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Okuwaki T, Kobayashi M, Kikuchi R, Tomoda Y, Ogawa M, Kasugai K, Seto Y, Tomizawa A, Otori K. Vancomycin-associated acute kidney injury in underweight patients: a propensity score matching analysis. Int Urol Nephrol 2025; 57:1329-1336. [PMID: 39652231 DOI: 10.1007/s11255-024-04306-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 11/22/2024] [Indexed: 03/14/2025]
Abstract
PURPOSE To investigate the effect of being underweight on the incidence of vancomycin-associated acute kidney injury (AKI) using propensity score matching analysis. METHODS This study is a retrospective analysis of patients who received vancomycin and had their serum concentration measured at Kitasato University Hospital between January 1, 2016 and December 31, 2020. Patients were divided into underweight and non-underweight groups based on body mass index (BMI), and propensity score matching analysis was used to evaluate whether underweight affected the incidence of acute kidney injury. RESULTS 480 patients met the selection criteria, and 111 patients from each group (BMI < 18.5 and BMI ≥ 18.5) were successfully matched using propensity score matching. After matching, there were no differences in non-physical characteristics between the two groups. The incidence of AKI was 23.4% (26 of 111) in the BMI < 18.5 group and 37.8% (42 of 111) in the BMI ≥ 18.5 group, with the BMI < 18.5 group having a significantly lower incidence. The odds ratio was 0.503 [95% CI 0.281-0.900]. CONCLUSION This study showed that underweight patients (BMI < 18.5) had a significantly lower incidence of vancomycin-associated AKI compared to those with BMI ≥ 18.5. As there have been no previous reports on the association between underweight and vancomycin-associated AKI, this study provides novel insights.
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Affiliation(s)
- Tatsuya Okuwaki
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
| | - Masahiro Kobayashi
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan.
| | - Rino Kikuchi
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Yoshinori Tomoda
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Moeka Ogawa
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Kumi Kasugai
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
| | - Yoshinori Seto
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
| | - Atsushi Tomizawa
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- Department of Patient Safety, Kitasato University Hospital, Sagamihara, Japan
| | - Katsuya Otori
- Department of Pharmacy, Kitasato University Hospital, Sagamihara, Japan
- School of Pharmacy, Kitasato University, Tokyo, Japan
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Lee YW, Kim JH, Park JJ, Park H, Seo H, Kim YK. Development and external validation of a machine learning model to predict the initial dose of vancomycin for targeting an area under the concentration-time curve of 400-600 mg∙h/L. Int J Med Inform 2025; 196:105817. [PMID: 39893767 DOI: 10.1016/j.ijmedinf.2025.105817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2024] [Revised: 12/30/2024] [Accepted: 01/28/2025] [Indexed: 02/04/2025]
Abstract
PURPOSE To develop and validate a novel artificial intelligence model for predicting the initial empiric dose of vancomycin, with the aim of achieving an area under the concentration-time curve (AUC) of 400-600 mg∙h/L, using individual clinical data. METHODS Machine learning models were developed and validated internally and externally using data from adult patients who received intravenous vancomycin treatment between November 2020 and June 2023, using records from July to September 2023, sourced from two hospitals. This study included 205, 44, and 35 patients in the training, internal validation, and external validation sets, respectively. The Random Forest, XGBoost, and Ensemble models were evaluated based on the mean squared error, root mean squared error, R-squared value, and accuracy (±20 % of the actual dose). FINDINGS In internal validation, the Random Forest model achieved the highest 20% Accuracy at 56.8%, while the XGBoost model achieved 56.8% and Voting Ensemble models attained 54.5% accuracy. In external validation, the XGBoost model achieved the highest 20% Accuracy at 74.3%, followed by Random Forest and Voting Ensemble, both also achieving 74.3% accuracy. The estimated glomerular filtration rate was the most significant predictor in all models, with body weight, serum creatinine, height, and age also prominently influencing the XGBoost model's predictions. IMPLICATIONS The proposed model is capable of accurately predicting the optimal dose of vancomycin, which could aid physicians in making more informed treatment decisions regarding early therapy, particularly when AUC estimation systems are not accessible or readily available in routine clinical practice.
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Affiliation(s)
- Yun Woo Lee
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Ji-Hun Kim
- Department of Emergency Medicine, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, Uijeongbu, Gyeonggi-do, Republic of Korea
| | - Jin Ju Park
- Division of Infectious Diseases, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hyejin Park
- Division of Infectious Diseases, Department of Internal Medicine, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
| | - Hyeonji Seo
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Yong Kyun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea.
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Lee H, Kim YJ, Kim JH, Kim SK, Jeong TD. Optimizing Initial Vancomycin Dosing in Hospitalized Patients Using Machine Learning Approach for Enhanced Therapeutic Outcomes: Algorithm Development and Validation Study. J Med Internet Res 2025; 27:e63983. [PMID: 40163845 PMCID: PMC11997519 DOI: 10.2196/63983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 11/13/2024] [Accepted: 03/10/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND Vancomycin is commonly dosed using standard weight-based methods before dose adjustments are made through therapeutic drug monitoring (TDM). However, variability in initial dosing can lead to suboptimal therapeutic outcomes. A predictive model that personalizes initial dosing based on patient-specific pharmacokinetic factors prior to administration may enhance target attainment and minimize the need for subsequent dose adjustments. OBJECTIVE This study aimed to develop and evaluate a machine learning (ML)-based algorithm to predict whether an initial vancomycin dose falls within the therapeutic range of the 24-hour area under the curve to minimum inhibitory concentration, thereby optimizing the initial vancomycin dosage. METHODS A retrospective cohort study was conducted using hospitalized patients who received intravenous vancomycin and underwent pharmacokinetic TDM consultation (n=415). The cohort was randomly divided into training and testing datasets in a 7:3 ratio, and multiple ML techniques were used to develop an algorithm for optimizing initial vancomycin dosing. The optimal algorithm, referred to as the OPTIVAN algorithm, was selected and validated using an external cohort (n=268). We evaluated the performance of 4 ML models: gradient boosting machine, random forest (RF), support vector machine (SVM), and eXtreme gradient boosting (XGB). Additionally, a web-based clinical support tool was developed to facilitate real-time vancomycin TDM application in clinical practice. RESULTS The SVM algorithm demonstrated the best predictive performance, achieving an area under the receiver operating characteristic curve (AUROC) of 0.832 (95% CI 0.753-0.900) for the training dataset and 0.720 (95% CI 0.654-0.783) for the external validation dataset. The gradient boosting machine followed closely with AUROC scores of 0.802 (95% CI 0.667-0.857) for the training dataset and 0.689 (95% CI 0.596-0.733) for the validation dataset. In contrast, both XGB and RF exhibited relatively lower performance. XGB achieved AUROC values of 0.769 (95% CI 0.671-0.853) for the training set and 0.707 (95% CI 0.644-0.772) for the validation set, while RF recorded AUROC scores of 0.759 (95% CI 0.656-0.846) for the test dataset and 0.693 (95% CI 0.625-0.757) for the external validation set. The SVM model incorporated 7 covariates: age, BMI, glucose, blood urea nitrogen, estimated glomerular filtration rate, hematocrit, and daily dose per body weight. Subgroup analyses demonstrated consistent performance across different patient categories, such as renal function, sex, and BMI. A web-based TDM analysis tool was developed using the OPTIVAN algorithm. CONCLUSIONS The OPTIVAN algorithm represents a significant advancement in personalized initial vancomycin dosing, addressing the limitations of current TDM practices. By optimizing the initial dose, this algorithm may reduce the need for subsequent dosage adjustments. The algorithm's web-based app is easy to use, making it a practical tool for clinicians. This study highlights the potential of ML to enhance the effectiveness of vancomycin treatment.
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Affiliation(s)
- Heonyi Lee
- Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
| | - Yi-Jun Kim
- Department of Environmental Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
- Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, Republic of Korea
| | - Jin-Hong Kim
- Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea
| | - Soo-Kyung Kim
- Department of Laboratory Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Tae-Dong Jeong
- Department of Laboratory Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
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Shiau J, Roy S, Sabourenkov P, Scheetz MH. Big Data Bayesian Truths: No Vancomycin Trough Concentration Target Is Sufficiently Precise for Safety or Efficacy. Open Forum Infect Dis 2025; 12:ofaf041. [PMID: 40070810 PMCID: PMC11893978 DOI: 10.1093/ofid/ofaf041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Accepted: 01/23/2025] [Indexed: 03/14/2025] Open
Abstract
Introduction Therapeutic drug monitoring is standard of care for vancomycin because of the known efficacy and safety exposure window (ie, area under the concentration-time curve [AUC] of 400-600 mg × 24 hours/L). Despite guideline recommendations, AUCs are infrequently calculated because of the perceived adequacy of trough (Cmin) concentrations. Yet, the percentage of real-world patients with goal measured vancomycin trough concentrations that achieve target vancomycin AUC remains unknown. Methods A large cohort of internationally represented adult patients treated with vancomycin in 2021 and 2022 and therapeutic drug monitoring performed had data anonymized via an electronic clearinghouse at DoseMe. Unique patients, dosing events, and measured Cmin were identified. Patient-individualized AUC was calculated using a Bayesian method with 4 validated models. For each dosing event, Cmin and AUC pairs were compared and categorized as "low," "target," and "high" using the therapeutic ranges for Cmin of 15-20 mg/L and AUC of 400-600 mg × 24 hours/L. Results In 2022, 17,711 adult patients from the European Union (4.9%), Australia (4.0%), and the United States (91.1%) had 26 769 measured trough levels obtained. Categorical disagreement between Cmin and AUC was 34.3%, with most disagreement (7959 Cmin levels, 30%) occurring with low Cmin but target AUC. Only 23% of paired Cmin and AUC were within range. AUC was variable for all trough categories (ie, low, target, and high). Conclusions These findings support AUC therapeutic drug monitoring and challenge Cmin as an adequate vancomycin AUC proxy. Because no trough concentration or range was sufficiently precise to ensure AUC targets, we suggest direct calculation of AUC.
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Affiliation(s)
- Justin Shiau
- Midwestern University College of Pharmacy, Pharmacometrics Center of Excellence, Department of Pharmacy Practice, Downers Grove, Illinois, USA
| | | | | | - Marc H Scheetz
- Midwestern University College of Pharmacy, Pharmacometrics Center of Excellence, Department of Pharmacy Practice, Downers Grove, Illinois, USA
- Midwestern University, College of Graduate Studies, Departments of Pharmacology and Biomedical Sciences College of Pharmacy, Downers Grove, Illinois, USA
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Oshima Y, Matsumoto M, Munakata S, Tokimatsu I, Hattori N, Kotani T, Kusumoto S, Sagara H, Kato M. Prediction of Area Under the Curve from Urinary Vancomycin Concentrations Measured Using a Simple Method. AAPS J 2025; 27:39. [PMID: 39904932 DOI: 10.1208/s12248-025-01021-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Accepted: 01/06/2025] [Indexed: 02/06/2025] Open
Abstract
Therapeutic drug monitoring (TDM) is recommended during vancomycin (VCM) administration to adjust the dosage such that the area under the curve (AUC) remains between 400 and 600 µg·h/mL (minimum inhibitory concentration = 1 µg/mL). However, measuring the AUC requires frequent blood sampling, which increases the burden of added time and cost for testing on both patients and healthcare personnel. Therefore, we aimed to address these issues by developing a simple and rapid method for measuring urinary VCM levels using solid-phase extraction and fluorescence spectrometry. The developed method had a quantification range of 100-2,000 µg/mL, with an accuracy of 100.0%-108.5% for concentrations of 200, 1,000, and 2,000 µg/mL. The intra- and inter-day relative standard deviations were below 3.39% and 4.48%, respectively. Furthermore, to predict the AUC from urinary VCM concentrations, we calculated the slope of the urinary concentrations at 7-12 h post-VCM administration in six patients. The slope for one patient differed significantly from that for the others, and the AUC was obtained using practical AUC-guided TDM for vancomycin (PAT) ver. 3.0c for the patient whose value deviated from the recommended range. A negative correlation was observed between the slope and AUC, with a correlation coefficient of 0.65, suggesting the potential for predicting AUC from urinary concentration trends. The use of urine samples, which can be easily obtained, for VCM dose adjustment is expected to contribute to providing more appropriate drug therapy to patients and reduce the burden on healthcare professionals.
