National treatment guidelines for invasive methicillin-resistant Staphylococcus aureus (MRSA) infections recommend targeting a vancomycin 24-h area under the concentration-time curve (AUC _0–24 )-to-MIC ratio of >400. The range of vancomycin trough concentrations that best predicts an AUC _0–24 of >400 in neonates is not known. This understanding would help clarify target trough concentrations in neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine the relationships between trough and AUC _0–24 in the study neonates. Monte Carlo simulations were performed to examine the effect of dose, postmenstrual age (PMA), and serum creatinine level on trough and AUC _0–24 achievement. A total of 1,702 vancomycin concentrations from 249 neonates were available for analysis. The median (interquartile range) PMA was 39 weeks (32 to 42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter, 89% of the study neonates had an AUC _0–24 of >400. Monte Carlo simulations demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of an AUC _0–24 of >400 across a range of PMA, serum creatinine levels, and vancomycin doses. However, a trough of ≥10 mg/liter was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ∼10 mg/liter is likely adequate for most neonates with invasive MRSA infections based on considerations of the AUC _0–24 . Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses is difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization.

Vancomycin area under the curve/minimal inhibitory concentration (AUC/MIC) >400 best predicts the outcome when treating invasive methicillin-resistant Staphylococcus aureus infection; however, trough serum concentrations are used clinically to assess the appropriateness of dosing. We used pharmacokinetic modeling and simulation to examine the relationship between vancomycin trough values and AUC/MIC in children receiving vancomycin 15 mg/kg every 6 hours and methicillin-resistant Staphylococcus aureus MIC of 1 μg/mL. A trough of 7–10 μg/mL predicted achievement of AUC/MIC >400 in >90% of children.

Background: Model-informed precision dosing (MIPD) can serve as a powerful tool during therapeutic drug monitoring (TDM) to help individualize dosing in populations with large pharmacokinetic variation. Yet, adoption of MIPD in the clinical setting has been limited. Overcoming technologic hurdles that allow access to MIPD at the point-of-care and placing it in the hands of clinical specialists focused on medication dosing may encourage adoption. Objective: To describe the hospital implementation and usage of a MIPD clinical decision support (CDS) tool for vancomycin in a pediatric population. Methods: Within an academic children’s hospital, MIPD for vancomycin was implemented via a commercial cloud-based CDS tool that utilized Bayesian forecasting. Clinical pharmacists were recognized as local champions to facilitate adoption of the tool and operated as end-users. Integration within the electronic health record (EHR) and automatic transmission of patient data to the tool were identified as important requirements. A web-link icon was developed within the EHR which when clicked sends users and needed patient-level clinical data to the CDS platform. Individualized pharmacokinetic predictions and exposure metrics for vancomycin are then presented in the form of a web-based dashboard. Use of the CDS tool as part of TDM was tracked and users were surveyed on their experience. Results: After a successful pilot phase in the neonatal intensive care unit, implementation of MIPD was expanded to the pediatric intensive care unit, followed by availability to the entire hospital. During the first 2+ years since implementation, a total of 853 patient-courses (n = 96 neonates, n = 757 children) and 2,148 TDM levels were evaluated using the CDS tool. For the most recent 6 months, the CDS tool was utilized to support 79% (181/230) of patient-courses in which TDM was performed. Of 26 users surveyed, > 96% agreed or strongly agreed that automatic transmission of patient data to the tool was a feature that helped them complete tasks more efficiently; 81% agreed or strongly agreed that they were satisfied with the CDS tool. Conclusions: Integration of a vancomycin CDS tool within the EHR, along with leveraging the expertise of clinical pharmacists, allowed for successful adoption of MIPD in clinical care.

BACKGROUND: The risk of early-onset sepsis is low in well-appearing late-preterm and term infants even in the setting of chorioamnionitis. The empirical antibiotic strategies for chorioamnionitis-exposed infants that are recommended by national guidelines result in antibiotic exposure for numerous well-appearing, uninfected infants. We aimed to reduce unnecessary antibiotic use in chorioamnionitis-exposed infants through the implementation of a treatment approach that focused on clinical presentation to determine the need for antibiotics. METHODS: Within a quality-improvement framework, a new treatment approach was implemented in March 2015. Well-appearing late-preterm and term infants who were exposed to chorioamnionitis were clinically monitored for at least 24 hours in a level II nursery; those who remained well appearing received no laboratory testing or antibiotics and were transferred to the level I nursery or discharged from the hospital. Newborns who became symptomatic were further evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing, culture results, and clinical outcomes were collected. RESULTS: Among 277 well-appearing, chorioamnionitis-exposed infants, 32 (11.6%) received antibiotics during the first 15 months of the quality-improvement initiative. No cases of culture result–positive early-onset sepsis occurred. No infant required intubation or inotropic support. Only 48 of 277 (17%) patients had sepsis laboratory testing. The implementation of the new approach was associated with a 55% reduction (95% confidence interval 40%–65%) in antibiotic exposure across all infants ≥34 weeks’ gestation born at our hospital. CONCLUSIONS: A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes.

Vancomycin dosing in neonates is challenging because of the large variation in pharmacokinetics. Existing empiric dosing recommendations use table-based formats, within which a neonate is categorized on the basis of underlying characteristics. The ability to individualize dosing is limited because of the small number of “dose categories,” and achieving narrow exposure targets is difficult. Our objective was to evaluate a model-based dosing approach (which we designated Neo-Vanco) designed to individualize empiric vancomycin dosing in neonates. Neo-Vanco was developed on the basis of a published, externally validated population pharmacokinetic model. Using a simulation-based methodology, individualized empiric doses that maximize the probability of attaining a 24-hour area under the curve/minimum inhibitory concentration ratio (AUC₂₄/MIC) of >400 while minimizing troughs >20 mg/L are calculated. To evaluate the Neo-Vanco strategy, retrospective data from neonates treated with vancomycin at 2 healthcare systems were used, and empiric dose recommendations from the following 4 sources were examined: Neo-Vanco, Neofax, Red Book, and Lexicomp. Predicted AUC₂₄ and troughs were calculated and compared. Overall, 492 neonates were evaluated (median postmenstrual age, 36 weeks [5th–95th percentiles (90% range), 25–47 weeks]; median weight, 2.4 kg [90% range, 0.6–4.8 kg]). The percentage of neonates predicted to achieve an AUC₂₄/MIC of >400 was 94% with Neo-Vanco, 18% with Neofax, 23% with Red Book, and 55% with Lexicomp (all P < .0001 vs Neo-Vanco). Predicted troughs of >20 mg/L were infrequent and similar across the dosing approaches (Neo-Vanco, 2.8%; Neofax, 1.0% [P = .03]; Red Book, 2.6% [P = .99]; and Lexicomp, 4.1% [P = .27]. A model-based dosing approach that individualizes empiric vancomycin dosing was predicted to improve achievement of target exposure levels in neonates. Prospective clinical evaluation is warranted.