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Epidemiological Characteristics of Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae Colonization

Open AccessPublished:May 20, 2022DOI:https://doi.org/10.1016/j.anr.2022.05.002

      Summary

      Purpose

      This study identified the epidemiological characteristics, including the size and major strains, of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and CP-CRE-related factors by comparing the characteristics of patients in the CP-CRE and non-CP-CRE groups and the CP-CRE and non-CRE groups.

      Methods

      This secondary data analysis study included 24 patients in the CP-CRE group, 113 patients in the non-CP-CRE group, and 113 in the non-CRE group. The size and type of CP-CRE were analyzed in terms of frequency and percentage, and CP-CRE risk factors were identified using multiple logistic regression analysis.

      Results

      The rate of CP-CRE positivity among patients with CRE was 17.5%, and the most common causative organism in the CP-CRE group was Klebsiella pneumoniae (81.8%). There were no significant differences between patients in the CP-CRE and non-CP-CRE groups. When compared with the non-CRE group, the isolation of multidrug-resistant organisms except for CRE, particularly vancomycin-resistant Enterococcus, was confirmed as a major risk factor.

      Conclusion

      To prevent CP-CRE acquisition, patients with multidrug-resistant organisms require treatment with more thorough adherence to CRE prevention and management guidelines.

      Keywords

      Introduction

      Carbapenem-resistant Enterobacteriaceae (CRE) are antibiotic-resistant strains and refer to Enterobacteriaceae that have acquired resistance to carbapenem antibiotics [
      • Korea Centers for Disease Control and Prevention (KCDC)
      Epidemic investigation report for imported CRE outbreak in Korea.
      ]. CRE emerged after carbapenem antibiotics were used as a treatment for extended-spectrum beta-lactamase-producing gram-negative strains [
      • Peleg A.Y.
      • Hooper D.C.
      Hospital-acquired infections due to gram-negative bacteria.
      ] and have become a global public health threat due to widespread antibiotic resistance and high mortality rates [
      • Falagas M.E.
      • Lourida P.
      • Poulikakos P.
      • Rafailidis P.I.
      • Tansarli G.S.
      Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence.
      ,
      • Tumbarello M.
      • Trecarichi E.M.
      • De Rosa F.G.
      • Giannella M.
      • Giacobbe D.R.
      • Bassetti M.
      • et al.
      Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.
      ,
      • Tängdén T.
      • Giske C.G.
      Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control.
      ,
      • Borer A.
      • Saidel-Odes L.
      • Riesenberg K.
      • Eskira S.
      • Peled N.
      • Nativ R.
      • et al.
      Attributable mortality rate for carbapenem-resistant Klebsiella pneumoniae bacteremia.
      ,
      • Albiger B.
      • Glasner C.
      • Struelens M.J.
      • Grundmann H.
      • Monnet D.L.
      European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working Group
      Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015.
      ]. In the United States, there were 13,100 cases of CRE infection in 2019, with 1100 infections resulting in death [
      U.S. Department of Health and Human Service (DHHS), Centers for Disease Control and Prevention (CDC)
      Antibiotic resistance threats in the United States.
      ]. In Korea, the number of reported CRE infections rose from 5717 in 2017 to 18,113 in 2020, with the number of deaths increasing sharply from 37 to 226 over the same period [
      • Korea Centers for Disease Control and Prevention (KCDC)
      Infectious diseases surveillance yearbook, 2020.
      ]. According to recent studies, including systematic literature review studies, exposure to antibiotics, especially carbapenems, is the most important risk factor for CRE acquisition [
      • Livorsi D.J.
      • Chorazy M.L.
      • Schweizer M.L.
      • Balkenende E.C.
      • Blevins A.E.
      • Nair R.
      • et al.
      A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States.
      ,
      • van Loon K.
      • Voor In 't Holt A.F.
      • Vos M.C.
      A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae.
      ]. In addition, underlying diseases, invasive procedures including mechanical ventilation, use of medical devices such as central venous tubes, admission to intensive care units (ICUs) [
      • van Loon K.
      • Voor In 't Holt A.F.
      • Vos M.C.
      A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae.
      ,
      • Seo S.M.
      • Jeong I.S.
      • Song J.Y.
      • Lee S.
      Development of a nomogram for carbapenem-resistant Enterobacteriaceae acquisition risk prediction among patients in the intensive care unit of a secondary referral hospital.
      ,
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ], multidrug-resistant organism (MDRO) colonization or infection [
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ], Acute Physiology and Chronic Health Evaluation (APACHE) II score [
      • Seo S.M.
      • Jeong I.S.
      • Song J.Y.
      • Lee S.
      Development of a nomogram for carbapenem-resistant Enterobacteriaceae acquisition risk prediction among patients in the intensive care unit of a secondary referral hospital.
      ,
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ], and transfer between hospitals [
      • Seo S.M.