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Affiliation(s)
- Yuki Oshima
- Division of Bioanalytical Chemistry, Department of Pharmaceutical Sciences, Showa University Graduate School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan
| | - Miyu Matsumoto
- Department of Bioanalytical Chemistry, School of Pharmacy, Showa University, Tokyo, Japan
| | - Sumika Munakata
- Department of Bioanalytical Chemistry, School of Pharmacy, Showa University, Tokyo, Japan
| | - Issei Tokimatsu
- Department of Medicine, Division of Clinical Infectious Diseases, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan
| | - Norimichi Hattori
- Division of Hematology, Department of Medicine, Showa University, School of Medicine, Tokyo, Japan
| | - Toru Kotani
- Department of Intensive Care Medicine, Showa University, School of Medicine, Tokyo, Japan
| | - Sojiro Kusumoto
- Division of Respiratory Medicine and Allergology, Showa University, School of Medicine, Tokyo, Japan
| | - Hironori Sagara
- Division of Respiratory Medicine and Allergology, Showa University, School of Medicine, Tokyo, Japan
| | - Masaru Kato
- Division of Bioanalytical Chemistry, Department of Pharmaceutical Sciences, Showa University Graduate School of Pharmacy, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan.
- Molecular Analysis Facility, Showa University, Tokyo, Japan.
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6
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Sugiyama K, Sato F, Yoshida K, Komatsu S, Ono T, Sasano Y, Iwabuchi Y, Fujimura T, Kashiwagi Y, Sato K. Colorimetric quantification of vancomycin by highly active nitroxyl radical compounds. ANAL SCI 2025; 41:179-183. [PMID: 39560905 DOI: 10.1007/s44211-024-00686-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/21/2024] [Indexed: 11/20/2024]
Abstract
Nitroxyl radicals, represented by 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO), are highly stable organic free radicals with unique properties and are used as functional molecules in various fields. However, TEMPO had low reactivity and sometimes did not provide enough response. Therefore, highly active nitroxyl radical compounds have been developed in which bicyclo and tricyclo structures stabilize the radicals. In this study, we found that nortropine N-oxyl (NNO), a type of highly active nitroxyl radical, can oxidize the 2,2'-dihydroxybiphenyl structure under physiological conditions, and succeeded in the colorimetric quantification of vancomycin containing 2,2'-dihydroxybiphenyl moieties in the molecular structure. The reaction took only a few minutes to complete and could be confirmed with the naked eye, with a quantitative range of 10-100 μM. High-performance analytical probes are expected to be developed that use highly active nitroxyl radical derivatives to replace TEMPO derivatives.
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Affiliation(s)
- Kyoko Sugiyama
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi, 981-8558, Japan
| | - Fumiya Sato
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi, 981-8558, Japan
| | - Kentaro Yoshida
- School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima, 963-8611, Japan.
| | - Sachiko Komatsu
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi, 981-8558, Japan
| | - Tetsuya Ono
- School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima, 963-8611, Japan
| | - Yusuke Sasano
- Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan
| | - Yoshiharu Iwabuchi
- Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan
| | - Tsutomu Fujimura
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi, 981-8558, Japan
| | - Yoshitomo Kashiwagi
- School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima, 963-8611, Japan
| | - Katsuhiko Sato
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba, Sendai, Miyagi, 981-8558, Japan.
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Schellong P, Joean O, Pletz MW, Hagel S, Weis S. Treatment of Complicated Gram-Positive Bacteremia and Infective Endocarditis. Drugs 2025; 85:193-214. [PMID: 39720961 PMCID: PMC11802659 DOI: 10.1007/s40265-024-02135-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2024] [Indexed: 12/26/2024]
Abstract
The Gram-positive cocci Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. are the most frequent causative organisms of bloodstream infections and infective endocarditis. "Complicated bacteremia" is a term used in S. aureus bloodstream infections and originally implied the presence of metastatic infectious foci (i.e. complications of S. aureus bacteremia). These complications demand longer antimicrobial treatment durations and, frequently, interventional source control. Several risk factors for the incidence of bacteremia complications have been identified and are often used for the definition of complicated bacteremia. Here, we discuss management and diagnostic approaches and treatment options for patients with complicated bacteremia, with particular focus on infective endocarditis. We also summarize the available evidence regarding imaging modalities and the choice of antimicrobial mono- or combination therapy according to resistance patterns for these pathogens as well as treatment durations and optimized application routes. Finally, we synopsize current and future areas of research in complicated bacteremia and infective endocarditis.
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Affiliation(s)
- Paul Schellong
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Am Klinikum 1, 07749, Jena, Germany.
- Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany.
| | - Oana Joean
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Am Klinikum 1, 07749, Jena, Germany
| | - Mathias W Pletz
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Am Klinikum 1, 07749, Jena, Germany
| | - Stefan Hagel
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Am Klinikum 1, 07749, Jena, Germany
| | - Sebastian Weis
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Friedrich-Schiller-University, Am Klinikum 1, 07749, Jena, Germany
- Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Jena, Germany
- Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany
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Telles JP, Coelho D, Migotto KC, Diegues MS, Leao ER, Reghini R, Martinez Martos N, Caruso P, França E Silva IL. Switching Vancomycin Monitoring From Trough Concentration to Area Under the Curve Estimation by Bayesian Forecasting: A Short Communication on a Cost-Benefit Study in Resource-Limited Settings. Ther Drug Monit 2024; 46:681-686. [PMID: 38967524 DOI: 10.1097/ftd.0000000000001223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 03/25/2024] [Indexed: 07/06/2024]
Abstract
BACKGROUND This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software. METHODS This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis. RESULTS There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy. CONCLUSIONS Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes.
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Affiliation(s)
- João Paulo Telles
- Department of Infectious Diseases, AC Camargo Cancer Center, São Paulo, Brazil
| | - Diogenes Coelho
- Department of Infectious Diseases, AC Camargo Cancer Center, São Paulo, Brazil
| | | | | | - Erica Rocha Leao
- Department of Pharmacy, AC Camargo Cancer Center, São Paulo, Brazil
| | - Rodrigo Reghini
- Department of Infectious Diseases, AC Camargo Cancer Center, São Paulo, Brazil
| | | | - Pedro Caruso
- Department of Intensive Care Medicine, AC Camargo Cancer Center, São Paulo, Brazil
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9
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Wong S, Selby PR, Reuter SE. Determination of a vancomycin nephrotoxicity threshold and assessment of target attainment in hematology patients. Pharmacol Res Perspect 2024; 12:e1231. [PMID: 38940223 PMCID: PMC11211924 DOI: 10.1002/prp2.1231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 05/29/2024] [Accepted: 06/11/2024] [Indexed: 06/29/2024] Open
Abstract
An area-under-the-curve (AUC24)-based approach is recommended to guide vancomycin therapeutic drug monitoring (TDM), yet trough concentrations are still commonly used despite associated risks. A definitive toxicity target is lacking, which is important for hematology patients who have a higher risk of nephrotoxicity. The aims were to (1) assess the impact of trough-based TDM on acute kidney injury (AKI) incidence, (2) establish a vancomycin nephrotoxicity threshold, and (3) evaluate the proportion of hematology patients achieving vancomycin therapeutic targets. Retrospective data was collected from 100 adult patients with a hematological malignancy or aplastic anemia who received vancomycin between April 2020 and January 2021. AKI occurrence was determined based on serum creatinine concentrations, and individual pharmacokinetic parameters were estimated using a Bayesian approach. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pharmacokinetic indices to predict AKI occurrence. The proportion of patients who achieved target vancomycin exposure was evaluated based on an AUC24/MIC ≥400 and the determined toxicity threshold. The incidence of AKI was 37%. ROC curve analysis indicated a maximum AUC24 of 644 mg.h/L over the treatment period was an important predictor of AKI. By Day 4 of treatment, 29% of treatment courses had supratherapeutic vancomycin exposure, with only 62% of courses achieving AUC24 targets. The identified toxicity threshold supports an AUC24 target range of 400-650 mg.h/L, assuming an MIC of 1 mg/L, to optimize vancomycin efficacy and minimize toxicity. This study highlights high rates of AKI in this population and emphasizes the importance of transitioning from trough-based TDM to an AUC-based approach to improve clinical outcomes.
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Affiliation(s)
- Sherilyn Wong
- UniSA Clinical and Health SciencesUniversity of South AustraliaAdelaideSouth AustraliaAustralia
| | - Philip R. Selby
- UniSA Clinical and Health SciencesUniversity of South AustraliaAdelaideSouth AustraliaAustralia
- School of MedicineThe University of AdelaideAdelaideSouth AustraliaAustralia
- SA Pharmacy, Royal Adelaide HospitalAdelaideSouth AustraliaAustralia
| | - Stephanie E. Reuter
- UniSA Clinical and Health SciencesUniversity of South AustraliaAdelaideSouth AustraliaAustralia
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10
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Liu J, Zhang X, Liang G, Zhu J, Yang Y, Zheng Y, Han Y, Yu L, Zhao Y, Yu Z. Is it time to recommend AUC-based vancomycin therapeutic drug monitoring only? A cross-sectional survey in China. Front Pharmacol 2024; 15:1370040. [PMID: 39070794 PMCID: PMC11272526 DOI: 10.3389/fphar.2024.1370040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 07/01/2024] [Indexed: 07/30/2024] Open
Abstract
Background The latest published therapeutic drug monitoring (TDM) guidelines for vancomycin recommend changing trough-based monitoring to area under the concentration-to-time curve (AUC)-based monitoring. This study aimed to evaluate the implementation status and perceptions of vancomycin AUC-based TDM in China and to determine the challenges in performing AUC-based TDM. Methods A nationwide cross-sectional survey was conducted in China using an online questionnaire. The questionnaire comprised a total of 25 questions with open- and closed-ended answers to collect information about the current implementation of vancomycin TDM and the participants' perceptions of these practices. The questionnaire responses were collected via the Questionnaire Star platform and analyzed. Results A total of 161 questionnaires were completed by 131 hospitals and were included. Approximately 59.5% (78/131) of the surveyed hospitals conducted vancomycin TDM; however, only 10.7% (14/131) of these hospitals performed AUC-based vancomycin TDM. Of the eligible participants, 58.4% (94/161) had experience with vancomycin TDM, and only 37 participants (37/161, 23.0%) had the ability to estimate the AUC, primarily through Bayesian simulation (33/161, 20.5%). The participants considered the following challenges to implementing AUC-based monitoring: (1) the high cost of AUC-based monitoring; (2) inadequate knowledge among pharmacists and/or physicians; (3) the complexity of AUC calculations; (4) difficulty obtaining AUC software; and (5) unclear benefit of AUC-based monitoring. Conclusion The majority of surveyed hospitals have not yet implemented AUC-based vancomycin TDM. Multiple challenges should be addressed before wide implementation of AUC-based monitoring, and guidance for trough-based monitoring is still needed.
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Affiliation(s)
- Jieqiong Liu
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, China
| | - Xuan Zhang
- Northern Jiangsu People’s Hospital, Yangzhou, China
| | - Gang Liang
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jianping Zhu
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Yang
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Zheng
- The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, China
| | - Yun Han
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- College of Pharmaceutical Science, Zhejiang University, Hangzhou, China
- Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, China
| | - Lingyan Yu
- Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, China
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuhua Zhao
- Affiliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China
| | - Zhenwei Yu
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, China
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11
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Xi L, Li S, Chen M, Huang X, Li N, Chen N, Wu H, Bian Q, Bian X, Li X, Yang M, Liang X, Wu J, Guo B, Fan Y, Zhang J. Age-Related Differences in Vancomycin-Associated Nephrotoxicity and Efficacy in Methicillin-Resistant Staphylococcus aureus Infection: A Comparative Study between Elderly and Adult Patients. Antibiotics (Basel) 2024; 13:324. [PMID: 38667000 PMCID: PMC11047698 DOI: 10.3390/antibiotics13040324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 03/22/2024] [Accepted: 03/28/2024] [Indexed: 04/29/2024] Open
Abstract
Elderly patients (age ≥ 65 years) are susceptible to methicillin-resistant Staphylococcus aureus (MRSA) infections, with potential for more adverse treatment outcomes or complications compared to younger adults (18-64 years). This study compared vancomycin-associated nephrotoxicity and efficacy in elderly and adult patients and investigated the correlation between vancomycin pharmacokinetic/pharmacodynamic (PK/PD) indices and clinical outcomes. A prospective study was conducted in 10 hospitals in Shanghai from October 2012 to November 2019. A total of 164 patients with MRSA infections were enrolled, including 83 elderly and 81 adult patients. Vancomycin therapeutic drug monitoring (TDM) was performed in all patients, indicating significantly higher vancomycin trough concentrations (Ctrough), 24-h area under the curve (AUC24) values, and AUC24/minimum inhibitory concentration (AUC24/MIC) values in elderly patients compared to adult patients. The incidence of vancomycin-associated nephrotoxicity was nearly three times higher in elderly patients (18.1% vs. 6.2%, p = 0.020), despite similar clinical and microbiological efficacy. Of particular importance, a Ctrough > 20 mg/L was found as an independent factor of nephrotoxicity in elderly patients. Further analysis of patients with an estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 also revealed that elderly patients had significantly higher vancomycin-related PK/PD indices and more nephrotoxicity than adult patients. In conclusion, elderly patients receiving vancomycin therapy face a higher risk of nephrotoxicity, which requires close vancomycin TDM, especially when the Ctrough exceeds 20 mg/L.
