Carbapenem-resistant Enterobacteriaceae Colonization Research Articles

High rates of intestinal colonization with carbapenemase producing Enterobacteriaceae inhematopoietic stem cell transplant recipients.

Carbapenem resistant Enterobacteriaceae (CRE) are major human pathogens because, these cause high number of difficult-to-treat infections. Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are highly exposed to these type of bacteria. The aim of our study was to investigate prevalence of CRE colonization in AHSCT patients and to determine genes encoding carbapenem resistance. Aretrospective study conducted between January 2015 and December 2019, involved 55 patients colonized with CRE strains. We determined the rate of antibiotic resistance according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the carbapenem resistance genes by PCR assays for genes encoding most frequent β-lactamases namely, blaGES, blaKPC, blaIMI, blaNDM, blaVIM, blaIMP and blaOXA-48. Eighty-one episodes of CRE colonization were recorded in 55 patients, mainly suffering from acute leukaemia (30%) and aplastic anemia (26%). History of hospitalization was noted in 80 episodes. Prior antibiotic treatment, severe neutropenia and corticosteroid therapy were respectively found in 94%, 76% and 58% of cases. Among the 55 patients, six patients (11%) developed a CRE infection. The CRE responsible for colonization were carbapenemase producers in 90% of cases. They belonged mostly to Klebsiella pneumoniae (61/81) and Escherichia coli species (10/81). Antibiotic resistance rates were 100% for ertapenem, 53% for imipenem, 42% for amikacin, 88% for ciprofloxacin and 27% for fosfomycin. Molecular study showed that blaOXA-48 gene was the most frequent (60.5%), followed by blaNDM (58%). Thirty-five (43%) strains were co-producers of carbapenemases. In our study, we report a high rate of CRE intestinal colonization in AHSCT recipients of our center.

Role of Probiotics in Preventing Carbapenem-Resistant Enterobacteriaceae Colonization in the Intensive Care Unit: Risk Factors and Microbiome Analysis Study.

Older patients with multiple comorbidities often necessitate prolonged hospital stays and antibiotic treatment in the intensive care unit (ICU), leading to a rise in multidrug-resistant organisms like carbapenem-resistant Enterobacteriaceae (CRE). This study examined risk factors for carbapenem-resistant Enterobacteriaceae colonization in the ICU and assessed probiotics' preventive role. In this single-center, retrospective study, 9099 ICU patients were tested for stool CRE culture from March 2017 to April 2022. We excluded 136 patients with CRE colonization within one week post-admission and 26 who received probiotics before CRE colonization. Ultimately, 8937 CRE-negative patients were selected. Logistic analysis identified CRE colonization risk factors and evaluated probiotics' influence, including Saccharomyces boulardii or Lactobacillus rhamnosus, used by 474 patients (5.3%) in the ICU. Compared with data on initial admission, 157 patients (1.7%) had newly discovered CRE colonization before discharge. In a multivariate analysis, coronavirus disease 2019, the ICU, tube feeding, antibiotics such as aminoglycoside, extended-spectrum penicillin, stool vancomycin-resistance enterococci colonization, and chronic kidney disease were significantly associated with de novo CRE infection. However, probiotic use was negatively correlated with CRE infection. Managing risk factors and administering probiotics in the ICU may help prevent CRE colonization; large randomized prospective studies are needed.

Risk factors for the colonization of carbapenem-resistant Enterobacteriaceae in patients transferred to a small/medium-size hospital in Korea: a retrospective study

Purpose: This study aimed to identify the colonization rate of carbapenem-resistant Enterobacteriaceae (CRE), the characteristics of CRE isolates, and risk factors for CRE colonization in patients transferred to the general wards of a small/medium-sized hospital.Methods: This retrospective study was conducted on patients who underwent CRE culture tests within 24 hours of admission among patients transferred to a small/medium-sized hospital. Forty-seven patients confirmed as positive for CRE were classified as belonging to the patient group. For the control group, 235 patients (five times the number of the patient group) were matched by sex, age, and diagnosis, and then selected at random. Data were analyzed using descriptive analysis and multiple logistic regression analysis.Results: The CRE colonization rate was 5% (47 out of 933 patients), and Klebsiella pneumoniae (68.0%) was the most common isolate of CRE. The positivity rate of carbapenemase-producing Enterobacteriaceae was 61.7%. The risk factors for CRE colonization included renal disease (odds ratio [OR]=4.93; 95% confidence interval [CI], 1.49-16.31), heart disease (OR=3.86; 95% CI, 1.35-11.01), indwelling urinary catheters (OR=4.43; 95% CI, 1.59-12.36), and cephalosporin antibiotic use (OR=8.57; 95% CI, 1.23-59.60). Conclusion: Having a comorbid renal or cardiac disease, an indwelling urinary catheter, or a history of exposure to cephalosporin antibiotics could be classified as risk factors for CRE colonization in patients transferred to small and medium-size hospitals. It is necessary to perform active infection control through proactive CRE culture testing of patients with risk factors.

