PharmacotherapyPub Date : 2025-06-01Epub Date: 2025-04-18DOI: 10.1002/phar.70021
David E Nix, Fekade Sime, Jason A Roberts
{"title":"Correction of posaconazole concentrations for hypoalbuminemia.","authors":"David E Nix, Fekade Sime, Jason A Roberts","doi":"10.1002/phar.70021","DOIUrl":"10.1002/phar.70021","url":null,"abstract":"<p><strong>Background: </strong>Posaconazole is an example of a highly protein-bound drug (>98%) in which therapeutic drug monitoring (TDM) is commonplace. Total drug concentration is typically measured, and in the setting of hypoalbuminemia, total concentrations are lower despite no anticipated change in unbound concentration. Data support that unbound posaconazole concentration is responsible for antifungal activity and, in theory, is responsible for adverse effects that are dose-related. However, the therapeutic range of posaconazole is expressed as total concentration. The objective of this study was to investigate the use of an equation to correct posaconazole concentrations for albumin concentration as a surrogate for measurement of unbound concentration.</p><p><strong>Methods: </strong>Data on unbound and total posaconazole concentration were acquired retrospectively from a study of posaconazole pharmacokinetics in critically ill patients. The relationship between total and unbound concentration was explored with and without albumin as a covariate using linear regression. Correction equations were used to normalize total concentration to an albumin concentration of 4.4 g/dL.</p><p><strong>Results: </strong>A total of 78 pairs of total and unbound concentrations were available. Total and unbound posaconazole concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The median fraction unbound was 0.00645 (interquartile range of 0.00331-0.00794). Albumin concentration plays a highly significant role in the interpretation of TDM results. In a patient with hypoalbuminemia, a corrected concentration (C<sub>corr</sub>) = C<sub>t</sub>/(0.01 + 0.99·Alb/4.4), where C<sub>t</sub> is the total concentration and Alb is the albumin concentration in units of g/dL, is suggested. This equation can be further simplified to C<sub>sim</sub> = C<sub>t</sub>·4.4/Alb, where C<sub>sim</sub> is a close approximation of C<sub>corr</sub>.</p><p><strong>Conclusions: </strong>Hypoalbuminemia is associated with lower total concentrations of posaconazole; however, the \"active\" unbound concentration is not expected to systematically change. As a result, total posaconazole concentrations in the therapeutic range for patients with hypoalbuminemia are more likely to be associated with toxicity, especially when doses are increased to achieve \"therapeutic\" concentrations.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"324-331"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977480","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}
Wesley D Kufel, Nabil Zeineddine, Aliaa Fouad, Hanna F Roenfanz, Ryan K Shields, Ellen G Kline, Jameson Warner, Kathleen Hanrahan, Joseph L Kuti
{"title":"Pharmacokinetic and pharmacodynamic evaluation of sulbactam-durlobactam in a critically ill patient on continuous venovenous hemofiltration infected with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex.","authors":"Wesley D Kufel, Nabil Zeineddine, Aliaa Fouad, Hanna F Roenfanz, Ryan K Shields, Ellen G Kline, Jameson Warner, Kathleen Hanrahan, Joseph L Kuti","doi":"10.1002/phar.70027","DOIUrl":"https://doi.org/10.1002/phar.70027","url":null,"abstract":"<p><strong>Background: </strong>Drug databases currently do not provide dosing guidance for sulbactam-durlobactam in continuous renal replacement therapy. Herein, we present the first in vivo pharmacokinetic (PK) evaluation of sulbactam-durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRAB) bacteremia and ventilator-associated bacterial pneumonia (VABP).</p><p><strong>Methods: </strong>A 59-year-old critically ill patient (body mass index 60 kg/m<sup>2</sup>) required CVVH and developed CRAB bacteremia secondary to VABP. Sulbactam-durlobactam 2 g every 4 h infused over 3 h was initiated based on previous ex vivo data and the effluent rate of 6 L/h. The sulbactam-durlobactam minimum inhibitory concentration (MIC) was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed. Steady-state pre-filter blood, post-filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC).</p><p><strong>Results: </strong>The sulbactam-durlobactam MIC was 4/4 mcg/mL (susceptible). WGS revealed penicillin-binding protein (PBP)-1b and PBP-3 mutations. The selected dose exceeded sulbactam and durlobactam PK/pharmacodynamic (PD) targets with 100% free time above MIC (fT > MIC) and the ratio of area under the unbound concentration-time curve to MIC (fAUC/MIC) = 139, respectively. The SC for sulbactam and durlobactam was 0.68 and 0.67, respectively, and protein binding was 54% and 51%, respectively. Sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for CRAB bacteremia but recurred later in hospitalization 11 days after sulbactam-durlobactam treatment. The patient was ultimately transitioned to comfort care.</p><p><strong>Conclusion: </strong>Sulbactam-durlobactam monotherapy dosed at 2 g every 4 h (3-h infusion) in CVVH achieved PD targets for this CRAB isolate with a MIC of 4/4 mcg/ml. Although sulbactam-durlobactam monotherapy resulted in initial microbiological clearance for the CRAB bacteremia, recurrence occurred, and the patient ultimately died.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079547","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":"Predictive performance of population pharmacokinetic models in InsightRX® for model-informed precision dosing for Cefepime.","authors":"Christina König, Joseph L Kuti, Andrew J Fratoni","doi":"10.1002/phar.70029","DOIUrl":"https://doi.org/10.1002/phar.70029","url":null,"abstract":"<p><strong>Background: </strong>Model-informed precision dosing (MIPD) is a promising tool used to ensure therapeutic antimicrobial concentrations. Model selection and sampling strategy might lead to different pharmacokinetic (PK) parameter estimates. Herein, we assess the predictive performance for cefepime PK in two models implemented within the InsightRX software using differing sampling approaches.</p><p><strong>Methods: </strong>Historic cefepime PK data and individual Bayesian estimates in predominantly critically ill patients, some of whom had extracorporeal support, served as the reference standard. Two population PK models (A; B) were evaluated using four sampling scenarios: (i) trough only, (ii) midpoint only, (iii) trough + midpoint, and (iv) peak + midpoint + trough. The median prediction error (MPE) and median absolute prediction error (MAPE) were calculated for clearance (CL) and volume of central compartment (V<sub>c</sub>). Predicted categorical achievement of ≥70% time that the free drug concentration was greater than the minimum inhibitory concentration [fT>MIC<sub>(8/16mg/L)</sub>] was compared.</p><p><strong>Results: </strong>MAPE and MPE for CL and V<sub>c</sub> resulted in variability that was dependent on model and sampling strategy. Both models' overall MPE and MAPE for CL were <±20 and <30% for all tested scenarios, respectively, with a low MPE of -2.4% to 4.4% on CL for sampling scenario 4. For V<sub>c</sub>, MPE and MAPE were >±20 and >30% for the majority of test scenarios across both models, respectively. When excluding patients with extracorporeal support, MPE/MAPE for V<sub>c</sub> decreased to 3.7-4.8/23.3%-34.5% and -7.9-2.5/25.2%-29.6% for model A and B, respectively. Using each model and sampling scheme, only four patients had discordant predicted achievement of ≥70% fT>MIC<sub>(8/16mg/L)</sub>.</p><p><strong>Conclusions: </strong>These two population PK models and all sampling scenarios demonstrated acceptable prediction of cefepime PK parameters and pharmacodynamic exposures; therefore, they demonstrated suitability for utilizing MIPD for cefepime therapeutic drug monitoring.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049783","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":"Proton pump inhibitor concomitant use to prevent oxaliplatin-induced peripheral neuropathy: Clinical retrospective cohort study.","authors":"Keisuke Mine, Takehiro Kawashiri, Kohei Mori, Yusuke Mori, Haruna Ishida, Hibiki Kudamatsu, Shunsuke Fujita, Mayako Uchida, Takaaki Yamada, Nobuaki Egashira, Ichiro Ieiri, Satoru Koyanagi, Shigehiro Ohdo, Takao Shimazoe, Daisuke Kobayashi","doi":"10.1002/phar.70028","DOIUrl":"https://doi.org/10.1002/phar.70028","url":null,"abstract":"<p><strong>Background: </strong>Oxaliplatin-induced peripheral neuropathy (OIPN) is a major clinical challenge because it leads to discontinuation of chemotherapy. Omeprazole, a proton pump inhibitor (PPI), has been shown to prevent OIPN in a rat model. Therefore, we aimed to test whether the concomitant use of a PPI reduces oxaliplatin discontinuation due to OIPN.</p><p><strong>Methods: </strong>This retrospective study used data from 1015 patients who started treatment with oxaliplatin and evaluated two cohorts (PPI vs. non-PPI). The primary outcome measure was oxaliplatin discontinuation due to OIPN. A Kaplan-Meier curve was generated for cumulative doses and evaluated using the log-rank test and Cox proportional hazards analysis.