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Affiliation(s)
- Lin Xi
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Shanshan Li
- Huashan Worldwide Medical Center, Huashan Hospital, Fudan University, Shanghai 200040, China;
| | - Mengting Chen
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Xiaolan Huang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Nanyang Li
- Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200040, China; (N.L.); (N.C.); (X.B.)
| | - Nanye Chen
- Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200040, China; (N.L.); (N.C.); (X.B.)
| | - Hailan Wu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Qiyu Bian
- Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK;
| | - Xingchen Bian
- Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200040, China; (N.L.); (N.C.); (X.B.)
| | - Xin Li
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Minjie Yang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Xiaoyu Liang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jufang Wu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
- Phase I Clinical Research Center, Huashan Hospital, Fudan University, Shanghai 200040, China; (N.L.); (N.C.); (X.B.)
| | - Beining Guo
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Yaxin Fan
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jing Zhang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai 200040, China; (L.X.); (M.C.); (X.H.); (H.W.); (X.L.); (M.Y.); (X.L.); (J.W.); (B.G.)
- Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission, Shanghai 200040, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
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Colaneri M, Genovese C, Valsecchi P, Calia M, Cattaneo D, Gori A, Bruno R, Seminari E. Optimizing Antibiotic Therapy for Intravenous Drug Users: A Narrative Review Unraveling Pharmacokinetics/Pharmacodynamics Challenges. Eur J Drug Metab Pharmacokinet 2024; 49:123-129. [PMID: 38332425 DOI: 10.1007/s13318-024-00882-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/24/2024] [Indexed: 02/10/2024]
Abstract
Intravenous drug users (IVDUs) face heightened susceptibility to life-threatening gram-positive bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA). While the standard antibiotic dosing strategies for special patients, such as obese or critically ill individuals, are known to be inadequate, raising concerns about treatment efficacy, a similar sort of understanding has not been assessed for IVDUs yet. With this in mind, this review examines the pharmacokinetic/pharmacodynamic characteristics of antibiotics commonly used against gram-positive bacteria in IVDUs. Focusing on daptomycin, vancomycin, teicoplanin, aminoglycosides, and the novel lipoglycopeptide dalbavancin, the study reveals significant pharmacokinetic variations in IVDUs, suggesting the need for personalized dosing. Concomitant opioid substitution therapy and other factors, such as malnutrition, contribute to altered pharmacokinetics/pharmacodynamics, emphasizing the importance of targeted therapeutic drug monitoring. Overall, our study calls for increased awareness among clinicians regarding the unique pharmacokinetic/pharmacodynamic challenges in IVDUs and advocates for tailored antibiotic dosing strategies to enhance treatment outcomes in this marginalized population.
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Affiliation(s)
- Marta Colaneri
- Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy.
- Infectious Diseases Unit, L. Sacco Hospital, Milan, Italy.
| | - Camilla Genovese
- Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy
| | | | - Matteo Calia
- Infectious Diseases I Unit, IRCCS San Matteo, Pavia, Italy
| | - Dario Cattaneo
- Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy
| | - Andrea Gori
- Department of Infectious Diseases, ASST Fatebenefratelli Sacco University Hospital, Milan, Italy
- Centre for Multidisciplinary Research in Health Science (MACH), University of Milano, Milan, Italy
| | - Raffaele Bruno
- Infectious Diseases I Unit, IRCCS San Matteo, Pavia, Italy
- Department of Medical, Surgical, Diagnostic and Paediatric Science, University of Pavia, Pavia, Italy
| | - Elena Seminari
- Infectious Diseases I Unit, IRCCS San Matteo, Pavia, Italy
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Lim WXS, Seah XFV, Thoon KC, Han Z. Comparison of Vancomycin Trough-Based and 24-Hour Area Under the Curve Over Minimum Inhibitory Concentration (AUC/MIC)-Based Therapeutic Drug Monitoring in Pediatric Patients. J Pediatr Pharmacol Ther 2023; 28:430-438. [PMID: 38130493 PMCID: PMC10731924 DOI: 10.5863/1551-6776-28.5.430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 10/07/2022] [Indexed: 12/23/2023]
Abstract
OBJECTIVES Vancomycin 24-hour area under the curve over minimum inhibitory concentration (AUC/MIC) monitoring has been recommended over trough-based monitoring in pediatric patients. This study compared the proportion of target attainment between vancomycin AUC/MIC and trough-based methods, and identified risk factors for subtherapeutic initial extrapolated targets. METHODS This was a retrospective, observational study conducted at KK Women's and Children's Hospital (KKH), Singapore. Patients aged 1 month to 18 years with stable renal function who received intravenous vancomycin between January 2014 and October 2017, with at least 2 vancomycin serum concentrations obtained after the first dose of vancomycin, were included. Using a pharmacokinetic software, namely Adult and Pediatric Kinetics (APK), initial extrapolated steady-state troughs and 24-hour AUC were determined by using a one-compartmental model. Statistical tests included Wilcoxon rank sum test, McNemar test, logistic regression, and classification and regression tree (CART) analysis. RESULTS Of the 82 pediatric patients included, a significantly larger proportion of patients achieved therapeutic targets when the AUC/MIC-based method (24, 29.3%) was used than with the trough-based method (9, 11.0%; p < 0.01). Patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or with age <13 years had an increased risk of obtaining subtherapeutic targets. However, empiric vancomycin doses of 60 mg/kg/day would be sufficient to achieve serum therapeutic targets, using the AUC/MIC-based method. CONCLUSION The AUC/MIC-based vancomycin monitoring may be preferred because a larger proportion of patients could achieve initial therapeutic targets. Future prospective studies with larger sample size will be required to determine the optimal vancomycin strategy for pediatric patients.
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Affiliation(s)
- Wan Xuan Selina Lim
- Department of Pharmacy (WXSL, XFVS), KK Women's and Children's Hospital, Singhealth, Singapore
| | - Xue Fen Valerie Seah
- Department of Pharmacy (WXSL, XFVS), KK Women's and Children's Hospital, Singhealth, Singapore
| | - Koh Cheng Thoon
- Department of Infectious Diseases (KCT), Pediatrics, KK Women's and Children's Hospital, Singhealth, Singapore
| | - Zhe Han
- Department of Pharmacy (ZH), National University of Singapore, Singapore
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14
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Frymoyer A, Schwenk HT, Brockmeyer JM, Bio L. Impact of model-informed precision dosing on achievement of vancomycin exposure targets in pediatric patients with cystic fibrosis. Pharmacotherapy 2023; 43:1007-1014. [PMID: 37401162 DOI: 10.1002/phar.2845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/02/2023] [Accepted: 05/04/2023] [Indexed: 07/05/2023]
Abstract
BACKGROUND Vancomycin is commonly used to treat acute pulmonary exacerbations in pediatric patients with cystic fibrosis (CF) and a history of methicillin-resistant Staphylococcus aureus. Optimizing vancomycin exposure during therapy is essential and area under-the-curve (AUC)-guided dosing is now recommended. Model-informed precision dosing (MIPD) utilizing Bayesian forecasting is a powerful approach that can support AUC-guided dose individualization. The objective of the current study was to examine the impact of implementing an AUC-guided dose individualization approach supported via a MIPD clinical decision support (CDS) tool on vancomycin exposure, target attainment rate, and safety in pediatric patients with CF treated with vancomycin during clinical care. METHODS A retrospective chart review was performed in patients with CF at a single children's hospital comparing pre- and post-implementation of a MIPD approach for vancomycin supported by a cloud-based, CDS tool integrated into the electronic health record (EHR). In the pre-MIPD period, vancomycin starting doses of 60 mg/kg/day (<13 years) or 45 mg/kg/day (≥13 years) were used. Dose adjustment was guided by therapeutic drug monitoring (TDM) with a target trough 10-20 mg/L. In the post-MIPD period, starting dose and dose adjustment were based on the MIPD CDS tool predictions with a target 24 h AUC (AUC24 ) 400-600 mg*h/L. Exposure and target achievement rates were retrospectively calculated and compared. Rates of acute kidney injury (AKI) were also compared. RESULTS Overall, 23 patient courses were included in the pre-MIPD period and 21 patient courses in the post-MIPD period. In the post-MIPD period, an individualized MIPD starting dose resulted in 71% of patients achieving target AUC24 compared to 39% in the pre-MIPD period (p < 0.05). After the first TDM and dose adjustment, target AUC24 achievement was also higher post-MIPD versus pre-MIPD (86% vs. 57%; p < 0.05). AKI rates were low and similar between periods (pre-MIPD 8.7% vs. post-MIPD 9.5%; p = 0.9). CONCLUSION An MIPD approach implemented within a cloud-based, EHR-integrated CDS tool safely supported vancomycin AUC-guided dosing and resulted in high rates of target achievement.
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Affiliation(s)
- Adam Frymoyer
- Department of Pediatrics, Stanford University, Palo Alto, California, USA
| | - Hayden T Schwenk
- Department of Pediatrics, Stanford University, Palo Alto, California, USA
| | - Jake M Brockmeyer
- Department of Pharmacy, Lucile Packard Children's Hospital Stanford, Palo Alto, California, USA
| | - Laura Bio
- Department of Pharmacy, Lucile Packard Children's Hospital Stanford, Palo Alto, California, USA
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15
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Impact of Pharmacist-Led Multidisciplinary Team to Attain Targeted Vancomycin Area under the Curved Monitoring in a Tertiary Care Center in Thailand. Antibiotics (Basel) 2023; 12:antibiotics12020374. [PMID: 36830284 PMCID: PMC9952732 DOI: 10.3390/antibiotics12020374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023] Open
Abstract
Vancomycin Area Under the Curve (AUC) monitoring has been recommended to ensure successful clinical outcomes and minimize the risk of nephrotoxicity, rather than traditional trough concentration. However, vancomycin AUC monitoring by a pharmacist-led multidisciplinary team (PMT) has not been well established in Southeast Asia. This study was conducted at Thammasat University Hospital. Adult patients aged ≥ 18 years who were admitted and received intravenous vancomycin ≥48 h were included. The pre-PMT period (April 2020-September 2020) was defined as a period using traditional trough concentration, while the post-PMT period (October 2020-March 2021) was defined as a period using PMT to monitor vancomycin AUC. The primary outcome was the rate of achievement of the therapeutic target of an AUC/MIC ratio of 400-600. There was a significantly higher rate of achievement of therapeutic target vancomycin AUC during post-PMT period (66.7% vs. 34.3%, p < 0.001). Furthermore, there was a significant improvement in the clinical cure rate (92.4% vs. 69.5%, p < 0.001) and reduction in 30-day ID mortality (2.9% vs. 12.4%, p = 0.017) during the post-PMT period. Our study demonstrates that PMT was effective to help attain a targeted vancomycin AUC, improve the clinical cure rate, and reduce 30-day ID mortality. This intervention should be encouraged to be implemented in Southeast Asia.