2076. Intestinal colonization with multidrug-resistant organisms, horizontal transmission and risk for bloodstream infection

Abstract Background The association between rectal colonization and subsequent bloodstream infections (BSI) by multidrug-resistant organisms (MDROs) remains to be clarified. We aimed to investigate the relative risk of BSI in rectal carriers of MDROs and in the case of carbapenem-resistant Enterobacteriaceae (CRE), whether BSI was due to the patient’s own colonizing strain. Methods We retrospectively included all adult inpatients hospitalized from Jan 2019 to Dec 2022, in ICUs or medical wards of 3 Greek hospitals (Athens: “Attikon” Hospital, Piraeus: Tzaneio Hospital, Thessaloniki: AHEPA Hospital), who were screened for intestinal MDRO carriage at admission and weekly. Screening was performed by selective media and immunochromatography for the carbapenemase in CRE. Patients were followed up for BSI by the same colonizing organism; relative risk (95% CI) was estimated after adjustment for ICU hospitalization and age. MDROs included CRE, carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Pseudomonas aeruginosa (CRPA) and vancomycin-resistant enterococci (VRE). The CRE-colonizers and BSI-pathogens were analyzed for carbapenemase type to identify potential similarities. Results Of 4,427 patients screened, 1,321 (29.8%) were colonized by CRE, 1,255 (28.3%) with CRAB, 252 (5.7%) with CRPA and 859 (27.9% of 3,082 patients tested) with VRE. Of those, 207 (15.7%), 247 (19.7%), 23 (9.1%) and 30 (3.5%) subsequently developed CRE-BSI, CRAB-BSI, CRPA-BSI and VRE-BSI, respectively. Intestinal CRE colonization was associated with 4-fold higher risk of subsequent CRE-BSI, after adjusted for ICU stay and age [RR (95%CI): 4.1 (3.2, 5.2)]. The respective relative risk (95%CI) for BSI in patients with colonization by CRAB, CRPA and VRE were 2.3 (1.9, 2.8), 8.2 (5.1, 13.4) and 2.1 (1.3, 3.4). To evaluate possible horizontal transmission, 286 paired CRE strains from 143 patients were analyzed; in 111 (77.6%), both colonizers and BSI pathogens belonged to the same bacterial species and carried the same carbapenemase type.Table 1:Rectal colonization with MDROs and the risk for BSI from the same pathogenTable 2:Carbapenemase types in rectal carriers of CRE who developed subsequent BSI with the same pathogen Conclusion Intestinal colonization by MDROs was associated with increased risk of BSI by the colonizing bacteria. Clinicians should evaluate this information for empiric treatment, while genome-wide data are needed to substantiate horizontal transmission. Disclosures All Authors: No reported disclosures

Clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae in pediatric inpatients in South China.