      • Jeong I.S.
      • Song J.Y.
      • Lee S.
      Development of a nomogram for carbapenem-resistant Enterobacteriaceae acquisition risk prediction among patients in the intensive care unit of a secondary referral hospital.
      ] are related to CRE acquisition.
      Carbapenemase-producing CRE (CP-CRE) is a CRE that exhibits resistance to β-lactam antibiotics through the production of carbapenemase-producing enzymes [
      • Livorsi D.J.
      • Chorazy M.L.
      • Schweizer M.L.
      • Balkenende E.C.
      • Blevins A.E.
      • Nair R.
      • et al.
      A systematic review of the epidemiology of carbapenem-resistant Enterobacteriaceae in the United States.
      ,
      • Durante-Mangoni E.
      • Andini R.
      • Zampino R.
      Management of carbapenem-resistant Enterobacteriaceae infections.
      ] and is distinguished from non-CP-CRE, which exhibits antibiotic resistance through mechanisms such as the production of extended-spectrum β-lactamases (ESBL) or AmpC cephalosporinases with decreased outer membrane permeability [
      • Tamma P.D.
      • Huang Y.
      • Opene B.N.
      • Simner P.J.
      Determining the optimal carbapenem MIC that distinguishes carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ,
      • Doi Y.
      • Paterson D.L.
      Carbapenemase-producing Enterobacteriaceae.
      ]. Since the carbapenemase gene of CP-CRE is located in a mobile genetic element, such as a plasmid or transposon, it can demonstrate faster patient-to-patient transmission than non-CP-CRE [
      • Tängdén T.
      • Giske C.G.
      Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control.
      ,
      • Tamma P.D.
      • Huang Y.
      • Opene B.N.
      • Simner P.J.
      Determining the optimal carbapenem MIC that distinguishes carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ]. Therefore, it is necessary to develop an effective CP-CRE management strategy based on an understanding of the characteristics that distinguish CP-CRE from non-CP-CRE or non-CRE.
      According to previous studies, the positivity rate for CP-CRE differs depending on the CRE-infected or colonized patients varies widely from 20% [
      • Goodman K.E.
      • Simner P.J.
      • Klein E.Y.
      • Kazmi A.Q.
      • Gadala A.
      • Toerper M.F.
      • et al.
      Predicting probability of perirectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and other carbapenem-resistant organisms (CROs) at hospital unit admission.
      ] to 67.9% [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ]. CP-CRE-related characteristics also showed different results depending on which of the CRE-infected or colonized patients were targeted. In a case-control study in which patients with CRE bacteremia were classified into CP-CRE and non-CP-CRE groups in China, old age, cancer, and use of carbapenem antibiotics were identified as risk factors for CP-CRE [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ]. In a cohort study of US veterans, heart disease and gastroesophageal reflux disease [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ] were identified as risk factors for CP-CRE. In contrast, in a study that divided patients with CRE into CP-CRE and non-CP-CRE groups at an Israeli tertiary hospital, prehospital antibiotic use, experience in nursing homes, and the presence or absence of pressure sores were identified as risk factors for CP-CRE; age was not a risk factor [
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ]. The use of mechanical ventilation was a protective factor for CP-CRE when the CP-CRE and non-CP-CRE groups were compared, whereas the use of mechanical ventilation appeared as a risk factor when compared with the non-CRE group [
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ]. In another study with CRE colonized group, the mechanical ventilation was identified as a risk factor for CP-CRE because the use of mechanical ventilation [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ] in the CP-CRE group was higher than that of the non-CP-CRE group.
      As a result of the literature review, studies on the CP-CRE positivity rate and related factors have been limited to a few countries, such as the United States, Israel, and China; therefore, information on epidemiologic characteristics is limited, and consistent results are not reported, with varying findings depending on the study population or design. In particular, the Korean government is strengthening efforts to identify the epidemiological characteristics of CP-CRE through the revision of regulations by requiring that CP-CRE clusters are identified, and an epidemiological investigation conducted to identify the source of infection [
      • Korea Centers for Disease Control and Prevention (KCDC)
      Guidelines for healthcare associated infection (VRSA/CRE) prevention and control.
      ]; nevertheless, there is very little research in this regard. Therefore, the purpose of this study was to identify the epidemiological characteristics of CP-CRE colonization in patients admitted to the ICU, a department where patients are at high risk of acquiring CRE. The specific objectives of this study were to investigate the size and major strains of CP-CRE and identify the CP-CRE-related factors by comparing the characteristics of patients in the CP-CRE and non-CP-CRE groups and the CP-CRE and non-CRE groups.

      Methods

      Study design

      This case-control study used secondary data analysis to understand the epidemiological characteristics of CP-CRE in patients in the ICU.

