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

Abstract

Wenwen Chu1 *, Xiubing Hang1 *, Xin Li,1 Naifang Ye,1 Wei Tang,1 Yafei Zhang,2 Xiyao Yang,3 Min Yang,4 Yansheng Wang,5 Zhou Liu,1 Qiang Zhou1 1Department of Clinical Laboratory Medicine, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 3Department of Hospital Infection Management, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 4Department of Intensive Care, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Hematopathology, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhou Liu; Qiang Zhou, Department of Clinical Laboratory Medicine, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, Anhui, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: 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

Keywords

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