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Walaiporn Wangchinda, Kanokwan Laohasakprasit, Kanokorn Lerdlamyong, Visanu Thamlikitkul Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandCorrespondence: Visanu Thamlikitkul, Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok, 10700, Thailand, Tel +66 81-820-6271, Fax +66 2-412-5994, Email visanu.tha@mahidol.ac.thPurpose: To investigate the epidemiology of carbapenem-resistant Enterobacterales (CRE) colonization or CRE infection relative to the natural history and clinical course of CRE colonization or CRE infection in hospitalized patients during admission and after discharge.Material and Methods: Two adult cohorts were enrolled. Cohort I comprised hospitalized patients who had CRE isolated from their clinical specimens during 2018– 2020. CRE colonization or CRE infection was based on the absence/presence of clinical features of infection. Information regarding the natural history and clinical course of these patients was collected during hospitalization. Stool samples were evaluated for CRE once a week during hospitalization, and then once every few months after discharge until negative for CRE. Cohort II comprised patients who had CRE isolated from clinical specimens during hospitalization and who were discharged during 2015– 2018. CRE in stool samples collected from these patients every few months was assessed to determine duration of CRE in stool.Results: CRE in stool was detected in 69.7% of 353 patients in cohort I. K. pneumoniae was the predominant CRE isolated from clinical samples (76.8%) and stool samples (65.7%). Among the 225 CRE-colonized patients, 20.4% developed subsequent CRE infections with a median duration from CRE colonization to CRE infection of 14 days. Among 174 CRE-infected patients, the most common infection was pneumonia with mortality at discharge of 47.7%. Duration of CRE colonization in stool was < 1 year in 50.0% of cohort I patients, and < 2 years in 91.4% of patients in cohort II.Conclusion: CRE isolated from clinical specimens in hospitalized patients are more likely to cause colonization than infection. Patients with CRE colonization are at risk of subsequent CRE infection with high mortality. Stool culture for CRE is needed to verify if contact precautions can be discontinued because the duration of CRE colonization in stool varied from days to years.Keywords: epidemiology, carbapenem-resistant Enterobacterales, infection, colonization, patients, university hospital, Thailand

Background Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. Methods The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. Results Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n = 15) and ST231 (n = 14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes. Conclusions This study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.

Additional file 1: Table S1. Detailed clinical information of 33 carbapenemase-producing Enterobacteriaceae (CPE) patients described in the study. Table S2. Antimicrobial resistance determinants for 45 carbapenemase-producing Enterobacteriaceae isolates identified from whole genome sequencing analysis.

Background: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.Methods: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.Results: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n=18) and CPE-colonised patients who developed CPE infections during the study (n=3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n=15) and ST231 (n=14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes.Conclusions: This study has revealed the genomic features of disease-causing or colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.