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Simple and rapid method for analysis of urinary vancomycin using solid phase extraction and fluorescence spectroscopy. AAPS OPEN 2023. [DOI: 10.1186/s41120-023-00071-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AbstractVancomycin (VCM) is an antimicrobial that is recommended for therapeutic drug monitoring (TDM) for maintaining the efficacy and safety of treatment. The trough monitoring has been used to guide VCM dosing regimens. However, newer guidelines recommend the use of area under the curve/minimum inhibitory concentration (AUC/MIC)-guided vancomycin dosing, and there is a need for easier and more frequent measurements of VCM concentrations. Therefore, in this study, we developed a simple and rapid analytical method for measuring urinary VCM by combining solid-phase extraction and fluorescence analysis. Urine samples are easier and less invasive than blood samples. In addition to the therapeutic range of blood VCM, this method was also able to measure 0.01–1 mg/mL, which is the concentration range of urinary VCM. The accuracy of 10, 20, and 30 μg/mL VCM solutions were between 93.18 and 109.76%. The relative standard deviation (RSD) of intra-day and inter-day analysis were less than 6.25% and 6.28%, respectively. Since this method does not use large equipment, it is expected to be better suited for clinical use.
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The Bayesian-Based Area under the Curve of Vancomycin by Using a Single Trough Level: An Evaluation of Accuracy and Discordance at Tertiary Care Hospital in KSA. Healthcare (Basel) 2023; 11:healthcare11030362. [PMID: 36766937 PMCID: PMC9914540 DOI: 10.3390/healthcare11030362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/20/2023] [Accepted: 01/23/2023] [Indexed: 02/01/2023] Open
Abstract
The AUC0-24 is the most accurate way to track the vancomycin level while the Cmin is not an accurate surrogate. Most hospitals in Saudi Arabia are under-practicing the AUC-guided vancomycin dosing and monitoring. No previous work has been conducted to evaluate such practice in the whole kingdom. The current study objective is to calculate the AUC0-24 using the Bayesian dosing software (PrecisePK), identify the probability of patients who receive the optimum dose of vancomycin, and evaluate the accuracy and precision of the Bayesian platform. This retrospective study was conducted at King Abdulaziz medical city, Jeddah. All adult patients treated with vancomycin were included. Pediatric patients, critically ill patients requiring ICU admission, patients with acute renal failure or undergoing dialysis, and febrile neutropenic patients were excluded. The AUC0-24 was predicted using the PrecisePK platform based on the Bayesian principle. The two-compartmental model by Rodvold et al. in this platform and patients' dose data were utilized to calculate the AUC0-24 and trough level. Among 342 patients included in the present study, the mean of the estimated vancomycin AUC0-24 by the posterior model of PrecisePK was 573 ± 199.6 mg, and the model had a bias of 16.8%, whereas the precision was 2.85 mg/L. The target AUC0-24 (400 to 600 mg·h/L) and measured trough (10 to 20 mg/L) were documented in 127 (37.1%) and 185 (54%), respectively. Furthermore, the result demonstrated an increase in odds of AUC0-24 > 600 mg·h/L among trough level 15-20 mg/L group (OR = 13.2, p < 0.05) as compared with trough level 10-14.9 mg/L group. In conclusion, the discordance in the AUC0-24 ratio and measured trough concentration may jeopardize patient safety, and implantation of the Bayesian approach as a workable alternative to the traditional trough method should be considered.
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Ghasemiyeh P, Vazin A, Mohammadi-Samani S. A Brief Review of Pharmacokinetic Assessments of Vancomycin in Special Groups of Patients with Altered Pharmacokinetic Parameters. Curr Drug Saf 2023; 18:425-439. [PMID: 35927907 DOI: 10.2174/1574886317666220801124718] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/22/2022] [Accepted: 05/26/2022] [Indexed: 11/22/2022]
Abstract
Vancomycin is considered the drug of choice against many Gram-positive bacterial infections. Therapeutic drug monitoring (TDM) is essential to achieve an optimum clinical response and avoid vancomycin-induced adverse reactions including nephrotoxicity. Although different studies are available on vancomycin TDM, still there are controversies regarding the selection among different pharmacokinetic parameters including trough concentration, the area under the curve to minimum inhibitory concentration ratio (AUC24h/MIC), AUC of intervals, elimination constant, and vancomycin clearance. In this review, different pharmacokinetic parameters for vancomycin TDM have been discussed along with corresponding advantages and disadvantages. Also, vancomycin pharmacokinetic assessments are discussed in patients with altered pharmacokinetic parameters including those with renal and/or hepatic failure, critically ill patients, patients with burn injuries, intravenous drug users, obese and morbidly obese patients, those with cancer, patients undergoing organ transplantation, and vancomycin administration during pregnancy and lactation. An individualized dosing regimen is required to guarantee the optimum therapeutic responses and minimize adverse reactions including acute kidney injury in these special groups of patients. According to the pharmacoeconomic data on vancomycin TDM, pharmacokinetic assessments would be cost-effective in patients with altered pharmacokinetics and are associated with shorter hospitalization period, faster clinical stability status, and shorter courses of inpatient vancomycin administration.
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Affiliation(s)
- Parisa Ghasemiyeh
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Afsaneh Vazin
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Soliman Mohammadi-Samani
- Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
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Aljutayli A, Thirion DJ, Nekka F. Critical assessment of the revised guidelines for vancomycin therapeutic drug monitoring. Biomed Pharmacother 2022; 155:113777. [DOI: 10.1016/j.biopha.2022.113777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 11/02/2022] Open
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Association between Vancomycin Pharmacokinetic Parameters and Clinical and Microbiological Efficacy in a Cohort of Neonatal Patients. Antimicrob Agents Chemother 2022; 66:e0110922. [PMID: 36222533 PMCID: PMC9664865 DOI: 10.1128/aac.01109-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC24), and the trough plasma concentration (Ct) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1 Ct available. The primary outcome was the association of Ct and AUC24 with clinical and microbiological efficacy at the beginning (early clinical evolution [ECE]) and the end (late clinical evolution [LCE]) of treatment with vancomycin. A total of 43 patients were included, 88.4% of whom were cured. In ECE, the cutoff points of the receiver operating characteristic (ROC) curve were 238 mg · h/L (sensitivity of 61% and specificity of 88%) for AUC24 and 6.8 μg/mL (sensitivity of 61% and specificity of 92%) for Ct. In LCE, the Ct value was 11 μg/mL, with a sensitivity of 80% and a specificity of 92%. In this analysis, AUC24 was not considered a good predictor. Logistic regression showed that a vancomycin Ct of ≤6.8 μg/mL was associated with an unfavorable ECE (P = 0.001), being 18 times more likely to progress poorly compared to those with higher levels. AUC24 and Ct are good predictors of ECE in this population. Concentrations close to 7 μg/mL and an AUC24 of around 240 mg · h/L 48 h after antibiotic initiation seem to be sufficient to achieve clinical cure in most cases.
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Sader HS, Castanheira M, Duncan LR, Mendes RE. Update on the In Vitro Activity of Ceftaroline against Staphylococcus aureus from United States (US) Medical Centers Stratified by Infection Type (2018-2020). Diagn Microbiol Infect Dis 2022; 105:115820. [DOI: 10.1016/j.diagmicrobio.2022.115820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 08/23/2022] [Accepted: 09/18/2022] [Indexed: 11/25/2022]
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Abdelmessih E, Patel N, Vekaria J, Crovetto B, SanFilippo S, Adams C, Brunetti L. Vancomycin area under the curve versus trough only guided dosing and the risk of acute kidney injury: Systematic review and meta-analysis. Pharmacotherapy 2022; 42:741-753. [PMID: 35869689 PMCID: PMC9481691 DOI: 10.1002/phar.2722] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Revised: 06/25/2022] [Accepted: 06/27/2022] [Indexed: 12/30/2022]
Abstract
Vancomycin is commonly used to treat methicillin-resistant Staphylococcus aureus infections and is known to cause nephrotoxicity. Previous Vancomycin Consensus Guidelines recommended targeting trough concentrations but the 2020 Guidelines suggest monitoring vancomycin area under the curve (AUC) given the reduced risk of acute kidney injury (AKI) at similar levels of efficacy. This meta-analysis compares vancomycin-induced AKI incidence using AUC-guided dosing strategies versus trough-based monitoring. Literature was queried from Medline (Ovid), Web of Science, and Google Scholar from database inception through November 5, 2021. Interventional or observational studies reporting the incidence of vancomycin-induced AKI between AUC- and trough-guided dosing strategies were included. In the primary analysis, the Vancomycin Consensus Guidelines definition for AKI was used if reported; otherwise, the Risk, Injury, and Failure; and Loss, and End-stage kidney disease (RIFLE) or Kidney Disease Improving Global Outcomes (KDIGO) definitions were used. The incidence of nephrotoxicity was evaluated between the two strategies using a Mantel-Haenszel random-effects model, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses for adjusted ORs and AKI definitions were performed. Heterogeneity was identified using Cochrane's Q test and I2 statistics. A total of 10 studies with 4231 patients were included. AUC-guided dosing strategies were associated with significantly less vancomycin-induced AKI than trough-guided strategies [OR 0.625, 95% CI (0.469-0.834), p = 0.001; I2 = 25.476]. A subgroup analysis of three studies reporting adjusted ORs yielded similar results [OR 0.475, 95% CI (0.261-0.863), p = 0.015]. Stratification by AKI definition showed a significant reduction in AKI with the Vancomycin Consensus Guidelines definition [OR 0.552, 95% CI (0.341-0.894), p = 0.016] but failed to find significance in the alternative definitions. Area under the curve-guided dosing strategies are associated with a lower incidence of vancomycin-induced AKI versus trough-guided dosing strategies (GRADE, low). Limitations included the variety of AKI definitions and the potential for confounding bias.
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Affiliation(s)
- Emily Abdelmessih
- Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA
| | - Nandini Patel
- Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA
| | - Janaki Vekaria
- Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA
| | - Brynna Crovetto
- Touro College of PharmacyNew YorkNew YorkUSA,Department of PharmacyMount Sinai HospitalNew YorkNew YorkUSA
| | - Savanna SanFilippo
- Tabula Rasa HealthcareMoorestownNew JerseyUSA,Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA,Robert Wood Johnson University Hospital SomersetSomervilleNew JerseyUSA
| | - Christopher Adams
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA,Robert Wood Johnson University Hospital SomersetSomervilleNew JerseyUSA,La Jolla Pharmaceutical CompanyWalthamMassachusettsUSA
| | - Luigi Brunetti
- Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, RutgersThe State University of New JerseyPiscatawayNew JerseyUSA,Robert Wood Johnson University Hospital SomersetSomervilleNew JerseyUSA
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Li Y, Lu W, Zheng X, Zhang L, Dong W, Zhao X, Zhao Z, Zhang Z. Norvancomycin for the Treatment of Central Nervous System MRSA Infections: a Randomized Controlled Trial: Norvancomycin for the Treatment of Central nervous system MRSA infections. Eur J Pharm Sci 2022; 177:106266. [PMID: 35868433 DOI: 10.1016/j.ejps.2022.106266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 07/15/2022] [Accepted: 07/18/2022] [Indexed: 11/20/2022]
Abstract
Combined intravenous and intrathecal administration of norvancomycin (NVCM) is routinely employed in treating methicillin-resistant Staphylococcus aureus (MRSA) ventriculitis in patients following craniotomy. However, the optimal dosing regimen, the pharmacokinetics (PK) of NVCM in cerebrospinal fluid (CSF), and the clinical outcome are yet to be elucidated. Herein, a single-center randomized controlled trial was conducted in the Neurosurgery Department of the Second Hospital of Hebei Medical University (Shijiazhuang, China). Patients with MRSA ventriculitis after craniotomy were randomly assigned to two groups. The control group received 800 mg NVCM intravenously every 12 h, and the experimental group received 800 mg NVCM intravenously every 12 h and 16 mg NVCM intrathecal administration every 24 h. The primary outcome was the length of therapy, while the secondary outcomes included the area under the concentration-time curve in 0-24 h/minimum inhibitory concentration ratio (AUC0-24h/MIC) of NVCM in CSF. A total of 29 patients (14 in the experimental group and 15 in the control group) were included in this study. Of these, 24 constituted the final analysis population, with 12 in each group. The average length of therapy in the experimental group was markedly shorter than that of the control group (11.2 ± 2.6 days vs. 16.6 ± 5.2 days, P = 0.005), while the AUC0-24h/MIC in the experimental group was significantly higher than that in the control group (2306.57 ± 928.58 vs. 46.83 ± 27.48, P <0.001) with no increase in adverse reactions. Combined intravenous and intrathecal administration can shorten the treatment time of intracranial infection without higher adverse reaction risks in our research. Further studies with larger sample size are warranted to verify its safety and efficacy.
