Daily Sepsis Research Analysis
Analyzed 4 papers and selected 3 impactful papers.
Summary
Preclinical and clinical-leaning studies advance sepsis-related science from prevention to diagnosis. Human milk–derived probiotics showed strain-specific protection in murine Gram-negative and LPS-induced sepsis, while a clinical study defined time-to-positivity cutoffs to distinguish true Bacillus cereus bacteremia from contamination. MRI work detailed predictors of levator ani involvement in perianal fistulas, informing surgical planning for pelvic sepsis.
Research Themes
- Microbiome-based prophylaxis for Gram-negative sepsis
- Diagnostic stewardship using blood culture time-to-positivity
- MRI mapping of pelvic sepsis and fistula complexity
Selected Articles
1. Assessment of Protective Role of Different Probiotic Strains against Bacterial and Endotoxin-Induced Sepsis in a Mouse Model.
In murine sepsis models induced by Gram-negative pathogens or LPS, pre-treatment with human milk–derived probiotics improved survival, attenuated organ injury and inflammation, and lowered pathogen burden. Protection was strain-specific, with Streptococcus lactarius most consistent in E. coli and LPS models and Streptococcus salivarius most effective against Salmonella.
Impact: Demonstrates strain-specific protective effects of human milk–derived probiotics in sepsis, expanding preventive/adjunctive strategies targeting host–microbe interactions. It provides mechanistic readouts (cytokines, biochemistry, histopathology) across multiple sepsis models.
Clinical Implications: While preclinical, findings support evaluating specific probiotic strains as prophylaxis or adjuncts in Gram-negative sepsis risk settings, with attention to strain selection and timing.
Key Findings
- Probiotic pre-treatment improved survival and preserved body weight in LPS-, E. coli-, and Salmonella-induced sepsis.
- Organ injury markers (ALT, AST, urea, creatinine) and intestinal TNF-α/IL-6 expression were reduced with probiotics.
- Fecal pathogen loads decreased, paralleling downregulation of pro-inflammatory cytokines.
- Streptococcus lactarius was most protective in E. coli and LPS models; Streptococcus salivarius was most effective in Salmonella sepsis.
Methodological Strengths
- Multiple sepsis models (pathogen- and LPS-induced) with consistent endpoints (survival, pathology, cytokines, biochemistry).
- Head-to-head comparison of four human milk–derived strains enabling strain-specific inference.
Limitations
- Murine pre-treatment model limits generalizability to human therapeutic contexts.
- Group sample sizes and randomization/blinding details are not reported in the abstract.
Future Directions: Validate efficacy and safety of specific strains in larger animal models and early-phase human studies; define dosing, timing, and mechanisms (barrier function, immune modulation, microbiome dynamics).
Sepsis caused by Gram-negative bacteria such as Escherichia coli and Salmonella enterica is a major contributor to global morbidity and mortality. This study investigated the protective effects of four human milk-derived probiotic strains, Staphylococcus hominis, Staphylococcus epidermidis, Streptococcus salivarius, and Streptococcus lactarius, in murine models of pathogen- and lipopolysaccharide (LPS)-induced sepsis. Mice received probiotic pre-treatment before challenge with LPS, E. coli, or Salmonella enterica typhimurium. Clinical signs, survival, body weight, gross and histopathological lesions, serum biochemical markers, fecal bacterial load, and intestinal cytokine gene expression (TNF-α, IL-6) were recorded. Pathogen- and LPS-challenged groups showed high mortality, significant weight loss, marked intestinal pathology, elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, and creatinine, increased fecal pathogen counts, and upregulated TNF-α and IL-6 expression. Probiotic pre-treatment improved survival, preserved body weight, reduced lesion severity, normalized biochemical parameters, lowered fecal pathogen load, and downregulated pro-inflammatory cytokines. Among the tested strains, Strep. lactarius provided the most consistent protection in E. coli and LPS models, whereas Strep. Salivarius was most effective against Salmonella-induced sepsis. The results indicate that specific human milk-derived probiotics can reduce systemic inflammation and organ injury in Gram-negative bacterial sepsis.
2. Optimizing diagnosis of Bacillus cereus bacteremia using time to positivity: a retrospective observational study to differentiate true bacteremia from contamination.
In a single-center cohort of 49 B. cereus blood culture positives, true bacteremia had a significantly shorter TTP (median 7.8 h) than contamination (11.2 h). A 9.0 h cutoff optimized sensitivity (77.8%) and specificity (90.3%), while TTP >13 h strongly indicated contamination.
Impact: Provides actionable TTP thresholds to differentiate true B. cereus bacteremia from contamination, informing antimicrobial decisions and resource use.
Clinical Implications: Use TTP around 9 h to prioritize treatment for suspected B. cereus bacteremia and consider TTP >13 h as likely contamination, integrated with clinical context and laboratory data.
Key Findings
- True bacteremia had a significantly shorter TTP (median 7.8 h; IQR 6.5–8.9) than contamination (11.2 h; IQR 9.9–13) with p<0.001.
- A TTP cutoff of 9.0 h achieved sensitivity 77.8% and specificity 90.3% for predicting true bacteremia.
- TTP >13.0 h yielded 100% sensitivity for identifying contamination (no true bacteremia beyond this threshold).
- All patients had at least two blood culture sets, strengthening classification.
