Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely
{"title":"Multiple Model Optimal Sampling Promotes Accurate Vancomycin Area-Under-the-Curve Estimation Using a Single Sample in Critically Ill Children.","authors":"Kevin J Downes, Anna Sharova, Judith Malone, Audrey R Odom John, Athena F Zuppa, Michael N Neely","doi":"10.1097/FTD.0000000000001293","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001293","url":null,"abstract":"<p><strong>Background: </strong>Area-under-the-curve (AUC)-directed vancomycin therapy is recommended; however, AUC estimation in critically ill children is difficult owing to the need for multiple samples and lack of informative models.</p><p><strong>Methods: </strong>The authors prospectively enrolled critically ill children receiving intravenous (IV) vancomycin for suspected infection and evaluated the accuracy of Bayesian estimation of AUC from a single, optimally timed sample. During the dosing interval, when clinical therapeutic drug monitoring was performed, an optimally timed sample was collected, which was determined for each subject using an established population pharmacokinetic model and the multiple model optimal function of Pmetrics, a nonparametric population pharmacokinetic modeling software. The model was embedded in InsightRx NOVA (InsightRx, Inc.) for individual Bayesian estimation of AUC using the optimal sample versus all available samples (optimally timed sample + clinical samples).</p><p><strong>Results: </strong>Eighteen children were included. The optimal sampling time to inform Bayesian estimation of vancomycin AUC was highly variable, with trough samples being optimally informative in 32% of children. Optimal samples were collected by clinical nurses within 15 minutes of the goal time in 14 of 18 participants (78%). Compared with all samples, Bayesian AUC estimation with optimal samples had a mean bias of 0.4% (±5.9%) and mean imprecision of 4.6% (±3.6%). Bias of optimal sampling was <10% for 17 of the 18 participants (94%). When estimating AUC using only a peak sample (≤2 hours after dose) or only a trough (≤30 minutes before next dose), bias was <10% for 78% and 86% of participants, respectively.</p><p><strong>Conclusions: </strong>Optimal sampling supports accurate Bayesian estimation of vancomycin AUC from a single plasma sample in critically ill children.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Personalized Dosing of Linezolid to Reduce the Risk of Thrombocytopenia: A Systematic Review and Meta-Analysis.","authors":"Kazutaka Oda, Takeru Tsuruta, Yuki Hanai, Tomoyuki Yamada, Toshiaki Komatsu, Shoji Kondo, Hirofumi Jono, Hideyuki Saito","doi":"10.1097/FTD.0000000000001300","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001300","url":null,"abstract":"<p><strong>Background: </strong>Linezolid-induced thrombocytopenia (LIT) occurs in a dose-dependent manner. There is no consensus regarding personalized dosing of linezolid in the real world. This study investigated the usefulness of personalized dosing for the potential mitigation of LIT compared with standard dosing.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were performed using 4 medical electronic databases. Inclusion criteria were original research articles published up to October 23, 2023, whereas nonoriginal articles were excluded. Eligible participants included adults who were administered linezolid. A random-effects model was used to synthesize the results.</p><p><strong>Results: </strong>Four studies were eligible for inclusion. There were 208 patients in the personalized dosing (intervention) group and 195 patients in the standard dosing (comparison) group. The odds ratio for the intervention was 0.648 (95% confidence interval: 0.150-2.797), although significant heterogeneity was observed (I2 = 83.3%). An ad hoc analysis was performed by excluding one study with a significant bias risk in the treatment duration. The odds ratio for the intervention in the ad hoc analysis was 0.356 (95% confidence interval: 0.179-0.708) with little heterogeneity, showing a lower incidence risk of LIT.</p><p><strong>Conclusions: </strong>Personalized dosing in linezolid therapy may mitigate the risk of LIT.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigation of Teicoplanin Trough Concentrations and Safety Following High-Dose Loading in a Pediatric Population.","authors":"Sayaka Okuzono, Takaaki Yamada, Yoshitomo Motomura, Hikaru Kanemasa, Masataka Ishimura, Yuhki Koga, Hiroyuki Torisu, Shunsuke Kanno, Ichiro Ieiri, Shouichi Ohga","doi":"10.1097/FTD.0000000000001302","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001302","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic drug monitoring-informed teicoplanin dosage adjustments are recommended for safe and effective use. The authors' group previously reported that only half of children reached the recommended blood concentration range at the standard teicoplanin loading dose. It has been suggested that higher loading doses are necessary; however, the usefulness and safety of high-dose loading in pediatric patients in clinical practice are unknown.