Pharmacotherapy最新文献

{"title":"User Beware: Inaccuracy and Inconsistency of Large Language Models in Providing Precision Dosing Recommendations for Patients With Kidney Impairment-A Case Series.","authors":"H Rhodes Hambrick, Samuel Dubinsky, Danica Quickfall, Shannon Reinert, Sonya Tang Girdwood, Gideon Stitt","doi":"10.1002/phar.70207","DOIUrl":"https://doi.org/10.1002/phar.70207","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence-based dosing guidance for medications in critically ill patients with acute kidney injury (AKI) and receiving continuous kidney replacement therapy (CKRT) is limited. Freely available large language models (LLMs) can generate confident, human-like outputs. The accuracy and reproducibility of LLMs in providing precision drug dosing recommendations in the setting of AKI and CKRT have not been evaluated.</p><p><strong>Objectives: </strong>We sought to characterize literature concordance and internal consistency of LLM-generated dosing recommendations for cefepime and meropenem in patients with AKI and receiving CKRT.</p><p><strong>Methods: </strong>Six investigators queried the freely available versions of six LLMs (ChatGPT, Claude, Google Gemini, Microsoft Copilot, OpenEvidence, and Perplexity) from July to September 2025 using three standardized vignettes asking for dosing recommendations and rationale to meet prespecified pharmacodynamic targets: (i) adult with AKI not on dialysis receiving cefepime, (ii) child receiving CKRT and cefepime, and (iii) toddler receiving high-effluent CKRT and meropenem. To assess inter-iteration consistency, each investigator also prompted one LLM three times for each vignette. Responses were parsed for concordance with recommendations in primary literature. LLM \"reasoning\" was evaluated for use of pharmacokinetic (PK) equations, citation accuracy versus confabulation, acknowledgment of uncertainty, and recommendations for therapeutic drug monitoring (TDM) for efficacy or safety.</p><p><strong>Results: </strong>LLM-generated dosing recommendations varied widely. Mean concordance with literature-based recommendations was 63% (range: 28%-94%). LLMs produced variable responses to the same user upon multiple iterations, with variance in daily maintenance doses recommended ranging from 0 to 1000%. OpenEvidence universally cited relevant sources, whereas other LLMs leveraged sources inconsistently or confabulated them. Each recommended TDM, though only Claude consistently acknowledged its own uncertainty.</p><p><strong>Conclusion: </strong>Freely available LLMs produce highly variable and often discordant antibiotic dosing recommendations for patients with AKI and receiving CKRT. Although valuable for hypothesis generation and literature retrieval, LLM outputs should not be used in isolation for drug dosing in critically ill patients with kidney dysfunction.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 10","pages":"e70207"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incretin Mimetics and Alcohol-Related Outcomes: A Structured Narrative Review.","authors":"Christopher Goodyear, Eric Mensah, Autumn Stewart-Lynch, Jordan R Covvey","doi":"10.1002/phar.70206","DOIUrl":"https://doi.org/10.1002/phar.70206","url":null,"abstract":"<p><p>Harmful alcohol use results in negative health outcomes for millions of patients each year, with limited effective treatment options available for those diagnosed with alcohol use disorder (AUD). Incretin mimetics, such as glucagon-like-peptide-1 receptor agonists (GLP-1RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1RAs (GIP/GLP-1RAs), have garnered interest for their positive effects across a host of conditions beyond type 2 diabetes mellitus (T2DM); this includes substance use, where interactions between GLP-1, dopamine modulation, and other neuroinflammatory mechanisms suggest potential benefit. Accordingly, this structured narrative review details evidence related to the role of incretin mimetics for alcohol-related outcomes. Relevant pathophysiology is explored, as well as 21 observational and experimental clinical studies in this area. Literature suggests that incretin mimetics offer an opportunity for a shift in how medicine approaches AUD, leveraging multifaceted pathology to reduce alcohol consumption, craving intensity, health care utilization, and alcohol-related complications. However, substantial gaps remain in establishing their place in therapy as a pharmacotherapeutic option in AUD and understanding the nuanced role that these agents may offer to addiction medicine.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 10","pages":"e70206"},"PeriodicalIF":4.