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Yoshikawa N, Miyata C, Koreeda H, Nakahara S, Matsusaki Y, Yamada Y, Nagano T, Ochiai H, Ikeda R. Pharmacist support in the entry of blood drug concentration test order avoids vancomycin-induced kidney injury. Ther Adv Drug Saf 2025; 16:20420986251339580. [PMID: 40417647 PMCID: PMC12103665 DOI: 10.1177/20420986251339580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 04/15/2025] [Indexed: 05/27/2025] Open
Abstract
Background Task shifting and sharing have been proposed as strategies to address healthcare staffing shortages and improve patient outcomes. In emergency and intensive care medicine, pharmacist interventions have shown potential to reduce medication errors and improve care quality. However, the precise benefits of pharmacist support in therapeutic drug monitoring (TDM) for emergency center inpatients require further verification. Objective To determine the contribution of pharmacist support in entering blood drug concentration test orders to patient safety during anti-methicillin-resistant Staphylococcus aureus (MRSA) drug administration in the emergency and critical care center, and investigate the association between this support and the frequency of vancomycin-induced kidney injury. Design Single-center retrospective cohort study comparing outcomes 2 years before and 2 years after implementing pharmacist support for blood concentration test order entry. Methods Patients receiving intravenous vancomycin with blood concentrations measured at the emergency center were included. Propensity score matching was used to minimize confounding. The primary outcome was the change in frequency of vancomycin-induced kidney injury before and after pharmacist support implementation. Results Pharmacist support significantly reduced the frequency of vancomycin-induced kidney injury (from 6.5% to 0.0%, p = 0.043) and shortened time to first TDM implementation (p = 0.019) in the overall cohort. Similar significant reductions were observed in the propensity score matched cohort (from 11.9% to 0.0%, p = 0.013). Conclusion Pharmacist support in entering blood drug concentration test orders significantly reduced vancomycin-induced kidney injury frequency and shortened time to first TDM, enhancing patient safety during anti-MRSA medication administration in the emergency and critical care center. This task-shifting approach demonstrates clear benefits for patient care and physician workload.
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Affiliation(s)
- Naoki Yoshikawa
- Department of Pharmacy, University of Miyazaki Hospital, 5200 Kihara, Kiyotake-Cho, Miyazaki 889-1692, Japan
| | - Chiaki Miyata
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
| | - Hidehiko Koreeda
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
| | - Shuichi Nakahara
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
| | - Yuki Matsusaki
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
| | - Yusei Yamada
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
| | - Takehiko Nagano
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Hidenobu Ochiai
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Ryuji Ikeda
- Department of Pharmacy, University of Miyazaki Hospital, Miyazaki, Japan
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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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Ji C, Garcia J, Sabuga AJ, Ricard M, Dion F, Rosu VA, Legris M, Marsot A, Nguyen VD. External evaluation of intravenous vancomycin population pharmacokinetic models in adults receiving high-flux intermittent haemodialysis. Br J Clin Pharmacol 2025; 91:856-865. [PMID: 39520248 PMCID: PMC11862783 DOI: 10.1111/bcp.16334] [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: 05/22/2024] [Revised: 10/21/2024] [Accepted: 10/28/2024] [Indexed: 11/16/2024] Open
Abstract
AIMS Patients undergoing haemodialysis (HD) are at greater risk of methicillin-resistant Staphylococcus aureus infections requiring intravenous vancomycin. Close vancomycin therapeutic drug monitoring is warranted in HD patients as renal clearance is the primary elimination pathway. Clinically, population pharmacokinetics (popPK) model-informed dosing is commonly used. This study aimed to perform an external evaluation of published vancomycin popPK models developed for adults undergoing high-flux intermittent HD, and to create a dosing nomogram derived from the model that performed best. METHODS A literature review was conducted through PubMed and EMBASE to identify relevant popPK models. an external dataset was collected retrospectively from patients of 2 healthcare centres in Quebec, Canada. Selected models were implemented in NONMEM (v7.5; ICON Development Solutions). Predictive performance was assessed through prediction and simulation-based diagnostics. RESULTS In total, 2386 vancomycin concentrations were collected from 274 patients and 476 antibiotic courses. Four vancomycin popPK models were selected for evaluation. None of the models demonstrated overall satisfactory or clinically acceptable predictive performance. Nonetheless, Bae et al.'s model performed best with a median prediction error of 16.25% and median absolute prediction error of 34.66%. Different predictive performance was also observed for vancomycin concentrations from samples collected during and between HD sessions. CONCLUSION All evaluated models presented poor overall predictive performance. Further studies are required, through existing popPK model parameter re-estimation or new model development, to adequately describe vancomycin pharmacokinetics for our high-flux intermittent HD patient cohort.
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Affiliation(s)
- Cheng Ji
- Pharmacy DepartmentMcGill University Health CenterMontréalQCCanada
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
| | - Jonathan Garcia
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Département de pharmacieHôpital Charles‐Le MoyneGreenfield ParkQCCanada
| | - Argem Joy Sabuga
- Pharmacy DepartmentMcGill University Health CenterMontréalQCCanada
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
| | - Maurane Ricard
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Département de pharmacieHôpital Charles‐Le MoyneGreenfield ParkQCCanada
| | - France Dion
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Département de pharmacieHôpital Charles‐Le MoyneGreenfield ParkQCCanada
| | - Vlad Alexandru Rosu
- Pharmacy DepartmentMcGill University Health CenterMontréalQCCanada
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
| | - Marie‐Ève Legris
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Département de pharmacieHôpital Charles‐Le MoyneGreenfield ParkQCCanada
| | - Amélie Marsot
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de PharmacieUniversité de MontréalMontréalQCCanada
- Centre de recherche du CHU Ste‐JustineCentre hospitalier universitaire Ste‐JustineMontréalQCCanada
| | - Van Dong Nguyen
- Pharmacy DepartmentMcGill University Health CenterMontréalQCCanada
- Faculty of PharmacyUniversité de MontréalMontréalQCCanada
- Laboratoire de Suivi Thérapeutique Pharmacologique et Pharmacocinétique, Faculté de PharmacieUniversité de MontréalMontréalQCCanada
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Onita T, Ishihara N, Yano T. PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance. Antibiotics (Basel) 2025; 14:92. [PMID: 39858377 PMCID: PMC11759776 DOI: 10.3390/antibiotics14010092] [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: 12/19/2024] [Revised: 01/11/2025] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
Antimicrobial resistance (AMR) poses a critical global health threat, necessitating the optimal use of existing antibiotics. Pharmacokinetic/pharmacodynamic (PK/PD) principles provide a scientific framework for optimizing antimicrobial therapy, particularly to respond to evolving resistance patterns. This review examines PK/PD strategies for antimicrobial dosing optimization, focusing on three key aspects. First, we discuss the importance of drug concentration management for enhancing efficacy while preventing toxicity, considering various patient populations, including pediatric and elderly patients with their unique physiological characteristics. Second, we analyze different PK modeling approaches: the classic top-down approach exemplified by population PK analysis, the bottom-up approach represented by physiologically based PK modeling, and hybrid models combining both approaches for enhanced predictive performance. Third, we explore clinical applications, including nomogram-based dosing strategies, Bayesian estimation, and emerging artificial intelligence applications, for real-time dose optimization. Critical challenges in implementing PK/PD simulation are addressed, particularly the selection of appropriate PK models, the optimization of PK/PD indices, and considerations concerning antimicrobial concentrations at infection sites. Understanding these principles and challenges is crucial for optimizing antimicrobial therapy and combating AMR through improved dosing strategies.
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Affiliation(s)
| | | | - Takahisa Yano
- Department of Pharmacy, Shimane University Hospital, 89-1 Enya, Izumo 693-8501, Shimane, Japan
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Nakano Y, Hirai T, Murata M, Yasukochi H, Ura K, Sueyasu Y, Shimono N, Hasuwa H. Impact of pharmacist-driven antimicrobial stewardship interventions in a secondary care facility in Japan: A pragmatic quasi-experimental study. J Infect Chemother 2025; 31:102503. [PMID: 39214387 DOI: 10.1016/j.jiac.2024.08.018] [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: 06/25/2024] [Revised: 08/17/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND Efforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory. METHODS This single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia. RESULTS Pharmacist-driven interventions significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95 % confidence intervals [CI]: 0.33-0.81, p = 0.003) and DASC (IRR: 0.87, 95 % CI: 0.78-0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95 % CI: 0.56-1.51, p = 0.74). Conversely, pharmacist-driven interventions significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥4 (adjusted HR: 0.52, 95 % CI: 0.28-0.99, p = 0.047). CONCLUSIONS Pharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis.
