Article
Pharmacology & Pharmacy
John Cerenzio, James Truong
Summary: The use of Bayesian-assisted AUC(24h) dosing was associated with a significant reduction in the incidence of AKI compared to trough-based dosing. The efficacy for patients with confirmed MRSA infection was similar between the two dosing groups. These findings may provide evidence for more institutions to adopt Bayesian software for vancomycin dosing.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Microbiology
Niloufar Salehpour, Lacey D. Riley, Marcos J. Gonzales, Emir Kobic, David E. Nix
Summary: A novel Bayesian method was developed to interpret serum vancomycin concentrations (SVCs) after the administration of one or more vancomycin doses with potential varying doses and intervals. The method was evaluated using retrospective data from 442 subjects from three hospitals, and it showed good predictive performance.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Joshua M. Knight, Tomona Iso, Katherine K. Perez, Joshua T. Swan, Charles E. Janak, Judy O. Ikwuagwu, William L. Musick
Summary: This study compared three vancomycin dosing modalities and found that the use of AUC-guided Bayesian software and AUC-targeted empiric dosing nomogram resulted in lower incidence of acute kidney injury (AKI) compared to trough-guided dosing. These findings suggest that AUC-guided Bayesian software can reduce the occurrence of AKI and abnormal trough values.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Elizabeth Keil, Rebekah H. H. Wrenn, Connor R. R. Deri, Cara N. N. Slaton, Jenny Shroba, Alice Parish, Alaattin Erkanli, Justin Spivey
Summary: This study compared the accuracy of vancomycin AUC calculated by open-access, online, trough-only calculators to AUCs calculated by the trapezoidal method using peak and trough concentrations. The results showed that VancoPK was the closest calculator to the trapezoidal method and had the most consistent dose adjustments. Therefore, VancoPK can be used as an alternative to the trapezoidal method for calculating vancomycin AUC.
ANNALS OF PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Nathan Fewel
Summary: The study aimed to assess the accuracy and precision of estimating the area under the curve (AUC) values using only vancomycin trough concentrations compared to both peak and trough values in a veteran population. Data from 5 Veterans Affairs hospitals in the US were analyzed, and the VancoPK model was found to be the most accurate and precise among the 4 evaluated models. The trough-only AUC estimation approach showed several advantages over the peak-trough approach.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
(2023)
Article
Pharmacology & Pharmacy
Luqman Vali, David R. Jenkins, Rakesh Vaja, Hussain Mulla
Summary: The study demonstrated that bedside Bayesian-guided personalised dosing of vancomycin in vascular surgery patients can increase the proportion of patients achieving target AUC(24) values and the percentage time in the target range.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Health Care Sciences & Services
Abdullah M. Alzahrani, Anjum Naeem, Rami M. Alzhrani, Manar A. Harbi, Sarah A. Alghamdi, Shahid Karim, Ahmed S. Ali, Ghusun Alsenaini, Hani Hasan, Ayed A. Alkatheeri, Samah S. Basudan, Yahya A. Alzahrani
Summary: AUC(0-24) is the most accurate way to track vancomycin levels, while C-min is not a reliable surrogate. Most hospitals in Saudi Arabia do not follow AUC-guided dosing and monitoring of vancomycin. This study aims to calculate AUC(0-24) using the Bayesian dosing software, identify the probability of optimal vancomycin dosage, and evaluate the accuracy and precision of the Bayesian platform.
Article
Pharmacology & Pharmacy
David E. Nix, Lisa E. Davis, Kathryn R. Matthias
Summary: This study aimed to investigate the relationship between area under the concentration-time curve (AUC) and trough concentration, as well as the impact of dosing regimen on goal achievement, in the monitoring of vancomycin therapy for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. The results showed that AUC is related to dosing interval divided by half-life in a nonlinear fashion, and trough concentration can be used as a surrogate for AUC. The study also proposed an AUC-trough equation to establish a patient-specific target for steady-state trough concentration.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
(2022)
Article
Infectious Diseases
Yazed Saleh Alsowaida, David W. Kubiak, Brandon Dionne, Mary P. Kovacevic, Jeffrey C. Pearson
Summary: This study compared the efficiency of Bayesian modeling software and first-order PK equations in calculating vancomycin AUC, finding that Bayesian software was more time-consuming without electronic health record integration, but more efficient after integration. Vancomycin concentrations were more likely to be usable for calculations in the Bayesian group.