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149138016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focused Update to International Consensus Recommendations for the Use of Prolonged-Infusion Beta-Lactam Antibiotics Among Severely Ill Adult Patients: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.","authors":"Lisa T Hong, Alireza FakhriRavari, Marta Ulldemolins, Jason A Roberts, Robert A Bonomo, Marc H Scheetz","doi":"10.1002/phar.70188","DOIUrl":"10.1002/phar.70188","url":null,"abstract":"<p><p>In 2023, international consensus recommendations suggested the use of prolonged-infusion beta-lactam antibiotics over short-infusion dosing in severely ill adult patients to improve mortality or clinical cure, although the certainty of evidence was very low. With the availability of several new randomized controlled trials (RCTs), this focused update re-evaluates the efficacy of prolonged versus short infusion among severely ill adult patients. The original Population, Intervention, Comparator, and Outcome (PICO) question VII was separated into two questions addressing mortality (VIIa) and clinical cure (VIIb). Methods used for study identification, screening, and evidence grading were consistent with the original guideline, with the addition of Bayesian meta-analyses. A total of 28 RCTs evaluating mortality in severely ill adults were analyzed, with pooled estimates favoring prolonged infusion (RR 0.91; 95% confidence interval 0.85 to 0.97), supported by Bayesian analyses demonstrating a 98.76% posterior probability of benefit. Across 21 RCTs evaluating clinical cure, prolonged infusion improved outcomes compared with short infusion (RR 1.11; 95% confidence interval 1.06 to 1.17), supported by Bayesian analyses demonstrating a 99.97% posterior probability of benefit. Certainty of evidence was strengthened to moderate for mortality and low for clinical cure. Consistent with the original recommendation (PICO X), subgroup analyses evaluating loading doses suggested improved outcomes when a loading dose is used before continuous infusion. Overall, the cumulative evidence reinforces and strengthens the recommendation for use of prolonged-infusion beta-lactam therapy in severely ill adult patients to improve survival and clinical cure. Continued use of loading doses when initiating continuous-infusion therapy is suggested. Future research should identify subpopulations most likely to benefit, clarify optimal prolonged-infusion strategies, and define the role of therapeutic drug monitoring.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 9","pages":"e70188"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenobarbital Versus Benzodiazepine-Based Pathways for Alcohol Withdrawal Syndrome in Critically Ill Adults: A Systematic Review and Meta-Analysis.","authors":"Zeeshan M Rizwan, Diane Brown, Simone Barry, Kern Guppy, Dana J Gerberi, Ognjen Gajic, Svetlana Herasevich","doi":"10.1002/phar.70197","DOIUrl":"10.1002/phar.70197","url":null,"abstract":"<p><strong>Objective: </strong>To compare outcomes of phenobarbital-based versus benzodiazepine-based pathways for alcohol withdrawal syndrome (AWS) in critically ill adults and evaluate whether pathway design and timing of phenobarbital use affect treatment outcomes.</p><p><strong>Data sources: </strong>A librarian-led search of MEDLINE, Embase, Cochrane Central, CINAHL, Web of Science, Scopus, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform was conducted through July 2024, with updates in December 2024, August 2025, and December 2025. Search concepts included phenobarbital, benzodiazepines, and alcohol withdrawal.</p><p><strong>Study selection and data extraction: </strong>Comparative studies of adults admitted or transferred to an intensive care unit (ICU) with AWS and treated with phenobarbital-based versus benzodiazepine-based pathways were included. Sixteen nonrandomized studies were included in the qualitative synthesis, and 12 treatment-oriented studies were included in the primary meta-analysis. Multiple reviewers independently screened studies, extracted data, and assessed risk of bias using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I).</p><p><strong>Data synthesis: </strong>Phenobarbital-based pathways were not associated with significantly different intubation (11 studies; odds ratio (OR), 0.62; 95% confidence interval (CI), 0.20-1.87; I² = 73%) or hospital length of stay (five studies; mean differences [MD], -1.75 days; 95% CI, -5.07 to 1.56; I² = 63%) compared with benzodiazepine-based pathways. ICU length of stay was shorter with phenobarbital-based pathways (eight studies; MD, -0.60 days; 95% CI, -0.79 to -0.41; I² = 0%). In exploratory subgroup analyses, front-loaded, protocolized phenobarbital-first pathways were associated with lower intubation and shorter hospital length of stay, but certainty of evidence was very low.