</p><p><strong>Results: </strong>The log-rank test showed that the number of patients who discontinued oxaliplatin due to OIPN was significantly lower in the PPI group (p = 0.0264). Cox proportional hazards analysis incorporated and analyzed factors previously reported as potentially affecting neuropathy (sex, age, use of PPIs, calcium channel antagonists, opioids and adjuvant analgesics, and the CAPOX [capecitabine + oxaliplatin] regimen). The analysis suggested that the concomitant use of PPIs was a factor in reducing oxaliplatin discontinuation (adjusted hazard ratio [HR] = 0.568, 95% confidence interval [CI], 0.344-0.937, p = 0.0269). Since there were significant differences in some patient demographics between the two groups, propensity score matching was performed to align the patient demographics and then reanalyzed. After propensity score matching, the same analysis as above showed that oxaliplatin discontinuation due to OIPN was significantly less common in the PPI group (p = 0.0081); cox proportional hazards analysis showed that PPI use was a factor that significantly reduced oxaliplatin discontinuation due to OIPN (adjusted HR = 0.478, 95% CI, 0.273-0.836, p = 0.0096).</p><p><strong>Conclusions: </strong>These results suggest that concomitant PPI use may reduce oxaliplatin discontinuation due to OIPN in patients receiving oxaliplatin.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048014","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-05-08DOI: 10.1002/phar.70016
Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim
{"title":"Response to comment on \"Association of atrial fibrillation with lamotrigine: An observational cohort study\".","authors":"Sodam Kim, Landon Welch, Bertha De Los Santos, Przemysław B Radwański, Mark A Munger, Kibum Kim","doi":"10.1002/phar.70016","DOIUrl":"10.1002/phar.70016","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"308-309"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020941","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-05-09DOI: 10.1002/phar.70012
Christen J Arena, Ali Abed, Rachel M Kenney, Geehan Suleyman, Anita Shallal, Susan L Davis, Michael P Veve
{"title":"Retrospective cohort study of oral switch versus intravenous antibiotics for carbapenem-resistant enterobacterales and Pseudomonas aeruginosa infections on hospital discharge.","authors":"Christen J Arena, Ali Abed, Rachel M Kenney, Geehan Suleyman, Anita Shallal, Susan L Davis, Michael P Veve","doi":"10.1002/phar.70012","DOIUrl":"10.1002/phar.70012","url":null,"abstract":"<p><strong>Objectives: </strong>To compare outcomes of oral switch versus intravenous antibiotics for the treatment of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA) infections at hospital discharge.</p><p><strong>Methods: </strong>Institutional review board approved, retrospective cohort of adults infected with CRE or CRPA who received oral switch or intravenous antibiotics at hospital discharge from January 1, 2017, to April 30, 2024. Patients were included if they were eligible for oral switch and infected with an isolate susceptible to one or more oral antibiotics; non-bacteremic urinary tract infections were excluded. The primary outcome was 30-day clinical success at end of therapy, defined as lack of infection-related hospitalization, infection-related recurrence, or change/escalation of therapy. Secondary outcomes included hospital length of stay (LOS) and 30-day all-cause mortality from end of therapy.</p><p><strong>Results: </strong>Fifty-five patients were included; 51% received oral switch antibiotics and 49% received intravenous antibiotics. Thirty-three percent of patients had CRE, 67% had CRPA, and 38% of cultures were polymicrobial. The most common infection types were pneumonia (33%), intra-abdominal (26%), and bone/joint (22%). The median (interquartile range [IQR]) duration of outpatient therapy was 12 (6-25) days versus 20 (4-34) days for the oral switch and intravenous antibiotic groups, respectively (p = 0.341). 30-day clinical success was 61% in the oral switch and 48% in the intravenous antibiotic groups (p = 0.349); the median (IQR) hospital LOS for the oral switch and intravenous antibiotic groups was 14 (9-25) days and 16 (9-49) days, respectively (p = 0.165); 30-day mortality was 4% in the oral switch group and 15% in the intravenous antibiotic group (p = 0.193).</p><p><strong>Conclusion: </strong>A limited sample of patients who received oral switch antibiotics had similar outcomes to intravenous outpatient treatment of carbapenem-resistant organisms, with a shorter hospital LOS.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"244-250"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987754","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-04-11DOI: 10.1002/phar.70015
Hee-Jin Kim, Heehyun Won, Suvin Park, Hui-Eon Lee, Haerin Cho, Jeong Ah Kim, Na-Young Jeong, HoJin Shin, Ye-Jee Kim, Nam-Kyong Choi