Article
Pharmacology & Pharmacy
Kai Shen, Yaxin Fan, Minjie Yang, Yuancheng Chen, Jinhao Tao, Guoping Lu, Hong Zhang, Qiwei Huang, Jing Zhang
Summary: This study aimed to establish a population pharmacokinetics model for Chinese pediatric patients receiving Vancomycin and evaluate the correlation between PK/PD indices and clinical outcomes. The results showed no significant correlation between PK/PD indices and clinical efficacy, suggesting that Chinese pediatric patients may be suitable for a lower AUC(0-24)/MIC target value. Further studies are needed to explore optimal dose regimens for Chinese pediatric patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kellie N. Arensman Hannan, Christina G. Rivera, Nathan Fewel
Summary: This study found that using a volume of distribution model that incorporates age and actual body weight, in combination with trough-only data, can accurately estimate the vancomycin area under the concentration-time curve (AUC) in an adult population at Mayo Clinic.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
(2023)
Article
Microbiology
Sean N. Avedissian, Gwendolyn Pais, Jiajun Liu, J. Nicholas O'Donnell, Thomas P. Lodise, Michael Neely, Walter C. Prozialeck, Peter C. Lamar, Leighton Becher, Marc H. Scheetz
Summary: The study identified that in a rat model, both the dosage and frequency of vancomycin administration significantly influenced the risk of kidney injury, with exposure-response relationships observed between pharmacokinetic exposure and kidney injury molecule-1 levels.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Review
Microbiology
Bruce R. Dalton
Summary: Therapeutic drug monitoring for vancomycin has shifted its focus from trough concentrations to area under the curve (AUC(24)). However, the evidence for this change is weak, with retrospective analyses and animal studies lacking conviction. In vitro data also present conflicting results. Therefore, the adoption of AUC(24):MIC based on animal experiments and in vitro evidence may be premature for vancomycin.
Article
Infectious Diseases
Yujin Sohn, John Hoon Rim, Yunsuk Cho, Jonghoon Hyun, Yaejee Baek, Moohyun Kim, Jung Ho Kim, Hye Seong, Jin Young Ahn, Sang-Guk Lee, Jong-Beack Lim, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Young Goo Song
Summary: In patients with enterococcal bacteremia, a vancomycin trough level of 15 µg/mL or lower was associated with 28-day mortality. However, larger prospective studies are needed to examine the efficacy of vancomycin PK/PD parameters in patients with enterococcal bacteremia.
BMC INFECTIOUS DISEASES
(2021)
Article
Pharmacology & Pharmacy
Sheryl A. Zelenitsky, Robert E. Ariano
Summary: The study developed an updated vancomycin dosing protocol for chronic intermittent high-flux hemodialysis patients based on Monte Carlo simulation methods and therapeutic drug monitoring guidelines. Different regimens were constructed for patients of varying weights to achieve target vancomycin plasma concentrations during dialysis sessions. The proposed protocol demonstrated high probability of target attainment and practical applicability in the dialysis setting.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
(2022)
Article
Infectious Diseases
Marco Falcone, Francesco Menichetti, Dario Cattaneo, Giusy Tiseo, Sara Baldelli, Valentina Galfo, Alessandro Leonildi, Enrico Tagliaferri, Antonello Di Paolo, Manjunath P. Pai
Summary: This study investigated dosing strategies for aztreonam with avibactam in critically ill patients, finding that pragmatic and lower daily dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Manjunath P. Pai, Mark H. Wilcox, Surya Chitra, Paul C. McGovern
Summary: This post-hoc analysis aimed to examine the safety and efficacy of omadacycline in adults with ABSSSI based on BMI categories and diabetes history. The results showed consistent clinical success and safety outcomes for omadacycline across different BMI groups and diabetes statuses.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Microbiology
Cinzia Auriti, Bianca M. Goffredo, Maria P. Ronchetti, Fiammetta Piersigilli, Sara Cairoli, Iliana Bersani, Andrea Dotta, Pietro Bagolan, Manjunath P. Pai
Summary: This study evaluated the efficacy and safety of micafungin at a dose of 8 mg/kg daily in 35 neonates and young infants with invasive candidiasis, showing that the treatment was effective in resolving the infection in 86.7% of patients treated for >= 14 days, with some patients experiencing transient hypertransaminasemia. Micafungin at this dosage was found to be well tolerated in this population.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Miao He, Ernane Souza, Aleksas Matvekas, Ryan L. Crass, Manjunath P. Pai
Summary: In mouse experiments, the dose of vancomycin (VAN) was found to be associated with the development of acute kidney injury (AKI). The risk of AKI can be reduced by combining VAN with piperacillin/tazobactam (TZP) or imipenem-cilastatin/relebactam (IMP-C/REL).