</p><p><strong>Relevance to patient care and clinical practice: </strong>This review distinguishes phenobarbital-first, protocolized ICU pathways from adjunctive or mixed phenobarbital strategies, suggesting that implementation design may influence outcomes.</p><p><strong>Conclusions: </strong>Although evidence remains very low certainty, these findings suggest that phenobarbital's role in ICU AWS may be pathway dependent. Front-loaded, protocolized phenobarbital-first pathways may be associated with favorable outcomes in exploratory analyses, but these findings should be considered hypothesis-generating and require confirmation in prospective randomized trials.</p><p><strong>Trial registration: </strong>CRD42024595819.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 9","pages":"e70197"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Coadministration of Continuous Infusions of Propofol and Clevidipine: A Multi-Site Retrospective Analysis.","authors":"Micaela N Warfield, Kristin C Cole, Kiyan Heybati, Nicholas J Vollmer, Erin D Wieruszewski, Hemang Yadav, Alejandro A Rabinstein, Caitlin S Brown","doi":"10.1002/phar.70196","DOIUrl":"10.1002/phar.70196","url":null,"abstract":"<p><strong>Introduction: </strong>Patients often receive propofol for sedation and clevidipine for hypertension in the intensive care unit. Both agents are formulated as a lipid emulsion, which may increase the risk of hypertriglyceridemia and acute pancreatitis with their coadministration. We aimed to determine the incidence of hypertriglyceridemia and acute pancreatitis with concurrent administration of propofol and clevidipine and identify patient risk factors for hypertriglyceridemia.</p><p><strong>Methods: </strong>This was a multicenter retrospective study of adult patients (≥ 18 years old) receiving concurrent propofol and clevidipine infusions for ≥ 6 h. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and acute pancreatitis. The secondary outcome was risk factors associated with hypertriglyceridemia during concurrent propofol and clevidipine infusions until both infusions had been discontinued. Univariable and multivariable logistic regression analyses were used to assess risk factors of hypertriglyceridemia in patients receiving concurrent propofol and clevidipine infusions.</p><p><strong>Results: </strong>Across 1,226 patients, the median duration of infusion overlap was 12.4 [interquartile range (IQR) 8.3, 22.7] hours. The mean age of the cohort was 59.6 [standard deviation (SD) 14.9] years, and 59.4% were male. Assuming those without a triglyceride level drawn did not have hypertriglyceridemia, hypertriglyceridemia after initiation of propofol and clevidipine infusion was found in 7.7% [95% confidence interval (CI) 6.3% to 9.3%] of the entire cohort. Twenty-six patients (2.1%) had a diagnosis of pancreatitis after initiation of lipid infusions, of which 12 cases were possibly infusion-related, and one case was likely infusion-related. After calculating the Naranjo Scale, all 13 cases of pancreatitis were possibly related to propofol or clevidipine infusions. Based on a multivariable logistic regression of those with a triglyceride level available, risk factors for hypertriglyceridemia included pancreatitis within the past 5 years [adjusted odds ratio (aOR) 2.77, 95% CI, 1.23 to 6.23] and statin use (aOR 1.94, 95% CI, 1.13 to 3.34).</p><p><strong>Conclusions: </strong>In our cohort of patients receiving concurrent propofol and clevidipine, the frequency of hypertriglyceridemia and acute pancreatitis was low. Further comparative studies are warranted to assess the risk of pancreatitis with the addition of clevidipine to propofol.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 9","pages":"e70196"},"PeriodicalIF":4.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Bayesian and First-Order Estimations of Vancomycin Area Under the Curve in Pediatrics Using One- and Two-Concentration Methods.","authors":"Katie B Olney, Joo Eun Jun, David S Burgess","doi":"10.1002/phar.70183","DOIUrl":"10.1002/phar.70183","url":null,"abstract":"<p><strong>Background: </strong>Current consensus guidelines recommend therapeutic drug monitoring of vancomycin to target a 24-h area under the curve (AUC₂₄) of 400-600 mg*hr/L. Recommended methods for estimation of AUC₂₄ include the use of first-order (linear) pharmacokinetic equations or Bayesian software. Limited data exist to compare these methods in pediatric patients. This study aimed to compare calculated AUC₂₄ using first-order equations with two drug concentrations at steady state to Bayesian one- and two-concentration estimations.