Daptomycin, an anti-methicillin-resistant Staphylococcus aureus drug, causes exposure-dependent muscle toxicity and eosinophilic pneumonia. Although the area under the concentration-time curve (AUC)-guided dosing is crucial, an optimal blood sampling strategy is lacking. This study aimed to identify an optimal limited sampling strategy using Bayesian forecasting to rapidly achieve the target AUC.
View Article and Find Full Text PDFIntroduction: Teicoplanin (TEIC) is typically administered as a loading dose over 36-48 h. Achieving an effective concentration quickly is expected to treat severe infections, such as sepsis and methicillin-resistant Staphylococcus aureus infections. We aimed to identify the TEIC loading dose to be completed within 24 h, targeting the concentration of 15-30 μg/mL and factors affecting the loading dose by utilizing the decision tree (DT) model.
View Article and Find Full Text PDFBackground: AWaRe (Access, Watch, Reserve) classification proposed by the World Health Organization (WHO) holds potential for assessing antimicrobial stewardship programs (ASPs). However, increase in antibiotics for non-infectious treatment might undermine the effectiveness of using the AWaRe classification for assessing ASPs. The study aimed to evaluate the antimicrobial usage by AWaRe classification and specify issues for assessing ASPs.
View Article and Find Full Text PDFBackground: Teicoplanin is used to treat serious Gram-positive bacterial infections. However, the optimal trough concentrations for pediatric patients remain unclear owing to the lack of monitoring guidelines. This study aimed to determine the optimal teicoplanin trough concentration for treating Gram-positive bacterial infections in children.
View Article and Find Full Text PDFBackground: Treating refractory status epilepticus (RSE) remains a challenge. Thiamylal can be used as a second- or third-line treatment; however, its potential to induce cytochrome P450 (CYP) activity may reduce the concentration of antiepileptic drugs (AEDs) administered prior to thiamylal. This report details a case of RSE patient treated with thiamylal, with monitored concentrations of thiamylal and other AEDs.
View Article and Find Full Text PDFAim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting.
Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted.
Background: Cefiderocol is a siderophore cephalosporin antibiotic with bactericidal activity against carbapenem-resistant Enterobacterales. However, an efficient dosing strategy is yet to be developed. This study aimed to evaluate efficient lower-dose regimens and estimate potential drug cost reductions.
View Article and Find Full Text PDFbacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration (T) of MEPM and its therapeutic efficacy in bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % T of MEPM as 75%.
View Article and Find Full Text PDFAims: Amikacin requires therapeutic drug monitoring for optimum efficacy; however, the optimal model-informed precision dosing strategy for the area under the concentration-time curve (AUC) of amikacin is uncertain. This simulation study aimed to determine the efficient blood sampling points using the Bayesian forecasting approach for early achievement of the target AUC range for amikacin in critically ill patients.
Methods: We generated a virtual population of 3000 individuals using 2 validated population pharmacokinetic models identified using a systematic literature search.
Objectives: In recent years, Vancomycin (VCM) dosing design using area under the concentration-time curve (AUC) has been recommended as a measure of efficacy and safety, but there are fewer reports on pediatric patients than on adults. In this study, we evaluated the threshold of AUC for AKI occurrence in pediatric patients and investigated the factors that contribute to the occurrence of AKI.
Methods: Pediatric patients aged 1-15 years on VCM treatment who underwent TDM at Kagoshima University Hospital from April 2016 to March 2022 were included in the computation of AUC using pediatric population pharmacokinetic parameters.
Background: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma.
Methods: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours.
In this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration-time curve (AUC) of vancomycin on the first and second day (AUC , AUC , respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model-informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations.
View Article and Find Full Text PDFBackground: The optimal timing for therapeutic drug monitoring (TDM) of voriconazole in Asians, who have higher rates of poor metabolisers than non-Asians, is unclear. This can cause unexpectedly high concentrations and delays in reaching steady-state levels.
Objectives: To determine the appropriate timing of TDM in Japanese patients receiving voriconazole.
Antimicrob Agents Chemother
June 2023
Model-informed precision dosing (MIPD) maximizes the probability of successful dosing in patients undergoing hemodialysis. In these patients, area under the concentration-time curve (AUC)-guided dosing is recommended for vancomycin. However, this model is yet to be developed.
View Article and Find Full Text PDFAs one of the efficient techniques for TDM, the population pharmacokinetic (popPK) model approach for dose individualization has been developed due to the rapidly growing innovative progress in computer technology and has recently been considered as a part of model-informed precision dosing (MIPD). Initial dose individualization and measurement followed by maximum a posteriori (MAP)-Bayesian prediction using a popPK model are the most classical and widely used approach among a class of MIPD strategies. MAP-Bayesian prediction offers the possibility of dose optimization based on measurement even before reaching a pharmacokinetically steady state, such as in an emergency, especially for infectious diseases requiring urgent antimicrobial treatment.
View Article and Find Full Text PDFPurpose: Tobramycin (TOB) exhibits variable pharmacokinetic properties due to the clinical condition of patients. This study aimed to investigate the AUC-guided dosing of TOB based on population pharmacokinetic analysis in the treatment of infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia.
Methods: This retrospective study was conducted between January 2010 and December 2020 after obtaining approval from our institutional review board.
Teicoplanin, a glycopeptide antimicrobial, is recommended for therapeutic drug monitoring, but it remains unclear how to target the area under the concentration-time curve (AUC). This simulation study purposed to demonstrate the potential of the Bayesian forecasting approach for the rapid achievement of the target AUC for teicoplanin. We generated concordant and discordant virtual populations against a Japanese population pharmacokinetic model.
View Article and Find Full Text PDFPurpose: Voriconazole, an antifungal drug, is metabolized by a cytochrome P450 isozyme. Increased adverse effects are observed in Asians because of the high rate of poor metabolizers. In this therapeutic drug monitoring (TDM) guideline, recommendations were made according to ethnic group.
View Article and Find Full Text PDFVancomycin is the first-choice antimicrobial for the lethal methicillin-resistant Staphylococcus aureus infections. Therefore, the therapeutic performance of vancomycin must be enhanced. The narrow therapeutic range between clinical efficacy and toxicity necessitates therapeutic drug monitoring.
View Article and Find Full Text PDFBackground: To promote model-informed precision dosing (MIPD) for vancomycin (VCM), we developed statements for therapeutic drug monitoring (TDM).
Methods: Ten clinical questions were selected. The committee conducted a systematic review and meta-analysis as well as clinical studies to establish recommendations for area under the concentration-time curve (AUC)-guided dosing.