Carbapenem-resistant Enterobacteriaceae (CRE) are a substantial health burden. Existing management guidelines are primarily based on clonal evidence. Therefore, epidemiological data are required. We evaluated the risk factors for CRE colonization and described the molecular and clinical characteristics of CRE colonization in pediatric inpatients in Guangzhou, China. Pediatric inpatients from three hospitals in Guangzhou, China, between July 2019 and January 2021 were included. Fecal samples were collected and screened for CRE. Microbiological cultures were grown on MacConkey agar plates, and bacteria were identified with a mass spectrometry microbial identification system. Antimicrobial susceptibility was tested with a VITEK2 system, and carbapenemase genes were amplified. A case-control study was conducted to evaluate the risk factors for fecal CRE colonization in pediatric inpatients. Of 4,033 patients screened, 158 (3.92%) were positive for CRE, including Escherichia coli (51.27%), Klebsiella pneumoniae (37.97%), and Enterobacter cloacae (6.96%). The most common carbapenemase genes were blaNDM-5 (51.89%), blaNDM-1 (15.19%), and blaIMP-4 (7.60%) and blaKPC-2 (3.80%). Hematological malignancies, respiratory diseases, otolaryngological diseases, nervous system diseases, oral administration of third-generation cephalosporins, and the combined use of two or more antibiotics were independently associated with CRE colonization. The most prevalent carbapenem-resistant K. pneumoniae sequence types (STs) were ST11 (8.06%), ST37 (8.06%), and ST76 (8.06%), and the most prevalent carbapenem-resistant E. coli STs were ST10 (9.88%), ST48 (13.58%), and ST58 (8.64%). Pediatric inpatients were colonized by a diversity of CRE strains. Infection control and prevention measures should be implemented to reduce CRE colonization. IMPORTANCE This study assessed the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae in pediatric inpatients at three hospitals in South China by means of screening stool samples for carbapenem-resistant genes and a nested case-control study to determine risk factors for carriage of carbapenem-resistant Enterobacteriaceae. Of 4,033 fecal samples screened, 158 (3.92%) were positive for CRE, including Escherichia coli (51.27 %), Klebsiella pneumoniae (37.97%), and Enterobacter cloacae (6.96%). The most common carbapenemase genes harbored by gastrointestinal CRE strains were blaNDM-5, blaNDM-1, and blaIMP-4. Hematological malignancies, respiratory diseases, otolaryngological diseases, nervous system diseases, oral administration of third-generation cephalosporins, and the combined use of two or more antibiotics were independently associated with CRE colonization.

Risk Factors for Carbapenem-Resistant Enterobacteriaceae Colonization and the Effect on Clinical Outcomes and Prognosis in Allogeneic Hematopoietic Stem Cell Transplanted Patients.

The current study assesses which are the main risk factors, clinical outcome and prognosis following the colonization of CRE in patients that underwent allo-HSCT. A total of 343 patients subjected to allo-HSCT in the period comprised between June 2021 and June 2022 were enrolled in this retrospective study. The CRE colonization was diagnosed by clinical history and routine microbial culture of perirectal swab. In this regard, a clinical prediction model was designed based on independent risk factors underlying the pre-transplantation CRE colonization using a backward stepwise logistic regression, followed by the evaluation of its discrimination and calibration efficacies, along with clinical usefulness. Furthermore, univariate and multivariate Cox regression analyses were then conducted to assess the risk factors for post-transplantation clinical outcomes. Out of 343 patients enrolled in this study, 135 (39.3%) reported CRE colonization. The independent risk factor variables for CRE colonization were incorporated into the nomogram to build a prediction model, which showed an area under the curve of 0.767 (95% CI: 0.716-0.818), and well-fitted calibration curves (χ2 = 1.737, P = 0.9788). The patients with CRE colonization reported a significantly lower platelet engraftment rate with a higher risk of post-transplantation BSI when compared with the non-CRE colonization group (P = 0.02 and P < 0.001; respectively). The non-relapse mortality (NRM) value was higher in the CRE patients (P < 0.05), consistently with a survival probability that was thus significantly lower for the same timeframe (P < 0.05). A reliable clinical prediction model for pre-transplantation CRE colonization was developed that demonstrated that the CRE colonization negatively affects platelet engraftment and survival outcomes following allo-HSCT.

Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites

The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.

Endogenous Bacteremia Caused by Intestinal Colonization of Carbapenem-Resistant Enterobacteriaceae (CRE) in Immunocompromised Children.

Carbapenem-resistant Enterobacteriaceae (CRE) infection is life-threatening, especially for immunocompromised children. The source tracking of CRE could prevent bacteremia during hospitalization. In this study, the intestinal colonization of CRE and their translocation to blood were investigated. Stool samples from immunocompromised pediatric patients were collected after admission, and secondary stool and blood samples were collected in case of fever. After CRE phonotypic detection, the OXA-48, NDM-1, VIM, IMP, and KPC genes were detected by PCR. Enterobacterial Repetitive Intergenic Consensus Polymerase Chain Reaction (ERIC-PCR) was used to determine the phylogenic relatedness of the blood and fecal isolates. Bacteremia was recorded in 71.4% of the patients. Enterobacteriaceae spp. were recorded in 100% of the stool samples and 31% of the blood samples. The correlation between the length of stay (LOS), days of fever, chemotherapy regimens, and death rate was significant (p-value ≤ 0.05). OXA-48 was present in all CRE isolates in both the primary and the secondary stool samples and the blood samples. According to the phylogenetic data, 58.33% of the patients with bacteremia had identical blood and stool isolates. The death rate was 24.4% in children with CRE bacteremia. The primary intestinal colonization with CRE in immunocompromised pediatrics and their translocation to blood was established in this study. The implementation of infection control programs and the application of infection prevention strategies for immunocompromised children is necessary.