</p><p><strong>Methods: </strong>This was a single center retrospective review of hospitalized pediatric patients receiving intravenous vancomycin. Patients with two concentrations collected at steady-state within 96 h of vancomycin initiation were screened. Pharmacokinetic parameters and AUC₂₄ were estimated using first-order equations and InsightRx Bayesian software. Pearson's correlation and clinical agreement were used to compare methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA) to assess variability.</p><p><strong>Results: </strong>Overall, 196 patients (22 neonates, 17 infants, 114 children, and 43 adolescents) were included in the final analysis. Reasonable agreement was observed between linear and Bayesian two-concentration methods (84.2%; R² = 0.723) and between Bayesian two- and one-concentration methods (82.7%, R² = 0.839). Some variability was noted with 95% LOA of -123 to 178 (MD = 27 mg*hr/L) and -88 to 110 (MD = 11 mg*hr/L), for the respective comparisons. Lower agreement was noted between linear and Bayesian one-concentration methods (73.9%, R² = 0.544), and the greatest amount of variability was demonstrated with 95% LOA of -179 to 211 (MD = 16 mg*hr/L). In subgroup analysis, neonates demonstrated significantly lower clinical agreement (54.5%) and correlation (R² = 0.2986) between linear and Bayesian one-concentration methods.</p><p><strong>Conclusions: </strong>Linear and Bayesian two-concentration methods demonstrated reasonable agreement with acceptable variability and may be considered comparable for estimating vancomycin AUC₂₄ in pediatric patients. Similarly, Bayesian two-concentration and one-concentration methods demonstrated reasonable agreement with acceptable variability, supporting the comparability of these methods to estimate AUC₂₄. As poor agreement was demonstrated between linear and Bayesian one-concentration methods in neonatal sub-analysis, additional investigation is warranted to determine the comparability of these methods in neonates.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70183"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13365635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to \"Comment on Cancer Treatment Modalities and Female Fertility Preservation\".","authors":"Seonga Song, Lilia Davenport, Samantha Paone, Jamie Chin-Hon","doi":"10.1002/phar.70191","DOIUrl":"10.1002/phar.70191","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70191"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148456497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Data-Driven Medication Regimen Complexity Score for Critically Ill Patients: MRC-ICU 2.0.","authors":"Bokai Zhao, Ye Shen, Kelli Henry, John W Devlin, David J Murphy, Susan E Smith, Brian Murray, Sandra Rowe, Andrea Sikora","doi":"10.1002/phar.70185","DOIUrl":"10.1002/phar.70185","url":null,"abstract":"<p><strong>Background: </strong>The 2019 medication regimen complexity-intensive care unit (MRC-ICU) score is associated with patient outcomes, ICU complications, and critical care pharmacist workload. This score was developed using heuristic component selection and validated in a single-center cohort of 130 ICU patients. We sought to apply data-driven reweighting methodology in a large, multicenter cohort of ICU adults to improve the predictive capabilities of MRC-ICU.</p><p><strong>Methods: </strong>This was a retrospective, observational cohort study of adults admitted to an ICU between 2015 and 2023 at two academic health systems. Machine learning-based methods, including Principal Component Analysis and Random Forest, were used to create an updated MRC-ICU score optimized to predict three outcomes: hospital mortality, ICU fluid overload (FO) occurrence, and invasive mechanical ventilation (IMV) use. MRC-ICU 2.1 used average mortality, FO, and IMV use; MRC-ICU 2.2 used average mortality and FO and adjusted for prolonged IMV use. Data from one center were used for training and testing, and data from the other for validation. The predictive abilities of MRC-ICU 2.1 and 2.2 for each outcome were compared to MRC-ICU 1.0 and to severity of illness scores (i.e., Acute Physiology and Chronic Health Evaluation [APACHE] II and Sequential Organ Failure Assessment [SOFA]).</p><p><strong>Results: </strong>A total of 19,117 patients across training, testing, and validation datasets were included. MRC-ICU 2.0 scores outperformed MRC-ICU 1.0 for predicting most outcomes, with improvements in Area Under the Receiver Operating Characteristic (AUROC) ranging from +0.03 to +0.08 across datasets. MRC-ICU 2.1 and 2.2 did not consistently outperform APACHE II and SOFA in predicting mortality. The addition of MRC-ICU 2.0 scores to models including APACHE II or SOFA resulted in statistically significant improvements in discrimination in several settings (DeLong p < 0.05), with AUROC increases generally ranging from approximately +0.01 to +0.13 depending on outcome and dataset.