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Affiliation(s)
- Yaqian Li
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wenpeng Lu
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xuecheng Zheng
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Linhui Zhang
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Weichong Dong
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaoxiao Zhao
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zongmao Zhao
- Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
| | - Zhiqing Zhang
- Department of Pharmacy, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
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Nix DE, Davis LE, Matthias KR. Response to Rybak et al. Am J Health Syst Pharm 2022; 79:1308-1311. [PMID: 35511826 DOI: 10.1093/ajhp/zxac126] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
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Affiliation(s)
- David E Nix
- Department of Pharmacy Practice & Science University of Arizona Tucson, AZ, USA
| | - Lisa E Davis
- Department of Pharmacy Practice & Science University of Arizona Tucson, AZ, USA
| | - Kathryn R Matthias
- Department of Pharmacy Practice & Science University of Arizona Tucson, AZ, USA
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Bian X, Qu X, Zhang J, Nang SC, Bergen PJ, Tony Zhou Q, Chan HK, Feng M, Li J. Pharmacokinetics and pharmacodynamics of peptide antibiotics. Adv Drug Deliv Rev 2022; 183:114171. [PMID: 35189264 PMCID: PMC10019944 DOI: 10.1016/j.addr.2022.114171] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/23/2022] [Accepted: 02/16/2022] [Indexed: 01/05/2023]
Abstract
Antimicrobial resistance is a major global health challenge. As few new efficacious antibiotics will become available in the near future, peptide antibiotics continue to be major therapeutic options for treating infections caused by multidrug-resistant pathogens. Rational use of antibiotics requires optimisation of the pharmacokinetics and pharmacodynamics for the treatment of different types of infections. Toxicodynamics must also be considered to improve the safety of antibiotic use and, where appropriate, to guide therapeutic drug monitoring. This review focuses on the pharmacokinetics/pharmacodynamics/toxicodynamics of peptide antibiotics against multidrug-resistant Gram-negative and Gram-positive pathogens. Optimising antibiotic exposure at the infection site is essential for improving their efficacy and minimising emergence of resistance.
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Affiliation(s)
- Xingchen Bian
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China
| | - Xingyi Qu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jing Zhang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Sue C Nang
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Phillip J Bergen
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Qi Tony Zhou
- Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, USA
| | - Hak-Kim Chan
- Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Meiqing Feng
- School of Pharmacy, Fudan University, Shanghai, China
| | - Jian Li
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia.
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Niwa T, Yasue M, Harada S, Yamada Y, Otsubo M, Yamada M, Matsuoka S, Yamamoto T, Mizusaki Y, Suzuki A. Comparison of single trough-based area under the concentration–time curve versus trough concentration for the incidence of vancomycin-associated nephrotoxicity. J Infect Chemother 2022; 28:923-928. [DOI: 10.1016/j.jiac.2022.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 03/17/2022] [Accepted: 03/22/2022] [Indexed: 10/18/2022]
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Clinical Practice Guidelines for Therapeutic Drug Monitoring of Vancomycin in the Framework of Model-Informed Precision Dosing: A Consensus Review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring. Pharmaceutics 2022; 14:pharmaceutics14030489. [PMID: 35335866 PMCID: PMC8955715 DOI: 10.3390/pharmaceutics14030489] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/16/2022] [Accepted: 02/17/2022] [Indexed: 01/08/2023] Open
Abstract
Background: To promote model-informed precision dosing (MIPD) for vancomycin (VCM), we developed statements for therapeutic drug monitoring (TDM). Methods: Ten clinical questions were selected. The committee conducted a systematic review and meta-analysis as well as clinical studies to establish recommendations for area under the concentration-time curve (AUC)-guided dosing. Results: AUC-guided dosing tended to more strongly decrease the risk of acute kidney injury (AKI) than trough-guided dosing, and a lower risk of treatment failure was demonstrated for higher AUC/minimum inhibitory concentration (MIC) ratios (cut-off of 400). Higher AUCs (cut-off of 600 μg·h/mL) significantly increased the risk of AKI. Although Bayesian estimation with two-point measurement was recommended, the trough concentration alone may be used in patients with mild infections in whom VCM was administered with q12h. To increase the concentration on days 1–2, the routine use of a loading dose is required. TDM on day 2 before steady state is reached should be considered to optimize the dose in patients with serious infections and a high risk of AKI. Conclusions: These VCM TDM guidelines provide recommendations based on MIPD to increase treatment response while preventing adverse effects.
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Vancomycin Use in Children and Neonates across Three Decades: A Bibliometric Analysis of the Top-Cited Articles. Pathogens 2021; 10:pathogens10101343. [PMID: 34684291 PMCID: PMC8537673 DOI: 10.3390/pathogens10101343] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 09/17/2021] [Accepted: 09/29/2021] [Indexed: 12/13/2022] Open
Abstract
Vancomycin is frequently prescribed in pediatrics, especially in intensive care unit settings, to treat Gram-positive bacterial infections. This work aims to collect the top-cited articles of pediatric and infectious diseases areas to gather the current evidence and gaps of knowledge on the use of vancomycin in these populations. The most relevant journals reported in the "pediatrics" and "infectious diseases" categories of the 2019 edition of Journal Citation Reports were browsed. Articles with more than 30 citations and published over the last three decades were collected. A bibliometric analysis was performed and 115 articles were retrieved. They were published in 21 journals, with a median impact factor of 4.6 (IQR 2.9-5.4). Sixty-eight of them (59.1%) belonged to "infectious diseases" journals. The most relevant topic was "bloodstream/complicated/invasive infections", followed by "antibiotic resistance/MRSA treatment". As for population distribution, 27 articles were on children only and 27 on neonates, most of which were from intensive care unit (ICU) settings. The current literature mainly deals with vancomycin as a treatment for severe infections and antibiotic resistance, especially in neonatal ICU settings. Lately, attention to new dosing strategies in the neonatal and pediatric population has become a sensible topic.
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Acute kidney injury associated with area under the curve versus trough monitoring of vancomycin in obese patients. Antimicrob Agents Chemother 2021; 66:e0088621. [PMID: 34633843 DOI: 10.1128/aac.00886-21] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-hour area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with Body Mass Indices (BMI) ≥30 kg/m2, admitted between August 2015-July 2017 or October 2017-September 2019, who received vancomycin for ≥72 hours and had level(s) drawn within 96 hours of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC24. AKI was identified using the highest serum creatinine value compared to the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC24 group meeting criteria for AKI (22.7% vs. 16.3%, p=0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC24 monitoring compared to trough monitoring (p=0.010). Monitoring of vancomycin with AUC24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.
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Marko R, Hajjar J, Nzeribe V, Pittman M, Deslandes V, Sant N, Cowan J, Kyermentang K, Ramsay T, Zelenitsky S, Kanji S. Therapeutic Drug Monitoring of Vancomycin in Adult Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia or Pneumonia. Can J Hosp Pharm 2021; 74:334-343. [PMID: 34602621 DOI: 10.4212/cjhp.v74i4.3195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Background Vancomycin remains widely used for methicillin-resistant Staphylococcus aureus (MRSA) infections; however, treatment failure rates up to 50% have been reported. At the authors' institution, monitoring of trough concentration is the standard of care for therapeutic drug monitoring of vancomycin. New guidelines support use of the ratio of 24-hour area under the concentration-time curve to minimum inhibitory concentration (AUC24/MIC) as the pharmacodynamic index most likely to predict outcomes in patients with MRSA-associated infections. Objectives To determine the discordance rate between trough levels and AUC24/MIC values and how treatment failure and nephrotoxicity outcomes compare between those achieving and not achieving their pharmacodynamic targets. Methods This retrospective cohort study involved patients with MRSA bacteremia or pneumonia admitted to the study hospital between March 1, 2014, and December 31, 2018, and treated with vancomycin. Data for trough concentrations were collected, and minimum concentrations (C min) were extrapolated. The AUC24/MIC values were determined using validated population pharmacokinetic models. The C min and AUC24/MIC values were characterized as below, within, or above pharmacodynamic targets (15-20 mg/L and 400-600, respectively). Discordance was defined as any instance where a patient's paired C min and AUC24/MIC values fell in different ranges (i.e., below, within, or above) relative to the target ranges. Predictors of treatment failure and nephrotoxicity were determined using logistic regression. Results A total of 128 patients were included in the analyses. Of these, 73 (57%) received an initial vancomycin dose less than 15 mg/kg. The discordance rate between C min and AUC24/MIC values was 21% (27/128). Rates of treatment failure and nephrotoxicity were 34% (43/128) and 18% (23/128), respectively. No clinical variables were found to predict discordance. Logistic regression identified initiation of vancomycin after a positive culture result (odds ratio [OR] 4.41, 95% confidence interval [CI] 1.36-14.3) and achievement of target AUC24/MIC after 4 days (OR 3.48, 95% CI 1.39-8.70) as modifiable predictors of treatment failure. Conclusions The relationship between vancomycin monitoring and outcome is likely confounded by inadequate empiric or initial dosing. Before any modification of practice with respect to vancomycin monitoring, empiric vancomycin dosing should be optimized.
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Affiliation(s)
- Ryan Marko
- , PharmD, is with The Ottawa Hospital, Ottawa, Ontario
| | - Julia Hajjar
- , MSc, is with The Ottawa Hospital, Ottawa, Ontario
| | | | | | | | - Nadia Sant
- , MD, is with The Ottawa Hospital, Ottawa, Ontario
| | | | | | - Tim Ramsay
- , PhD, is with the Ottawa Hospital Research Institute, Ottawa, Ontario
| | | | - Salmaan Kanji
- , PharmD, is with The Ottawa Hospital and the Ottawa Hospital Research Institute, Ottawa, Ontario
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Therapeutic drug monitoring of antimicrobial drugs in neonates. An opinion paper. Ther Drug Monit 2021; 44:65-74. [PMID: 34369442 PMCID: PMC8994040 DOI: 10.1097/ftd.0000000000000919] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 06/29/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Neonatal infections are associated with high morbidity and mortality rates. Optimal treatment of these infections requires knowledge of neonatal pharmacology and integration of neonatal developmental pharmacokinetics of antimicrobial drugs in the design of dosing regimens for use with different gestational and postnatal ages. Population pharmacokinetic (PK) and pharmacodynamic (PD) models are used to personalize the use of these drugs in these fragile patients. The final step to further minimize variability in an individual patient is therapeutic drug monitoring (TDM), where the same population PK/PD models are used in concert with optimally drawn blood samples to further fine-tune therapy. The purpose of this manuscript is to describe the present status and future role of model-based precision dosing and TDM of antimicrobial drugs in neonates. METHODS PubMed was searched for clinical trials or clinical studies of TDM in neonates. RESULTS A total of 447 papers were retrieved, of which 19 were concerned with antimicrobial drugs. Two papers (one aminoglycoside and one vancomycin) addressed the effects of TDM in neonates. We found that, in addition to aminoglycosides and vancomycin, TDM also plays a role in beta-lactam antibiotics and antifungal drugs. CONCLUSION There is a growing awareness that, in addition to aminoglycosides and vancomycin, the use of beta-lactam antibiotics, such as amoxicillin and meropenem, and other classes of antimicrobial drugs, such as antifungal drugs, may benefit from TDM. However, the added value must be shown. New analytical techniques and software development may greatly support these novel developments.