</p><p><strong>Methods: </strong>This retrospective cohort study was conducted between January 2018 and June 2021 using electronic medical records. The analysis included 2- to 16-year-old patients treated with teicoplanin who met the eligibility criteria. We assessed the trough concentration of teicoplanin and its safety after high-dose loading in pediatric patients.</p><p><strong>Results: </strong>Overall, 86 patients received a high-dose loading regimen (15 mg/kg every 12 hours for 3 doses, followed by 10 mg/kg once daily). Notably, 55 of the 86 patients (64%) achieved the target trough concentration (>15 mg/L) at significantly higher rates without increasing the incidence of organ damage compared with the standard loading regimen. Multivariate analysis revealed significant differences in age and renal function as factors that inhibited the attainment of the target trough concentration. Simulation analysis using a nomogram stratified by age and renal function revealed that the predicted teicoplanin trough levels were within the target trough values in 73% of patients.</p><p><strong>Conclusions: </strong>High-dose teicoplanin loading safely increases trough blood concentrations in the pediatric population. For further optimization, the dose selection should be stratified according to age and renal function.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daphne den Besten-Bertholee, Ilse Wegner, Daan J Touw, Peter G J Horst, Paola Mian
{"title":"Lamotrigine Use in Lactating Women: Passage into Breast Milk and Infant Exposure: Grand Round/A Case Study.","authors":"Daphne den Besten-Bertholee, Ilse Wegner, Daan J Touw, Peter G J Horst, Paola Mian","doi":"10.1097/FTD.0000000000001299","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001299","url":null,"abstract":"<p><strong>Background: </strong>Lamotrigine, an antiseizure medication used for epilepsy and bipolar disorders, is often prescribed to women of childbearing age due to relatively low teratogenic risk. It is known that lamotrigine use in lactation leads to detectable concentrations in breast milk, although concentrations vary significantly among individuals.</p><p><strong>Case presentation: </strong>A 35-year-old pregnant woman with epilepsy presented to our outpatient clinic. She was seizure-free and was taking lamotrigine 200 mg once daily. She is highly motivated to breastfeed her baby after birth but is concerned about the infant's exposure to lamotrigine through lactation. Lamotrigine concentrations were measured in both the breast milk and plasma of the suckling infants.</p><p><strong>Conclusions: </strong>Although lamotrigine is excreted into breast milk, and detectable in infants, the benefits of breastfeeding should not be overlooked. Higher plasma concentrations generally lead to higher breast milk concentrations, so aiming for the lowest possible maternal plasma levels is beneficial. These findings underscore the importance of TDM in this population.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot
{"title":"Determination of 31 Antimicrobials in Human Serum Using Ultra-High Performance Liquid Chromatography With Diode Array Detection for Application in Therapeutic Drug Monitoring.","authors":"Ibrahim El-Haffaf, Mehdi El Hassani, Amélie Marsot","doi":"10.1097/FTD.0000000000001284","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001284","url":null,"abstract":"<p><strong>Background: </strong>A versatile ultra-high performance liquid chromatography method with diode array detection was developed to quantify a wide range of antibiotics in human serum. This method addresses the need for rapid and accurate determination of antibiotic levels to ensure effective patient treatment and support the fight against antibiotic resistance.</p><p><strong>Methods: </strong>This method assesses 31 different compounds covering β-lactams, fluoroquinolones, antifungals, antituberculars, and more. Proteins were precipitated using methanol or acetonitrile, and drugs were extracted by liquid-liquid extraction with dichloromethane. Separation of the antimicrobials was achieved on a pentafluorophenyl column, using a mobile phase of phosphoric acid (0.01 mol/L) and acetonitrile in a gradient elution mode, with a flow rate of 500 μL/min.</p><p><strong>Results: </strong>Almost all compounds were detected at 200 nm. The total analysis time for this method was kept under 18 minutes, including equilibration time.</p><p><strong>Conclusions: </strong>This efficient method enables fast determination of numerous antimicrobial classes, providing clinicians with an essential tool for ensuring effective patient treatment and combating antimicrobial resistance.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manon Launay, Manon Vogrig, Marlene Damin-Pernik, Hubert Marotte, Sophie Perinel-Ragey