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Affiliation(s)
- Yuki Nakano
- Department of Pharmacy, Saiseikai Futsukaichi Hospital, Fukuoka, Japan.
| | - Toshinori Hirai
- Department of Pharmacy, Tokyo Medical and Dental University Hospital, Tokyo, Japan
| | - Masayuki Murata
- Department of Environmental Medicine and Infectious Disease, Kyushu University, Fukuoka, Japan
| | | | - Kazuya Ura
- Department of General Internal Medicine, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Yoshiko Sueyasu
- Department of Respiratory Medicine, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
| | - Nobuyuki Shimono
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hirotsugu Hasuwa
- Department of Pharmacy, Saiseikai Futsukaichi Hospital, Fukuoka, Japan
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Moritsuka A, Miyamoto H, Takahashi Y, Hirata H, Kawauchi Y, Fumoto S, Nishida K. Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries. Biol Pharm Bull 2025; 48:80-85. [PMID: 39894559 DOI: 10.1248/bpb.b24-00687] [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] [Indexed: 02/04/2025]
Abstract
Peritonitis is a serious complication in peritoneal dialysis patients and requires antibiotic administration. Intraperitoneal vancomycin is an empiric therapy for peritonitis caused by Gram-positive cocci; however, there is no way to predict vancomycin absorption after intraperitoneal administration. Therefore, we aimed to evaluate the changes in vancomycin absorption after intraperitoneal injection into mice with chlorhexidine gluconate (CG) induced peritoneal injuries. Additionally, we examined the correlation between intraperitoneal vancomycin absorption and peritoneal equilibration test (PET) score. PET score was determined using glucose concentration in the peritoneal dialysis fluid at each dwell time (Dt) and D2 (2 h of dwell time)/D0 (0 h of dwell time) glucose ratio. Vancomycin was injected into the peritoneal cavity of mice, blood was collected after 1-8 h, and peritoneal fluid was recovered. The residual ratio of intraperitoneal vancomycin was significantly decreased in the CG group at all time points compared to that in the vehicle group. CG group significantly exhibited higher serum vancomycin concentrations than the vehicle group, and the maximum serum concentration increased depending on CG concentration, with 0.05 and 0.1% CG groups showing 3.9- and 6.1-times higher vancomycin concentrations, respectively, than the vehicle group. A significant correlation was observed between the Dt/D0 glucose ratios and residual vancomycin ratios in the peritoneal fluid 2 or 6 h after intraperitoneal injection. A good correlation was observed between the D2/D0 glucose and residual vancomycin ratios 6 h after intraperitoneal vancomycin injection. Thus, PET score can predict residual intraperitoneal vancomycin, aiding in dosing decisions.
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Affiliation(s)
- Akihiro Moritsuka
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Hirotaka Miyamoto
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Yukina Takahashi
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Haruna Hirata
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Yuki Kawauchi
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Shintaro Fumoto
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
| | - Koyo Nishida
- Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan
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Recht J, Evans TJ, Chansamouth V, Phommasone K, Mayxay M, Ashley EA. Which trial do we need? A pragmatic randomized trial of trimethoprim-sulfamethoxazole vs. vancomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteraemia in low-resource settings. Clin Microbiol Infect 2025; 31:13-17. [PMID: 39067512 DOI: 10.1016/j.cmi.2024.07.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/13/2024] [Accepted: 07/20/2024] [Indexed: 07/30/2024]
Affiliation(s)
- Judith Recht
- Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
| | - Terry John Evans
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Vilada Chansamouth
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Koukeo Phommasone
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Microbiology Laboratory, Mahosot Hospital, Vientiane, Lao PDR
| | - Mayfong Mayxay
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Institute of Research and Education Development (IRED), University of Health Sciences, Ministry of Health, Vientiane, Lao PDR
| | - Elizabeth A Ashley
- Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Lao PDR; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
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8
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Peng H, Zhang R, Zhou S, Xu T, Wang R, Yang Q, Zhong X, Liu X. Impact of vancomycin therapeutic drug monitoring on mortality in sepsis patients across different age groups: a propensity score-matched retrospective cohort study. Front Med (Lausanne) 2024; 11:1498337. [PMID: 39726684 PMCID: PMC11669523 DOI: 10.3389/fmed.2024.1498337] [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: 09/18/2024] [Accepted: 11/11/2024] [Indexed: 12/28/2024] Open
Abstract
Background Due to its potent antibacterial activity, vancomycin is widely used in the treatment of sepsis. Therapeutic drug monitoring (TDM) can optimize personalized vancomycin dosing regimens, enhancing therapeutic efficacy and minimizing nephrotoxic risk, thereby potentially improving patient outcomes. However, it remains uncertain whether TDM affects the mortality rate among sepsis patients or whether age plays a role in this outcome. Methods We analyzed data from the Medical Information Mart of Intensive Care-IV database, focusing on sepsis patients who were admitted to the intensive care unit (ICU) and treated with vancomycin. The primary variable of interest was the use of vancomycin TDM during the ICU stay. The primary outcome was 30-day mortality. To control for potential confounding factors and evaluate associations, we used Cox proportional hazards regression and propensity score matching (PSM). Subgroup and sensitivity analyses were performed to assess the robustness of our findings. Furthermore, restricted cubic spline models were utilized to investigate the relationship between age and mortality among different groups of sepsis patients, to identify potential non-linear associations. Results A total of 14,053 sepsis patients met the study criteria, of whom 6,826 received at least one TDM during their ICU stay. After PSM, analysis of 4,329 matched pairs revealed a significantly lower 30-day mortality in the TDM group compared with the non-TDM group (23.3% vs.27.7%, p < 0.001). Multivariable Cox proportional hazards regression showed a significantly reduced 30-day mortality risk in the TDM group [adjusted hazard ratio (HR): 0.66; 95% confidence interval (CI): 0.61-0.71; p < 0.001]. This finding was supported by PSM-adjusted analysis (adjusted HR: 0.71; 95% CI: 0.66-0.77; p < 0.001) and inverse probability of treatment weighting analysis (adjusted HR: 0.72; 95% CI: 0.67-0.77; p < 0.001). Kaplan-Meier survival curves also indicated significantly higher 30-day survival in the TDM group (log-rank test, p < 0.0001). Subgroup analyses by gender, age, and race yielded consistent results. Patients with higher severity of illness-indicated by sequential organ failure assessment scores ≥6, acute physiology score III ≥40, or requiring renal replacement therapy, vasopressors, or mechanical ventilation-experienced more pronounced mortality improvement from vancomycin TDM compared with those with lower severity scores or not requiring these interventions. The results remained robust after excluding patients with ICU stays <48 h, those with methicillin-resistant Staphylococcus aureus infections, or when considering only patients with septic shock. In subgroup analyses, patients under 65 years (adjusted HR: 0.50; 95% CI: 0.43-0.58) benefited more from vancomycin TDM than those aged 65 years and older (adjusted HR: 0.75; 95% CI: 0.67-0.83). Notably, sepsis patients aged 18-50 years had the lowest mortality rate among all age groups, at 15.2% both before and after PSM. Furthermore, in this age group, vancomycin TDM was associated with a greater reduction in 30-day mortality risk, with adjusted HRs of 0.32 (95% CI: 0.24-0.41) before PSM and 0.30 (95% CI: 0.22-0.32) after PSM. Conclusion Vancomycin TDM is associated with reduced 30-day mortality in sepsis patients, with the most significant benefit observed in patients aged 18-50. This age group exhibited the lowest mortality rates and experienced the greatest reduction in mortality following TDM compared with older patients.
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Affiliation(s)
- Huaidong Peng
- Department of Pharmacy, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ruichang Zhang
- Department of Critical Care, Guangzhou Twelfth People' Hospital, Guangzhou, China
| | - Shuangwu Zhou
- The Second School of Clinical Medicine, Guangzhou Medical University, Guangzhou, China
| | - Tingting Xu
- School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China
| | - Ruolun Wang
- Department of Pharmacy, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qilin Yang
- Department of Critical Care, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xunlong Zhong
- Department of Pharmacy, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xiaorui Liu
- Department of Pharmacy, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
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9
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Shi Y, Yin Z, Zhang Q, Yi L, Dou Y. Factors influencing vancomycin trough concentration in burn patients: a single center retrospective study. Front Pharmacol 2024; 15:1377930. [PMID: 39734407 PMCID: PMC11672795 DOI: 10.3389/fphar.2024.1377930] [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: 01/28/2024] [Accepted: 11/28/2024] [Indexed: 12/31/2024] Open
Abstract
Objective To analyze factors influencing the vancomycin trough concentration in burn patients to provide a basis for the more rational use of vancomycin in these patients. Materials and methods We collected the clinical data of adult burn patients treated with vancomycin in a Chinese hospital. Vancomycin was administered at a dosing regimen of 1.0 g q12 h. Patients were divided into a therapeutic group with vancomycin trough concentration in the target therapeutic range (10-20 μg/mL) and a subtherapeutic group with vancomycin trough concentration in the subtherapeutic range (<10 μg/mL). Results The therapeutic group included 14 patients (17.5%), with an average trough concentration of 14.36 ± 2.82 μg/mL; the subtherapeutic group included 66 patients (82.5%), with an average trough concentration of 5.18 ± 2.77 μg/mL. The serum creatinine level was significantly higher in the therapeutic group (84.93 ± 47.26 μmol/L) than that in the subtherapeutic group (62.44 ± 14.49 μmol/L) (p < 0.01). Serum albumin levels were significantly lower in the therapeutic group (30.50 ± 2.28 g/L) than those in the subtherapeutic group (34.00 ± 6.22 g/L) (p < 0.05). Using receiver operating characteristic (ROC) curve analysis, for serum albumin, the area under the ROC curve (AUC) (95% confidence interval [CI]) was 0.67 (0.553, 0.788); the optimal cut-off point was 34.50 g/L (p = 0.046), the sensitivity was 0.379, and the specificity was 1.0. For creatinine clearance, the AUC (95% CI) was 0.72 (0.537, 0.902); the optimal cut-off point was 76.64 mL/min (p = 0.01), the sensitivity was 0.985, and the specificity was 0.5. The linear stepwise regression equation was as follows: trough concentration = 0.14 × age + 0.071 × serum creatinine -4.196. Conclusion In this study, a high proportion of burn patients had a vancomycin trough concentration below the standard range. Serum creatinine clearance and albumin levels are important indicators for predicting whether the vancomycin trough concentration is within the standard range. Using a linear stepwise regression equation, the vancomycin trough concentration can be estimated using the patient's age and serum creatinine level.
