Impact of Intravenous Fat Emulsion Choice on Candida Biofilm, Hyphal Growth, and Catheter-Related Bloodstream Infections in Pediatric Patients.

BACKGROUND: Use of mixed-oil (MO) intravenous fat emulsion (IFE) was shown to inhibit Candida albicans biofilm formation and overall rate of catheter-related bloodstream infections (CR-BSIs) compared with soybean-oil (SO) IFE). We aimed to delineate this inhibitory mechanism and impact of IFE choice on distribution of fungal CR-BSIs. METHODS: Transcriptional profiling was conducted on C. albicans grown in SO-IFE, MO-IFE, or SO-IFE with capric acid. Overexpression strains of shared down-regulated genes were constructed using a tetracycline-off system to assess hypha and biofilm formation in IFEs. A 5-year retrospective multicenter cohort study was performed to assess differences in CR-BSIs caused by Candida species based on the IFE formulation received in pediatric patients. RESULTS: Genes significantly down-regulated in MO-IFE and SO-IFE with capric acid included CDC11, HGC1, and UME6. Overexpression of HGC1 or UME6 enabled filamentation in capric acid and MO-IFE. Interestingly, only overexpression of UME6 was sufficient to rescue biofilm growth in MO-IFE. MO-IFE administration was associated with a higher proportion of non-albicans Candida versus C. albicans CR-BSIs (42% vs 33%; odds ratio, 1.22 [95% confidence interval, .46-3.26]). CONCLUSIONS: MO-IFE affects C. albicans biofilm formation and hyphal growth via a UME6-dependent mechanism. A numerical but not statistically significant difference in distribution of Candida spp. among CR-BSIs was observed.

Delivery of carbohydrates, amino acids, and lipids via intravenous catheters is necessary for some patients to supply daily caloric needs. These nutrient-dense parenteral solutions can promote microbial biofilm growth on the catheter surface, which may seed subsequent catheter-related bloodstream infection (CR-BSI). In fact, receipt of parenteral nutrition is an established risk factor for CR-BSI caused by the polymorphic fungal pathogen Candida albicans. New intravenous fat emulsions (IFEs) have gained market share and IFEs containing capric acid (mixed-oil [MO] IFE) compared with those without (soybean-oil [SO] IFE) impair the C. albicans yeast-to-hypha switch­a trait strongly associated with pathogenicity and biofilm formation. In this study, we found that MO-IFE and capric acid reduced expression of a transcriptional regulator involved in hyphal extension (UME6) and down-regulated genes involved in cell partitioning (HGC1). Overexpression of these genes enabled hyphal growth in MO-IFE. Secondly, we sought to determine whether the type of IFE administered was associated with the clinical incidence of CR-BSIs caused by C. albicans or other common non-albicans Candida species. There was a nonsignificant numerical reduction in C. albicans infections in patients administered MO-IFE compared with SO-IFE. Collectively, this work shows that IFEs differentially affect Candida biology with potential infectious consequences for the patient.

Real-World Clinical Characteristics and Outcomes with Daptomycin Use in Pediatric Patients: A Retrospective Case Series.

INTRODUCTION: Daptomycin (DAP) is a cyclic lipopeptide that exhibits potent in vitro activity against many drug-resistant gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Despite substantial reports evaluating the clinical outcomes of DAP within the adult population, real-world data are lacking in children. The primary goal of this evaluation was to describe the clinical characteristics and outcomes of DAP use in pediatric patients across a wide range of infections. METHODS: This retrospective evaluation included patients < 18 years of age who were treated with DAP from January 2014 to May 2023. The primary objective was to evaluate the composite clinical success, which was defined as a 30-day survival, the lack of a 30-day microbiological recurrence, and the resolution of signs and symptoms of an acute infection without therapy modifications based on clinical failures. Secondary objectives included adverse effects potentially attributable to DAP and reasons for DAP utilization. RESULTS: Forty patients were included, which were predominately male (62.5%) and white (52.5%), with a median age of 8.7 [IQR, 4.4-16.0] years. DAP was used for a wide range of infections, including central line-associated bloodstream infections (CLABSIs; 32.5%), infective endocarditis (15.0%), surgical-site infections (12.5%), and osteomyelitis (12.5%). The most common pathogen isolated was MRSA (37.5%), and most patients were bacteremic (60.0%). The median DAP dose was 8 [IQR, 6-10] mg/kg, and the median duration of the DAP therapy was 11.5 [IQR, 4.8-18.8] days. Most patients achieved composite clinical success (75.0%). An adverse effect occurred in 5.0% of the patients. DAP was prescribed the most for its ease of use/ability to facilitate discharge (40.0%) and/or for issues with alternative therapies (37.5%). CONCLUSION: Most pediatric patients that received DAP demonstrated clinical success with a low incidence of adverse effects. Larger, real-world studies of DAP use are necessary to further assess clinical outcomes.

Comparison of catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition with soybean oil-based intravenous fat emulsion versus a mixed oil fat emulsion.

STUDY OBJECTIVE: To compare rates of catheter-related bloodstream infections (CR-BSI) in pediatric patients who received parenteral nutrition (PN) with either soybean oil-based intravenous fat emulsion (SO-IFE) or mixed oil-IFE (MO-IFE). We hypothesized that the use of MO-IFE would be independently associated with reduced infection rates compared with SO-IFE. DESIGN: Retrospective cohort study. SETTING: Tertiary referral children's hospital and its associated gastrointestinal rehabilitation clinic (01 January, 2015-31 July, 2019). PATIENTS: Days of IFE exposure were counted for patients aged <18 years on IFE initiated during the review period, who had a central venous catheter (CVC) placed for PN administration, received IFE at least three times weekly, and for at least 7 days. MEASUREMENTS: The primary outcome included total and categorical CR-BSI rates expressed as the average with standard error (SE) number of infections per 1000 fat emulsion days. The following categories were specified: Candida albicans, non-albicans Candida spp., coagulase-negative Staphylococcus (CoNS), Enterobacterales, methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and Pseudomonadales. Average infection rate comparisons were quantified as incidence rate ratios (IRR) using generalized linear mixed modeling with a Poisson distribution. MAIN RESULTS: Seven hundred and forty-three SO-IFE and 450 MO-IFE exposures were reviewed from 1131 patients, totaling 37,599 and 19,796 days of therapy, respectively. From those found significantly different, the average rate of infections with CoNS was 3.58 (SE 0.5)/1000 days of SO-IFE and 1.39 (SE 0.45)/1000 days of MO-IFE (IRR [95% confidence interval, CI]: 0.27 [0.16-0.46]; p < 0.01). Total average rates of infection were 7.33 (SE 0.76)/1000 days of SO-IFE and 4.52 (SE 0.75)/1000 days of MO-IFE (IRR [95% CI]: 0.60 [0.44-0.81]; p < 0.01). Other factors associated with higher infection rates include female gender, neonatal age, and inpatient-only IFE exposure. CONCLUSIONS: Receipt of MO-IFE was associated with lower rates of CoNS and total CR-BSIs compared with SO-IFE in pediatric patients. These findings could have major implications on IFE selection for pediatric patients receiving PN.