{"title":"Misleading Renal Function Evaluation Leading to Severe Methotrexate-Induced Toxicity.","authors":"Manon Launay, Manon Vogrig, Marlene Damin-Pernik, Hubert Marotte, Sophie Perinel-Ragey","doi":"10.1097/FTD.0000000000001297","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001297","url":null,"abstract":"<p><strong>Abstract: </strong>Low-dose methotrexate has been proposed as therapy for patients with severely disabling psoriasis and psoriatic arthritis. However, it can be associated with severe toxicity, such as pancytopenia, characterized by anemia (hemoglobin level <13 g/dL in men), thrombocytopenia (platelet count <150 × 109/L), and neutropenia or agranulocytosis (neutrophil count <1.5 × 109/L and 0.5 × 109/L, respectively). Here, we report a challenging clinical scenario characterized by pancytopenia and acute renal failure to inform clinicians about potential drug-drug interactions and subclinical renal insufficiency.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye Yang, Zhanzhang Wang, Tao Xiao, Xiaojia Ni, Emei Song, Lijing Dai, Yuqing Chen, Haoyang Lu, Dewei Shang, Yuguan Wen
{"title":"Preliminary Determination of the Therapeutic Reference Range of Lurasidone in Chinese Patients and Analysis of the Factors Influencing Lurasidone Dose-Corrected Concentrations.","authors":"Ye Yang, Zhanzhang Wang, Tao Xiao, Xiaojia Ni, Emei Song, Lijing Dai, Yuqing Chen, Haoyang Lu, Dewei Shang, Yuguan Wen","doi":"10.1097/FTD.0000000000001298","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001298","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to determine the therapeutic reference range of lurasidone, and to analyze the factors influencing the dose-corrected concentration of lurasidone in Chinese psychiatric patients, thereby providing a basis for the development of individualized dosing of lurasidone.</p><p><strong>Methods: </strong>A retrospective analysis was conducted for hospitalized patients who had received lurasidone and undergone blood concentration monitoring from May 2022 to September 2023 at the Affiliated Brain Hospital of Guangzhou Medical University. Analyses were based on patient demographic data, treatment regimens, and administered drug concentrations.</p><p><strong>Results: </strong>Data for a total of 123 lurasidone steady-state trough concentrations were collected from 120 hospitalized patients. It was found that 85.56% of lurasidone steady-state trough concentrations were below the lower limit of the lurasidone therapeutic reference range (15 ng·mL-1), and that the median steady-state trough concentration was 7.09 ng·mL-1 (IQ1-IQ3 = 4.12-11.82 ng·mL-1). Gender, age, and co-medication with valproic acid were found to be significant factors influencing lurasidone steady-state trough concentration/daily dose (C/D) values. C/D values for females were 14% higher than those obtained for males. Among patients who did not receive concomitant administration of valproic acid, the C/D values were 55% higher than those who had received co-administered valproic acid. Furthermore, C/D values obtained for elderly patients (≥60 years) were 140% higher than those recorded for adolescents (<18 years) and 157% higher than those in younger adults (18-60 years).</p><p><strong>Conclusions: </strong>The findings of this study indicated that the guideline-recommended therapeutic reference range (15-40 ng·mL-1) for lurasidone may not be appropriate, at least for the Chinese population. More extensive therapeutic drug monitoring is recommended for elderly female patients and those receiving co-medication with lurasidone and valproic acid.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clinical Efficacy and Safety of Vancomycin Based on Unbound Vancomycin Concentration Monitoring.","authors":"Fefei Ren, Shan Li, Yixin Liu, Xiangchen Li, Xikun Wu, Zhiqing Zhang","doi":"10.1097/FTD.0000000000001292","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001292","url":null,"abstract":"<p><strong>Objective: </strong>To monitor total trough concentration (Cmin_total) and unbound trough concentration (Cmin_free) of vancomycin in clinical samples and analyze the factors influencing them, and to assess their correlation with clinical efficacy and acute kidney injury (AKI).</p><p><strong>Methods: </strong>Plasma samples were processed by protein precipitation, followed by hollow-fiber centrifugal ultrafiltration to separate unbound vancomycin from plasma. Thereafter, Cmin_total and Cmin_free were determined using high-performance liquid chromatography. Clinical data of patients were collected. Factors affecting vancomycin Cmin_total, Cmin_free, and their correlation with clinical efficacy and nephrotoxicity were investigated.</p><p><strong>Results: </strong>A total of 146 samples from 105 included patients were collected. Cmin_total and Cmin_free of vancomycin ranged from 0.62 to 56.08 mcg·mL-1 and 0.61-38.51 mcg·mL-1, respectively. Cmin_total and Cmin_free were correlated (r = 0.8899), influenced by basal creatinine and cystatin C. Higher level of Cmin_free (˃8.6 mcg·mL-1) and nephrotoxic drugs concomitant were risk factors of vancomycin-associated AKI (P < 0.05); Cmin_total and Cmin_free thresholds of vancomycin-associated AKI were 15.35 and 6.83 mcg·mL-1, respectively.</p><p><strong>Conclusions: </strong>vancomycin Cmin_total and Cmin_free, higher Cmin_total and Cmin_free were correlated and higher concentrations of both may increase the risk of AKI.