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Affiliation(s)
| | | | | | - Lei Yi
- Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Yi Dou
- Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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10
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Mohd Rozi NA, Mohd Tahir NA, Mohd Saffian S, Makmor-Bakry M, Mohamad Yusof A, Mustafar R, M Saud MN. Therapeutic drug monitoring-guided piperacillin dosing in critically ill patients undergoing continuous renal replacement therapy: a systematic review. J Antimicrob Chemother 2024; 79:3078-3090. [PMID: 39321326 DOI: 10.1093/jac/dkae332] [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] [Received: 04/08/2024] [Accepted: 09/05/2024] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND Continuous renal replacement therapy (CRRT) complicates antibiotic dosing in critically ill patients due to altered pharmacokinetics. The optimal dosing of piperacillin remains unclear. Therapeutic drug monitoring (TDM) can personalize piperacillin therapy and improve outcomes. OBJECTIVES This review investigates the effects of TDM-guided piperacillin dosing on pharmacokinetic target attainment and clinical outcomes in CRRT patients, analyses correlations with clinical outcomes, provides optimal dosing strategies for piperacillin and identifies future research areas. METHODS A systematic search of PubMed, Scopus and Web of Science was conducted until December 2023, identifying studies on piperacillin pharmacokinetics and clinical outcomes in adult CRRT patients. Data on study characteristics, piperacillin exposures, TDM use, target attainment rates, mortality and length of stay were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS Eleven observational studies were included. High pharmacokinetic variability was evident, with piperacillin target non-attainment in up to 74% of cases without TDM. Two studies with routine TDM showed increased target attainment rates of 80%-100%. Mortality ranged from 17% to 56%, with supratherapeutic concentrations (≥100 mg/L) associated with higher mortality. The impact of optimized piperacillin exposures on outcomes was inconclusive. Most studies demonstrated a low risk of bias. CONCLUSIONS TDM-guided piperacillin dosing in CRRT patients improved target attainment rates (≥80%). Mortality rates ranged from 17% to 56%, with inconsistent correlations between drug exposures and survival. Supratherapeutic concentrations were linked to higher mortality. Standardized TDM protocols are needed. Future research should establish clear exposure-response relationships and the impact of TDM on clinical outcomes.
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Affiliation(s)
- Nazatul Adhwa Mohd Rozi
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia
| | - Nor Asyikin Mohd Tahir
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia
| | - Shamin Mohd Saffian
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia
| | - Mohd Makmor-Bakry
- Centre for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Aziz, 50300 Kuala Lumpur, Malaysia
- Faculty of Pharmacy, Universitas Airlangga, PQMM+9Q6, Gedung Nanizar Zaman Joenoes Kampus C UNAIR, Jl. Mulyorejo, Mulyorejo, Surabaya, East Java 60115, Indonesia
| | - Aliza Mohamad Yusof
- Department of Anaesthesiology and Intensive Care, Faculty of Medicine and Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif Kuala Lumpur, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Ruslinda Mustafar
- Department of Medicine, Faculty of Medicine and Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif Kuala Lumpur, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
| | - Muhammad Nordin M Saud
- Department of Pharmacy, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif Kuala Lumpur, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia
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11
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Peng H, Ou Y, Zhang R, Wang R, Wen D, Yang Q, Liu X. Monitoring vancomycin blood concentrations reduces mortality risk in critically ill patients: a retrospective cohort study using the MIMIC-IV database. Front Pharmacol 2024; 15:1458600. [PMID: 39611174 PMCID: PMC11602295 DOI: 10.3389/fphar.2024.1458600] [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: 07/02/2024] [Accepted: 10/31/2024] [Indexed: 11/30/2024] Open
Abstract
Background The incidence and mortality of severe Gram-positive cocci infections are particularly high in intensive care units (ICUs). Vancomycin remains the treatment of choice for severe infections caused by Gram-positive cocci, particularly methicillin-resistant Staphylococcus aureus (MRSA). Some guidelines recommend therapeutic drug monitoring (TDM) for critically ill patients treated with vancomycin; however, there is currently a lack of evidence to support that TDM improves the mortality rates of these patients. Therefore, we designed this cohort study to compare the impact of monitoring vancomycin blood concentrations on mortality rates in critically ill patients and to provide evidence to support this routine clinical practice. Methods Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database for a retrospective cohort analysis of critically ill patients receiving intravenous vancomycin treatment. The primary outcome was the 28 day mortality rate. The propensity score matching (PSM) method was used to match the baseline characteristics between patients in the TDM group and the non-TDM group. The relationship between 28 day mortality and vancomycin TDM in the critically ill cohort was evaluated using Cox proportional hazards regression analysis and Kaplan-Meier survival curves. Validation of the primary outcomes was conducted by comparing the PSM model and the Cox proportional hazards regression model. The robustness of the conclusion was subsequently verified by subgroup and sensitivity analyses. Results Data for 18,056 critically ill patients who met the study criteria were collected from the MIMIC-IV database. Of these, 7,451 patients had at least one record of vancomycin blood concentration monitoring, which we defined as the TDM group. The TDM group exhibited a 28 day mortality rate of 25.7% (1,912/7,451) compared to 16.2% in the non-TDM group (1,723/10,605). After PSM, 4,264 patients were included in each of the TDM and non-TDM groups, with a 28 day mortality rate of 20.0% (1,022/4,264) in the TDM group and 26.4% (1,126/4,264) in the non-TDM group. Multivariate Cox proportional hazards analysis revealed a significantly lower 28 day mortality risk in the TDM group when compared to the non-TDM group (adjusted hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.79, 0.93; p < 0.001). Further PSM analyses (adjusted HR: 0.91; 95% CI: 0.84, 0.99; p = 0.033) confirmed the lower risk of mortality in the TDM group. Kaplan-Meier survival analysis revealed a significantly higher survival rate at 28 days for the TDM group (log-rank test, p < 0.001). Subgroup analysis results indicated that patients with sepsis, septic shock, estimated glomerular filtration rate ≤ 60 mL/min/1.73 m2, undergoing renal replacement therapy, using vasoactive drugs, on mechanical ventilation, and those with higher severity scores (Acute Physiology Score III ≥40, Oxford Acute Severity of Illness Score ≥30, Simplified Acute Physiology Score II ≥ 30) significantly benefited from monitoring vancomycin blood concentrations. The results remained unchanged excluding patients staying in ICU for less than 48 h or those infected with MRSA. Conclusion This cohort study showed that monitoring vancomycin blood concentrations is associated with a significantly lower 28 day mortality rate in critically ill patients, highlighting the importance of routinely performing vancomycin TDM in these patients.
