Dataset Information

Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection.

ABSTRACT:

Background

Risk-based guidelines aid empiric antibiotic selection for critically ill adults with suspected infection with Gram-negative bacilli with high potential for antibiotic resistance (termed high-risk GNRs). Neither evidence-based guidelines for empiric antibiotic selection nor validated risk factors predicting high-risk GNR growth exist for critically ill children. We developed and validated a model for predicting high-risk GNR growth in critically ill children with suspected infection.

Methods

This is a retrospective cohort study involving 2 pediatric cohorts admitted to a pediatric intensive care unit (ICU) with suspected infection. We developed a risk model predicting growth of high-risk GNRs using multivariable regression analysis in 1 cohort and validated it in a separate cohort.

Results

In our derivation cohort (556 infectious episodes involving 489 patients), we identified the following independent predictors of high-risk GNR growth: hospitalization >48 hours before suspected infection, hospitalization within the past 4 weeks, recent systemic antibiotics, chronic lung disease, residence in a chronic care facility, and prior high-risk GNR growth. The model sensitivity was 96%, the specificity was 48%, performance using the Brier score was good, and the area under the receiver operator characteristic curve (AUROC) was 0.722, indicating good model performance. In our validation cohort (525 episodes in 447 patients), model performance was similar (AUROC, 0.733), indicating stable model performance.

Conclusions

Our model predicting high-risk GNR growth in critically ill children demonstrates the high sensitivity needed for ICU antibiotic decisions, good overall predictive capability, and stable performance in 2 separate cohorts. This model could be used to develop risk-based empiric antibiotic guidelines for the pediatric ICU.

SUBMITTER: Karsies T

PROVIDER: S-EPMC6247662 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection.

Karsies Todd T Moore-Clingenpeel Melissa M Hall Mark M

Open forum infectious diseases 20181024 11

<h4>Background</h4>Risk-based guidelines aid empiric antibiotic selection for critically ill adults with suspected infection with Gram-negative bacilli with high potential for antibiotic resistance (termed high-risk GNRs). Neither evidence-based guidelines for empiric antibiotic selection nor validated risk factors predicting high-risk GNR growth exist for critically ill children. We developed and validated a model for predicting high-risk GNR growth in critically ill children with suspected inf ...[more]

PMID: 30488040

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Project description:Objective: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. Design: A prospective cross-sectional study. Setting: A 20-bed general intensive care unit of a tertiary referral hospital. Patients: Seventy-two patients admitted to the intensive care unit. Interventions: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiements were then performed examing the expression level of 19,232 genes in each sample. Measurements and Main Results: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, ninety-four genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients, but not between gram-positive and gram-negative patients. Conclusion: Gram-positive and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is non-specific and is designed to provide a more general response that can be elicited by a wide range of different micro-organisms. The study included seventy-two critically ill patients admitted to the intensive care unit (ICU) of Nepean Hospital, Sydney, Australia. Of these, fifty-five patients were diagnosed to have sepsis, as confirmed by microbiological culture. The remaining seventeen patients did not have sepsis and were therefore used as controls. The study was approved by the hospital ethics committee and informed consent was obtained from all patients or their relatives. Patient Samples. Whole blood was taken from each patient on admission to ICU. Neutrophils were separated from whole blood using density-gradient separation with Ficoll-PaqueP P(Amersham). Subsequent neutrophil RNA extraction was performed using guanidinium thiocyanate (Ambion). Microarray Experiment. The neutrophil RNA was converted to cDNA, fluorescently labeled and hybridized to its complimentary sequences on the microarray (Invitrogen). The fluorescent signals on each micrroarray were captured using the GenePix 4000B laser scanner (Axon Instruments). Expression level of each gene was represented by the intensity of its fluorescent signal. Data Extraction. All signal intensity values were processed using background-subtraction method. Prior to analysis, all values were log-transformed and normalized by fitting a print-tip group Lowess curve. Normalization minimizes bias due to dye chemistry, signal intensity or location of a gene on the array. It ensures the detection of genes that are truly differentially expressed, instead of those caused by experimental artifacts or variation in the hybridization process. After normalization, genes that had more than 50% of data missing were removed. We then selected genes that had at least 80% of the data showing two-fold changes from the geneâs median values. After filtering, 1617 genes were available for further analysis.

Project description:IntroductionVentilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10-14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections.MethodsWe reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs.ResultsEleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes.ConclusionDespite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences.Key messageVentilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

Dataset Information

Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection.

Background

Methods

Results

Conclusions

Publications

Development and Validation of a Model to Predict Growth of Potentially Antibiotic-Resistant Gram-Negative Bacilli in Critically Ill Children With Suspected Infection.

Similar Datasets

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