Editors' ChoiceInfectious Disease

Don’t just blame the hospital, bloodborne pathogens were hiding inside the whole time

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Science Translational Medicine  31 Oct 2018:
Vol. 10, Issue 465, eaav3894
DOI: 10.1126/scitranslmed.aav3894


Microbial sequencing reveals incorrect assumptions about the origin of certain infections, possibly altering prevention and treatment strategies.

Bloodstream infections are a significant source of morbidity and mortality, especially in hospitalized patients. Certain bloodstream infections in the hospital may be preventable as it is believed that these pathogens are acquired from environmental reservoirs and introduced into patients through catheters. There are no standard methods for assessing the origin of bloodstream pathogens, which can ensure proper treatment. Physicians and hospitals generally rely on historical evidence to determine the pathogen source, tailor treatments, and develop preventive strategies to reduce patient risk of acquiring these infections. Current strategies to assess bloodborne pathogens focus on species identity and antibiotic susceptibility but are insufficient for organism tracking, which requires strain level identity. To address this problem, Tamburini et al. combined whole-genome sequencing of pathogen isolates with metagenomic shotgun sequencing of stool samples to track pathogen strains. Patients undergoing hematopoietic stem cell transplant are at high risk for hospital-acquired infections and were sampled as part of a prospective study at Stanford University. Thirty patients were identified with a bloodstream infection during the study and had a stool sample collected prior to the infection. To track bloodstream pathogens, the authors developed a program called StrainSifter. Pathogens were whole-genome sequenced and single-nucleotide variants used to define the pathogen strain. The authors then used StrainSifter to track pathogen strains in shotgun metagenomic sequencing from samples, such as stool, to determine if this site was a potential reservoir. Using this pipeline, 15 of 32 bloodstream pathogens were identified in stool samples from the corresponding patient. It is thought that abundant gastrointestinal organisms commonly seed the blood, but in this study, the majority of pathogens were present in the stool in low abundance. Interestingly, five bloodstream pathogens were found in the stool microbiome despite their historical association with the environment (Pseudomonas aeruginosa) and the skin (Staphylococcus epidermidis). The authors confirmed strains were not transmitted between patients and identified antibiotic resistance genes that paralleled in vitro assays. Unfortunately, current gene sequencing and bioinformatics methods are cumbersome and will need faster turnaround before their clinical application. Now physicians and researchers must consider that current strategies to target and treat bloodborne infections may be misguided, and future studies must broadly sample the patient and environmental microbiome to define pathogen reservoirs and improve outcomes of bloodborne infections.

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