Carbapenem-Resistant Enterobacteriaceae Infection in Immunocompromised Children with CRE Colonization: Incidence and Outcomes in an Antibiotic-Limited Setting

Objective: To determine the incidence of carbapenem-resistant Enterobacteriaceae (CRE) infection in patients with CRE colonization and compare the treatment outcomes between febrile patients with non-septic presentation who received empirical treatment with meropenem and those who did not. Material and Methods: The medical records of febrile patients with CRE colonization aged &lt;15 years who were hospitalized at Songklanagarind Hospital between January 2018 and December 2020 were reviewed. Results: Among the 61 patients with CRE colonization, CRE infection was identified during eight febrile episodes in six patients (9.8%). Hematologic malignancies, solid tumors, and other diseases were diagnosed in 21 (34.4%), 25 (41.0%), and 15 (24.6%) patients, respectively. The median (interquartile range [IQR]) duration from CRE colonization to the first episode of fever was 22 (1.8–60.8) days. Among the 82 febrile episodes without initial sepsis or central nervous system infection, 19 and 63 episodes, respectively, were initially treated with meropenem and non-carbapenems. Treatment outcomes—including the proportion of patients needing step-up antibiotics (21.1% vs. 36.5%), development of sepsis (5.3% vs. 15.9%), and death within 30 days (6.6% vs. 9.8%) - were not significantly different between the two groups.Patients who developed sepsis had significantly higher resistance to empirical antibiotics (75% vs. 26.3%) as well as a significantly higher incidence of severe neutropenia lasting more than one week (85.7% vs. 21.9%) than those without sepsis.Conclusion: Patients with CRE colonization who exhibit fever without clinical sepsis and have an absolute neutrophil count &gt;100 cells/mm3 can be empirically treated with non-carbapenems.

Importance of carbapenem-resistant Enterobacteriaceae screening to prevent transmission within an acute-care hospital

Background: Carbapenem-resistant Enterobacteriaceae (CRE) present a serious public health risk because they are transmissible within the acute-care hospital setting, and they are associated with significant morbidity and mortality. Timely identification of CRE among hospitalized patients is essential to ensure that appropriate infection prevention measures are enforced to prevent transmission events. In 2022, 9 index CRE cases (5 Klebsiella pneumoniae carbapenemase (KPC)–producing and 4 New Delhi Metallo-β-lactamase (NDM)–producing cases) were identified within the University of Colorado Hospital (UCH) inpatient population. In response to index case identification, tracing was performed to identify patients with an epidemiologic link for targeted CRE screening to detect asymptomatic CRE carriage. Methods: In total, 645 patients were screened allowing for timely identification of CRE colonization within 6 patients (3-KPC; 1-OXA-48; 1-NDM; 1-KPC/OXA-48). Secondary case identification elicited additional evaluation of service team and mobile-device crossover between positive patients, as well as primary and ancillary treatment locations. Results: Investigations revealed 3 possible transmission events in 0.47% of the total screened population. Identification of secondary CRE cases prompted additional testing of exposed patients performed at 7-day intervals to capture a 21-day colonization period. In total, 95 additional patients were screened for CRE during secondary and tertiary CRE screening events. Discussion: Nursing staff collaboration and engagement were critical to achieving a high rate of compliance with CRE screening activities, not only collecting screening specimens but also providing explanation and reassurance to patients. Due to this partnership and diligence, UCH was able to achieve 77% compliance with initial CRE screening events. Secondary and tertiary CRE screening revealed testing compliance of 83% and 69%, respectively. To further reduce the risk of CRE transmission within hospitalized patients, UCH has implemented an enhanced cleaning process for high-risk patient rooms, which includes patients infected or asymptomatically colonized with CRE. This enhanced process is prompted based on CRE or infection status as documented in the electronic medical record (EMR), and it initiates a mandatory 2-phase cleaning process. Future plans include environmental testing audits to validate room decontamination and leveraging the EMR to capture pertinent healthcare and travel histories. Active engagement with public health partners will be pursued to enable molecular testing of high-risk touch points. Conclusions: Patient screening, enhanced decontamination, and monitoring activities are key elements to effectively prevent the spread of CRE within vulnerable patient populations and must be continuously evaluated for improvement opportunities.Disclosures: None

Active surveillance for carbapenem resistant enterobacteriaceae (CRE) using stool cultures as a method to decrease CRE infections in the pediatric intensive care unit (PICU)