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Daniel L. Hertz, Li Chen, N. Lynn Henry, Jennifer J. Griggs, Daniel F. Hayes, Brian A. Derstine, Grace L. Su, Stewart C. Wang, Manjunath P. Pai
Summary: This study aimed to investigate morphomic parameters as predictors of paclitaxel pharmacokinetics to identify alternative dosing strategies that may improve treatment outcomes. The results showed that extending paclitaxel infusion duration in patients with low skeletal muscle area predicted to reduce peripheral neuropathy while maintaining systemic exposure.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Letter
Endocrinology & Metabolism
Shuhan Liu, Manjunath P. Pai, Corey A. Lester
Article
Biochemical Research Methods
Abbie D. Leino, John Takyi-Williams, Bo Wen, Duxin Sun, Manjunath P. Pai
Summary: This study describes the development of a laboratory and analytical technique for quantifying tacrolimus and mycophenolic acid from Tasso-M20 in human whole blood. The sampling and extraction procedures allowed for accurate quantification of these drugs and identified important education points for future home-based sample collections.
Article
Pharmacology & Pharmacy
Hyun Gi Yun, Andrew J. F. Smith, Kenneth C. C. DeBacker, Manjunath P. P. Pai
Summary: The study aimed to explore the precision in dosing with different equations for estimating glomerular filtration rate (eGFR) by using a model drug (vancomycin) dependent on kidney function clearance. The findings suggest that the nonrace-based serum cystatin C (S-cys) eGFR model outperformed other clearance models and improved the probability of target attainment. When S-cys data is not available, the new 2021 CKD-EPI eGFR(cr) equation without race factor performs equally well as the conventional approach. This study highlights the importance of removing race as a factor for kidney function dose adjustment.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Immunology
Manjunath P. Pai, Pier Giorgio Cojutti, Valentina Gerussi, Paola Della Siega, Carlo Tascini, Federico Pea
Summary: Linezolid-induced myelosuppression is likely to occur in cardiosurgical patients due to reduced kidney function and potential drug interactions. Population modeling and simulation demonstrate that lower doses coupled with therapeutic drug monitoring are necessary in this vulnerable population. Thus, reducing the empiric linezolid doses in cardiosurgical patients may help avoid toxicities, and further studies are needed to verify potential drug interactions.
CLINICAL INFECTIOUS DISEASES
(2023)
Article
Pharmacology & Pharmacy
Manjunath P. Pai, Sirima Sitaruno, Mohamed Abdelnabi
Summary: This study examined the precision gain or loss in drug dosing with estimated creatinine clearance (eCLcr) and estimated glomerular filtration rate (eGFR) using serum creatinine (eGFRcr) with and without race and body surface area (BSA) indexation. The results showed that the eGFR equation without race and BSA indexation provided a better method for drug dosing in terms of precision.
Article
Microbiology
Ronald G. Hall, Shuhan Liu, William C. Putnam, Rajareddy Kallem, Tawanda Gumbo, Manjunath P. Pai
Summary: Echinocandins like anidulafungin are first-line therapies for candidemia and invasive candidiasis, but their dosing may be suboptimal in obese patients. This study aimed to evaluate the impact of body size on anidulafungin pharmacokinetics (PK) and found that a higher maintenance dose of anidulafungin is needed in larger adults to achieve the desired effect.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Review
Medicine, Research & Experimental
Radin Alikhani, Manjunath P. Pai
Summary: As human lifespan increases, there is a decline in kidney function that affects the pharmacokinetics and pharmacodynamics of drugs. Various equations have been developed to estimate glomerular filtration rate (GFR), but the trajectory of changes differs with age. Biological age is recognized as an important parameter in kidney function equations, and efforts to quantify it have grown in recent years. This narrative review examines how different equations model the changes in GFR across chronological age and discusses the challenges and potential of incorporating biological age in drug dosing for older adults.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Pharmacology & Pharmacy
Abbie D. Leino, John C. Magee, David B. Kershaw, Manjunath P. Pai, Jeong M. Park
Summary: This study aimed to evaluate the impact of food intake on 24-hour pharmacokinetics of tacrolimus in pediatric kidney transplant recipients through meta-analysis. The results showed that food intake is the major driver of diurnal variation in tacrolimus exposure, but these changes are not reflected by trough concentrations alone.
JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Theodore S. Jennaro, Michael A. Puskarich, Thomas L. Flott, Laura A. Mclellan, Alan E. Jones, Manjunath P. Pai, Kathleen A. Stringer
Summary: The study aimed to describe the population pharmacokinetics of high-dose L-carnitine in patients with septic shock, test various estimates of kidney function, and evaluate the correlation of PK parameters with pre-treatment metabolites. The results indicated that kidney function estimates and baseline metabolic status are important factors influencing the therapeutic effect of L-carnitine supplementation in septic shock patients.
Article
Biochemical Research Methods
John Takyi-Williams, Abbie D. Leino, Ruiting Li, Kevin J. Downes, Athena F. Zuppa, Amanda Bwint, Bo Wen, Duxin Sun, Marc H. Scheetz, Manjunath P. Pai
Summary: This study developed a bioanalytical method for the simultaneous quantification of multiple antibiotics from VAMS, which can facilitate pharmacokinetic/pharmacodynamic studies.