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Affiliation(s)
- Huaidong Peng
- Department of Pharmacy, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yuantong Ou
- Department of Critical Care, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Ruichang Zhang
- Department of Critical Care, Guangzhou Twelfth People’ Hospital, Guangzhou, China
| | - Ruolun Wang
- Department of Pharmacy, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Deliang Wen
- Department of Critical Care, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qilin Yang
- Department of Critical Care, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Xiaorui Liu
- Department of Pharmacy, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, China
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12
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Dyer CJ, De Waele JJ, Roberts JA. Antibiotic dose optimisation in the critically ill: targets, evidence and future strategies. Curr Opin Crit Care 2024; 30:439-447. [PMID: 39150038 DOI: 10.1097/mcc.0000000000001187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
PURPOSE OF REVIEW To highlight the recent evidence for antibiotic pharmacokinetics and pharmacodynamics (PK/PD) in enhancing patient outcomes in sepsis and septic shock. We also summarise the limitations of available data and describe future directions for research to support translation of antibiotic dose optimisation to the clinical setting. RECENT FINDINGS Sepsis and septic shock are associated with poor outcomes and require antibiotic dose optimisation, mostly due to significantly altered pharmacokinetics. Many studies, including some randomised controlled trials have been conducted to measure the clinical outcome effects of antibiotic dose optimisation interventions including use of therapeutic drug monitoring. Current data support antibiotic dose optimisation for the critically ill. Further investigation is required to evolve more timely and robust precision antibiotic dose optimisation approaches, and to clearly quantify whether any clinical and health-economic benefits support expanded use of this treatment intervention. SUMMARY Antibiotic dose optimisation appears to improve outcomes in critically ill patients with sepsis and septic shock, however further research is required to quantify the level of benefit and develop a stronger knowledge of the role of new technologies to facilitate optimised dosing.
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Affiliation(s)
- Christopher J Dyer
- Herston Institute of Infectious Diseases (HeIDI), Metro North Health
- Pharmacy Department
- Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital (RBWH), Herston, Australia
| | - Jan J De Waele
- Department of Critical Care Medicine, Ghent University Hospital
- Dept of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Jason A Roberts
- Herston Institute of Infectious Diseases (HeIDI), Metro North Health
- Pharmacy Department
- Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital (RBWH), Herston, Australia
- UQ Centre for Clinical Research (UQCCR), Faculty of Medicine, University of Queensland, Herston, Australia
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Ben Romdhane H, Woillard JB, Ben Fadhel N, Chadli Z, Chaabane A, Boughattas N, Ben Fredj N, Aouam K. Population Pharmacokinetic of Vancomycin Administered by Continuous Infusion in Critically Ill Patients. Pharmacology 2024; 110:65-76. [PMID: 39154639 DOI: 10.1159/000539866] [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: 12/02/2022] [Accepted: 06/13/2024] [Indexed: 08/20/2024]
Abstract
INTRODUCTION Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes. OBJECTIVE The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions. METHODS The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset. RESULTS A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance. CONCLUSION We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic.
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Affiliation(s)
- Haifa Ben Romdhane
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Jean Baptiste Woillard
- Department of Pharmacology and Toxicology, Centre Hospitalier Universitaire à Limoges, Limoges, France
| | - Najah Ben Fadhel
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Zohra Chadli
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Amel Chaabane
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Naceur Boughattas
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Nadia Ben Fredj
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
| | - Karim Aouam
- Department of Pharmacology, EPS Fattouma Bourguiba, Faculty of Medicine, University of Monastir, Monastir, Tunisia
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14
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Mohamed RG, Saber R, Hussein MA, Shalaby A, Yasser N, Kamal S, Shalaby L, Nagy M. Optimizing vancomycin therapeutic drug monitoring compliance in pediatric oncology: towards personalized medication management. Per Med 2024; 21:211-218. [PMID: 38963131 DOI: 10.1080/17410541.2024.2360386] [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: 12/26/2023] [Accepted: 05/23/2024] [Indexed: 07/05/2024]
Abstract
Aim: Vancomycin, a crucial treatment for Gram-positive bacteria, necessitates therapeutic drug monitoring (TDM) to prevent treatment failures. We investigated the healthcare professional's compliance toward TDM of vancomycin recommendations and follow-up levels. Materials & methods: We collected data from 485 patients who received vancomycin in the Children's Cancer Hospital Egypt 57357 medical records system (Cerner) over 4 months, from January to April 2020. Results: Our data shows that only 54% of patients had TDM requests from healthcare professionals for the total patients who received vancomycin treatment. The healthcare professionals' compliance with the recommendations was 91.7%, while the follow-up levels were 66.7%. Conclusion: While overall adherence to recommendations is strong, enhancing compliance with follow-up levels remains a priority for improvement.
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Affiliation(s)
- Rewan Gamal Mohamed
- Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
| | - Rania Saber
- Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
- Personalized Medication Management Unit, Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
| | - Mohamed Ali Hussein
- Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
- Personalized Medication Management Unit, Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
| | - Amira Shalaby
- Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
- Infectious Disease Unit, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
| | - Nouran Yasser
- Department of Epidemiology & Clinical Research, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
| | | | - Lobna Shalaby
- Infectious Disease Unit, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
- Department of Pediatric Oncology, National Cancer Institute, Cairo, Egypt
| | - Mohamed Nagy
- Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
- Personalized Medication Management Unit, Department of Pharmaceutical Services, Children's Cancer Hospital Egypt (57357), Cairo, Egypt
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15
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Moran JL, Linden A. Problematic meta-analyses: Bayesian and frequentist perspectives on combining randomized controlled trials and non-randomized studies. BMC Med Res Methodol 2024; 24:99. [PMID: 38678213 PMCID: PMC11056075 DOI: 10.1186/s12874-024-02215-4] [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: 10/25/2022] [Accepted: 04/10/2024] [Indexed: 04/29/2024] Open
Abstract
PURPOSE In the literature, the propriety of the meta-analytic treatment-effect produced by combining randomized controlled trials (RCT) and non-randomized studies (NRS) is questioned, given the inherent confounding in NRS that may bias the meta-analysis. The current study compared an implicitly principled pooled Bayesian meta-analytic treatment-effect with that of frequentist pooling of RCT and NRS to determine how well each approach handled the NRS bias. MATERIALS & METHODS Binary outcome Critical-Care meta-analyses, reflecting the importance of such outcomes in Critical-Care practice, combining RCT and NRS were identified electronically. Bayesian pooled treatment-effect and 95% credible-intervals (BCrI), posterior model probabilities indicating model plausibility and Bayes-factors (BF) were estimated using an informative heavy-tailed heterogeneity prior (half-Cauchy). Preference for pooling of RCT and NRS was indicated for Bayes-factors > 3 or < 0.333 for the converse. All pooled frequentist treatment-effects and 95% confidence intervals (FCI) were re-estimated using the popular DerSimonian-Laird (DSL) random effects model. RESULTS Fifty meta-analyses were identified (2009-2021), reporting pooled estimates in 44; 29 were pharmaceutical-therapeutic and 21 were non-pharmaceutical therapeutic. Re-computed pooled DSL FCI excluded the null (OR or RR = 1) in 86% (43/50). In 18 meta-analyses there was an agreement between FCI and BCrI in excluding the null. In 23 meta-analyses where FCI excluded the null, BCrI embraced the null. BF supported a pooled model in 27 meta-analyses and separate models in 4. The highest density of the posterior model probabilities for 0.333 < Bayes factor < 1 was 0.8. CONCLUSIONS In the current meta-analytic cohort, an integrated and multifaceted Bayesian approach gave support to including NRS in a pooled-estimate model. Conversely, caution should attend the reporting of naïve frequentist pooled, RCT and NRS, meta-analytic treatment effects.
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Affiliation(s)
- John L Moran
- The Queen Elizabeth Hospital, Woodville, SA, 5011, Australia.
| | - Ariel Linden
- Department of Medicine, School of Medicine, University of California, San Francisco, USA
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16
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Liu H, Yang H, Guo X, Bai Y, SiRi G. Clinical benefits of therapeutic drug monitoring of vancomycin therapy in patients with postoperative intracerebral hemorrhage: a retrospective cohort study. Eur J Hosp Pharm 2024; 31:240-246. [PMID: 36207132 PMCID: PMC11042452 DOI: 10.1136/ejhpharm-2022-003455] [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: 06/30/2022] [Accepted: 09/21/2022] [Indexed: 11/07/2022] Open
Abstract
OBJECTIVE The objective of this study was to investigate the clinical efficacy and safety of conducting therapeutic drug monitoring (TDM) of vancomycin in patients with postoperative intracerebral haemorrhage. METHODS We conducted a retrospective analysis of 435 patients who experienced postoperative cerebral haemorrhage and were treated with vancomycin in the Department of Neurosurgery of Inner Mongolia Autonomous Region People's Hospital from January 2017 to December 2021. Patients were then matched using the propensity score matching method in a ratio of 1:1. Ninety-two pairs of cases were successfully matched, and the data before and after performing vancomycin TDM were analysed. RESULTS After PSM, the baseline data of the two groups were balanced. There were no significant differences in the 14-day mortality and length of hospital stay (p>0.05) between the two groups. Compared with the non-TDM group, the TDM group had a higher proportion of patients with normal white blood cells (83.7% vs 56.5%, p=0.000), neutrophil count (57.6% vs 25.0%, p=0.000) and attaining desirable reductions of 80% in procalcitonin (65.2% vs 10.9%, p=0.000) and C-reactive protein (78.3% vs 41.3%, p=0.000) levels. At US$15.82 per additional TDM, TDM significantly promoted patient outcomes, as seen in improvements in the proportion of patients attaining desirable levels of white blood cells, neutrophil count, procalcitonin and C-reactive protein. CONCLUSIONS Vancomycin TDM is a safe and effective approach for the treatment of patients with postoperative intracerebral haemorrhage. The empirical use of TDM of vancomycin significantly improved normal values of white blood cells and neutrophil count, achieved desirable reductions of 80% in procalcitonin and C-reactive protein, and reduced nephrotoxicity in patients with postoperative intracerebral haemorrhage.
