Population pharmacokinetics of vancomycin in very low birth weight neonates

Alsultan, Abdullah; Munjem, Manea Fares Al; Atiq, Khulood Mohammed; Aljehani, Zekra Kamel; Muqati, Hessa Al; Almohaizeie, Abdullah; Ballal, Dalia Ahmed; Refaei, Tahani Makki; Jeraisy, Majed Al; Assiri, Abdulmohsen; Abouelkheir, Manal

doi:10.3389/fped.2023.1093171

Cited by 6 publications

(1 citation statement)

References 41 publications

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“…The American Thoracic Society Guidelines on Antibiotic Management of Lung Infections recommend IV vancomycin as the first line treatment for pulmonary exacerbations due to MRSA in PwCF (2). Even though, the pharmacokinetics of vancomycin is well studied in other populations (26)(27)(28), there are minimal data on PK of vancomycin in PwCF. Furthermore, the dosing of vancomycin is not consistent across multiple institutions across the United States and is dosed at a wide range between 500 to 2000 mg (6).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Yellepeddi,

Lindley,

Radetich

et al. 2023

Preprint

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Vancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin dosing in this population among health institutions, and there is large variability in dosing regimens across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model was obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different dosing scenarios. The area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400 mg*h/L was used as a target for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A one-compartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (p < 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at lower MIC levels (MIC = 1), doses greater than and equal to 1000 mg every 8 hours and 1250 mg every 12 hours resulted in >90% PTA. The PTA results from this study may potentially inform the design of vancomycin dosing regimens to treat pulmonary infections due to MRSA in PwCF.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Yellepeddi,

Lindley,

Radetich

et al. 2023

Preprint

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External evaluation of neonatal vancomycin population pharmacokinetic models: Moving from first‐order equations to Bayesian‐guided therapeutic monitoring

Blouin,

Métras,

Gaudreault

et al. 2024

Pharmacotherapy

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IntroductionGuidelines for vancomycin therapeutic monitoring recommend using a Bayesian approach with a population pharmacokinetic model to estimate the 24 h area under the concentration‐time curve over first‐order equations. Thus, we performed an external evaluation of population pharmacokinetic models of vancomycin in neonates and compared Bayesian results with those observed in clinical practice via pharmacokinetic equations to improve therapeutic monitoring by proposing optimized initial dosing nomograms and assessing the feasibility of reduced blood sampling strategies using the most predictive models.MethodsModels were identified from the literature and evaluated via an external neonatal population. A priori predictive performance was first assessed by prediction‐based diagnostics, then by simulation‐based diagnostics and a posteriori analyses only if deemed satisfactory; model‐informed vancomycin exposure was also compared with reference first‐order pharmacokinetic equations. The best‐performing models were ultimately subjected to Monte Carlo simulations to develop new initial dosing nomograms offering the highest probability of achieving therapeutic target.ResultsA total of 28 population pharmacokinetic models were evaluated in the external dataset, which includes 72 neonates and 380 vancomycin concentrations. Eleven models had an adequate predictive performance with bias ≤ ± 15% and imprecision 30%, while the Bayesian approach yielded over 75% agreement with reference exposure values in most cases. Nonetheless, Capparelli et al. and Mehrotra et al. models performed the best overall, showing the lowest imprecisions of 16.8% and 16.9%, respectively; both models recommended higher dosage regimens than the theoretical nomogram currently applied to favor therapeutic target attainment.DiscussionWe externally evaluated numerous neonatal population pharmacokinetic models of vancomycin and used the most predictive ones to advocate new initial dosing nomograms. Clinical implementation of the Bayesian approach could reduce the time needed to reach therapeutic target and limit the number of blood samples in newborns compared with traditional pharmacokinetic equations.

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