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Hou Y, Ren J, Li J, Jin X, Gao Y, Li R, Zhang J, Wang X, Li X, Wang G. Relationship Between Mean Vancomycin Trough Concentration and Mortality in Critically Ill Patients: A Multicenter Retrospective Study. Front Pharmacol 2021; 12:690157. [PMID: 34349650 PMCID: PMC8326564 DOI: 10.3389/fphar.2021.690157] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/06/2021] [Indexed: 12/30/2022] Open
Abstract
Background: It remains unclear whether the mean vancomycin trough concentration (VTC) derived from the entire course of therapy is of potential benefit for critically ill patients. This study was conducted to explore the association between mean serum VTC and mortality in intensive care units (ICUs). Methods: 3,603 adult patients with two or more VTC records after receiving vancomycin treatment in the eICU Collaborative Research Database were included in this multicenter retrospective cohort study. Mean VTC was estimated using all measured VTCs and investigated as a continuous and categorical variable. Patients were categorised into four groups according to mean VTC: <10, 10-15, 15-20, and >20 mg/L. Multivariable logistic regression and subgroup analyses were performed to investigate the relationship of mean VTC with mortality. Results: After adjusting for a series of covariates, logistic regression analyses indicated that mean VTC, as a continuous variable, was positively correlated with ICU (odds ratio, 1.038, 95% confidence interval, [1.014-1.063]) and hospital (1.025 [1.005-1.046]) mortalities. As a categorical variable, mean VTC of 10-15 mg/L was not associated with reduced ICU (1.705 [0.975-2.981]) and hospital (1.235 [0.829-1.841]) mortalities. Mean VTC of 15-20 mg/L was not correlated with a lower risk of hospital mortality (1.370 [0.924-2.029]). Moreover, mean VTCs of 15-20 and >20 mg/L were significantly associated with higher ICU mortality (1.924 [1.111-3.332]; 2.428 [1.385-4.258]), and mean VTC of >20 mg/L with higher hospital mortality (1.585 [1.053-2.387]) than mean VTC of <10 mg/L. Similar results were observed in patients with different Acute Physiology and Chronic Health Evaluation IV score, creatinine clearance, age, and body mass index subgroups. Conclusion: Mean VTC was not associated with reduced ICU/hospital related mortality. Our results suggested that VTC monitoring might not guarantee vancomycin efficacy for ICU patients.
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Affiliation(s)
- Yanli Hou
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiajia Ren
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiamei Li
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xuting Jin
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ya Gao
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ruohan Li
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jingjing Zhang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaochuang Wang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xinyu Li
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Medical University, Xi'an, China
| | - Gang Wang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Dilworth TJ, Schulz LT, Rose WE. Vancomycin Advanced Therapeutic Drug Monitoring: Exercise in Futility or Virtuous Endeavor to Improve Drug Efficacy and Safety? Clin Infect Dis 2021; 72:e675-e681. [PMID: 32898221 DOI: 10.1093/cid/ciaa1354] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 09/04/2020] [Indexed: 12/15/2022] Open
Abstract
Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.
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Affiliation(s)
| | | | - Warren E Rose
- School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA
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Optimizing Antimicrobial Drug Dosing in Critically Ill Patients. Microorganisms 2021; 9:microorganisms9071401. [PMID: 34203510 PMCID: PMC8305961 DOI: 10.3390/microorganisms9071401] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/25/2021] [Accepted: 06/25/2021] [Indexed: 12/23/2022] Open
Abstract
A fundamental step in the successful management of sepsis and septic shock is early empiric antimicrobial therapy. However, for this to be effective, several decisions must be addressed simultaneously: (1) antimicrobial choices should be adequate, covering the most probable pathogens; (2) they should be administered in the appropriate dose, (3) by the correct route, and (4) using the correct mode of administration to achieve successful concentration at the infection site. In critically ill patients, antimicrobial dosing is a common challenge and a frequent source of errors, since these patients present deranged pharmacokinetics, namely increased volume of distribution and altered drug clearance, which either increased or decreased. Moreover, the clinical condition of these patients changes markedly over time, either improving or deteriorating. The consequent impact on drug pharmacokinetics further complicates the selection of correct drug schedules and dosing during the course of therapy. In recent years, the knowledge of pharmacokinetics and pharmacodynamics, drug dosing, therapeutic drug monitoring, and antimicrobial resistance in the critically ill patients has greatly improved, fostering strategies to optimize therapeutic efficacy and to reduce toxicity and adverse events. Nonetheless, delivering adequate and appropriate antimicrobial therapy is still a challenge, since pathogen resistance continues to rise, and new therapeutic agents remain scarce. We aim to review the available literature to assess the challenges, impact, and tools to optimize individualization of antimicrobial dosing to maximize exposure and effectiveness in critically ill patients.
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Wahby KA, Cunmuljaj L, Mouabbi K, Almadrahi Z, Wilpula L. Evaluation of dosing strategies and trough concentrations of vancomycin in patients undergoing continuous venovenous hemofiltration. Pharmacotherapy 2021; 41:554-561. [PMID: 33963536 DOI: 10.1002/phar.2535] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 04/09/2021] [Accepted: 04/11/2021] [Indexed: 11/07/2022]
Abstract
STUDY OBJECTIVE Recommendations regarding vancomycin dosing in critically ill patients on continuous venovenous hemofiltration (CVVH) are limited. The purpose of this study was to evaluate current dosing practices of pharmacists for patients treated with CVVH, develop guidelines for optimal dosing and monitoring of vancomycin to improve target trough attainment, and reduce pharmacist workload. DESIGN A retrospective cohort study. was performed of critically ill adult patients from January 2015 to December 2018. Patients were included if they received vancomycin during CVVH for at least 48 h. Patients with significant residual kidney function, defined as daily urine output >400 ml or significant fluctuations (≥1000 ml/h in a 24-h period) in their hemofiltration rates, were excluded. Interruptions in CVVH up to 6 h/day were permitted. Dosing strategies with two dosing categories were defined: (1) dosing based on random serum levels (dosing by level, DBL) or (2) scheduled vancomycin dosing (SD). SETTING Academic medical center in Detroit, Michigan. PATIENTS Critically ill adult patients. MEASUREMENTS AND MAIN RESULTS During the study period, 942 patients were evaluated and 200 met inclusion criteria, for a total of 586 serum vancomycin levels. There were 141 patients with 443 random vancomycin serum levels in the DBL group and 59 patients with143 vancomycin trough levels in the SD group. Mean vancomycin trough levels were similar between groups (17.1 ± 6 vs. 16.5 ± 4 mcg/ml) for the DBL and SD groups, respectively. For the primary end point of overall target trough achievement of 15-20 mcg/ml, significantly more trough levels in the SD group were in the 15-20 mcg/ml range compared with the DBL group, 50% vs. 38%; p < 0.001, respectively. When target trough range was extended to 10-20 mcg/ml, success rates were similar between groups (74% DBL vs. 82% SD, p = 0.021). The number of interventions required by the pharmacist, including notes per day and orders per day, were reduced by approximately 50% when the SD strategy was utilized. Scheduled vancomycin dosing regimens of 15-22 mg/kg every 12-24 h were required to yield trough levels in the 15-20 mcg/ml range. CONCLUSIONS Target vancomycin trough achievement of 15-20 mcg/ml occurred more frequently when vancomycin was scheduled at a dose of 15-22 mg/kg every 12-24 h based on ultrafiltration rate and may alleviate the time and cost associated with frequent vancomycin serum monitoring.
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Affiliation(s)
| | | | | | | | - Liz Wilpula
- Harper University Hospital, Detroit, Michigan, USA
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Ono T, Sugiyama K, Komatsu S, Kumano M, Yoshida K, Dairaku T, Fujimura T, Sasano Y, Iwabuchi Y, Kashiwagi Y, Sato K. Catalysis of electro-oxidation of antibiotics by nitroxyl radicals and the electrochemical sensing of vancomycin. RSC Adv 2021; 11:21622-21628. [PMID: 35478798 PMCID: PMC9034136 DOI: 10.1039/d1ra03681e] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 06/04/2021] [Indexed: 11/21/2022] Open
Abstract
Quantifying drug concentrations in vivo quickly and easily is possible using electrochemical methods. The present study describes the electrochemical detection of vancomycin (VCM) and other antibiotics from the current obtained using nitroxyl radicals as electrocatalysts. Nortropine N-oxyl (NNO), which is more active than 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), a typical nitroxyl radical compound, produced greater current values for drugs with intramolecular hydroxy groups and secondary and tertiary amines. However, because the catalytic action of NNO is inactivated by primary amines in the substrate, VCM and teicoplanin with primary amines could not be detected. TEMPO was less active than NNO but not inactivated against primary amines. Therefore, electrochemical sensing of vancomycin was done using 4-acetamido-2,2,6,6-tetramethylpiperidine 1-oxyl (A-TEMPO), which has a greater oxidation capacity than TEMPO due to its electron-withdrawing groups. As a result, the current of A-TEMPO increased in the low concentration range of VCM as compared to TEMPO. This method also was able to quantify VCM in the concentration range of 10-100 μM, which is an important concentration range for drug monitoring in blood.
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Affiliation(s)
- Tetsuya Ono
- School of Pharmaceutical Sciences, Ohu University 31-1 Misumido, Tomita-machi Koriyama Fukushima 963-8611 Japan
| | - Kyoko Sugiyama
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University 4-4-1 Komatsushima, Aoba Sendai Miyagi 981-8558 Japan
| | - Sachiko Komatsu
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University 4-4-1 Komatsushima, Aoba Sendai Miyagi 981-8558 Japan
| | - Masayuki Kumano
- Graduate School of Pharmaceutical Sciences, Tohoku University 6-3 Aoba, Aramaki Aoba-ku Sendai 980-8578 Japan
| | - Kentaro Yoshida
- School of Pharmaceutical Sciences, Ohu University 31-1 Misumido, Tomita-machi Koriyama Fukushima 963-8611 Japan
| | - Takenori Dairaku
- School of Pharmaceutical Sciences, Ohu University 31-1 Misumido, Tomita-machi Koriyama Fukushima 963-8611 Japan
| | - Tsutomu Fujimura
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University 4-4-1 Komatsushima, Aoba Sendai Miyagi 981-8558 Japan
| | - Yusuke Sasano
- Graduate School of Pharmaceutical Sciences, Tohoku University 6-3 Aoba, Aramaki Aoba-ku Sendai 980-8578 Japan
| | - Yoshiharu Iwabuchi
- Graduate School of Pharmaceutical Sciences, Tohoku University 6-3 Aoba, Aramaki Aoba-ku Sendai 980-8578 Japan
| | - Yoshitomo Kashiwagi
- School of Pharmaceutical Sciences, Ohu University 31-1 Misumido, Tomita-machi Koriyama Fukushima 963-8611 Japan
| | - Katsuhiko Sato
- Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University 4-4-1 Komatsushima, Aoba Sendai Miyagi 981-8558 Japan .,Department of Creative Engineering, National Institute of Technology, Tsuruoka College 104 Sawada, Inooka Tsuruoka Yamagata 997-8511 Japan
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Wei X, Zhao M, Xiao X. Optimization of dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus in neutropenic patients with cancer by Monte Carlo simulations. J Chemother 2021; 33:547-553. [PMID: 34080519 DOI: 10.1080/1120009x.2021.1931758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.
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Affiliation(s)
- Xiaochen Wei
- Department of Pharmacy, Tianjin First Central Hospital, Tianjin, PR China
| | - Mingfeng Zhao
- Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China
| | - Xia Xiao
- Department of Hematology, Tianjin First Central Hospital, Tianjin, PR China
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Jorgensen SCJ, Spellberg B, Shorr AF, Wright WF. Should Therapeutic Drug Monitoring Based on the Vancomycin Area Under the Concentration-Time Curve Be Standard for Serious Methicillin-Resistant Staphylococcus aureus Infections?-No. Clin Infect Dis 2021; 72:1502-1506. [PMID: 33740050 DOI: 10.1093/cid/ciaa1743] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Indexed: 12/16/2022] Open
Abstract
In this counterpoint we critically appraise the evidence supporting therapeutic drug monitoring based on the vancomycin 24-hour area under the concentration-time curve (AUC24) for serious methicillin-resistant Staphylococcus aureus infections. We reveal methodologically weaknesses and inconsistencies in the data and suggest that, in the absence of clear and convincing evidence of benefit compared with modestly reducing trough targets, alternative strategies are more likely to result in superior safety and efficacy. These include focusing on fundamental antibiotic stewardship to limit vancomycin exposure overall, achieving earlier and more complete source control, and establishing alternative therapeutic options to vancomycin. Implementation of AUC24-based therapeutic drug monitoring will take resources away from these more promising, alternative solutions.