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Affiliation(s)
- Huanhuan Liu
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
- Department of Pharmacy, Baotou Medical College, Baotou, Inner Mongolia, China
| | - Hongxin Yang
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
| | - Xiaobin Guo
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
| | - Yingchun Bai
- Department of Pharmacy, Baotou Medical College, Baotou, Inner Mongolia, China
| | - Guleng SiRi
- Department of Pharmacy, Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia, China
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17
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Chappell B, Suckling B, Pattullo C. Measuring and improving the timeliness of vancomycin therapeutic drug monitoring and potential patient safety impacts. EXPLORATORY RESEARCH IN CLINICAL AND SOCIAL PHARMACY 2024; 13:100403. [PMID: 38204885 PMCID: PMC10776972 DOI: 10.1016/j.rcsop.2023.100403] [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: 09/19/2023] [Revised: 12/03/2023] [Accepted: 12/13/2023] [Indexed: 01/12/2024] Open
Abstract
Background Timely vancomycin therapeutic drug monitoring (TDM) enables prompt dose adjustments and safe treatment. Local incidents prompted an investigation into the reasons for prolonged reporting times. Objectives To investigate the variation in reporting times of vancomycin concentrations between hospitals with and without on-site TDM processing, and patient safety implications. Methods Vancomycin concentration results for Hospital 1 (off-site monitoring), Hospitals 2 and 3 (both on-site monitoring) from June to December 2021 were retrospectively analysed. Retrospective data collection was repeated for Hospital 1 three months post on-site TDM commencement for comparison. Vancomycin clinical incidents at Hospital 1 were reviewed to identify examples of when delays in reporting of results potentially contributed towards adverse patient outcomes. Results Hospital 1 had a median reporting time of 11.13 h compared with Hospital 2 and Hospital T3 (1.73 h and 1.70 h respectively). Following the commencement of on-site TDM at Hospital 1, the reporting time reduced to 1.33 h (p < 0.001). Several incidents at Hospital 1 during the period of off-site monitoring involved delays to TDM results. Conclusions Off-site processing of TDM introduced significant delays in reporting of vancomycin concentrations, which was significantly improved by transitioning to onsite availability of testing. This study also highlights the impact of accurate problem identification in improving patient safety.
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Affiliation(s)
- Belinda Chappell
- Caboolture Hospital Pharmacy Department, Metro North Health, Queensland Health, Caboolture, Queensland, Australia
- School of Pharmacy, The Pharmacy Australia Centre of Excellence (PACE), University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia
| | - Benita Suckling
- Caboolture Hospital Pharmacy Department, Metro North Health, Queensland Health, Caboolture, Queensland, Australia
| | - Champika Pattullo
- School of Public Health, University of Queensland, Herston, Queensland 4006, Australia
- Safety and Implementation Service, Royal Brisbane and Women's Hospital, Butterfield St, Herston, Queensland 4006, Australia
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Kim Y, Choi CY, Sunwoo Y, Go C, Kim S, Eom SH, Shin S, Choi YJ. A Real-World Data Derived Pharmacovigilance Assessment on Drug-Induced Nephropathy: Implication on Gaps in Patient Care. Healthcare (Basel) 2023; 12:95. [PMID: 38201001 PMCID: PMC10778829 DOI: 10.3390/healthcare12010095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 12/19/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
This retrospective cross-sectional study aims to investigate the prevalence and seriousness of drug-induced nephrotoxicity and to identify clinical predictors intensifying the seriousness of nephrotoxicity. Adverse drug events (ADEs) reported to the Korean Adverse Event Reporting System Database (KAERS DB) from January 2012 to December 2021 were investigated. The association between the seriousness and the etiologic drug was estimated in reporting odds ratio (ROR) based on disproportionality analysis. Logistic regression was utilized to recognize predictors associated with serious nephrotoxicity. The majority of ADEs were reported in ages 30 to 59, and immunosuppressants were the most etiologic medications. ADEs involving antibiotics, including vancomycin (ROR 0.268; 95% CI 0.129-0.557), were less likely to be serious. More than 93% of cyclosporine-related ADEs were serious nephrotoxicity, whereas tacrolimus was less likely to report serious nephrotoxicity (ROR 0.356; 95% CI 0.187-0.680). The risk of serious nephrotoxicity was decreased with aging (ROR 0.955; 95% CI 0.940-0.972) while increased in women (OR 2.700; 95% CI 1.450-5.008). Polypharmacy was associated with increased risk of interstitial nephritis (OR 1.019; 95% CI 1.001-1.038). However, further studies investigating the impact of clinical practice on ADE incidences as well as clinical prognosis related to nephrotoxicity are obligated.
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Affiliation(s)
- Yujin Kim
- Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
| | - Chang-Young Choi
- Department of Internal Medicine, Ajou University Medical Center, Suwon 16499, Republic of Korea;
| | - Yongjun Sunwoo
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (C.G.); (S.K.); (S.H.E.)
| | - Chaerin Go
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (C.G.); (S.K.); (S.H.E.)
| | - Semi Kim
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (C.G.); (S.K.); (S.H.E.)
| | - Sae Hyun Eom
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (C.G.); (S.K.); (S.H.E.)
| | - Sooyoung Shin
- Department of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Republic of Korea
- Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Republic of Korea
| | - Yeo Jin Choi
- Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea;
- Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (C.G.); (S.K.); (S.H.E.)
- Institute of Regulatory Innovation through Science (IRIS), Kyung Hee University, Seoul 02447, Republic of Korea
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19
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Goutelle S, Wallet F, Thoma Y, Peclard JR, Bourguignon L, Cohen S, Kipnis E, Roberts J, Allaouchiche B, Friggeri A. AUC-based monitoring and model-informed precision dosing of vancomycin in critically ill patients: why and how? Anaesth Crit Care Pain Med 2023; 42:101286. [PMID: 37517689 DOI: 10.1016/j.accpm.2023.101286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/01/2023]
Affiliation(s)
- Sylvain Goutelle
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France; Université of Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne, France; Université of Lyon, Université Claude Bernard Lyon 1, Facultés de Médecine et de Pharmacie de Lyon, Lyon, France.
| | - Florent Wallet
- Hospices Civils de Lyon, GH Sud, Services d'Anesthésie-réanimation Médecine Intensive, Lyon, France; Université of Lyon, Université Claude Bernard Lyon 1, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Lyon, France
| | - Yann Thoma
- School of Management and Engineering Vaud (HEIG-VD), HES-SO University of Applied Sciences and Arts Western Switzerland, Yverdon-les-Bains, Switzerland
| | - Jean-Rémi Peclard
- School of Management and Engineering Vaud (HEIG-VD), HES-SO University of Applied Sciences and Arts Western Switzerland, Yverdon-les-Bains, Switzerland
| | - Laurent Bourguignon
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie, Lyon, France; Université of Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Villeurbanne, France; Université of Lyon, Université Claude Bernard Lyon 1, Facultés de Médecine et de Pharmacie de Lyon, Lyon, France
| | - Sabine Cohen
- Hospices Civils de Lyon, GH Sud, Laboratoire de Pharmaco-toxicologie, France
| | - Eric Kipnis
- Université of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, Lille, France
| | - Jason Roberts
- University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Australia; Herston Infectious Diseases Institute (HeIDI), Metro North Health, Brisbane, Australia; Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
| | - Bernard Allaouchiche
- Université of Lyon, Université Claude Bernard Lyon 1, Facultés de Médecine et de Pharmacie de Lyon, Lyon, France; Hospices Civils de Lyon, GH Sud, Services d'Anesthésie-réanimation Médecine Intensive, Lyon, France; Lyon University, VetAgro Sup, Lyon Veterinary Campus, UPSP 2016. A101, Pulmonary and Cardiovascular Agression in Sepsis, Marcy l'Étoile, France
| | - Arnaud Friggeri
- Université of Lyon, Université Claude Bernard Lyon 1, Facultés de Médecine et de Pharmacie de Lyon, Lyon, France; Hospices Civils de Lyon, GH Sud, Services d'Anesthésie-réanimation Médecine Intensive, Lyon, France; Université of Lyon, Université Claude Bernard Lyon 1, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Lyon, France
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20
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Friedel M, Thompson IAP, Kasting G, Polsky R, Cunningham D, Soh HT, Heikenfeld J. Opportunities and challenges in the diagnostic utility of dermal interstitial fluid. Nat Biomed Eng 2023; 7:1541-1555. [PMID: 36658344 DOI: 10.1038/s41551-022-00998-9] [Citation(s) in RCA: 109] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 12/06/2022] [Indexed: 01/21/2023]
Abstract
The volume of interstitial fluid (ISF) in the human body is three times that of blood. Yet, collecting diagnostically useful ISF is more challenging than collecting blood because the extraction of dermal ISF disrupts the delicate balance of pressure between ISF, blood and lymph, and because the triggered local inflammation further skews the concentrations of many analytes in the extracted fluid. In this Perspective, we overview the most meaningful differences in the make-up of ISF and blood, and discuss why ISF cannot be viewed generally as a diagnostically useful proxy for blood. We also argue that continuous sensing of small-molecule analytes in dermal ISF via rapid assays compatible with nanolitre sample volumes or via miniaturized sensors inserted into the dermis can offer clinically advantageous utility, particularly for the monitoring of therapeutic drugs and of the status of the immune system.