</p><p><strong>Conclusions: </strong>The updated MRC-ICU 2.0 score (MRC-ICU 2.1 and 2.2) demonstrated consistently improved discrimination compared with the original MRC-ICU 1.0 across outcomes and datasets. The performance of MRC-ICU 2.0 (MRC-ICU 2.1 and 2.2) was generally comparable to established severity-of-illness scores (SOFA and APACHE II), although it did not consistently outperform these measures. When incorporated into combined models, MRC-ICU 2.0 provided additional predictive value, indicating that it captures information complementary to traditional severity-of-illness scores. Overall, these findings suggest that MRC-ICU 2.0 represents an improved and clinically interpretable measure of medication regimen complexity that is useful as a complementary predictor.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70185"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13354895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148423138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus Guidance for Beta-Lactam Antibiotic Dose Individualization in Acutely Ill Patients: Endorsed by the American College of Clinical Pharmacy, European Society of Clinical Microbiology and Infectious Diseases, European Society of Clinical Microbiology and Infectious Diseases PK/PD of Anti-Infectives Study Group, Infectious Diseases Society of America, International Association of Therapeutic Drug Monitoring and Clinical Toxicology, Society of Critical Care Medicine, and the Society of Infectious Diseases Pharmacists.","authors":"Erin F Barreto, Erin K McCreary, Rekha Pai Mangalore, Sonya Tang Girdwood, Rebecca Arriola, Cynthia Bens, Robert A Bonomo, Andrea N Edginton, Lisa T Hong, Angela Huttner, Birgit C P Koch, Nicole Maranchick, Michael N Neely, Charles R Peloquin, Gauri G Rao, Jason A Roberts, Anka C Röhr, Marc H Scheetz, Audrey N Schuetz, Paul R Yarnold, Andres Zuluaga, Nathaniel J Rhodes","doi":"10.1002/phar.70181","DOIUrl":"10.1002/phar.70181","url":null,"abstract":"<p><p>Beta-lactam antibiotics (beta-lactams) are first-line treatments for most major infectious syndromes in acutely ill patients, with in vitro activity against common pathogens, demonstrated efficacy in trials, and a perceived low risk of adverse effects. The current dosing approach, informed by population-level data, tends to be simplistically reduced to a \"one size fits all\" dosing method which only accounts for body weight (i.e., in pediatrics) and end organ function to estimate drug clearance (e.g., estimated glomerular filtration rate); this approach results in substantial variability in observed serum concentrations in acutely ill patients, which can compromise real-world effectiveness and safety. Beta-lactam dose individualization, therefore, defined as a dosing regimen for one patient informed by measured concentrations from that patient, has been recommended in international clinical guidelines. Comprehensive guidance on best practices for beta-lactam dose individualization is lacking. To address this knowledge gap and develop guidance, a multidisciplinary panel of international experts was assembled from the disciplines of infectious diseases, critical care, pharmacometrics, and laboratory medicine, representing both adults and pediatrics. The panel systematically evaluated the literature, using the GRADE approach where feasible, to address broad thematic questions pertaining to whether beta-lactam dose individualization should be pursued, for what indications beta-lactam dose individualization is warranted, and the most critical considerations and best practices for implementation of beta-lactam individualization. The resultant consensus recommendations will equip healthcare professionals caring for acutely ill patients treated with beta-lactam therapy with the evidence and tools necessary to guide optimal use of beta-lactam dose individualization.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70181"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Cancer Treatment Modalities and Female Fertility Preservation\".","authors":"Mehmet Ertugrul Balkar","doi":"10.1002/phar.70190","DOIUrl":"10.1002/phar.70190","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":"46 8","pages":"e70190"},"PeriodicalIF":4.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13370044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148448710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}