Precision identification of diverse bloodstream pathogens in the gut microbiome

Abstract

A comprehensive evaluation of every patient with a bloodstream infection includes an attempt to identify the infectious source. Pathogens can originate from various places, such as the gut microbiome, skin, and external environment. Identifying the definitive origin of an infection would enable precise interventions focused on management of the source 1 , 2 . Unfortunately, hospital infection control practices are often informed by assumptions about the source of various specific pathogens; if these assumptions are incorrect they lead to interventions that do not decrease pathogen exposure 3 . Here, we develop and apply a streamlined bioinformatic tool, named StrainSifter, to match bloodstream pathogens precisely to a candidate source. We then leverage this approach to interrogate the gut microbiome as a potential reservoir of bloodstream pathogens in a cohort of hematopoietic cell transplantation recipients. We find that patients with Escherichia coli and Klebsiella pneumoniae bloodstream infections have concomitant gut colonization with these organisms, suggesting that the gut may be a source of these infections. We also find cases where classically non-enteric pathogens, such as Pseudomonas aeruginosa and Staphylococcus epidermidis , are found in the gut microbiome, thereby challenging existing informal dogma of these infections originating from environmental or skin sources. Thus, we present an approach to distinguish the source of various bloodstream infections, which may facilitate more accurate tracking and prevention of hospital-acquired infections.

Bacillus cereus biofilm formation on central venous catheters of hospitalised cardiac patients

“…Recent publications, such as that from Tamburini et al (2018), highlight the importance of using powerful genomic tools such as WGS for strain tracking and more precise identification of the origins of BSIs, in order for hospitals and health care providers to most effectively work to prevent infections. Here WGS was used successfully as a predictive tool for the antimicrobial resistance profile of the B. cereus CVC_S1 strain.…”

Butyrate‐producing gut bacteria and viral infections in kidney transplant recipients: A pilot study

“…With respect to bacterial complications, Taur et al performed a study of 94 allogeneic hematopoietic stem cell transplant (HSCT) recipients and reported that Enterococcus gut domination increased the risk for future development of Enterococcus sepsis by 9‐fold . In a different cohort of allogeneic HSCT recipients, Tamburini et al did a strain level analysis on bloodstream isolates and reported that strains of Escherichia coli and Klebsiella pneumoniae that caused septicemia likely originated from the gut …”

Compartmentalization of intestinal bacteria by hepatic ILC3s prevents infections after surgery

“…Nevertheless, despite all efforts using hygiene, asepsis, antisepsis and antibiotics, SSI occur in one-tenth of all patients undergoing surgery (3,4). Our studies demonstrate the mechanistic basis for the observation that SSI as well as sepsis have an intestinal microbial signature (24,48). These findings emphasize that the prevention of SSIs requires further understanding of the communication between the intestinal microbiome and systemic host responses.…”

“…This was not dependent on the intestinal microbial composition given that the bacterial species identified in the liver, spleens, MLNs and lungs of Rag2 -/-Il2r -/mice mainly included Escherichia coli, Enterococcus faecalis and Enterobacter hormaechei and to a lesser abundance Staphylococci ss, which are all members of the intestinal microbiota ( Fig. S4f-i) (24). We next assessed the effect of intestinal bacterial dissemination on proliferative hepatocyte indices, which are the most relevant outcome parameters after hepatic surgery.…”