Posaconazole is a broad‐spectrum antifungal used for prophylaxis and treatment of invasive fungal diseases. There are limited data on the optimal dosing, safety, and efficacy of the DRT and IV formulations in immunocompromised pediatric and adolescent patients. We describe our experience including dosing, plasma trough concentrations, safety, and tolerability. Plasma concentrations ≥.7 µg/mL were considered therapeutic for prophylaxis and ≥1.0 µg/mL for treatment. Fifty‐four patients (median age of 16 years) received DRT or IV formulations of posaconazole. Thirty‐one (57%) patients received posaconazole for treatment and 23 (43%) for prophylaxis. Overall, 36 (67%) patients achieved targeted initial plasma trough concentrations (median 1.3 µg/mL) (Figure 1). The median daily dose among patients <13 years of age who achieved the targeted initial concentrations was 7.3 mg/kg/day for the DRT formulation and 9.8 mg/kg/day for the IV formulation. The median daily dose among patients ≥13 years of age who achieved the targeted initial concentrations was 4.9 mg/kg/day for the DRT formulation and 5.6 mg/kg/day for the IV formulation. Thirty‐six patients (67%) developed transaminitis, mostly grade 1. Our observations show that DRT and IV formulations are safe and effective in immunocompromised children, adolescents, and young adults. Higher dosing per body weight of DRT and IV posaconazole may be required in patients <13 years of age compared with patients 13 years of age and older to achieve therapeutic plasma concentrations. 1FIGURE Distribution of posaconazole plasma trough levels by indication groups
Background Evaluation for bacterial bloodstream infections (BSIs) is often associated with prescribing empiric antibiotics while awaiting blood culture results, typically 48 hours. We examined characteristics associated with positive cultures treated as BSI vs contaminant in children and BSIs associated with prolonged (≥ 24 hours) time-to-positivity (TTP). Methods In a retrospective study of children (≤ 21 years) at our pediatric healthcare system, we abstracted demographic, clinical, and blood culture data from the electronic medical record for all initial positive bacterial blood cultures from March 2021 to February 2022. We excluded fungi and cultures collected within 14 days of a previous positive. TTP was calculated from time/date of collection to Gram stain report. Host status was categorized as previously healthy, immunocompromised (IC), and chronic condition/s. A BSI was defined as a positive culture treated for ≥ 3 days. BSI cultures were categorized as Gram-positive definite (GPD) pathogens, other Gram-positive (OGP), Gram-negative (GN), or polymicrobial (PM). Characteristics associated with prolonged TTP for BSIs were identified using mixed-effects logistic regression. Results There were 816 positive cultures identified in 697 children, with 582 (71%) treated as BSIs and 536 of those (92%) positive in < 36 hours. Positive cultures drawn with adequate blood volume, in the setting of fever, severe neutropenia, and from IC children were significantly more likely to be treated as BSIs (all p< 0.05, Table 1). The most common BSI was a GN pathogen (34.2%, Figure 1). Characteristics associated with prolonged TTP were absence of fever and cultures drawn peripherally. Early TTP (< 24 hours) was associated with cultures drawn outpatient and growth of high likelihood pathogenic organisms (GPD, GN, PM) compared to OGP (all p< 0.05). On multivariate analysis, cultures drawn peripherally remained associated with prolonged TTP (p< 0.01), while GPD, GN, and PM cultures remained associated with early TTP (p< 0.01, Table 2). Conclusion We found that 92% of clinically significant BSIs in children were identified by 36 hours with BSIs with pathogenic organisms (GPD, GN, PM) associated with TTP < 24 hours. Reassessment of the need for antibiotics after 24–36 hours should be considered. Disclosures Pratik A. Patel, MD, Cardinal Health, Inc: Advisor/Consultant.
Background: Easy identification of immunocompromised hosts (ICH) would allow for stratification of culture results based on host type. Methods: We utilized antimicrobial stewardship (ASP) team notes written during handshake stewardship rounds in the pediatric intensive care unit as the gold standard for host status; clinical notes from the primary team, medication orders during the encounter, problem list and billing diagnoses documented prior to the ASP documentation were extracted to develop models that predict host status. We calculated performance for three models based on diagnoses/medications, with and without natural language processing from clinical notes. The susceptibility of pathogens causing bacteremia to commonly used empiric antibiotic regimens was then stratified by host status. Results: We identified 844 antimicrobial episodes from 666 unique patients; 160 (18.9%) were identified as an ICH. We randomly selected 675 initiations (80%) for model training and 169 initiations (20%) for testing. A rule-based model using diagnoses and medications alone yielded sensitivity of 0.87 (08.6-0.88), specificity of 0.93 (0.92-0.93), and positive predictive value (PPV) of 0.74 (0.73-0.75). Adding clinical notes into XGBoost model led to improved specificity of 0.98 (0.98 - 0.98) and PPV of 0.9 (0.88 - 0.91), but with decreased sensitivity 0.77 (0.76 - 0.79). There were 77 bacteremia episodes during the study period identified and a host specific visualization was created. Conclusions: An EHR phenotype based on notes, diagnoses and medications identifies ICH in the PICU with high specificity.
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