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Affiliation(s)
| | - Brad Spellberg
- Los Angeles County + University of Southern California (LAC+USC) Medical Center, Los Angeles, California, USA
| | - Andrew F Shorr
- Division of Pulmonary and Critical Care, Department of Medicine, Washington Hospital Center, Washington, DC, USA
| | - William F Wright
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Narayan SW, Thoma Y, Drennan PG, Yejin Kim H, Alffenaar JW, Van Hal S, Patanwala AE. Predictive Performance of Bayesian Vancomycin Monitoring in the Critically Ill. Crit Care Med 2021; 49:e952-e960. [PMID: 33938713 DOI: 10.1097/ccm.0000000000005062] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES It is recommended that therapeutic monitoring of vancomycin should be guided by 24-hour area under the curve concentration. This can be done via Bayesian models in dose-optimization software. However, before these models can be incorporated into clinical practice in the critically ill, their predictive performance needs to be evaluated. This study assesses the predictive performance of Bayesian models for vancomycin in the critically ill. DESIGN Retrospective cohort study. SETTING Single-center ICU. PATIENTS Data were obtained for all patients in the ICU between 1 January, and 31 May 2020, who received IV vancomycin. The predictive performance of three Bayesian models were evaluated based on their availability in commercially available software. Predictive performance was assessed via bias and precision. Bias was measured as the mean difference between observed and predicted vancomycin concentrations. Precision was measured as the SD of bias, root mean square error, and 95% limits of agreement based on Bland-Altman plots. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 466 concentrations from 188 patients were used to evaluate the three models. All models showed low bias (-1.7 to 1.8 mg/L), which was lower with a posteriori estimate (-0.7 to 1.8 mg/L). However, all three models showed low precision in terms of SD (4.7-8.8 mg/L) and root mean square error (4.8-8.9 mg/L). The models underpredicted at higher observed vancomycin concentrations (bias 0.7-3.2 mg/L for < 20 mg/L; -5.1 to -2.3 for ≥ 20 mg/L) and the Bland-Altman plots showed a great deviation between observed and predicted concentrations. CONCLUSIONS Bayesian models of vancomycin show not only low bias, but also low precision in the critically ill. Thus, Bayesian-guided dosing of vancomycin in this population should be used cautiously.
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Affiliation(s)
- Sujita W Narayan
- 1 The University of Sydney, Faculty of Medicine and Health, School of Pharmacy, Sydney, NSW, Australia. 2 Reconfigurable and Embedded Digital Systems Institute, School of Business and Engineering Vaud, University of Applied Sciences Western Switzerland, Yverdon-les-Bains, Switzerland. 3 Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. 4 Westmead Hospital, Westmead, NSW, Australia. 5 Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia. 6 New South Wales Health Pathology, Department of Infectious Diseases and Microbiology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 7 Royal Prince Alfred Hospital, Sydney, NSW, Australia
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Ren J, Hou Y, Li J, Gao Y, Li R, Jin X, Zhang J, Wang X, Wang G. An evaluation on the association of vancomycin trough concentration with mortality in critically ill patients: A multicenter retrospective study. Clin Transl Sci 2021; 14:1780-1790. [PMID: 33835715 PMCID: PMC8504840 DOI: 10.1111/cts.13020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 01/28/2021] [Accepted: 01/31/2021] [Indexed: 11/29/2022] Open
Abstract
To determine the impact of initial vancomycin trough concentration (VTC) on mortality in adult patients in the intensive care unit (ICU) undergoing vancomycin therapy. During their first ICU stay, patients with initial VTC records after vancomycin treatment were recruited from the eICU Collaborative Research Database to this multicenter retrospective cohort study, and classified into four groups according to VTC: less than 10, 10–15, 15–20, and greater than 20 mg/L. Multivariable logistic regression and sensitivity analyses were performed to explore the association of VTC, as a continuous and categorical variable, with mortality. This study enrolled 7220 patients from 335 different ICUs at 208 hospitals. Multivariable logistic regression models indicated that VTC was positively correlated with ICU (odds ratio [OR], 1.028, 95% confidence interval [CI], 1.019–1.037) and hospital (OR 1.028, 95% CI, 1.020–1.036) mortalities. Moreover, compared with VTC less than 10 mg/L, VTCs of 10–15, 15–20, and greater than 20 mg/L were associated with a higher risk of ICU mortality (OR, 1.330, 95% CI, 1.070–1.653; OR, 1.596, 95% CI, 1.265–2.015; abd OR, 1.875, 95% CI, 1.491–2.357, respectively), and VTCs of 15–20 and greater than 20 mg/L were also correlated with increased hospital mortality (OR, 1.482, 95% CI, 1.225–1.793; and OR, 1.831, 95% CI, 1.517–2.210, respectively). Similar results persisted in patients with different Acute Physiology and Chronic Health Evaluation Ⅳ scores, creatinine clearance levels, ages, and body mass indexes. Our findings indicated a potential relationship of initial VTC with ICU and hospital mortalities in patients in the ICU. However, due to the retrospective nature of this study, future prospective studies or randomized controlled trials are needed to validate those results.
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Affiliation(s)
- Jiajia Ren
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yanli Hou
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jiamei Li
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ya Gao
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ruohan Li
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xuting Jin
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jingjing Zhang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xiaochuang Wang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Gang Wang
- Department of Critical Care Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Rybak MJ, Le J, Lodise TP, Levine DP, Bradley JS, Liu C, Mueller BA, Pai MP, Wong-Beringer A, Rotschafer JC, Rodvold KA, Maples HD, Lomaestro BM. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2021; 77:835-864. [PMID: 32191793 DOI: 10.1093/ajhp/zxaa036] [Citation(s) in RCA: 695] [Impact Index Per Article: 173.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Michael J Rybak
- Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI, School of Medicine, Wayne State University, Detroit, MI, and Detroit Receiving Hospital, Detroit, MI
| | - Jennifer Le
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA
| | - Thomas P Lodise
- Albany College of Pharmacy and Health Sciences, Albany, NY, and Stratton VA Medical Center, Albany, NY
| | - Donald P Levine
- School of Medicine, Wayne State University, Detroit, MI, and Detroit Receiving Hospital, Detroit, MI
| | - John S Bradley
- Department of Pediatrics, Division of Infectious Diseases, University of California at San Diego, La Jolla, CA, and Rady Children's Hospital San Diego, San Diego, CA
| | - Catherine Liu
- Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA, and Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | | | | | | | | | | | - Holly D Maples
- University of Arkansas for Medical Sciences College of Pharmacy & Arkansas Children's Hospital, Little Rock, AR
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Cristinacce A, Wright JG, Macpherson M, Iaconis J, Das S. Comparing probability of target attainment against Staphylococcus aureus for ceftaroline fosamil, vancomycin, daptomycin, linezolid, and ceftriaxone in complicated skin and soft tissue infection using pharmacokinetic/pharmacodynamic models. Diagn Microbiol Infect Dis 2021; 99:115292. [PMID: 33360809 DOI: 10.1016/j.diagmicrobio.2020.115292] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 10/31/2019] [Accepted: 12/07/2020] [Indexed: 12/29/2022]
Abstract
For recently licensed antibiotics, such as the cephalosporin ceftaroline fosamil, probability of target attainment (PTA) curves, showing the percentage of patients reaching a predefined pharmacokinetic (PK)/pharmacodynamic (PD) target at different bacterial minimum inhibitory concentrations (MICs), have been used to support and justify dose recommendations across patient populations. However, information on PTA for older antibiotics is limited. A retrospective analysis was conducted to construct PTA curves for 4 antibiotics against Staphylococcus aureus in patients with complicated skin and soft tissue infections (cSSTIs). PK models for vancomycin, linezolid, daptomycin, and ceftriaxone were selected from the literature based on large numbers of subjects with covariates representative of patients in Europe and/or the United States. An existing model was available for ceftaroline fosamil. Standard and high-dosage regimens were used to compare the PTA of each antibiotic at MIC values 0.03 to 64 mg/L for a simulated set of patients with cSSTI caused by S. aureus. These were compared to proportions of S. aureus isolates at each MIC from global surveillance data. Ceftaroline achieved PTAs >99.9% for bacteriostatic and bactericidal targets at the MIC90 (1 mg/L), whereas the comparators failed to achieve PTAs >90%, at bacteriostatic or bactericidal targets, even when clinical doses were increased beyond those recommended. PTA analysis can be used to compare different drugs with the same simulated patient dataset, subject to availability of an appropriate PK model and robust exposure targets. This analysis shows that some antibiotics commonly used to treat cSSTIs may fail to reach high PTAs relative to contemporary MIC90 estimates.
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Affiliation(s)
| | | | | | | | - Shampa Das
- Clinical Pharmacology, AstraZeneca, Macclesfield, UK.
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Eads AV, Cole JL. Efficacy and Safety of Vancomycin Therapy After the Transition to AUC/MIC Monitoring in a Primary Facility. J Pharm Pract 2021; 35:680-685. [PMID: 33759615 DOI: 10.1177/08971900211003439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND New guidance recommends area under the curve/minimum inhibitory concentration (AUC/MIC) instead of trough-based monitoring for vancomycin therapy. While this transition has demonstrated improved safety and efficacy in large, tertiary centers, this has not been assessed in the primary hospital setting. OBJECTIVE The primary objectives were to evaluate the efficacy and safety of AUC/MIC monitoring in inpatient veterans treated with intravenous vancomycin for ≥72 hours compared to a historical cohort of trough-based monitoring. METHODS This was a retrospective, quasi-experimental study over 2 five-month study periods. Efficacy was evaluated by comparing clinical failure rates as defined by a persistent fever, clinical deterioration, or escalation of gram-positive therapy. Safety was determined by the incidence of acute kidney injury (AKI) defined by an acute increase in serum creatinine ≥0.3 mg/dL over 48 hours. RESULTS 25 patients met the criteria in the before group and 19 in the after group. Efficacy was equivalent between groups; no patients exhibited clinical failure of vancomycin therapy. In the before group, 2 patients (8%) met defined criteria for AKI, while none in the after group experienced AKI (P = 0.21). Total vancomycin exposure was similar between groups (P = 0.56). CONCLUSION AUC-based monitoring was equally efficacious as trough-based monitoring with similarly low rates of AKI.
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Affiliation(s)
- Andrea V Eads
- Veterans Health Care System of the Ozarks, Fayetteville, AR, USA
| | - Jennifer L Cole
- Clinical Pharmacy Specialist, Veterans Health Care System of the Ozarks, Fayetteville, AR, USA
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Point-Counterpoint: Should Clinical Microbiology Laboratories Report Vancomycin MICs? J Clin Microbiol 2021; 59:JCM.00239-21. [PMID: 33536296 DOI: 10.1128/jcm.00239-21] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTIONWith numerous reported challenges to reporting MICs for vancomycin, clinical laboratories are attempting to identify accurate methods for MIC testing. However, the issues of poor reproducibility, accuracy, and clinical utility remain a challenge. In this Point-Counterpoint, Dr. Sara Revolinski discusses the pros of reporting MICs for vancomycin, while Dr. Christopher Doern argues for the use of caution.
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Lodise TP, Drusano G. Vancomycin Area Under the Curve–Guided Dosing and Monitoring for Adult and Pediatric Patients With Suspected or Documented Serious Methicillin-Resistant Staphylococcus aureus Infections: Putting the Safety of Our Patients First. Clin Infect Dis 2021; 72:1497-1501. [DOI: 10.1093/cid/ciaa1744] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Indexed: 12/12/2022] Open
Abstract
Abstract
The revised vancomycin consensus guidelines recommended area under the curve (AUC)–guided dosing/monitoring for patients with serious invasive methicillin-resistant Staphylococcus aureus (MRSA) infections as a measure to minimize vancomycin-associated acute kidney injury (VA-AKI) while maintaining similar effectiveness. Data indicate that the intensity of vancomycin exposure drives VA-AKI risk. Troughs of 15–20 mg/L will ensure an AUC ≥400 mg × hr/L but most patients will have daily AUCs >600. VA-AKI increases as a function of AUC, especially when >600. In addition to minimizing VA-AKI risk while maintaining similar efficacy, AUC-guided dosing/monitoring is a more precise way to conduct therapeutic drug monitoring for vancomycin relative to trough-only control.