      Study participants

      The primary data for this study came from previous studies that developed a CRE acquisition risk prediction model [
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ] and evaluated the external validity of the developed predictive model [
      • Song J.Y.
      • Jeong I.S.
      Validation of a carbapenem-resistant Enterobacteriaceae colonization risk prediction model: a retrospective cohort study in Korean intensive care units.
      ]. Each study was conducted using data between October 1, 2016 and October 31, 2017 and between November 1, 2017 and May 31, 2018, respectively. Eight hundred fifty-eight patients admitted to the ICU of a tertiary general hospital located in Y-city, and acquired CRE from the CRE active surveillance culture test at least once within 1 week of admission and from 1 week after admission until discharge, were included in the primary data (137 in the CRE acquisition group and 721 in the nonacquired group). In the study hospital, CRE active surveillance culture test was performed for every patient admitted to the ICUs using a perirectal swab within 7 days of hospitalization (baseline screening), and weekly thereafter until 7 days after discharge [
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ,
      • Song J.Y.
      • Jeong I.S.
      Validation of a carbapenem-resistant Enterobacteriaceae colonization risk prediction model: a retrospective cohort study in Korean intensive care units.
      ]. And all patients with CRE isolated from clinical specimens were also subjected to the test. CRE acquisition was confirmed not using clinical specimens but using a rectal swab for the purpose of active surveillance testing for CRE colonization. CRE colonization was confirmed by carbapenem antimicrobial susceptibility testing (imipenem ≤22 mm, ≥2 μg/mL minimum inhibitory concentration (MIC); ertapenem ≤21 mm, ≥1 μg/mL MIC) using the disk diffusion method, which was performed in accordance with the legal communicable disease diagnostic criteria of the Korea Centers for Disease Control and Prevention (KCDC) [
      • Korea Centers for Disease Control and Prevention (KCDC)
      ]. For CRE cases, carbapenemase production was tested using the modified Hodge test (MHT) method based on the Clinical & Laboratory Standards Institute's recommendations. MHT is known to have a high level of sensitivity (>90.0%) and specificity (>90.0%) in detecting Klebsiella pneumoniae carbapenemase-type carbapenemases [
      Clinical and Laboratory Standards Institute (CLSI)
      Performance standards for antimicrobial susceptibility testing.
      ]. As a result of the test, 24 and 113 patients were allocated to the CP-CRE and non-CP-CRE groups, respectively.
      The study participants were classified into three groups: CP-CRE, non-CP-CRE, and non-CRE groups. The non-CRE group was randomly selected to have the same number of participants as the non-CP-CRE group. For achieving this, 721 people in the non-CRE group were assigned a serial number; random numbers were generated using Excel, and 113 subjects with a serial number matching the generated numbers were selected as the non-CRE group. Therefore, the final numbers of the study participants were 24, 113, and 113 in the CP-CRE, non-CP-CRE, and non-CRE groups, respectively. The sample size for the case-control study design was calculated using an online program called the Open Source Epidemiologic Statistics for Public Health [
      • Dean A.G.
      • Sullivan K.M.
      • Soe M.M.
      OpenEpi: Open source epidemiologic statistics for public health, version.
      ] at .05 as the significance level (α), .80 as the power, and 1:5 as the ratio of cases to controls [
      • Groenwold R.H.H.
      • van Smeden M.
      Efficient sampling in unmatched case-control studies when the total number of cases and controls is fixed.
      ]. For an exposure ratio of 20.8% and odds ratio of 4.1 for the control group, assuming that mechanical ventilation was a risk factor for CP-CRE based on a previous study [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ], the minimum sample required was 19–24 in the case group and 94–119 in the control group.

      Study variables

      The variables examined in this study were demographic characteristics, clinical characteristics at the time of admission to the ICU, and clinical characteristics during ICU stay, which were mainly considered for CRE-related factor studies [
      • van Loon K.
      • Voor In 't Holt A.F.
      • Vos M.C.
      A systematic review and meta-analyses of the clinical epidemiology of carbapenem-resistant Enterobacteriaceae.
      ,
      • Seo S.M.
      • Jeong I.S.
      • Song J.Y.
      • Lee S.
      Development of a nomogram for carbapenem-resistant Enterobacteriaceae acquisition risk prediction among patients in the intensive care unit of a secondary referral hospital.
      ,
      • Song J.Y.
      • Jeong I.S.
      Development of a risk prediction model of carbapenem-resistant Enterobacteriaceae colonization among patients in intensive care units.
      ,
      • Goodman K.E.
      • Simner P.J.
      • Klein E.Y.
      • Kazmi A.Q.
      • Gadala A.
      • Toerper M.F.
      • et al.
      Predicting probability of perirectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and other carbapenem-resistant organisms (CROs) at hospital unit admission.
      ] or CP-CRE-related factor studies [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ,
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ,
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ,
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ]. Sex and age variables were included as demographic characteristics, and clinical characteristics at the time of admission to the ICU included APACHE II score, Charlson comorbidity index score (CCIS), and underlying diseases (diabetes, heart disease, respiratory disease, renal disease, liver disease, and solid cancer). APACHE II score was used instead of APACHE III because the study hospital uses a computerized system that automatically calculates the APACHE II score. A recent study showed a very similar diagnostic accuracy of in-hospital mortality between APACHE II and III [
      • Czajka S.
      • Ziębińska K.
      • Marczenko K.
      • Posmyk B.
      • Szczepańska A.J.
      • Krzych Ł.J.
      Validation of APACHE II, APACHE III and SAPS II scores in in-hospital and one year mortality prediction in a mixed intensive care unit in Poland: a cohort study.
      ]. Clinical characteristics during the ICU stay included three items: invasive procedures and instruments, use of antibiotics, and isolation of multidrug-resistant organisms (MDROs). Invasive procedures and instruments included surgery, transplantation, endoscopy, bronchoscopy, continuous renal replacement therapy, indwelling catheters, central venous catheters, ventilators, and drainage tubes. Antibiotics comprised penicillin, carbapenem, cephalosporin, fluoroquinolone, and vancomycin. The isolation of multidrug-resistant bacteria included vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL), and MDR Acinetobacter baumannii. Data were collected from the date of hospitalization until the date of CRE colonization for the CRE-colonized group (CP-CRE group and non-CP-CRE group) and until the date of discharge from ICUs for the non-CRE group.

