The gut commensal Bacteroides vulgatus mpk reduces Candida albicans pathogenicity towards epithelial cells

The human body is colonized by various microbes, among them the yeast Candida albicans. Mostly harmless, this opportunist causes also disease, ranging from superficial infections to sepsis. Risk factors are disturbed host defenses, mucosal barrier breakdown, and antibiotic-induced dysbiosis. Hence, residing bacteria are important to protect from Candida-mediated damage or inflammation. Bacteroides vulgatus mpk, e.g., is described as positively immunomodulatory in mouse models of inflammatory bowel disease, but its effect on the mycobiota is unknown. In this study we aimed to determine if B. vulgatus mpk affects C. albicans pathogenicity. Therefore, intestinal and oral epithelial cellswere pre-infectedin vitrowith B. vulgatus mpk and then challenged with C. albicans SC5314. The role of soluble factors was investigated by spatial separation or use of Bacteroides-conditioned medium (BCM). Preincubation of host cells with B. vulgatus mpk strongly reduced C. albicans-mediated damage while fungal burden and hyphal length were unaffected by the bacterium. The protective effect did not depend on direct contact of Bacteroidesto host cellsor Candida and could be mimicked using BCM. Contact independency suggests that diffusible factors modulate host cell susceptibility. Ongoing experiments aim to identifykey soluble Bacteroides mediators as well as subsequent host cell signaling. Additionally, co-colonization experiments of germ-free mice are planned to investigate B. vulgatus mpk’s potential to mediate colonization resistance towards C. albicans. This will contribute to our understanding of how commensal bacteria affect C. albicans and host protection.

Implementation of the Early-Onset Sepsis Risk Calculator at a Community Level I Nursery

The objective of this retrospective cohort study was to decrease the frequency of laboratory draws and the number of neonates receiving empiric antibiotics who are born to mothers with chorioamnionitis from 100% to 50% 6 months following implementation of the sepsis risk calculator (SRC) at a level 1 community nursery. Data were compared pre- and post-implementation of the SRC using the Fischer’s exact test. The rate of intravenous (IV) antibiotic use decreased from 93% to 7% ( P < .0001). The rate of blood culture collection decreased from 100% to 46% ( P < .0001). With implementation of the SRC, administration of IV antibiotics, laboratory draws, and IV placement significantly decreased without increasing rates of early-onset sepsis in our patient population. Our study demonstrated that the SRC can be effectively and safely implemented at a level 1 community–based newborn nursery, resulting in a decrease in unnecessary medical treatment without negative patient outcomes.

Framework for considering abnormal heart rate characteristics and other signs of sepsis in very low birth weight infants

Objective: A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the NICU. A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are indicated. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants. Study Design We developed easy-recall acronyms for ten signs of sepsis in VLBWs. Over 12 months in a level IV NICU, Neonatology Fellows completed a brief survey after each shift to document changes prompting sepsis work-ups. We analyzed associations between survey data, hourly HRC data, and the diagnosis of the work-up, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures, <3 days antibiotics). Results We analyzed 93 sepsis work-ups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, 38 SRO). The most frequently cited changes prompting the work-ups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0-12h before the blood culture compared to 12-72h prior occurred in 31% of work-ups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO. Conclusion The HeRO score can alert clinicians to VLBW infants at high or increasing risk for a sepsis-like illness, but HRC patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis work-ups and the duration of antibiotics.

The Framing of machine learning risk prediction models illustrated by evaluation of sepsis in general wards

Problem framing is critical to developing risk prediction models because all subsequent development work and evaluation takes place within the context of how a problem has been framed and explicit documentation of framing choices makes it easier to compare evaluation metrics between published studies. In this work, we introduce the basic concepts of framing, including prediction windows, observation windows, window shifts and event-triggers for a prediction that strongly affects the risk of clinician fatigue caused by false positives. Building on this, we apply four different framing structures to the same generic dataset, using a sepsis risk prediction model as an example, and evaluate how framing affects model performance and learning. Our results show that an apparently good model with strong evaluation results in both discrimination and calibration is not necessarily clinically usable. Therefore, it is important to assess the results of objective evaluations within the context of more subjective evaluations of how a model is framed.