Antimicrobial exposure during infancy in a longitudinal California cohort.

BACKGROUND: To describe temporal and sociodemographic patterns of antimicrobial exposure during the first year of life in a large US cohort. METHODS: Singleton infants born 1998-2014 enrolled in Kaiser Permanente Northern California integrated health system (n = 345,550) were followed longitudinally via comprehensive electronic health records, capturing all systemic antimicrobial inpatient administrations and outpatient dispensings. Antimicrobial exposure was summarized by maternal and infant characteristics, birth year, inpatient/outpatient status, age in months, and drug class. RESULTS: Overall, 44% of infants in this cohort received at least one dose of antimicrobials during infancy. Decreases over time were driven by reduced outpatient dispensings specifically in later infancy, primarily for penicillins. Among infants receiving any antimicrobials the median number of exposure-days was 16. Inpatient dispensings peaked in the first 30 days of life and outpatient dispensings peaked at 10-11 months. Birth characteristics (i.e., NICU admission, gestational age) were strong independent predictors of antimicrobial exposure between 0- < 3 months; sociodemographic factors were modest predictors of exposure for 3-12 months. CONCLUSION: Predictors of antimicrobial exposure in early and late infancy are distinct with early infancy exposures highly correlated to birth characteristics. The cumulative proportion of infants exposed has decreased due to fewer late infancy outpatient dispensings. IMPACT: Comprehensive antimicrobial exposure histories and the maternal and infant characteristics predicting exposure have not been well described in US populations. This analysis provides estimates of cumulative antimicrobial exposures by sociodemographic factors, delivery characteristics, month of life, inpatient/outpatient status, and antibiotic class among one of the largest US HMOs. Predictors of early infancy antimicrobial exposures differ from those in late infancy, with early exposures strongly correlated to birth characteristics and late infancy exposures modestly related to sociodemographic factors. Antimicrobial exposure among infants decreased over the time period primarily due to reduced outpatient dispensings in later infancy.

Antimicrobial Stewardship and Improved Antibiotic Utilization in the Pediatric Cardiac Intensive Care Unit.

Background: We developed a multidisciplinary antimicrobial stewardship team to optimize antimicrobial use within the Pediatric Cardiac Intensive Care Unit. A quality improvement initiative was conducted to decrease unnecessary broad-spectrum antibiotic use by 20%, with sustained change over 12 months. Methods: We conducted this quality improvement initiative within a quaternary care center. PDSA cycles focused on antibiotic overuse, provider education, and practice standardization. The primary outcome measure was days of therapy (DOT)/1000 patient days. Process measures included electronic medical record order-set use. Balancing measures focused on alternative antibiotic use, overall mortality, and sepsis-related mortality. Data were analyzed using statistical process control charts. Results: A significant and sustained decrease in DOT was observed for vancomycin and meropenem. Vancomycin use decreased from a baseline of 198 DOT to 137 DOT, a 31% reduction. Meropenem use decreased from 103 DOT to 34 DOT, a 67% reduction. These changes were sustained over 24 months. The collective use of gram-negative antibiotics, including meropenem, cefepime, and piperacillin-tazobactam, decreased from a baseline of 323 DOT to 239 DOT, a reduction of 26%. There was no reciprocal increase in cefepime or piperacillin-tazobactam use. Key interventions involved electronic medical record changes, including automatic stop times and empiric antibiotic standardization. All-cause mortality remained unchanged. Conclusions: The initiation of a dedicated antimicrobial stewardship initiative resulted in a sustained reduction in meropenem and vancomycin usage. Interventions did not lead to increased utilization of alternative broad-spectrum antimicrobials or increased mortality. Future interventions will target additional broad-spectrum antimicrobials.

Antibiotic waste in a pediatric healthcare system: Wasting drugs that are in limited supply.

In a pediatric hospital system over 2 years, 58,607 doses of antibiotic were wasted, an average of 80 doses per day, including drugs in shortage nationwide. Approximately 50% of waste occurred within the first 2 days of admission or the day of discharge, with ampicillin being the most wasted drug (N = 7,789 doses).

Automated Identification of Immunocompromised Status in Critically Ill Children.

BACKGROUND: Easy identification of immunocompromised hosts (ICHs) would allow for stratification of culture results based on host type. METHODS: We utilized antimicrobial stewardship program (ASP) team notes written during handshake stewardship rounds in the pediatric intensive care unit (PICU) 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 ICHs. 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 a 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 electronic health record-based phenotype based on notes, diagnoses, and medications identifies ICH in the PICU with high specificity.

Initial posaconazole dosing to achieve therapeutic serum posaconazole concentrations among children, adolescents, and young adults receiving delayed-release tablet and intravenous posaconazole.

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. [Figure: see text].