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Affiliation(s)
- Mark Friedel
- Novel Device Laboratory, Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA
| | - Ian A P Thompson
- Department of Electrical Engineering, Stanford University, Stanford, CA, USA
| | - Gerald Kasting
- The James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USA
| | - Ronen Polsky
- Nano and Micro Sensors, Sandia National Laboratories, Albuquerque, NM, USA
| | - David Cunningham
- Department of Chemistry and Physics, Southeast Missouri State University, Cape Girardeau, MO, USA
| | - Hyongsok Tom Soh
- Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
- Department of Radiology, Stanford University, Stanford, CA, USA.
| | - Jason Heikenfeld
- Novel Device Laboratory, Department of Biomedical Engineering, University of Cincinnati, Cincinnati, OH, USA.
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21
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Takahashi N, Kondo Y, Kubo K, Egi M, Kano KI, Ohshima Y, Nakada TA. Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: a systematic review and meta-analysis of randomized controlled trials. J Intensive Care 2023; 11:48. [PMID: 37936203 PMCID: PMC10631080 DOI: 10.1186/s40560-023-00699-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 11/02/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based regimen in these patients. METHODS Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3. RESULTS In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I2 = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes. CONCLUSION TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required. TRIAL REGISTRATION Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.
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Affiliation(s)
- Nozomi Takahashi
- Centre for Heart Lung Innovation, St. Paul's Hospital, The University of British Columbia, 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
| | - Yutaka Kondo
- Department of Emergency and Critical Care Medicine, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Kenji Kubo
- Department of Emergency Medicine and Department of Infectious Diseases, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan
| | - Moritoki Egi
- Department of Anesthesia and Intensive Care, Kyoto University Hospital, Kyoto, Japan
| | - Ken-Ichi Kano
- Department of Emergency Medicine, Fukui Prefectural Hospital, Fukui, Fukui, Japan
| | | | - Taka-Aki Nakada
- Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, Japan
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22
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Morales Junior R, Juodinis VD, de Souza DC, Santos SRCJ. Pharmacokinetics and therapeutic target attainment of vancomycin in pediatric post-liver transplant patients. Braz J Infect Dis 2023; 27:103688. [PMID: 37977199 PMCID: PMC10698562 DOI: 10.1016/j.bjid.2023.103688] [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: 06/18/2023] [Revised: 09/26/2023] [Accepted: 10/31/2023] [Indexed: 11/19/2023] Open
Abstract
INTRODUCTION Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. MATERIALS AND METHODS Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. RESULTS Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2 = 0.5). CONCLUSIONS Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.
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Affiliation(s)
- Ronaldo Morales Junior
- Universidade de São Paulo, Faculdade de Ciências Farmacêuticas, Centro de Farmacocinética Clínica, São Paulo, SP, Brazil; Hospital Sírio-libanês, Unidade Pediátrica, São Paulo, SP, Brazil.
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23
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Westerdijk K, Steeghs N, Tacke CSJ, van der Graaf WTA, van Erp NP, van Oortmerssen G, Hermens RPMG, Desar IME, In collaboration with the Dutch Pharmacology Oncology Group (DPOG). Therapeutic drug monitoring to personalize dosing of imatinib, sunitinib, and pazopanib: A mixed methods study on barriers and facilitators. Cancer Med 2023; 12:21041-21056. [PMID: 37902257 PMCID: PMC10709747 DOI: 10.1002/cam4.6663] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 08/20/2023] [Accepted: 10/03/2023] [Indexed: 10/31/2023] Open
Abstract
BACKGROUND Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib. METHODS We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. RESULTS In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). CONCLUSION We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.
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Affiliation(s)
- Kim Westerdijk
- Department of Medical OncologyResearch Institute for Medical Innovation, Radboud University Medical CenterNijmegenThe Netherlands
| | - Neeltje Steeghs
- Department of Medical OncologyNetherlands Cancer Institute, Antoni van LeeuwenhoekAmsterdamThe Netherlands
| | - Casper S. J. Tacke
- Department of Medical OncologyResearch Institute for Medical Innovation, Radboud University Medical CenterNijmegenThe Netherlands
| | - Winette T. A. van der Graaf
- Department of Medical OncologyNetherlands Cancer Institute, Antoni van LeeuwenhoekAmsterdamThe Netherlands
- Department of Medical OncologyErasmus MC Cancer Institute, Erasmus Medical Center RotterdamRotterdamThe Netherlands
| | - Nielka P. van Erp
- Department of PharmacyResearch Institute for Medical Innovation, Radboud University Medical CenterNijmegenThe Netherlands
| | | | | | - Ingrid M. E. Desar
- Department of Medical OncologyResearch Institute for Medical Innovation, Radboud University Medical CenterNijmegenThe Netherlands
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24
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Zhang G, Zhang N, Xu J, Yang T, Yin H, Cai Y. Efficacy and safety of vancomycin for the treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis. Int J Antimicrob Agents 2023; 62:106946. [PMID: 37543121 DOI: 10.1016/j.ijantimicag.2023.106946] [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: 08/31/2022] [Revised: 06/11/2023] [Accepted: 08/01/2023] [Indexed: 08/07/2023]
Abstract
OBJECTIVES To evaluate the safety and efficacy of vancomycin with the other anti-Gram-positive bacteria antibiotics in the treatment of Staphylococcus aureus bacteraemia. METHODS We searched the PubMed, MEDLINE, Embase and Cochrane Library databases until August 2022 for studies that compared vancomycin with other antibiotic regimens for treating Staphylococcus aureus bacteraemia. Clinical and microbiological responses, adverse events, relapse rate and mortality were considered. RESULTS Fifteen randomized controlled trials and nine retrospective studies were included. The efficacy and safety data of vancomycin differed from those of the comparators group. After subgroup analysis, the differences came mainly from the trials compared with daptomycin. Compared to daptomycin, vancomycin showed a lower microbiological cure rate (OR = 0.58, 95% CI = 0.41∼0.82, I2 = 0%, P = 0.002) and clinical cure rate (OR = 0.53, 95% CI = 0.42∼0.68, I2 = 3%, P < 0.00001), as well as more adverse events (OR = 3.21, 95% CI = 1.43∼7.19, I2 = 59%, P = 0.005). CONCLUSION The efficacy of vancomycin in treating Staphylococcus aureus bacteraemia is still excellent but slightly inferior in adverse events. However, this does not affect its use as a first-line drug. Daptomycin is expected to be a better antimicrobial drug.
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Affiliation(s)
- Guanxuanzi Zhang
- Medical School of Chinese PLA, Graduate School of Chinese PLA General Hospital, Beijing, China; Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Na Zhang
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Juan Xu
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Tianli Yang
- Medical School of Chinese PLA, Graduate School of Chinese PLA General Hospital, Beijing, China; Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China
| | - Hong Yin
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China.
| | - Yun Cai
- Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, China.
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25
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Elzieny M, Fisher JA, Sims MD, Lauter CB, Carey-Ballough RA, Sun Q. Falsely decreased vancomycin caused by rheumatoid factor: A case report. Clin Chim Acta 2023; 548:117460. [PMID: 37390942 DOI: 10.1016/j.cca.2023.117460] [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: 05/31/2023] [Revised: 06/16/2023] [Accepted: 06/27/2023] [Indexed: 07/02/2023]
Abstract
BACKGROUND Vancomycin is associated with potential nephrotoxicity and trough concentrations need to be monitored in certain patients. Falsely decreased vancomycin measurement may result in overtreatment and need to be identified promptly by clinicians and pharmacists to avoid toxicities. METHODS AND RESULTS We report a case of rheumatoid factor-mediated falsely low vancomycin measurement with Abbott particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method. Reanalyzing the sample using an alternative method, removing the interferences using heterophile blocking reagent as well as rheumatoid factor clean-up solution all helped to solve the false results. Results from alternative method and interference studies showed vancomycin concentrations reached toxic concentrations in the patient and administration of the drug was immediately terminated. The patient experienced a transient increase in serum creatinine. CONCLUSIONS Even though most modern immunoassays use blocking agents to neutralize interfering antibodies such as rheumatoid factor, it is important for health care professionals to understand that occasional interference still occurs due to the heterogeneous nature of rheumatoid factor.