{"title":"Risk of acute kidney injury in dapagliflozin users with type 2 diabetes: A nationwide propensity score-matched cohort study in Korea.","authors":"Hee-Jin Kim, Heehyun Won, Suvin Park, Hui-Eon Lee, Haerin Cho, Jeong Ah Kim, Na-Young Jeong, HoJin Shin, Ye-Jee Kim, Nam-Kyong Choi","doi":"10.1002/phar.70015","DOIUrl":"10.1002/phar.70015","url":null,"abstract":"<p><strong>Background: </strong>Several previous studies have identified a potential risk of acute kidney injury (AKI) associated with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, based on adverse event reports. However, recent European observational studies have shown conflicting results.</p><p><strong>Objective: </strong>To evaluate the risk of AKI in patients with type 2 diabetes (T2DM) who were treated with dapagliflozin compared with sitagliptin.</p><p><strong>Method: </strong>We conducted a retrospective cohort study on patients with T2DM who were newly prescribed dapagliflozin or sitagliptin between September 1, 2014, and June 30, 2021, using the nationwide National Health Insurance Review and Assessment (HIRA) Service database in Korea. Propensity scores were estimated using a multivariable logistic regression model, and matching was performed at a 1:1 ratio to balance the dapagliflozin and sitagliptin groups. The outcome of interest was the occurrence of AKI hospitalization 90 days post-exposure, captured by a validated algorithm based on the International Classification of Diseases 10th Revision (ICD-10) code: N17. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a Cox proportional hazards model.</p><p><strong>Results: </strong>Among 94,977 dapagliflozin users matched to sitagliptin users, AKI events occurred in 132 dapagliflozin users versus 198 sitagliptin users, with incidence rates of 2.92 and 8.93 per 1000 person-years, respectively. The risk of AKI events was 34% lower in dapagliflozin users (HR: 0.66, 95% CI: 0.53-0.83) compared with sitagliptin users. This protective effect remained consistent in sensitivity analyses.</p><p><strong>Conclusion: </strong>Contrary to the United States Food and Drug Administration's safety warning, our findings suggest that dapagliflozin may have a protective effect against AKI in patients with T2DM. This is consistent with recent findings from European post-marketing safety studies and may serve as supportive evidence.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"282-290"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049800","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-04-16DOI: 10.1002/phar.70018
Nadine K El-Nagdy, Noha O Mansour, Adel Al-Hady Ahmed Diab, Moetaza M Soliman
{"title":"Efficacy of adjuvant use of midodrine in patients with septic shock: An open label randomized controlled trial.","authors":"Nadine K El-Nagdy, Noha O Mansour, Adel Al-Hady Ahmed Diab, Moetaza M Soliman","doi":"10.1002/phar.70018","DOIUrl":"10.1002/phar.70018","url":null,"abstract":"<p><strong>Background: </strong>Midodrine has been primarily studied as an adjunctive oral therapy to reduce the need for vasopressors in intensive care units (ICU). Nonetheless, the available results evaluating midodrine as an adjuvant therapy in the treatment of septic shock are limited and inconclusive. This study aims to evaluate the efficacy of midodrine, specifically focusing on its effect on mortality outcomes in patients with septic shock.</p><p><strong>Methods: </strong>This was an open-label randomized controlled trial. Patients with septic shock (n = 100) were randomized to either the control group, who received intravenous norepinephrine, or the midodrine group, who received intravenous norepinephrine and midodrine 10 mg every 8 h. The primary outcome was the 28-day in-hospital mortality. Secondary outcomes were 7-day ICU mortality, average dose of norepinephrine, duration of intravenous norepinephrine, ICU length of stay (LOS), and in-hospital LOS.</p><p><strong>Results: </strong>The 28-day mortality rate was 68% in the control group compared to 54% in the midodrine group (risk difference -14% (95% confidence interval (CI)) -32.9% to 4.9%). Similarly, the 7-day ICU mortality rate was 56% in the control group and 42% in the midodrine group (risk difference -14% (95% CI -33.4% to 5.4%)). The average intravenous norepinephrine dose in the midodrine group was significantly lower compared to the control group (mean difference 0.06 (95% CI 0.01-0.11), p = 0.002). However, midodrine did not have a significant impact on the duration of intravenous norepinephrine use (mean difference 0.66 (95% CI -0.56 to 1.88)). Midodrine did not significantly shorten the course of hospitalization. There was no significant difference in median ICU LOS between the control group and the midodrine group (4 vs. 5 days, respectively).</p><p><strong>Conclusion: </strong>The findings did not demonstrate a significant reduction in mortality with adjuvant midodrine use in the treatment of septic shock. Midodrine appears to reduce the need for vasopressors. However, our findings did not support that midodrine shortens the duration of vasopressor use nor the course of hospitalization for patients with septic shock.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"264-272"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020940","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-03-24DOI: 10.1002/phar.70011