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unbound Ceftriaxone Concentrations in Plasma Measured Using Ultrafiltration Versus Equilibrium Dialysis: A Short Communication.","authors":"Matthias Gijsen, Dorian Vanneste, Pieter Annaert, Yves Debaveye, Joost Wauters, Isabel Spriet","doi":"10.1097/FTD.0000000000001294","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001294","url":null,"abstract":"<p><strong>Background: </strong>Ceftriaxone is a first-line beta-lactam antibiotic used in diverse clinical settings. Owing to pharmacokinetic alterations, ceftriaxone therapeutic drug monitoring is currently recommended for patients in the intensive care unit. Ultrafiltration is typically used to measure unbound ceftriaxone concentrations, as it is less costly and time-consuming compared with equilibrium dialysis. However, the reference method, equilibrium dialysis, has not been compared with equilibrium dialysis for ceftriaxone to measure the unbound ceftriaxone concentrations. Therefore, unbound ceftriaxone fractions measured by ultrafiltration versus equilibrium dialysis were compared in patients in the intensive care unit.</p><p><strong>Methods: </strong>Total and unbound ceftriaxone plasma fractions were measured by ultrafiltration (9500g at 37°C for 30 minutes) and equilibrium dialysis (12 kDa, 37°C for 4 hours) in 32 plasma samples from 28 patients who were critically ill collected during a previous prospective pharmacokinetic study. Passing-Bablok regression and Bland-Altman analyses were performed to evaluate the agreements between both methods.</p><p><strong>Results: </strong>The median (range) total ceftriaxone plasma concentration was 108.6 (5.2-233) mg/L. The median unbound concentration measured by equilibrium dialysis and ultrafiltration was 14.5 (0.7-52.9) and 23.3 (0.9-79.2) mg/L, respectively, showing a significant difference. Passing-Bablok regression analysis revealed significant proportional and systematic bias. This result was confirmed by Bland-Altman analysis, with a mean relative bias of 43.3% and wide agreement limits (-21% to 108%).</p><p><strong>Conclusions: </strong>Ultrafiltration substantially overestimates the unbound ceftriaxone fraction compared with equilibrium dialysis at 37°C. It is important to report methodological details and consider this information when interpreting unbound fractions of ceftriaxone and other drugs. These findings may impact the therapeutic drug monitoring of ceftriaxone.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nada Dia, Sabrina De Winter, Matthias Gijsen, Stefanie Desmet, Peter Vanbrabant, Willy Peetermans, Isabel Spriet, Erwin Dreesen
{"title":"Dose Optimization of Amikacin in the Emergency Department: A Population Pharmacokinetics Simulation Study.","authors":"Nada Dia, Sabrina De Winter, Matthias Gijsen, Stefanie Desmet, Peter Vanbrabant, Willy Peetermans, Isabel Spriet, Erwin Dreesen","doi":"10.1097/FTD.0000000000001279","DOIUrl":"https://doi.org/10.1097/FTD.0000000000001279","url":null,"abstract":"<p><strong>Background: </strong>In adult patients with sepsis or septic shock admitted to the emergency department, a single intravenous 15 mg/kg amikacin dose provides inadequate pharmacokinetic-pharmacodynamic target attainment at the locally reported minimum inhibitory concentration (MIC) of 2 mg/L and the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint for Enterobacterales of 8 mg/L.</p><p><strong>Objectives: </strong>To provide an amikacin dosing strategy with a clinically acceptable probability of target attainment (PTA) for all patients.</p><p><strong>Methods: </strong>Stochastic simulations were performed using a two-compartment population pharmacokinetics model of amikacin (NONMEM 7.5). PTA was evaluated for various dosing strategies across a range of virtual patients' body weight, body mass index, serum total protein, serum sodium, fluid balance, and estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI), at the locally reported MIC of 2 mg/L and the clinical breakpoint of 8 mg/L. The pharmacokinetic-pharmacodynamic targets were a 24-hour area under the concentration-time curve (AUC24h)/MIC of ≥80 and a 24-hour postdose concentration (C24h) of < 3 mg/L for efficacy and safety, respectively.</p><p><strong>Results: </strong>The PTA for the clinical breakpoint of 8 mg/L was <90% with standard 15 mg/kg dosing, across all patient characteristics. A flat 1500-mg dose achieved ≥90% PTA for the entire population at a MIC of 2 mg/L. However, at the clinical breakpoint of 8 mg/L, a flat 3500-mg dose provided ≥90% PTA only when the eGFRCKD-EPI was <96 mL/min/1.73 m2. The C24h was similar for 1500 mg and 15 mg/kg dosing, whereas 3500 mg resulted in a higher C24h.</p><p><strong>Conclusions: </strong>A flat dose is recommended over weight-based dosing. However, selecting a 1500-mg or 3500-mg dose may compromise either efficacy (MIC 2 mg/L) or safety (clinical breakpoint 8 mg/L), posing a dilemma. Clinical validation is warranted.</p>","PeriodicalId":23052,"journal":{"name":"Therapeutic Drug Monitoring","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}