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Affiliation(s)
- Mai Elzieny
- Department of Pathology and Laboratory Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Jordan A Fisher
- Section of Infectious Diseases, Department of Internal Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Matthew D Sims
- Section of Infectious Diseases, Department of Internal Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Department of Internal Medicine, Oakland University William Beaumont School of Medicine, Auburn Hills, MI, USA
| | - Carl B Lauter
- Section of Infectious Diseases, Department of Internal Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Department of Internal Medicine, Oakland University William Beaumont School of Medicine, Auburn Hills, MI, USA; Section of Allergy - Immunology, Department of Internal Medicine, Corewell Health William, Beaumont University Hospital, Royal Oak, MI, USA
| | - Robin A Carey-Ballough
- Department of Pathology and Laboratory Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA
| | - Qian Sun
- Department of Pathology and Laboratory Medicine, Corewell Health William Beaumont University Hospital, Royal Oak, MI, USA; Department of Pathology and Laboratory Medicine, Oakland University William Beaumont School of Medicine, Auburn Hills, MI, USA.
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26
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Nguyen TA, Kirubakaran R, Schultz HB, Wong S, Reuter SE, McMullan B, Bolisetty S, Campbell C, Horvath AR, Stocker SL. Analytical and Non-Analytical Variation May Lead to Inappropriate Antimicrobial Dosing in Neonates: An In Silico Study. Clin Chem 2023:7146664. [PMID: 37116191 DOI: 10.1093/clinchem/hvad036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Accepted: 03/01/2023] [Indexed: 04/30/2023]
Abstract
BACKGROUND Therapeutic drug monitoring (TDM) of aminoglycosides and vancomycin is used to prevent oto- and nephrotoxicity in neonates. Analytical and nonanalytical factors potentially influence dosing recommendations. This study aimed to determine the impact of analytical variation (imprecision and bias) and nonanalytical factors (accuracy of drug administration time, use of non-trough concentrations, biological variation, and dosing errors) on neonatal antimicrobial dosing recommendations. METHODS Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing. RESULTS Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin). CONCLUSIONS Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.
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Affiliation(s)
- Thi A Nguyen
- School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Ranita Kirubakaran
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
- Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia
- Seberang Jaya Hospital, Penang, Malaysia
| | - Hayley B Schultz
- UniSA: Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia
| | - Sherilyn Wong
- UniSA: Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia
| | - Stephanie E Reuter
- UniSA: Clinical & Health Sciences, University of South Australia, Adelaide, SA, Australia
| | - Brendan McMullan
- Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, NSW, Australia
- Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
| | - Srinivas Bolisetty
- Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
| | - Craig Campbell
- NSW Health Pathology, Department of Chemical Pathology, Prince of Wales Hospital, Sydney, NSW, Australia
| | - Andrea R Horvath
- Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
- NSW Health Pathology, Department of Chemical Pathology, Prince of Wales Hospital, Sydney, NSW, Australia
| | - Sophie L Stocker
- School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
- School of Clinical Medicine, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
- Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia
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27
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Telles JP, Morales R, Yamada CH, Marins TA, D'Amaro Juodinis V, Sztajnbok J, Silva M, Bassetti BR, Albiero J, Tuon FF. Optimization of Antimicrobial Stewardship Programs Using Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics Protocols: A Cost-Benefit Review. Ther Drug Monit 2023; 45:200-208. [PMID: 36622029 DOI: 10.1097/ftd.0000000000001067] [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: 08/30/2022] [Accepted: 10/08/2022] [Indexed: 01/10/2023]
Abstract
PURPOSE Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics-pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures. METHODS A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole. RESULTS TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays. CONCLUSIONS TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.
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Affiliation(s)
- João Paulo Telles
- - AC Camargo Cancer Center, Infectious Diseases Department, São Paulo
- - Laboratory of Emerging Infectious Diseases, Pontifical Catholic University of Paraná, Curitiba
| | - Ronaldo Morales
- - Clinical Pharmacokinetics Center, School of Pharmaceutical Sciences, University of São Paulo
- - Pediatric Intensive Care Unit, Department of Pediatrics, Hospital Sírio-Libanês. São Paulo
| | - Carolina Hikari Yamada
- - Laboratory of Emerging Infectious Diseases, Pontifical Catholic University of Paraná, Curitiba
- - Hospital Universitário Evangélico Mackenzie, Department of Infectious Diseases, Curitiba
| | - Tatiana A Marins
- - Hospital Israelita Albert Einstein, Department of Clinical Pharmacy, São Paulo
| | | | - Jaques Sztajnbok
- - Instituto de Infectologia Emílio Ribas, São Paulo
- - Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (ICr/HC-FMUSP)
| | - Moacyr Silva
- - Hospital Israelita Albert Einstein, Department of Infection Prevention and Control, São Paulo
| | - Bil Randerson Bassetti
- - Hospital Santa Rita de Cássia, Department of Infectious Disease and Infection Control, Vitória ; and
| | - James Albiero
- - Universidade Estadual de Maringá, Pharmacy Department, Programa de Pós-Graduação em Assistência Farmacêutica, Maringá, Brazil
| | - Felipe Francisco Tuon
- - Laboratory of Emerging Infectious Diseases, Pontifical Catholic University of Paraná, Curitiba
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Implementing Vancomycin Population Pharmacokinetic Models: An App for Individualized Antibiotic Therapy in Critically Ill Patients. Antibiotics (Basel) 2023; 12:antibiotics12020301. [PMID: 36830212 PMCID: PMC9952184 DOI: 10.3390/antibiotics12020301] [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: 11/10/2022] [Revised: 01/17/2023] [Accepted: 01/25/2023] [Indexed: 02/05/2023] Open
Abstract
In individualized therapy, the Bayesian approach integrated with population pharmacokinetic models (PopPK) for predictions together with therapeutic drug monitoring (TDM) to maintain adequate objectives is useful to maximize the efficacy and minimize the probability of toxicity of vancomycin in critically ill patients. Although there are limitations to implementation, model-informed precision dosing (MIPD) is an approach to integrate these elements, which has the potential to optimize the TDM process and maximize the success of antibacterial therapy. The objective of this work was to present an app for individualized therapy and perform a validation of the implemented vancomycin PopPK models. A pragmatic approach was used for selecting the models of Llopis, Goti and Revilla for developing a Shiny app with R. Through ordinary differential equation (ODE)-based mixed effects models from the mlxR package, the app simulates the concentrations' behavior, estimates whether the model was simulated without variability and predicts whether the model was simulated with variability. Moreover, we evaluated the predictive performance with retrospective trough concentration data from patients admitted to the adult critical care unit. Although there were no significant differences in the performance of the estimates, the Llopis model showed better accuracy (mean 80.88%; SD 46.5%); however, it had greater bias (mean -34.47%, SD 63.38%) compared to the Revilla et al. (mean 10.61%, SD 66.37%) and Goti et al. (mean of 13.54%, SD 64.93%) models. With respect to the RMSE (root mean square error), the Llopis (mean of 10.69 mg/L, SD 12.23 mg/L) and Revilla models (mean of 10.65 mg/L, SD 12.81 mg/L) were comparable, and the lowest RMSE was found in the Goti model (mean 9.06 mg/L, SD 9 mg/L). Regarding the predictions, this behavior did not change, and the results varied relatively little. Although our results are satisfactory, the predictive performance in recent studies with vancomycin is heterogeneous, and although these three models have proven to be useful for clinical application, further research and adaptation of PopPK models is required, as well as implementation in the clinical practice of MIPD and TDM in real time.
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Kunming P, Xiaotian J, Qing X, Chenqi X, Xiaoqiang D, Qian Zhou L. Impact of pharmacist intervention in reducing vancomycin-associated acute kidney injury: A systematic review and meta-analysis. Br J Clin Pharmacol 2023; 89:526-535. [PMID: 35285970 DOI: 10.1111/bcp.15301] [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: 12/09/2021] [Revised: 02/16/2022] [Accepted: 03/03/2022] [Indexed: 01/18/2023] Open
Abstract
AIMS The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.
