The role of antimicrobials in the treatment of sepsis and critical illness‐related bacterial infections: Examination of the evidence

Keir, Iain; Dickinson, Amy E.

doi:10.1111/vec.12272

Cited by 14 publications

(8 citation statements)

References 46 publications

(48 reference statements)

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“…Our simulated results suggest that the anti-agent treatments are effective within a constrained time window (Fig 17). These findings support contentions that timing of therapy is critical to success [11, 148, 149]. As initial loads of Salmonella increase, the probability of a hyperinflammtory response or organ dysfunction increases (Figs 12 and 13).…”

Section: Discussionsupporting

confidence: 79%

“…We saw distinct changes in the outcome of HIR when we added acquired immune components. Although experimental studies have shown that sepsis in humans is not a model of veterinary sepsis and implementation of an animal sepsis model to human medicine must be further validated [148], IMMABM modeling techniques could be applied to human medicine and the IMMABM can be refined as human data becomes available in the future. As the IMMABM is constructed now and by future refinements, this tool will allow us to explore various types of treatments to evaluate their possible effectiveness and could help in the design of future preclinical experiments.…”

Section: Discussionmentioning

confidence: 99%

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An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

et al. 2016

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We present an agent-based model (ABM) to simulate a hepatic inflammatory response (HIR) in a mouse infected by Salmonella that sometimes progressed to problematic proportions, known as “sepsis”. Based on over 200 published studies, this ABM describes interactions among 21 cells or cytokines and incorporates 226 experimental data sets and/or data estimates from those reports to simulate a mouse HIR in silico. Our simulated results reproduced dynamic patterns of HIR reported in the literature. As shown in vivo, our model also demonstrated that sepsis was highly related to the initial Salmonella dose and the presence of components of the adaptive immune system. We determined that high mobility group box-1, C-reactive protein, and the interleukin-10: tumor necrosis factor-α ratio, and CD4+ T cell: CD8+ T cell ratio, all recognized as biomarkers during HIR, significantly correlated with outcomes of HIR. During therapy-directed silico simulations, our results demonstrated that anti-agent intervention impacted the survival rates of septic individuals in a time-dependent manner. By specifying the infected species, source of infection, and site of infection, this ABM enabled us to reproduce the kinetics of several essential indicators during a HIR, observe distinct dynamic patterns that are manifested during HIR, and allowed us to test proposed therapy-directed treatments. Although limitation still exists, this ABM is a step forward because it links underlying biological processes to computational simulation and was validated through a series of comparisons between the simulated results and experimental studies.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

et al. 2016

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“…In our hospital, antibiotic therapy is recommended within 1 to 2 h from the time sepsis is recognized/suspected. However, it is unknown what percentage of critically ill dogs with suspected sepsis receive early antimicrobial interventions (4).…”

mentioning

confidence: 99%

Agreement between Parallel Canine Blood and Urine Cultures: Is Urine Culture the Poor Man's Blood Culture?

et al. 2018

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Bloodstream infections are a significant cause of morbidity and mortality in critically ill dogs, but due to cost and difficulties in sample acquisition, blood cultures are infrequently obtained. In ill dogs, urine cultures may be recommended as surrogates for blood cultures. In order to determine the outcome agreement between parallel urine and blood cultures, we retrospectively analyzed parallel blood and urine specimens submitted for culture from dogs at the NC State Veterinary Hospital between 2011 and 2016. Positive cultures were reported from 15% of the submitted blood specimens and 23% of the submitted urine specimens. A total of 295 urine and blood samples were submitted in parallel, with positive growth demonstrated in 14 concordant and five discordant pairs. A kappa statistic comparing blood and urine culture outcomes was 0.266 (fair) when all parallel growth was included, including concordant and discordant results, and 0.170 (poor) when restricted to parallel concordant growth. The sensitivity of urine to reflect concordant bloodstream bacterial organisms was 30%, with a specificity of 87%. The positive and negative predictive values were 30% and 88%, respectively. Of dogs with both specimens positive on bacterial culture, 7 of 7 (100%) with suspected urogenital infection sources were concordant. All dogs with discordant bloodstream and urinary infections were immunosuppressed. Urinary coagulase-positive isolates were most likely to be concordant with bloodstream infections. In conclusion, we found that urine culture is neither a substitute nor a screen for blood culture. Blood cultures should be performed in any potentially septic animal, especially those that are considered immunosuppressed.

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“…What’s more, PCT-guided treatment on sepsis had been listed into the Diagnostic and Therapeutic Guidance in several developed countries [36, 37]. However, PCT level might also be elevated by other reasons except bacterial infections, including operation, trauma, burns, cardiac shock, multiple organs dysfunction syndrome, pancreatitis, autoimmune diseases, etc.…”

Section: Discussionmentioning

confidence: 99%

Procalcitonin-guided antibiotic therapy in critically ill adults: a meta-analysis

et al. 2017

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BackgroundAs a novel biomarker of inflammation, procalcitonin (PCT) has proven useful to guide antibiotic therapy in intensive care unit (ICU). However, there are controversial on mortality. The aim of this study was to evaluate the utility of PCT-guided antibiotic therapy in critically ill adults and determine whether studies are sufficient.MethodsA systematic search in PubMed, Embase and Cochrane was performed. We included only randomized controlled trials which compared the safety and efficacy between PCT-guided or standard antibiotic therapy groups in ICU adults. Trial sequential analysis and GARDE approach were performed.ResultsFifteen studies met our criteria for inclusion finally, with a cumulative number of 5486 ICU patients. There was no difference in 28-day mortality between two compared groups (P = 0.626), but significant decreases were observed in the duration of antibiotic therapy for the first episode of infection (P < 0.001) and length of hospitalization (P = 0.049). No significant deference was found in secondary endpoints except total duration of antibiotic therapy (P < 0.001). TSA revealed that the pooled sample sizes of 28-day mortality and the duration of antibiotic therapy for the first episode of infection exceeded the estimated required information size, but not the length of hospitalization.ConclusionsPCT-guided therapy is a better and safer algorithm to be applied into ICU patients, which appears no effect on 28-day mortality while performing preferable utility in reducing the duration of antibiotic therapy for the first episode of infection. More studies on these endpoints were not recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2622-3) contains supplementary material, which is available to authorized users.

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The role of antimicrobials in the treatment of sepsis and critical illness‐related bacterial infections: Examination of the evidence

Cited by 14 publications

References 46 publications

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

An Agent-Based Model of a Hepatic Inflammatory Response to Salmonella: A Computational Study under a Large Set of Experimental Data

Agreement between Parallel Canine Blood and Urine Cultures: Is Urine Culture the Poor Man's Blood Culture?

Procalcitonin-guided antibiotic therapy in critically ill adults: a meta-analysis

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