BackgroundThe incidence of Carbapenem Resistant Enterobacteriaceae (CRE) infections is increasing worldwide. Due to dearth of alternative antibiotics, prevention of infection transmission is a part of CRE infection management strategy. Early detection of CRE by active surveillance coupled with contact isolation is much more appropriate compared to contact isolation upon receipt of routine cultures dictated by the patient's clinical condition. ObjectivesTo determine whether active CRE surveillance will decrease CRE infection rates in the Pediatric Intensive Care Unit (PICU). MethodsRetrospective observational study done in the 10-bed PICU of a tertiary care teaching children's hospital from July 2013 to June 2015. Rectal swabs for CRE were sent from all PICU patients except stable post-operative patients. Contact isolation precautions were followed for rectal swab positive patients. CRE colonization and infection rates were calculated and compared. ResultsTotal of 1262 rectal swabs were sent from 1022 patients. CRE colonization rate was 19.5%. Post intervention, ICU acquired CRE colonization decreased by 36% and ICU acquired CRE infection rates decreased by 100%, both showed significant decrease (p ​< ​0.0001). ConclusionActive CRE surveillance and institution of contact isolation in appropriate situations is helpful in decreasing CRE colonization and infection rates in the PICU.

Carbapenem-resistant Enterobacteriaceae infection in children less than one year old in an Asian medical center.

The emergence of carbapenem-resistant Enterobacteriaceae (CRE) is a threat to public health worldwide. This study aimed to determine the risk factors and outcomes for CRE colonization and infection in infants. Children aged <1 year hospitalized with CRE pathogens isolated from January 2016 to June 2019 were retrospectively analyzed. Demographic and clinical data were examined. A total of 48 infections were identified in 70 infants aged <1 year, and 66.7% (32/48) of these infants were born preterm. The infection rate in infants aged <1 month was higher than that of others (P=0.005). The most commonly isolated CRE was Klebsiella pneumoniae (60.4%, 29/48), followed by Enterobacter cloacae complex (18.8%, 9/48). Sputum (37.5%, 18/48), blood (27.1%, 13/48), and urine (25.0%, 12/48) were the most common clinical samples. Urinary tract infection was common in infants aged 6-12 months. CRE infection was associated with mechanical ventilation (P=0.037), central venous catheter (CVC) insertion (P=0.034), and congenital heart disease (P=0.027). The hospital stay of patients with CRE infection was longer (median, 75 days; SD, 66.4 days), and their all-cause mortality (6.4%) was higher than those with colonization. CRE infection was common in infants aged <1 month, and patients usually had longer hospitalization. Carbapenemase production was not common. Mechanical ventilation, CVC insertion, and congenital heart disease were associated with a higher risk of CRE acquisition in infants aged <1 year.

Intestinal Carriage of Carbapenemase-Producing Enterobacteriaceae Members in Immunocompromised Children During COVID-19 Pandemic

Background: Hospital-acquired infection with carbapenem-resistant Enterobacteriaceae (CRE) is a global concern. The administration of antibiotics among the infected and non-infected immunocompromised children with SARS-CoV-2 is associated with an increased risk of intestinal CRE colonization and bacteremia during hospitalization. Objectives: The present study aimed to detect the correlation between the intestinal colonization of carbapenemase encoding Enterobacteriaceae with SARS-CoV-2 infection and antibiotic prescription among immunocompromised children admitted to the oncology and Bone Marrow Transplantation (BMT) wards. Methods: Stool samples were collected from the immunocompromised children, and the members of Enterobacteriaceae were isolated using standard microbiological laboratory methods. Carbapenem resistance isolates were initially characterized by the disc diffusion method according to CLSI 2021 and further confirmed by the PCR assay. SARS-CoV-2 infection was also recorded according to documented real-time PCR results. Results: In this study, 102 Enterobacteriaceae isolates were collected from the stool samples. The isolates were from Escherichia spp. (59/102, 57.8%), Klebsiella spp. (34/102, 33.3%), Enterobacter spp. (5/102, 4.9%), Citrobacter spp. (2/102, 1.9%), and Serratia spp. (2/102, 1.9%). The carbapenem resistance phenotype was detected among 42.37%, 73.52%, 40%, 50%, and 100% of Escherichia spp., Klebsiella spp., Enterobacter spp., Citrobacter spp., and Serratia spp., respectively. Moreover, blaOXA-48 (49.1%) and blaNDM-1 (29.4%), as well as blaVIM (19.6%) and blaKPC (17.6%) were common in the CRE isolates. SARS-CoV-2 infection was detected in 50% of the participants; however, it was confirmed in 65.45% (36/55) of the intestinal CRE carriers. The administration of antibiotics, mainly broad-spectrum antibiotics, had a significant correlation with the CRE colonization in both the infected and non-infected children with SARS-CoV-2 infection. Conclusions: Regardless of the COVID-19 status, prolonged hospitalization and antibiotic prescription are major risk factors associated with the CRE intestinal colonization in immunocompromised children.