      Data analysis

      The collected data were analyzed using the SPSS/WIN software (version 25.0; IBM Corp., Armonk, NY, USA). A two-tailed test was performed with a significance level (α) of .05. The size and type of CP-CRE and participants' baseline characteristics were analyzed as frequency and percentage for categorical data and median and interquartile range for continuous data because they were not normally distributed.
      Bivariate analysis was conducted using simple logistic analysis to compare the baseline characteristics between the two groups (CP-CRE group vs. non-CP-CRE or non-CRE group), and the unadjusted odds ratios (ORs) and associated 95.0% confidence intervals (CIs) were calculated. With all variables as significant factors at a significance level (α) of .05, the adjusted ORs and the associated 95.0% CIs were calculated through forward stepwise multiple logistic regression analysis after confirming no deviation from the assumption of multicollinearity with a coefficient of determination of less than .80 [
      • Kim J.H.
      Multicollinearity and misleading statistical results.
      ], and variance inflation factor of ranging from 1.03 to 1.19.

      Ethical considerations

      This study was conducted after receiving approval of exemption from review (No. 05-2021-127) from the Institutional Review Board (IRB) of Pusan National University Yangsan Hospital. All data were anonymized.

      Results

      Among the 137 patients in the CRE group in this study, 24 patients were included in the CP-CRE group, giving a CP-CRE positivity rate of 17.5%. The most common infectious agent in the CP-CRE group was K. pneumoniae (79.1%), followed by Escherichia coli (12.5%); in the non-CP-CRE group, K. pneumoniae (82.3%) was the most common, followed by Enterobacter spp. (8.8%) and E. coli (7.1%) (Table 1).
      Table 1Microbiological Characteristics of CP-CRE and Non-CP-CRE.
      MicroorganismsCP-CRE (n = 24)

      n (%)
      Non-CP-CRE (n = 113)

      n (%)
      Total (137)