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Affiliation(s)
- Thomas P Lodise
- Albany College of Pharmacy and Health Sciences, Albany, New York, USA
| | - George Drusano
- Institute for Therapeutic Innovation, University of Florida, Orlando, Florida, USA
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Stewart JJ, Jorgensen SCJ, Dresser L, Lau TTY, Gin A, Thirion DJG, Nishi C, Dalton B. A Canadian perspective on the revised 2020 ASHP-IDSA-PIDS-SIDP guidelines for vancomycin AUC-based therapeutic drug monitoring for serious MRSA infections. JOURNAL OF THE ASSOCIATION OF MEDICAL MICROBIOLOGY AND INFECTIOUS DISEASE CANADA = JOURNAL OFFICIEL DE L'ASSOCIATION POUR LA MICROBIOLOGIE MEDICALE ET L'INFECTIOLOGIE CANADA 2021; 6:3-9. [PMID: 36340210 PMCID: PMC9612435 DOI: 10.3138/jammi-2020-0028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 10/06/2020] [Indexed: 04/13/2023]
Abstract
BACKGROUND A revised consensus guideline on therapeutic drug monitoring (TDM) of vancomycin for serious methicillin-resistant Staphylococcus aureus (MRSA) infections was recently published with endorsement of numerous American pharmacy and medical societies. Changing practice from trough TDM to area-under-the-curve-(AUC)-guided dosing was suggested. METHODS Recent literature was critically appraised to determine whether AUC TDM is appropriate for Canadian hospital practice. RESULTS Previous 2009 vancomycin consensus guidelines recommended trough levels of 15-20 mg/L for serious MRSA infections, based on relatively poor evidence for efficacy or safety. In the past decade, aggressive trough targets have led to unnecessary toxicity. Adoption of a TDM strategy using an alternative parameter (AUC) has been suggested, although the evidence for any outcome benefits is low quality. In addition, implementation would require greater resources at health care institutions in the forms of more frequent serum levels or acquisition of costly Bayesian software programs. Most studies on this subject have been observational and retrospective; therefore, relationships between TDM parameters and outcomes have not been convincingly and consistently demonstrated to be causal in nature. Despite claims to the contrary, based on few in silico experiments, available clinical data suggest correlation of trough levels and AUC is high. TDM with lower target trough levels is a simpler solution to reduce risk of toxicity. CONCLUSIONS There are serious concerns with adoption of AUC TDM of vancomycin into routine practice in Canada. Trough-based monitoring with modest reduction in target levels remains the most evidence-informed practice at this time.
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Affiliation(s)
- Jackson J Stewart
- Pharmacy Department, Alberta Health Services, Edmonton, Alberta, Canada
| | | | - Linda Dresser
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
- Department of Pharmacy, Sinai Health System, Toronto, Ontario, Canada
| | - Tim TY Lau
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, British Columbia, Canada
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
- Division of Infectious Diseases, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Alfred Gin
- Winnipeg Regional Health Authority Regional Pharmacy Program, Winnipeg, Manitoba, Canada
- Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Daniel JG Thirion
- Pharmacy Department, McGill University Health Centre, Montreal, Quebec, Canada
- Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
| | - Cesilia Nishi
- Pharmaceutical Sciences, Vancouver General Hospital, Vancouver, British Columbia, Canada
- Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
- Division of Infectious Diseases, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Bruce Dalton
- Pharmacy Department, Alberta Health Services, Edmonton, Alberta, Canada
- Correspondence: Dr Bruce Dalton, Alberta Health Services—Pharmacy Services, 1403 29th St NW, Calgary, Alberta T2N3Z5 Canada. Telephone: 403-919-2416. E-mail:
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47
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Jorgensen SCJ, Dersch-Mills D, Timberlake K, Stewart JJ, Gin A, Dresser LD, Dalton BR. AUCs and 123s: a critical appraisal of vancomycin therapeutic drug monitoring in paediatrics. J Antimicrob Chemother 2021; 76:2237-2251. [PMID: 33675656 DOI: 10.1093/jac/dkab048] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The revised vancomycin guidelines recommend implementing AUC24-based therapeutic drug monitoring (TDM) using Bayesian methods in both adults and paediatrics. The motivation for this change was accumulating evidence showing aggressive dosing to achieve high troughs, as recommended in the first guidelines for adults and extrapolated to paediatrics, is associated with increased nephrotoxicity without improving clinical outcomes. AUC24-based TDM requires substantial resources that may need to be diverted from other valuable interventions. It can therefore be justified only after certain assumptions are shown to be true: (i) there is a clear relationship between vancomycin efficacy and/or toxicity and the proposed therapeutic range; and (ii) maintaining exposure within the target range with AUC24-based TDM improves clinical outcomes and/or decreases toxicity. In this review, we critically appraise the scientific basis for these assumptions. We find studies evaluating the relationship between vancomycin AUC24/MIC and efficacy in adults and children do not offer strong support for the recommended lower limit of the proposed therapeutic range (i.e. AUC24/MIC ≥400). Nephrotoxicity in children increases in a stepwise manner along the vancomycin exposure continuum but it is unclear if one parameter (AUC24 versus trough) is a superior predictor. Overall, evidence in children suggests good-to-excellent correlation between AUC24 and trough. Most importantly, there is no convincing evidence that the method of vancomycin TDM has a causal role in improving efficacy or reducing toxicity. These findings question the need to transition to resource-intensive AUC24-based TDM over retaining trough-based TDM with lower targets to minimize nephrotoxicity in paediatrics.
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Affiliation(s)
| | | | - Kathryn Timberlake
- Department of Pharmacy, The Hospital for Sick Children, Toronto, ON, Canada
| | - Jackson J Stewart
- Pharmacy Services, University of Alberta Hospital, Edmonton, AB, Canada
| | - Alfred Gin
- Department of Pharmacy, Winnipeg Regional Health Authority, Winnipeg, MB, Canada.,Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Linda D Dresser
- Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.,Antimicrobial Stewardship Program, University Health Network, Toronto, ON, Canada
| | - Bruce R Dalton
- Pharmacy Services, Alberta Health Services, Calgary, AB, Canada
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48
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Lodise TP, Hall RG, Scheetz MH. Vancomycin Area Under the Curve-guided Dosing and Monitoring: "Is the Juice Worth the Squeeze"? Pharmacotherapy 2020; 40:1176-1179. [PMID: 33368454 DOI: 10.1002/phar.2482] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Thomas P Lodise
- Albany College of Pharmacy and Health Sciences, Albany, New York, USA
| | - Ronald G Hall
- Department of Pharmacy Practice, Texas Tech University Health Sciences Center, Jerry H. Hodge School of Pharmacy, Amarillo, Texas, USA.,Dose Optimization and Outcomes Research (DOOR) Program, Dallas, Texas, USA
| | - Marc H Scheetz
- Pharmacometrics Center of Excellence, Department of Pharmacy Practice, College of Pharmacy, Midwestern University, Downers Grove, Illinois, USA.,Department of Pharmacology, College of Graduate Studies, Midwestern University, Downers Grove, Illinois, USA.,Department of Pharmacy, Northwestern Medicine, Chicago, Illinois, USA
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49
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Stocker SL, Carland JE, Reuter SE, Stacy AE, Schaffer AL, Stefani M, Lau C, Kirubakaran R, Yang JJ, Shen CFJ, Roberts DM, Marriott DJE, Day RO, Brett J. Evaluation of a Pilot Vancomycin Precision Dosing Advisory Service on Target Exposure Attainment Using an Interrupted Time Series Analysis. Clin Pharmacol Ther 2020; 109:212-221. [PMID: 33190285 DOI: 10.1002/cpt.2113] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 11/10/2020] [Indexed: 12/30/2022]
Abstract
This study evaluated the ability of a pilot therapeutic drug monitoring (TDM) Advisory Service to facilitate vancomycin therapeutic target attainment within a real-world clinical setting. The Service provided area under the concentration-time curve (AUC)-guided vancomycin dose recommendations, using Bayesian forecasting software and clinical expertise, to prescribers at an Australian hospital. A retrospective audit of intravenous vancomycin therapy (> 48 hours) in adults (≥ 18 years old) was undertaken over a 54-month period to evaluate attainment of established vancomycin pharmacokinetic/pharmacodynamic targets (AUC over 24 hours / minimum inhibitory concentration: 400-600) before (36-month period) and after (18-month period) Service implementation. Interrupted time series analysis was employed to evaluate monthly measures of the median proportion of therapy spent within the target range. Indices of time to target attainment were also assessed before and after Service implementation. The final cohort comprised 1,142 courses of vancomycin (816 patients); 835 courses (596 patients) and 307 courses (220 patients) administered before and after Service implementation, respectively. Prior to piloting the Service, the median proportion of time in the target range was 40.1% (95% CI, 34.3-46.0%); this increased by 10.4% (95% CI, 1.2-19.6%, P = 0.03) after the Service, and was sustained throughout the post-Service evaluation period. Post-Service target attainment at 48-72 hours after initiation of therapy was increased (7.8%, 95% CI, 1.3-14.3%, P = 0.02). The findings of this study provide evidence that a consultative TDM Service can facilitate attainment of vancomycin therapeutic targets; however, optimization of the Service may further improve the use of vancomycin.
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Affiliation(s)
- Sophie L Stocker
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.,Sydney Pharmacy School, Faculty of Medicine & Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Jane E Carland
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Stephanie E Reuter
- UniSA Clinical & Health Sciences, University of South Australia, Adelaide, South Australia, Australia
| | - Alexandra E Stacy
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,School of Medicine, The University of Notre Dame Australia, Sydney, New South Wales, Australia
| | - Andrea L Schaffer
- Centre for Big Data Research in Health, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Maurizio Stefani
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Cindy Lau
- Sydney Pharmacy School, Faculty of Medicine & Health, The University of Sydney, Sydney, New South Wales, Australia.,Pharmacy Department, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Ranita Kirubakaran
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Jennifer J Yang
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Catriona F J Shen
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Darren M Roberts
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Deborah J E Marriott
- St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia.,Department of Clinical Microbiology & Infectious Diseases, St Vincent's Hospital, Sydney, New South Wales, Australia
| | - Richard O Day
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
| | - Jonathan Brett
- Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital, Sydney, New South Wales, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, New South Wales, Australia
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50
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Mcgrady KA, Benton M, Tart S, Bowers R. Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program. Pharm Pract (Granada) 2020; 18:2024. [PMID: 33005260 PMCID: PMC7508472 DOI: 10.18549/pharmpract.2020.3.2024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/06/2020] [Indexed: 11/24/2022] Open
Abstract
Background: Area under the curve to minimum inhibitory concentration (AUC/MIC) has been
recommended by the 2020 updated vancomycin guidelines for dosing vancomycin
for both efficacy and safety. Previously, AUC/MIC has been cumbersome to
calculate so surrogate trough concentrations of 15-20 mg/dL were utilized.
However, trough-based dosing is not a sufficient surrogate as AUC/MIC
targets of 400-600 can usually be reached without achieving troughs of 15-20
mg/dL. Targeting higher trough levels may also lead to adverse events
including acute kidney injury (AKI) and nephrotoxicity. Objective: To compare the mean total first day vancomycin dose in traditional
trough-based dosing versus dosing recommended by an AUC/MIC dosing
program. Methods: Adult inpatients who received at least 24 hours of IV vancomycin treatment
were included in this single-center, retrospective cohort study. The primary
endpoint was difference in mean total first day vancomycin dose in
milligrams (mg) received between patients’ traditional trough-based
dosing and recommended dose via AUC/MIC electronic dosing calculator.
Patients served as their own control by analyzing both actual dose received
and dose recommended by the electronic AUC/MIC program. Rates of vancomycin
induced adverse events, including acute kidney injury, elevated steady-state
trough concentrations, and Red Man’s syndrome were also compared
between patients who received doses consistent with the AUC/MIC dosing
recommendation versus those who did not. Results: 264 patients were included in this study. Initial 24-hour vancomycin exposure
was significantly lower with the recommended AUC/MIC dose versus the dose
received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI
114.7:423.1] p=0.0007). Conclusions: Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in
lower total first day vancomycin doses.
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Affiliation(s)
- Kerri A Mcgrady
- PharmD. College of Pharmacy and Health Sciences, Campbell University. Buies Creek, NC (United States).
| | - Makenzie Benton
- BS. College of Pharmacy and Health Sciences, Campbell University. Buies Creek, NC (United States).
| | - Serina Tart
- PharmD. Cape Fear Valley Health. Fayetteville, NC (United States).
| | - Riley Bowers
- PharmD. College of Pharmacy and Health Sciences, Campbell University. Buies Creek, NC (United States).
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