2111. Impact of Colonization by Multi Drug Resistant Bacteria on Graft Survival, Risk of Infection, and Mortality in Recipients of Solid Organ Transplant: Systematic Review and Meta-analysis

Abstract Background Colonization with multi-drug resistant bacteria (MDR) in solid organ transplant (SOT) recipients increases the risk of post-transplant bacterial infection. MDR colonization impact on graft survival and mortality is not well established. Methods A search was executed by an expert librarian on PROSPERO, OVID Medline, Ovid EMBASE, Wiley Cochrane Library, ProQuest dissertations and Theses Global and SCOPUS, from inception until October 26, 2021. Adult SOT colonized with Methicillin resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococci (VRE), Extended-spectrum beta-lactamase (ESBL) or AmpC producing bacteria, carbapenem resistant Enterobacteriaceae (CRE), or MDR Pseudomonas were included and compared to non-colonized SOT. Pairs of reviewers screened abstracts and full studies for inclusion, and extracted data independently. We used RevMan to conduct a meta-analysis using random effects models to calculate the pooled risk ratio (RR) with 95% confidence interval (CI) for the incidence of infection, mortality, and graft failure. Statistical heterogeneity was determined using the I2 statistic. Figure-1 PRISMA chart, systemic review and metanalysis on Impact Of Colonization By Multi Drug Resistant Bacteria on Graft Survival, Risk of Infection, and Mortality in Recipients of Solid Organ Transplant. Results 59 articles spanning from 1989 to 2021 were included (Figure-1). Liver transplant (43 studies) and VRE colonization (17 studies) were the most common organ and MDR pathogen. MDR surveillance was performed by culture (71%) and PCR (6.7%). In liver transplant recipients, VRE and MRSA colonization were associated with increased infection risk, but not mortality (VRE infection: RR= 2.40 (95%CI 1.54-3.73; p&amp;lt; 0.001), I2= 66%; VRE mortality: RR= 1.64 (95%CI 0.88-3.05; p=0.12), I2= 44%; MRSA infection: RR= 4.07 (95%CI 2.66-6.24; p&amp;lt; 0.001), I2= 59%; MRSA mortality RR=1.47 (95%CI 0.79-2.76; p=0.23), I2= 35%). ESBL and CRE colonization were associated with increased risk of infection (ESBL: RR=9.87 (6.12-15.93); p&amp;lt; 0.001), I2=13%; CRE: RR= 13.64 (95%CI 5.73-32.47); p&amp;lt; 0.001), I2= 66%). CRE colonization was associated with increased mortality, RR=5.79 (95% CI 1.80-18.63; p=0.003), I2=0%. Conclusion While colonization with MRSA and VRE in liver transplant was not associated with increase mortality, CRE colonization was associated with almost 6-fold increased risk of death. These data should be taken into account when stratifying the risk of transplant. Disclosures Carlos Cervera, Associate Professor, Astra-Zeneca: Advisor/Consultant|AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Sunovion: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Honoraria|VerityPharma: Advisor/Consultant Dima Kabbani, MD, MSc, AVIR Pharma: Grant/Research Support|AVIR Pharma: Honoraria|GSK: Honoraria|Merck: Grant/Research Support.

Clinical Risk Factors and Microbiological and Intestinal Characteristics of Carbapenemase-Producing Enterobacteriaceae Colonization and Subsequent Infection.