      n (%)
      Klebsiella pneumoniae19 (79.1)93 (82.3)112 (81.8)
      Escherichia coli3 (12.5)8 (7.1)11 (8.0)
      Enterobacter aerogens0 (0.0)6 (5.3)6 (4.4)
      Enterobacter cloacae0 (0.0)4 (3.5)4 (2.9)
      Citrobacter freundii1 (4.2)1 (0.9)2 (1.5)
      Serratia marcescens1 (4.2)0 (0.0)1 (0.7)
      Providencia rettgeri0 (0.0)1 (0.9)1 (0.7)
      CP-CRE = Carbapenemase producing carbapenem-resistant Enterobacteriaceae.
      Table 2 presents the baseline characteristics of the participants. For the CP-CRE group, 62.5% were male, 20.8% were transferred from another medical institution, the median CCIS score was 1.5, 79.2% had an underlying disease, 50.0% underwent bronchoscopy, 41.7% received carbapenem antibiotics, and 79.2% had MDROs other than CRE. There was no significant difference in variables between the CP-CRE and non-CP-CRE groups; however, the CP-CRE group had a higher median CCIS score (1.50 vs. 1.00, p = .044), bronchoscopy rate (50.0% vs. 26.5%, p = .027), and overall MDROs (except MRSA) isolation rate (79.2% vs. 34.5%, p < .001) than those in the non-CRE group (Table 2).
      Table 2Comparison of Characteristics of Study Participants Among Three Groups.
      VariablesCP-CRE (n = 24)Non-CP-CRE (n = 113)Non-CRE (n = 113)CP-CRE vs. Non-CP-CRECP-CRE vs. non-CRE
      n (%) or median (IQR)n (%) or median (IQR)n (%) or median (IQR)OR (95% CI)pOR (95% CI)p
      Demographic characteristics
      Men15 (62.5)76 (67.3)67 (59.3).81 (.33–2.03).6541.14 (.46–2.84).771
      Age (years)56.5 (24–69)59.0 (26–67)60.0 (28–74)1.00 (.98–1.02).9511.00 (.98–1.01).646
      Clinical characteristics at ICU admission
      Transfer from LTCF4 (16.7)7 (6.2)7 (6.2).73 (.25–2.12).561.88 (.30–2.59).817
      APACHE Ⅱ19 (12–27)21 (16–25)16 (12–22).97 (.91–1.03).2891.06 (1.00–1.14).069
      CCIS1.50 (0–3)2.00 (0–3)1.00 (0–2)1.03 (.79–1.33).8461.35 (1.01–1.82).044
      Underlying disease
       DM4 (16.7)26 (23.0)23 (20.4)0.67 (.21–2.13).497.78 (.24–2.51).681
       CHD11 (45.8)44 (38.9)56 (49.6)1.33 (.55–3.22).532.86 (.36–2.08).740
       CRD4 (16.7)13 (11.5)7 (6.2)1.54 (.46–5.21).4893.03 (.81–11.31).099
       CLD5 (20.8)22 (19.5)18 (15.9)1.09 (.37–3.24).8791.39 (.46–4.20).561
       CKD1 (4.2)11 (9.7)7 (6.2).40 (.05–3.28).396.66 (.08–5.61).702
       Cancer4 (16.7)19 (16.8)9 (8.0).99 (.30–3.22).9862.31 (.65–8.24).197
       Any disease19 (79.2)82 (72.6)80 (70.8)1.44 (.49–4.18).5061.57 (.54–4.55).408
      Clinical characteristics during ICU stay
      Invasive procedures/device
       Surgery11 (45.8)52 (46.0)36 (31.9).99 (.41–2.40).9871.81 (.74–4.43).194
       Transplantation4 (16.7)18 (15.9)13 (11.5)1.06 (.32–3.46).9291.54 (.46–5.21).489
       Bronchoscopy12 (50.0)51 (45.1)30 (26.5)1.22 (.50–2.94).6642.77 (1.12–6.82).027
       Endoscopy7 (29.2)28 (24.8)15 (13.3)1.25 (.47–3.33).6552.69 (.96–7.57).061
       CRRT6 (25.0)41 (36.3)25 (22.1).59 (.22–1.59).2941.17 (.42–3.27).760
       Urinary catheter23 (95.8)108 (95.6)105 (92.9)1.07 (.12–9.55).9551.75 (.21–14.71).605
       CVC21 (87.5)106 (93.8)93 (82.3).46 (.11–1.93).2911.51 (.41–5.54).538
       MV19 (79.2)98 (86.7)71 (62.8).58 (.19–1.79).3452.25 (.78–6.47).133
       Drainage tube14 (58.3)71 (62.8)48 (42.5).83 (.34–2.03).6801.90 (.78–4.63).160
      Antibiotic treatment
       Penicillin18 (75.0)91 (80.5)67 (59.3).73 (.26–2.04).5432.06 (.76–5.58).156
       Carbapenem10 (41.7)61 (54.0)28 (24.8).61 (.25–1.49).2762.17 (.87–5.43).098
       Cephalosporin20 (83.3)84 (74.3)80 (70.8)1.73 (.55–5.47).3542.06 (.66–6.50).216
       Fluoroquinolone17 (70.8)78 (69.0)62 (54.9)1.09 (.42–2.86).8622.00 (.77–5.19).156
       Vancomycin9 (37.5)52 (46.0)37 (32.7).70 (.29–1.74).4471.23 (.49–3.08).654
      MDROs carrier
       VRE14 (58.3)46 (40.7)23 (20.4)2.04 (.83–4.99).1185.48 (2.16–13.91)<.001
       MRSA2 (8.3)20 (17.7)6 (5.3).42 (.09–1.94).2691.62 (.31–8.57).569
       ESBL7 (29.2)46 (40.7)13 (11.5).60 (.23–1.56).2953.17 (1.11–9.08).032
       MDR A. baumannii6 (25.0)31 (27.4)10 (8.8).88 (.32–2.43).8073.43 (1.11–10.62).032
       Any MDROs19 (79.2)93 (82.3)39 (34.5).82 (.27–2.45).7187.21 (2.50–20.79)<.001
      APACHE = Acute physiology and chronic health evaluation; CCIS = Charlson comorbidity index score; CHD = Chronic heart disease; CI = Confidence interval; CKD = Chronic kidney disease; CLD = Chronic liver disease; CP-CRE = Carbapenemase producing carbapenem-resistant Enterobacteriaceae; CRD = Chronic respiratory disease; CRE = Carbapenem-resistant Enterobacteriaceae; CRRT = Continuous renal replacement therapy; CVC = Central venous catheter; d = days; DM = Diabetes mellitus; Dx = Disease; ESBL = Extended spectrum beta-lactamase; IQR = Interquartile range; MDROs = Multidrug resistant organisms; MRSA = Methicillin resistant Staphylococcus aureus; OR = Odds ratio; VRE = Vancomycin resistant Enterococci.
      Table 3 shows the results of multiple logistic regression analyses to identify the CRE risk factors using variables that were significant in the simple logistic regression analysis for the CP-CRE and non-CRE groups as explanatory variables. In Model 1, regardless of the type of multidrug-resistant bacteria, isolation was used as an explanatory variable, and as a result, the risk factor for acquiring CP-CRE was confirmed as an isolate of multidrug-resistant bacteria, which was related to a 5.88 times increase the risk of acquiring CP-CRE (p = .001) relative to when multidrug-resistant bacteria were not isolated. In Model 2, when individual multidrug-resistant bacteria were included in the model, only VRE was identified as a risk factor for acquiring CP-CRE.
      Table 3Multivariate Analysis of Risk Factors of CP-CRE: CP-CRE versus non-CRE.
      VariablesBSEOR (95% CI)pVIF
      Model 1
       Charlson comorbidity index score.27.171.32 (.95–1.82).0971.03
       Any MDROs isolated1.77.555.88 (1.99–17.43).0011.12
       Bronchoscopy.66.501.93 (.73–5.13).1871.10
      Model 2
       Charlson comorbidity index score.19.171.21 (.86–1.70).2801.11
       Vancomycin resistant enterococci1.37.513.92 (1.44–10.70).0081.15
       Extended spectrum beta-lactamase.76.612.14 (.65–6.99).2101.05
       MDR A. baumannii.98.682.67 (.70–10.13).1501.14
       Bronchoscopy.51.531.67 (.59–4.75).3391.19
      APACHE = Acute physiology and chronic health evaluation; CI = Confidence interval; HR = Hazard ratio; CP-CRE = Carbapenemase producing carbapenem-resistant Enterobacteriaceae; CRE = Carbapenem-resistant Enterobacteriaceae; SE = Standard error; VIF = Variance inflation factor.