Alyssa Christensen, Ethan Ryberg, Zachary Nelson, Ella Chrenka, Maxx Enzmann, S Rebecca Peglow, Brent Footer
{"title":"Better together? Reducing vancomycin use and acute kidney injury with a blended AUC and trough-based dosing guideline.","authors":"Alyssa Christensen, Ethan Ryberg, Zachary Nelson, Ella Chrenka, Maxx Enzmann, S Rebecca Peglow, Brent Footer","doi":"10.1002/phar.70011","DOIUrl":"10.1002/phar.70011","url":null,"abstract":"<p><strong>Background: </strong>Vancomycin guidelines recommend area-under-the-curve (AUC) therapeutic monitoring for patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections. No recommendations exist for patients with non-severe staphylococcal infections or those with other Gram-positive infections. AUC-based vancomycin dosing can be resource-intensive and may not be necessary for all patients.</p><p><strong>Methods: </strong>New institutional guidelines for vancomycin dosing were implemented across an eight-hospital health system in 2023. The new guidelines recommended either AUC or trough-based dosing depending on the severity of the infection and the likelihood of MRSA. Adult patient encounters with at least one vancomycin administration were compared retrospectively 6 months pre-implementation and 6 months post-implementation. Cumulative vancomycin dose, administrations, and serum levels were assessed. The rate of acute kidney injury (AKI) was compared in a subgroup of patient encounters with four or more administrations. Pharmacist time saved using a blended approach compared to a uniform AUC dosing guideline was estimated based on the number of patients receiving trough-based dosing in the post-implementation group.</p><p><strong>Results: </strong>A total of 8155 patient encounters were included in the analysis (3916 pre-implementation, 4239 post-implementation). The primary outcome of median cumulative vancomycin dose (mg) was 500 mg lower in the post-implementation group (3000 mg pre-implementation vs 2500 mg post-implementation, Odds ratio [OR] 0.94 95% confidence interval [CI] 0.90-0.97, p < 0.001). Patients in the post-implementation group were significantly less likely to have vancomycin serum levels drawn (OR 0.86; 95% CI 0.78, 0.96, p = 0.005). A subgroup of patient encounters receiving four or more vancomycin administrations included 2483 patient encounters (1251 pre-implementation, 1232 post-implementation). AKI occurred in 120 (9.6%) cases pre-implementation and 89 (7.2%) cases post-implementation. The risk of AKI was significantly lower post-implementation (OR 0.73; 95% CI 0.55, 0.98, p = 0.038). Estimated pharmacist time saved was between 2229 to 5201 min, equating to an estimated $16,851.24 to $39,319.56 saved over 6 months, with blended vancomycin dosing.</p><p><strong>Conclusion: </strong>In this large multi-hospital cohort, the implementation of a blended dosing method using a majority of AUC-based dosing reduced cumulative vancomycin doses, serum levels, and AKI. Including trough recommendations for patients with less severe infections and non-MRSA, Gram-positive pathogens may have saved significant pharmacist time and associated costs compared to a uniform AUC dosing policy. This study further highlights the sizeable amount of unnecessary vancomycin use with a corresponding low incidence of severe MRSA infections.</p>","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"273-281"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692873","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}
PharmacotherapyPub Date : 2025-05-01Epub Date: 2025-04-09DOI: 10.1002/phar.70017
Kui Dang, Youbin Luo
{"title":"Comment on \"Association of atrial fibrillation with lamotrigine: An observational cohort study\".","authors":"Kui Dang, Youbin Luo","doi":"10.1002/phar.70017","DOIUrl":"10.1002/phar.70017","url":null,"abstract":"","PeriodicalId":20013,"journal":{"name":"Pharmacotherapy","volume":" ","pages":"307"},"PeriodicalIF":2.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811980","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}