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SantaLucia, J.

Publications and source records attributed to SantaLucia, J..

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bioRxiv2021

Measurement of Klebsiella Intestinal Colonization Density to Assess Infection Risk

BackgroundKlebsiella pneumoniae and closely related species K. variicola and K. quasipneumoniae are common causes of healthcare-associated infections, and patients frequently become infected with their intestinal colonizing strain. To assess the association between Klebsiella colonization density and subsequent infections, a case-control study was performed. MethodsA multiplex qPCR assay was developed and validated to quantify Klebsiella (K. pneumoniae, K. variicola, and K. quasipneumoniae combined) relative to total bacterial DNA copies in rectal swabs. Cases of Klebsiella infection were identified based on clinical definitions and having a clinical culture isolate and preceding or co-incident colonization isolate with the same wzi capsular sequence type. Controls were colonized patients without subsequent infection and were matched 2:1 to cases based on age, sex, and rectal swab collection date. Quantitative PCR (qPCR) from rectal swab samples was used to measure the association between relative abundance (RA) of Klebsiella and subsequent infections. ResultsKlebsiella RA by qPCR highly correlated with 16S sequencing ({rho}=0.79; P <.001). The median Klebsiella RA in the study group was 2.6% (interquartile range (IQR) 0.1-22.5, n=238), and was higher in cases (15.7%, IQR 0.93-52.6%, n=83) than controls (1.01%, IQR 0.02-12.8%; n=155; P <0.0001). After adjusting for multiple clinical covariates using inverse probability of treatment weighting, subjects with a Klebsiella RA > 22% had a 2.87-fold (1.64-5.03, P =0.0003) increased odds of infection compared to those with lower colonization density levels. ConclusionsMeasurement of colonization density by qPCR could represent a novel approach to identify hospitalized patients at risk for Klebsiella infection. ImportanceColonization by bacterial pathogens often precedes infection, and offers a window of opportunity to prevent these infections. Klebsiella colonization is significantly and reproducibly associated with subsequent infection, however factors that enhance or mitigate this risk in individual patients are unclear. This study developed an assay to measure the density of Klebsiella colonization, relative to total fecal bacteria, in rectal swabs from hospitalized patients. Applying this assay to 238 colonized patients, high Klebsiella density defined as >22% of total bacteria, was significantly associated with subsequent infection. Based on widely available polymerase chain reaction (PCR) technology, this type of assay could be deployed in clinical laboratories to identify patients at increased risk of Klebsiella infections. As novel therapeutics are developed to eliminate pathogens from the gut microbiome, a rapid Klebsiella colonization density assay could identify patients who would benefit from this type of infection prevention interventions.

microbiology↗
bioRxiv2021

Gut microbiome features are associated with sepsis onset and outcomes

BackgroundEpidemiologic studies have linked antibiotic exposure to subsequent sepsis, suggesting that microbiome disruption may be in the causal pathway and an independent risk factor. This study tests whether variation in the gut microbiota associates with risk of sepsis onset and its outcomes. MethodsUsing a validated surveillance definition, patients with an archived rectal swab from intensive care and hematology units were screened for sepsis. After confirmation by chart review, cases were matched to controls in a 1:2 ratio based on age, gender, and collection date. Relative taxon abundance was measured by sequence analysis of 16S rRNA gene amplicons; total bacterial abundance was measured by qPCR of the 23S rRNA gene. Conditional logistic regression identified clinical and microbiota variables associated with sepsis. ResultsThere were 103 sepsis cases matched to 206 controls. In a final model adjusting for exposure to broad-spectrum antibiotics and indwelling vascular catheters, high relative abundance (RA) of Enterococcus (Odds Ratio (OR) 1.36 per 10% increase, P=.016) and high total bacterial abundance (OR 1.50 per 10-fold increase in 23S copies/L, P =.001) were independently associated with sepsis. Decreased RA of butyrate-producing bacteria also independently associated with sepsis (OR 1.20 for 10% decrease in RA, P =.041), and mortality in unadjusted analysis (OR=1.47 for 10% decrease in RA, P=.034). ConclusionsThis study indicates that the microbiota is altered at sepsis onset. The decreased RA of butyrate-producing bacteria in sepsis also associates with mortality, suggesting a therapeutic role for prebiotics and probiotics in the prevention and treatment of sepsis. ImportanceEarly detection of patients at risk for sepsis could enable interventions to prevent or rapidly treat this life-threatening condition. Prior antibiotic treatment is associated with sepsis, suggesting that disruption of the bacterial population in the gut (the intestinal microbiome) could be an important step leading to disease. To investigate this theory, we matched hospitalized patients with and without sepsis and characterized the patients microbiomes close to or at onset of sepsis. We found that several microbiome alterations, including having more total bacteria in the gut was associated with onset, regardless of prior antibiotic treatment. This signature of microbiome disruption brings us closer to identifying the biological causes of sepsis and could be used to develop new diagnostic tests to identify patients at risk of sepsis.

microbiology↗