The pathogens of secondary infection in septic patients share a similar genotype to those that predominate in the gut

Abstract

Background Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. Methods In this prospective, observational case–control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. Results The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. Conclusion Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.

Alterations of gut microbiota in cirrhotic patients with spontaneous bacterial peritonitis: A distinctive diagnostic feature

“…Clinical outcomes of SBP due to ESBL-producing K. pneumoniae are confirmed to be worse, with 30-day mortality rates ranging between 40 and 67% ( Cheong et al., 2009 ; Kim et al., 2014 ). Consistent with another study, the gut microbiota of most septic patients was dominated by Klebsiella , indicating that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens ( Mu et al., 2022 ). S. marcescens is also a common clinical infectious microorganism that causes septicaemia, pneumonia, urinary tract infection, endocarditis and arthritis acquired both in the community and the hospital ( Su et al., 2003 ).…”

Human microbiome and microbiota identification for preventing and controlling healthcare-associated infections: A systematic review

“…Actually, Klebsiella pneumoniae was not the only opportunistic pathogen showing a higher abundance in both septic and non-septic ICU patient than in healthy adults; indeed, also Enterococcus strains were detected. In this study, the amount of other health-promoting bacteria, such as Faecalibacterium, was significantly lower in both septic and non-septic ICU patient than in healthy control ( 58 ).…”

Lower gut dysbiosis and mortality in acute critical illness: a systematic review and meta-analysis

“…Robust and replicable disease-specific patterns were rare [35]. It is plausible that pathogen expansion is largely patient-specific with determination of invasive behaviour by interdependent metabolic, ecological and pharmacologic factors, a hypothesis supported by animal studies [26,50].…”