      Discussion

      In this study, CP-CRE was confirmed in 17.5% of patients in the CRE group. This result is similar to the 20.0% CP-CRE-positive rate [
      • Goodman K.E.
      • Simner P.J.
      • Klein E.Y.
      • Kazmi A.Q.
      • Gadala A.
      • Toerper M.F.
      • et al.
      Predicting probability of perirectal colonization with carbapenem-resistant Enterobacteriaceae (CRE) and other carbapenem-resistant organisms (CROs) at hospital unit admission.
      ] obtained in a study in patients with CRE admitted to ICUs and transplant wards of a single hospital in the United States. However, it is much lower than the 27.7% [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ] reported in a study using a cohort of patients admitted to 127 veterans hospitals in the United States and the 31.5% reported by the US Centers for Disease Control and Prevention' Antibiotic Resistance Laboratory Network [
      • Woodworth K.R.
      • Walters M.S.
      • Weiner L.M.
      • Edwards J.
      • Brown A.C.
      • Huang J.Y.
      • et al.
      Vital signs: containment of novel multidrug-resistant organisms and resistance mechanisms – United States, 2006-2017.
      ], and 44.7% of national surveillance report using both active surveillance cultures and clinical samples from 189 institutions in Korea [
      • Lee E.
      • Lee S.
      • Bahk H.
      • Kim S.
      • Lee H.
      Analysis of carbapenemase-producing Enterobacteriaceae (CPE) surveillance results for 2017 in Korea: comparison with the surveillance results of the previous 5 years (2012-2016).
      ]. This result may be related to the difference in the sample mix; colonized by or infected with CRE. The former two studies, including this study, targeted those colonized by CRE, while the latter three studies with higher positivity rates for CP-CRE examined the CRE-infected group or both. In particular, it showed a higher CP-CRE positivity rate in patients with bloodstream infections. Zou et al [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ] study of patients with CRE bacteremia showed a CP-CRE-positive rate of 67.9%. In a cohort study of patients with CRE bacteremia at a tertiary hospital in Korea, the CP-CRE positivity rate was as high as 47.4% [
      • Seo H.
      • Lee S.C.
      • Chung H.
      • Ra S.H.
      • Sung H.
      • Kim M.N.
      • et al.
      Clinical and microbiological analysis of risk factors for mortality in patients with carbapenem-resistant Enterobacteriaceae bacteremia.
      ]. Therefore, even in the same CRE group, it seems that the CP-CRE positivity rate is higher in patients who are infected, especially in the bloodstream infection stage, compared with those at the colonized stage. Nevertheless, it is necessary to confirm this through repeated studies in various settings.
      The major strain in the CP-CRE group in this study was K. pneumoniae, which supports the results of previous studies which reported that K. pneumoniae was the most common CP-CRE strain, regardless of whether it was a CP-CRE-colonized [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ] or CP-CRE-infected group [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ,
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ]. In addition, K. pneumoniae is the most common CP-CRE strain over the past 10 years from the analysis of national surveillance data in the Korea [
      • Lee E.
      • Lee S.
      • Bahk H.
      • Kim S.
      • Lee H.
      Analysis of carbapenemase-producing Enterobacteriaceae (CPE) surveillance results for 2017 in Korea: comparison with the surveillance results of the previous 5 years (2012-2016).
      ,
      • Joo S.
      • Kim M.
      • Shin E.
      • Kim J.
      • Yoo J.
      Molecular characteristic analysis and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Republic of Korea, 2017-2020.
      ]. K. pneumoniae accounted for 62.8% [
      • Lee E.
      • Lee S.
      • Bahk H.
      • Kim S.
      • Lee H.
      Analysis of carbapenemase-producing Enterobacteriaceae (CPE) surveillance results for 2017 in Korea: comparison with the surveillance results of the previous 5 years (2012-2016).
      ] to 88.7% [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ] of CP-CRE strains, and the result in this study was within this range. The next most frequently isolated strains were E. coli and Enterobacter spp., which is consistent with the previous reports using national surveillance data [
      • Lee E.
      • Lee S.
      • Bahk H.
      • Kim S.
      • Lee H.
      Analysis of carbapenemase-producing Enterobacteriaceae (CPE) surveillance results for 2017 in Korea: comparison with the surveillance results of the previous 5 years (2012-2016).
      ,
      • Joo S.
      • Kim M.
      • Shin E.
      • Kim J.
      • Yoo J.
      Molecular characteristic analysis and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae (CRE) isolates in the Republic of Korea, 2017-2020.
      ]. However, the rankings differed depending on the study. E. coli was found in 4.4% [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ] to 20.0% [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ,
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ] of the CP-CRE group, and Enterobacter spp. in 9.1% [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ] to 13.1% [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ]. In this study, only E. coli was detected in the CP-CRE group, whereas both strains were detected in the non-CP-CRE group.