Gastrointestinal colonization with carbapenem-resistant Enterobacteriaceae (CRE) is always a prerequisite for the development of translocated infections. Here, we sought to screen for fecal carriage of CRE and identify the risk factors for CRE colonization as well as subsequent translocated pneumonia in critically ill patients admitted to the intensive care unit (ICU) of a university hospital in China. We further focused on the intestinal flora composition and fecal metabolic profiles in CRE rectal colonization and translocated infection patients. Animal models of gastrointestinal colonization with a carbapenemase-producing Klebsiella pneumoniae (carbapenem-resistant K. pneumoniae [CRKP]) clinical isolate expressing green fluorescent protein (GFP) were established, and systemic infection was subsequently traced using an in vivo imaging system (IVIS). The intestinal barrier, inflammatory factors, and infiltrating immune cells were further investigated. In this study, we screened 54 patients hospitalized in the ICU with CRE rectal colonization, and 50% of the colonized patients developed CRE-associated pneumonia, in line with the significantly high mortality rate. Upon multivariate analysis, risk factors associated with subsequent pneumonia caused by CRE in patients with fecal colonization included enteral feeding and carbapenem exposure. Furthermore, CRKP colonization and translocated infection influenced the diversity and community composition of the intestinal microbiome. Downregulated propionate and butyrate probably play important and multiangle roles in regulating immune cell infiltration, inflammatory factor expression, and mucus and intestinal epithelial barrier integrity. Although the risk factors and intestinal biomarkers for subsequent infections among CRE-colonized patients were explored, further work is needed to elucidate the complicated mechanisms. IMPORTANCE Carbapenem-resistant Enterobacteriaceae have emerged as a major threat to modern medicine, and the spread of carbapenem-resistant Enterobacteriaceae is a clinical and public health problem. Gastrointestinal colonization by potential pathogens is always a prerequisite for the development of translocated infections, and there is a growing need to assess clinical risk factors and microbiological and intestinal characteristics to prevent the development of clinical infection by carbapenem-resistant Enterobacteriaceae.

Colonization with Carbapenem-Resistant Enterobacteriaceae Contributes to Unfavorable Outcomes in End-Stage Liver Disease Patients.

Carbapenem-resistant Enterobacteriaceae (CRE) are the highest priority pathogens of the World Health Organization, and their prevalence in end-stage liver disease (ESLD) patients is increasing. CRE colonization is an independent risk factor for CRE infections. We aimed to assess risk factors and explore the relationship between CRE colonization, infection, and prognosis in patients with ESLD. A total of 311 patients with ESLD were screened for CRE colonization by fecal swabs from October 2020 to January 2022. Antimicrobial susceptibility was tested using the broth microdilution method. Carbapenem resistance genes, multilocus sequence type, and capsular serotype were analyzed by polymerase chain reaction (PCR). Seventeen CRE strains were detected, among which the most common was Klebsiella pneumoniae. The CRE colonization rate was 5.5%. Artificial liver support was an independent risk factor for CRE colonization. Compared to the non-CRE colonization group, the colonization group had a higher incidence of CRE infection and a worse prognosis. Furthermore, these strains were not closely related, and all were sensitive to polymyxin and tigecycline. There was a high colonization rate in ESLD patients, and colonization strains were highly diverse. CRE colonization deserves attention in these patients, especially when treated with artificial liver support.

Active Screening of Intestinal Colonization of Carbapenem-Resistant Enterobacteriaceae for Subsequent Bloodstream Infection in Allogeneic Hematopoietic Stem Cell Transplantation.

PurposeTo investigate the prevalence, risk factors of intestinal carbapenem-resistant Enterobacteriaceae (CRE) colonization and bloodstream infection (BSI) caused by CRE in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.MethodsWe analyzed the clinical data of 185 patients with hematological malignancies who underwent allo-HSCT from May 2019 to December 2021. All patients received regular CRE monitoring by rectal swab during allo-HSCT, and some CRE strains were further identified for carbapenemase phenotypes. The rates, distribution and risk factors of CRE colonization, CRE-induced BSI were analyzed.ResultsCRE was detected in 44 of 185 recipients, with colonization rate of 23.8%. A total of 46 strains of CRE were isolated, including 22 Escherichia coli, 17 Klebsiella pneumoniae, three Klebsiella oxytoca, two Enterobacter hormaechei, and two other Enterobacteriaceae. Among the 19 strains identified with carbapenemase phenotypes, eight strains of E. coli produced metal β-lactamase, five K. pneumoniae produced serine carbapenemase, two K. pneumoniae produced metal β-lactamase, two K. oxytoca produced metal β-lactamase, a Citrobacter malonic acid-free produced metal β-lactamase and a Citrobacter freundii produced metal β-lactamase. In 10 patients developed with CRE-related BSI, the types and combined drug sensitivity of strains detected by rectal swab were highly consistent with blood culture. Multivariate analysis revealed that pulmonary infection, perianal infection and carbapenem application in the 3 months pre-transplant were independent risk factors for rectal CRE colonization, while rectal colonization with carbapenem-resistant K. pneumoniae (CR-KP) was an independent risk factor for CRE-induced BSI. The mortality rate within 30 days of CRE-related BSI was 50.0%, and patients receiving multi-drug therapy within 24 hours showed slightly lower mortality than that in the single-drug treatment group.ConclusionAllo-HSCT patients with CRE-induced BSI have poor prognosis, and CR-KP rectal colonization is an independent risk factor for CRE-related BSI. Rectal swab screening during allo-HSCT could provide early warning for later CRE-induced BSI.

