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

Abstract

Purpose

Carbapenem-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 Methods

This 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.

Results

Of 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.

Conclusion

In 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.

Keywords:

• bloodstream infection
• carbapenem-resistant Enterobacteriaceae
• whole-genome sequencing

Ethical Approval

The Ethical Committee for the Second Hospital of Anhui Medical University (No. YX2022083) approved the study. All samples were collected as part of routine management/surveillance and were anonymized prior to research use. The research was conducted in accordance with the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This study was supported by the Anhui Province University Natural Science Research Major Project of China (No. KJ2021ZD0029), Anhui Translational Medicine Research Fund Project (No. 2021zhyx-C47) and the Second Hospital of Anhui Medical University clinical research training program (No. 2021LCYB04).