      For CP-CRE-related factors, some variables, such as invasive procedures and instruments, and antibiotics, were analyzed for correlations with CP-CRE depending on whether they were used [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ,
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ,
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ] or their period of use [
      • Wilson G.M.
      • Suda K.J.
      • Fitzpatrick M.A.
      • Bartle B.
      • Pfeiffer C.D.
      • Jones M.
      • et al.
      Risk factors associated with carbapenemase producing carbapenem-resistant Enterobacteriaceae (CP-CRE) positive cultures in a cohort of U.S. veterans.
      ]. In this study, only the model including this category was used because there was a difference in the data collection period between the CRE group and non-CRE group, which may distort the results. After confirming the factors related to CP-CRE, there were no distinct characteristics between the CP-CRE and non-CP-CRE groups. However, when compared with the non-CRE group, the isolation of MDROs except for CRE, particularly VRE, was confirmed as a major risk factor. A previous study showed that the presence of MDRO colonization within one year in patients admitted to acute-care hospitals from long-term care facilities is a risk factor for new MDRO colonization [
      • Jeong H.
      • Kang S.
      • Cho H.J.
      Prevalence of multidrug-resistant organisms and risk factors for carriage among patients transferred from long-term care facilities.
      ]. However, it is difficult to find results suggesting that other types of MDRO are risk factors for CP-CRE. In a study conducted in Israel, other types of multidrug-resistant bacteria were associated with CP-CRE, but these were not identified as significant variables in the multiple logistic regression analysis [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ]. Unlike other MDROs, VRE was derived as a risk factor for acquiring CRE. The reason may relate to the fact that the major reservoir of VRE and CRE is common in the lower gastrointestinal tract [
      • Park S.H.
      Management of multi-drug resistant organisms in healthcare settings.
      ]. A healthy gastrointestinal microbiota can provide resistance to multi-drug resistant organisms such as VRE and CRE. However, antibiotic-mediated destruction of the intestinal microbiota and consequent loss of colonization resistance leads to antibiotic-resistant organisms' colonization and infection [
      • Caballero S.
      • Carter R.
      • Ke X.
      • Sušac B.
      • Leiner I.M.
      • Kim G.J.
      • et al.
      Distinct but spatially overlapping intestinal niches for vancomycin-resistant Enterococcus faecium and carbapenem-resistant Klebsiella pneumoniae.
      ,
      • Keith J.W.
      • Pamer E.G.
      Enlisting commensal microbes to resist antibiotic-resistant pathogens.
      ,
      • Miller W.R.
      • Murray B.E.
      • Rice L.B.
      • Arias C.A.
      Resistance in vancomycin-resistant Enterococci.
      ].
      CCIS and bronchoscopy use were associated with CP-CRE in the univariate analysis but not with CP-CRE in multivariate analyses. The CCIS score of the CP-CRE group was higher than that of the non-CRE group in this study. In a study by Kassem et al [
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ] conducted in Israel, the CCIS score was significantly higher in the non-CP-CRE group than in the CP-CRE group, but multiple logistic regression analysis showed that CCIS was not related, which was consistent with the finding that it was not a risk factor for CP-CRE. CCIS is an index developed to predict the risk of death within one year of hospitalization based on the number of comorbidities and is often used to evaluate the prognosis or survival of patients [
      • Charlson M.E.
      • Pompei P.
      • Ales K.L.
      • MacKenzie C.R.
      A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.
      ]. Kassem et al [
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ] reported that as the CCIS score increased by 1 point, the in-hospital mortality rate increased by 1.09 times, indicating that CCIS reflects in-hospital mortality. The CCIS score has been reported to be related to increased mortality rates for the coronavirus disease in 2019 [
      • Tuty Kuswardhani R.A.
      • Henrina J.
      • Pranata R.
      • Anthonius Lim M.
      • Lawrensia S.
      • Suastika K.
      Charlson comorbidity index and a composite of poor outcomes in COVID-19 patients: a systematic review and meta-analysis.
      ]. Regarding the relationship between bronchoscopy and CRE infection, Mehta and Muscarella [
      • Mehta A.C.
      • Muscarella L.F.
      Bronchoscope-related “superbug” infections.
      ] reported suspected cases of CRE infection due to inappropriate reprocessing of bronchoscopy following literature review and Internet searches. In these cases, the risk of CRE transmission due to bronchoscopy is underestimated, emphasizing the interest of healthcare workers and the importance of appropriate reprocessing of bronchoscopies [
      • Mehta A.C.
      • Muscarella L.F.
      Bronchoscope-related “superbug” infections.
      ]. In this study, the statistical power of the use of bronchoscopy was only 42.0%; therefore, it was not confirmed as a factor related to CP-CRE. Repeated studies using a larger sample are required in the future.