Bloodstream Infections in Patients with Rectal Colonization by Carbapenem-Resistant Enterobacteriaceae: A Prospective Cohort Study.

PurposeCarbapenem-resistant Enterobacteriaceae (CRE) infection has become a concerning threat, especially in hospital settings; however, its phenotypic characterization, association with rectal colonization and subsequent bloodstream infections (BSI) remain to be clarified. This study aimed to investigate the incidence and risk factors of CRE infection in rectal CRE carriers and to understand the clonality of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains and their association with subsequent BSI in these patients.Patients and MethodsThis was a prospectively designed cohort study. Hospitalized patients treated at our institution from April 2019 to October 2020 with intestinal CRE carriage were screened at admission and weekly thereafter until death or discharge from the hospital. Stool and blood samples were obtained for strain growth and mass spectrometry. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRE. The clonality of the CRE strains and their corresponding clinical infection strains was studied by whole-genome sequencing to explore the mechanism of drug resistance and evaluate possible transmission. CRE-associated risk factors were analyzed in combination with epidemiological data.ResultsOf the 1203 patients, 85 were colonized by CRE and 21 developed CRE infection, of whom 13 developed CRE bloodstream infection (BSI). Ninety-one CRE strains were isolated from the rectal specimens of the 85 patients. Tracheotomy and chemotherapy in the past three months were independent risk factors for CRE infection in intestinal CRE carriers. ST11-KL64 (92.3%, 24/26) was the most dominant capsule and multilocus sequence typing (MLST) type among clonal CRKP isolates. Single-nucleotide polymorphism clustering showed homology of representative colonization and infection CRKP strain pairs (n=13) in the same patient. One group of leading clones was endemic in surgical intensive care units (ICUs). Twenty-four CRKP strains carried β-lactamase K. pneumonia carbapenemase 2, and 73.1% (19 strains) of CRKP carried mucoid phenotype regulator genes A2 and iucABCD.ConclusionIn summary, intestinal CRE colonization was detectable at an elevated rate among hospitalized patients and prevalent in ICU patients, with potential rapid horizontal transmission, providing evidence that CRE BSI infection in hospitalized patients might be due to their colonized strains and indicates the correlation between intestinal colonization and BSI.

Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool: A Quality Improvement Project.

Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE. In 2017, an increase in the rate of health care-associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance. A pre-/post-intervention project was conducted from November 2017 through December 2020. The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST). Hand hygiene compliance increased from 49% to 76.9% after the Improve phase ( P = .0001), and to 81.9% after the second Control phase ( P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% ( P = .0001). Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.

Intestinal Colonization with Carbapenem-Resistant Enterobacteriaceae in Acute Leukemia Patients: Risk Factors and Molecular Characteristics.

BackgroundCarbapenem-resistant Enterobacteriaceae (CRE) colonization is associated with bacterial translocation, which can result in subsequent endogenous CRE infection. In the present study, we aim to investigate the colonization-related risk factors and molecular epidemiological characteristics of CRE in patients with acute leukemia.MethodsFrom January 2021 to December 2021, acute leukemia patients were screened for CRE by fecal/perianal swabs. We identified the species, carbapenemase-encoding genes, and virulence genes of the colonizing strains and performed antimicrobial susceptibility tests and ERIC-PCR typing. Risk factors for CRE colonization were identified by univariate and multivariate analysis.ResultsWe collected a total of 21 colonizing strains from 320 patients. All strains were resistant to meropenem. Klebsiella pneumoniae was the most abundant species, and ERIC-PCR typing showed low diversity. Univariate analysis showed that age, cephalosporins, penicillins, tigecyclines, and hematopoietic stem cell transplantation status were risk factors for CRE colonization; simultaneously discovered CRE strains played a dominant role in invasive infection of colonized patients. Logistic multivariate regression analysis showed that age, cephalosporins, and tigecyclines were independent risk factors for CRE intestinal colonization.ConclusionCRE colonization can increase the incidence of CRE infection in patients with acute leukemia. Early detection of CRE colonization through CRE screening is an important measure to control the spread of CRE.