Predictors of mortality and clinical characteristics among carbapenem-resistant or carbapenemase-producing Enterobacteriaceae bloodstream infections in Spanish children

Abstract

Background Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging problem in the paediatric population worldwide with high mortality rates in bloodstream infection (BSI). Objectives To evaluate predictors of 30 day mortality in CRE BSI in a paediatric cohort. Methods A retrospective observational single-centre study (December 2005–August 2018) was conducted. Cases of CRE BSI in children 0 to 16 years were included. Microbiological identification (MALDI Biotyper) and antimicrobial susceptibility testing (Vitek2® and MicroScan panel NBC44) according to EUCAST breakpoints were performed. PCR OXVIKP® was used to confirm carbapenemase genes (OXA-48, VIM, KPC, NDM). Demographic characteristics, underlying diseases, source of bacteraemia, antimicrobial therapy and outcomes were collected from medical records. Survival analysis to establish predictors of 30 day mortality was performed. Results Thirty-eight cases were included; 76.3% were hospital-acquired infections and 23.7% related to healthcare. All patients had at least one underlying comorbidity and 52.6% were recipients of an organ transplant. VIM carbapenemase was the predominant mechanism (92.1%). Previous CRE colonization or infection rate was 52.6%. Intestinal tract (26.3%) and vascular catheter (21.1%) were the most common sources of infection. Crude mortality within 30 days was 18.4% (7/38); directly related 30 day mortality was 10.5%. Conditions associated with an increment in 30 day mortality were intensive care admission and inadequate empirical therapy (P < 0.05). Combination-antibiotic targeted treatment and a low meropenem MIC were not related to improved survival. Conclusions CRE BSI mortality rate is high. The most important factor related to 30 day survival in our CRE BSI cohort in children was empirical treatment that included at least one active antibiotic.

Clinical Profile, Prognostic Factors, and Outcome Prediction in Hospitalized Patients With Bloodstream Infection: Results From a 10-Year Prospective Multicenter Study

“…Accurate identification of predictors associated with mortality in patients with BSI is critical to informing clinical interventions and improving clinical outcomes. Although some prognostic factors have been identified as potential predictors for BSI mortality, most previous reports particularly focused on a single group of people, such as children or the aged, or with specific clinical conditions including cancer and trauma as well as causative organisms equipped with multidrug resistance (8)(9)(10)(11). In addition, multiple machine learning approaches have been developed and increasingly used in predicting unfavorable outcomes and in identifying predictors of mortality for different types of disease, with better performance than the classical multivariate regression analysis method (12).…”

Clinical Characteristics Of Carbapenem Resistant Enterobacteriaceae Bloodstream Infection: A Retrospective Study Among Children

“…Beside the increasing prevalence, the terrible mortality for CRE infection was up to 52.0% according to published data, ranging from 18.4-52.0% [17,37] ,which is another important reason to attract attention of infectious disease physician. The mortality rate of CRE BSI in our study was 25% which is below the average level of published mortality.…”

Caspase-3 Cleaves Extracellular Vesicle Proteins During Auditory Brainstem Development

“…To explore the association of ABC3 substrates and EVs directly, we used size exclusion chromatography (SEC) columns (''Q26Voriginal'' columns; IZON Science) to enrich for EVs from dissociated auditory brainstem tissue of E10 embryos. These columns are specifically designed to separate EVs from free protein, a capacity that has been independently shown to consistently yield high-purity samples of EVs in specific SEC fractions (Vogel et al, 2016;Stranska et al, 2018;Théry et al, 2018;Antounians et al, 2019;Brennan et al, 2020). E10 was chosen because ABC3 substrates were identified in the E10 brainstems.…”

“…E10 was chosen because ABC3 substrates were identified in the E10 brainstems. To quantitatively assess proteomic purity of our EV samples following the Minimal Information for Studies of Extracellular Vesicles (MISEV; Lötvall et al, 2014;Théry et al, 2018), we used Western blotting to compare levels of positive and negative EV markers in three biological replicates of auditory brainstem EV (ABEV) samples and crude brainstem lysates (Figures 6A,B). Neural Cell Adhesion Molecule, a positive marker for EVs released from neural tissue, was enriched more than 20-fold in ABEVs compared to crude brainstem lysates (Student's t-test, p = 0.019).…”

“…We used several additional approaches to characterize particles enriched from the auditory brainstem according to MISEV guidelines (Lötvall et al, 2014;Théry et al, 2018). ABEVs used for proteomic characterization were derived from SEC fractions within the ''EV zone'' based on the recommendation of the column manufacturer (IZON Science) and independent studies verifying this claim (Böing et al, 2014;Vogel et al, 2016;Stranska et al, 2018;Antounians et al, 2019;Brennan et al, 2020).…”