Methodological Strengths
- Defined outcome groups with objective TTP measurement and ROC analysis for threshold selection.
- All patients had ≥2 blood culture sets, reducing misclassification from single-bottle contaminants.
Limitations
- Single-center retrospective design with small sample size (N=49) limits generalizability.
- Potential residual confounding and reliance on clinical adjudication for true bacteremia vs contamination.
Future Directions: Multicenter validation with standardized adjudication; integrate TTP with organism load, source, and host factors into diagnostic algorithms and stewardship protocols.
BACKGROUND: Bacillus cereus can occasionally cause invasive infections, irrespective of the host's immune status. However, the presence of B. cereus in a single blood culture is typically considered a contaminant, potentially leading to an underestimation of the true incidence of B. cereus bacteremia. This study aimed to evaluate the cut-off value for time to positivity (TTP) to distinguish true bacteremia from contamination. METHODS: This single-center retrospective study included patients with positive blood cultures for B. cereus between November 2011 and February 2025. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic performance of TTP, which was achieved by plotting the sensitivity (the true-positive rate) on the y-axis against 1 - specificity (the false-positive rate) on the x-axis for a series of potential TTP cut-off points. RESULTS: During the study period, 49 patients were enrolled, of whom 18 were classified into the true bacteremia group and 31 into the contamination group. All patients had at least two sets of blood cultures collected. The median TTP was significantly shorter among patients in the true bacteremia group (7.8 h; interquartile range [IQR], 6.5-8.9) than in the contamination group (11.2 h; IQR, 9.9-13) (p < 0.001). ROC curve analysis indicated that a cutoff value of 9.0 h achieved the highest sensitivity (77.8%) and specificity (90.3%) for predicting true bacteremia, while a more lenient threshold of TTP > 13.0 h yielded 100% sensitivity for identifying contamination. CONCLUSIONS: A cut-off value of 9.0 h can differentiate true B. cereus bacteremia from contamination, whereas a TTP > 13 h is indicative of contamination. Given its suboptimal diagnostic accuracy, TTP can help differentiate true B. cereus bacteremia from contamination but should be interpreted with clinical and laboratory data for the diagnosis of sepsis.
3. Levator ani involvement in perianal fistulas: MRI-based insights into complex anatomy.
Among 89 perilevator fistulas identified from 1,697 MRIs, 80% involved the levator ani, often without an external orifice. Transsphincteric configuration and increased fistula wall and external anal sphincter thickness independently predicted levator involvement (AUC 0.938).
Impact: Defines MRI predictors of levator ani involvement in complex perianal fistulas, enabling targeted surgical planning and reducing missed extensions of pelvic sepsis.
Clinical Implications: Preoperative MRI assessment focusing on transsphincteric tracts and increased fistula/EAS thickness can guide exploration for hidden extensions and tailor sphincter-sparing approaches.
Key Findings
- Of 89 perilevator fistulas, 71 (79.8%) involved the levator ani; one-third of LA(+) tracts lacked an external orifice (blind sinuses).
- LA(+) fistulas were predominantly transsphincteric and cryptoglandular; LA(−) were more often extrasphincteric and associated with IBD.
- Independent predictors of levator involvement included fistula type, etiology, and increased fistula wall and external anal sphincter thickness (AUC 0.938).
Methodological Strengths
- Large MRI dataset with detailed morphometrics and standardized classification of levator involvement.
- Multivariable logistic regression with ROC analysis demonstrating strong discrimination.
Limitations
- Retrospective single-center design without surgical/pathologic correlation for all cases.
- Clinical outcomes and management impact were not directly assessed.
Future Directions: Prospective validation linking MRI predictors to surgical outcomes and recurrence; integrate imaging features into risk-based surgical algorithms.
PURPOSE: This study aimed to characterize the magnetic resonance imaging (MRI) features of perilevator fistulas involving the levator ani (LA) muscle and to evaluate whether anatomical or systemic factors are associated with LA involvement. METHODS: A retrospective review of 1,697 pelvic MRI scans (2011-2025) identified 89 patients with perilevator fistulas. Patients were classified as LA (+) when the tract directly abutted any component of the levator ani and as LA (-) when separated by ischioanal fat. MRI evaluation included fistula type, orifice localization, associated complications, tract diameter, wall thickness, and morphometric features including the anorectal angle, anal canal length, and the thickness of the anal sphincters and intersphincteric groove. Clinical and etiologic data were also compared between groups. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of LA involvement. The discriminative performance of the final model was assessed using ROC curve analysis. RESULTS: Seventy-one patients (79.8%) had LA (+) and 18 (20.2%) had LA (-) fistulas. One-third of LA (+) tracts lacked an external orifice, ending as blind sinuses in deep pelvic planes. LA (+) fistulas were predominantly transsphincteric and cryptoglandular, whereas LA (-) fistulas were more often extrasphincteric and associated with inflammatory bowel disease. Multivariable analysis demonstrated that fistula type, etiology, and increased thickness of the fistulous wall and external anal sphincter (EAS) were independently associated with LA involvement, yielding an AUC of 0.938. CONCLUSION: In perilevator fistulas, transsphincteric configuration and increased thickness of the fistulous wall and EAS represent imaging factors associated with levator ani involvement, likely reflecting upward extension of sepsis along the outer sphincteric space. Accurate MRI mapping is essential for identifying hidden extensions and tailoring the most appropriate surgical management.