      Clinical implications

      As a result of this study, CP-CRE acquisition was found to occur frequently in patients admitted to the ICU. Factors that increase the risk of CP-CRE in patients with CRE were not identified, but the risk of CP-CRE increases when MDROs are isolated from patients without CRE. When a specific MDRO is identified in a patient, even though precautions such as contact isolation are applied, inappropriate or incomplete application of precaution or the patient's vulnerability to any kind of MDRO should be considered [
      • Schwartz-Neiderman A.
      • Braun T.
      • Fallach N.
      • Schwartz D.
      • Carmeli Y.
      • Schechner V.
      Risk factors for carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) acquisition among contacts of newly diagnosed CP-CRE patients.
      ]. If MDROs are isolated from a patient for any reason, such patients require treatment with more thorough adherence to CRE prevention and management guidelines. Our findings added the importance of prevention and control of CRE acquisition and spread in the ICUs, as CP-CRE is more easily transmitted between patients by using a mobile genetic element than non-CP-CRE [
      • Tängdén T.
      • Giske C.G.
      Global dissemination of extensively drug-resistant carbapenemase-producing Enterobacteriaceae: clinical perspectives on detection, treatment and infection control.
      ,
      • Tamma P.D.
      • Huang Y.
      • Opene B.N.
      • Simner P.J.
      Determining the optimal carbapenem MIC that distinguishes carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ]. In addition, with the advancement of personalized care, CP-CRE/non-CP-CRE/non-CRE stratification can better guide the prevention and control of CP-CRE acquisition.

      Strengths and limitations

      Management of CP-CRE through an understanding of the epidemiologic characteristics of CP-CRE is important to prevent the rapid transmission of CRE. In particular, when the CP-CRE test is difficult to perform or the patient refuses the test, the population at high risk of CP-CRE can be managed more effectively by identifying the characteristics that distinguish CP-CRE from non-CP-CRE or non-CRE. Given that studies on the epidemiologic characteristics of CP-CRE at home and abroad are very limited, the results of this study can improve understanding of the progression of CP-CRE among CRE-colonized patients or non-CRE patients admitted to ICUs.
      However, careful interpretation of the results is required because of the following limitations. First, since this study is a secondary data analysis study using existing data, variables identified as CP-CRE-related factors in previous studies [
      • Kassem A.
      • Raed A.
      • Michael T.
      • Sagi O.
      • Shimoni O.
      • Borer A.
      • et al.
      Risk factors and outcomes of patients colonized with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae.
      ] but were not included in the primary data sources (for example, pressure ulcers and use of antibiotics prior to admission) were excluded from the explanatory variables. Second, data were collected from the date of hospitalization until the date of CRE colonization for the CRE colonized group (CP-CRE group, non-CP-CRE group) and until the date of discharge from the ICU for the non-CRE group, where differences in data collection time can influence the length of stay in the ICU. Therefore, the duration of ICU stay was not considered in this study. Consequently, while the length of stay in the ICU has been identified as a factor related to CP-CRE in previous studies [
      • Zou H.
      • Xiong S.J.
      • Lin Q.X.
      • Wu M.L.
      • Niu S.Q.
      • Huang S.F.
      CP-CRE/non-CP-CRE stratification and CRE resistance mechanism determination help in better managing CRE bacteremia using ceftazidime-avibactam and aztreonam-avibactam.
      ], it was excluded as an explanatory variable in this study. Third, this study could not identify the factors related to the acquisition of CP-CRE among those with CRE colonization. This is thought to be because poor statistical power was expected when the sample size was calculated, and repeated studies using a larger sample are suggested in the future. Last, the primary data included ICU patients hospitalized in a single hospital, and the generalizability of the findings to other hospitals or settings may be limited.

      Conclusion

      As a result of this study, approximately 2 out of 10 patients who were colonized by CRE after admission to the ICU had CP-CRE, and the most common causative strain was K. pneumoniae. The CP-CRE group did not have any characteristics distinguishing it from the non-CP-CRE group; however, the isolation rate of multidrug-resistant bacteria, especially VRE, was higher than that in the non-CRE group. When multidrug-resistant bacteria are primarily isolated from hospitalized patients, strict adherence to CRE prevention and management guidelines is required to prevent the rapid spread of CRE between patients. In the case of patients with isolated VRE, it is recommended to conduct a screening test to confirm the presence of CP-CRE colonization and isolate carriers promptly, according to the results.

      Conflicts of interest

      The authors declared no conflict of interest.

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