacy and high mortality. Thus, the established risk prediction model for intestinal infection after CRE colonization in hospitalized patients has a good prediction efficacy for high-risk departments.\u003c/p\u003e","manuscriptTitle":"Correlation between intestinal CRE colonization and subsequent systemic infection in hospitalized patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-18 15:55:38","doi":"10.21203/rs.3.rs-3869345/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a68eb8de-9396-43d1-bbba-9c822e988852","owner":[],"postedDate":"January 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-30T07:18:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-18 15:55:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3869345","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3869345","identity":"rs-3869345","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}