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Affiliation(s)
- Pan Kunming
- Department of Pharmacy, ZhongShan Hospital FuDan University, ShangHai, China
| | - Jiang Xiaotian
- Department of Nephrology, ZhongShan Hospital FuDan University, ShangHai, China
| | - Xu Qing
- Department of Pharmacy, ZhongShan Hospital FuDan University, ShangHai, China
| | - Xu Chenqi
- Department of Nephrology, ZhongShan Hospital FuDan University, ShangHai, China
| | - Ding Xiaoqiang
- Department of Nephrology, ZhongShan Hospital FuDan University, ShangHai, China
| | - Lv Qian Zhou
- Department of Pharmacy, ZhongShan Hospital FuDan University, ShangHai, China
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30
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Papastergiou P, Tsioutis C, Mendris M. Implementation of a hospital antimicrobial stewardship program to improve vancomycin use in Cyprus: Challenges and opportunity. Infect Prev Pract 2022; 4:100254. [PMID: 36387606 PMCID: PMC9646909 DOI: 10.1016/j.infpip.2022.100254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 08/15/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND The Republic of Cyprus is among the highest consumers of antibacterials for systemic use in Europe. The antimicrobial resistance of invasive isolates in Cyprus is also high compared to the European Union. Formal antimicrobial stewardship initiatives are scarce in Cyprus, raising an urgent need to address the challenges for implementing hospital antimicrobial stewardship. AIM To implement an antimicrobial stewardship program and improve vancomycin use in a tertiary care hospital in Cyprus, through implementation of a protocol for treatment and therapeutic drug monitoring (TDM) and to discuss the current challenges present in Cyprus. METHODS Following a local audit of practices, we established a hospital antimicrobial stewardship program with limited resources, towards a model of stewardship which included a persuasive approach, education, selective reporting of antimicrobial susceptibility, providing comments on the microbiology results and regular microbiology clinical ward rounds. FINDINGS By implementing our vancomycin protocol, we achieved a statistically significant improvement (P<0.01) in achieving vancomycin therapeutic levels over a 2-year period, while improving administration practices. CONCLUSION Meaningful steps toward implementing a local antimicrobial stewardship program are possible even in resource-limited and unfavourable settings.
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Affiliation(s)
- Panagiotis Papastergiou
- Limassol General Hospital, Microbiology Department, Leoforos Nikaias 1, Kato Polemidia Municipality, Limassol, 4131, Cyprus
| | | | - Michail Mendris
- Limassol General Hospital, Microbiology Department, Leoforos Nikaias 1, Kato Polemidia Municipality, Limassol, 4131, Cyprus
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31
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Zhao S, Zaytseva O, Chang X, Zhang B. Therapeutic drug monitoring (TDM) as intervention: A cross-sectional analysis of characteristics of 173 registered clinical trials. Contemp Clin Trials Commun 2022; 30:101014. [PMID: 36276264 PMCID: PMC9579326 DOI: 10.1016/j.conctc.2022.101014] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Revised: 08/30/2022] [Accepted: 10/01/2022] [Indexed: 11/13/2022] Open
Abstract
Background To examine fundamental characteristics of clinical trials with therapeutic drug monitoring (TDM) as intervention on world major clinical trials registry platform. Methods Cross-sectional analysis of clinical trials with TDM as intervention that were registered on WHO International Clinical Trials Registry Platform (ICTRP) or ClinicalTrials.gov. Relevant trial entries registered before and on March 2nd, 2022 were downloaded, deduplicated, and reviewed. Recruit country, monetary source, start years, study design, medical conditions, involved drugs, outcome measure, and subject information were extracted and analyzed. Results Overall, 173 clinical trials were included in this study. Majority of the trials were conducted in several economically prosperous countries. The earliest initiated trials dates back to 2002. Most of the trials were funded by hospitals (36.4%). A higher proportion of trials were conducted within one country (86.1%), as phase Ⅳ (34.1%) interventional study (82.7%), randomized (52.6%), parallel assignment (53.8%) and open label (67.0%). The most concerned medical condition were infectious or parasitic disease and neoplasms, with the most monitored drugs were immunosuppressants and β-lactam antibacterials. Most of the trials enroll no more than 50 subjects (30.6%), with both gender (95.4%), and adults (67.0%). Conclusion The trials were mainly conducted in several economically prosperous countries. The number of registered trials had gradually increased during the past years. Novel biological drugs have increasingly become the research hotspot. We expect that with abundant financial support, more high-quality large-scale, multicenter randomized clinical trials (RCTs) are designed and implemented to promote the development of TDM in the future.
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Affiliation(s)
- Shanshan Zhao
- Clinical Trial Institution Office/Department of Pharmacy, China Emergency General Hospital, Beijing, 100028, China
- Corresponding author.
| | - Olga Zaytseva
- Pharmacology Department, Bashkir State Medical University, Ufa, 450008, Bashkortostan, Russia
| | - Xiaohong Chang
- Clinical Trial Institution Office/Department of Pharmacy, China Emergency General Hospital, Beijing, 100028, China
| | - Boquan Zhang
- Clinical Trial Institution Office/Department of Pharmacy, China Emergency General Hospital, Beijing, 100028, China
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32
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Liu Y, Jiang L, Lou R, Wang M, Si Q. Vancomycin therapeutic drug monitoring in patients on continuous renal replacement therapy: a retrospective study. J Int Med Res 2022; 50:3000605221126871. [PMID: 36177821 PMCID: PMC9528032 DOI: 10.1177/03000605221126871] [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] [Indexed: 11/16/2022] Open
Abstract
Objectives This study aimed to investigate vancomycin therapeutic drug monitoring (TDM) in patients on continuous renal replacement therapy (CRRT) and explore the risk factors for exceeding the target concentration. Methods This retrospective study enrolled patients aged ≥18 years who were admitted to the intensive care unit and treated with ≥3 intravenous vancomycin doses during CRRT, and who underwent vancomycin TDM. Demographic and other information were collected. Multivariate logistic regression was used assess the risk factors for exceeding the target concentration. Results Sixty-nine patients were included, and 40.6% patients underwent TDM. Additionally, 14.5% of patients reached the optimal concentration, and 87.5% of patients who exceeded the target received a daily dose adjustment. The cumulative dose of vancomycin and serum albumin were risk factors for exceeding the target concentration in patients on CRRT. Conclusions Patients on CRRT did not meet the optimal vancomycin management; <50% of the patients routinely received vancomycin TDM, and <15% achieved the optimal concentration. Fewer patients in the subtherapeutic group received a daily dose adjustment than those who exceeded the target concentration. Cumulative vancomycin and serum albumin doses before TDM were the risk factors for exceeding the target concentration in CRRT patients.
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Affiliation(s)
- Yuyan Liu
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing 10053, China
| | - Li Jiang
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing 10053, China
| | - Ran Lou
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing 10053, China
| | - Meiping Wang
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing 10053, China
| | - Quan Si
- Department of Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing 10053, China
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33
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Wong S, Reuter SE, Jones GR, Stocker SL. Review and evaluation of vancomycin dosing guidelines for obese individuals. Expert Opin Drug Metab Toxicol 2022; 18:323-335. [PMID: 35815356 DOI: 10.1080/17425255.2022.2098106] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals. AREAS COVERED Literature was explored using PubMed, Embase and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC24/MIC) target (400-650) in obese individuals. EXPERT OPINION Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.
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Affiliation(s)
- Sherilyn Wong
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Stephanie E Reuter
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Graham Rd Jones
- St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.,Department of Chemical Pathology and Clinical Pharmacology, SydPath, St Vincent's Hospital, Darlinghurst, Australia
| | - Sophie L Stocker
- St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.,Sydney School of Pharmacy, The University of Sydney, Sydney, Australia.,Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney, Darlinghurst, Australia
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34
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Xu KY, Li D, Hu ZJ, Zhao CC, Bai J, Du WL. Vancomycin dosing in an obese patient with acute renal failure: A case report and review of literature. World J Clin Cases 2022; 10:6218-6226. [PMID: 35949852 PMCID: PMC9254177 DOI: 10.12998/wjcc.v10.i18.6218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/19/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vancomycin is the most commonly used drug for methicillin-resistant Staphylococcus aureus. The empirical clinical doses of vancomycin based on non-obese patients may not be optimal for obese ones.
CASE SUMMARY This study reports a case of vancomycin dosing adjustment in an obese patient (body mass index 78.4 kg/m2) with necrotizing fasciitis of the scrotum and left lower extremity accompanied with acute renal failure. Dosing adjustment was performed based on literature review and factors that influence pharmacokinetic parameters are analyzed. The results of the blood drug concentration monitoring confirmed the successful application of our dosing adjustment strategy in this obese patient. Total body weight is an important consideration for vancomycin administration in obese patients, which affects the volume of distribution and clearance of vancomycin. The alterations of pharmacokinetic parameters dictate that vancomycin should be dose-adjusted when applied to obese patients. At the same time, the pathophysiological status of patients, such as renal function, which also affects the dose adjustment of the patient, should be considered.
CONCLUSION Monitoring vancomycin blood levels in obese patients is critical to help adjust the dosing regimen to ensure that vancomycin concentrations are within the effective therapeutic range and to reduce the incidence of renal injury.
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Affiliation(s)
- Kun-Yan Xu
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Dan Li
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Zhen-Jie Hu
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Cong-Cong Zhao
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Jing Bai
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Wen-Li Du
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
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Tiseo G, Brigante G, Giacobbe DR, Maraolo AE, Gona F, Falcone M, Giannella M, Grossi P, Pea F, Rossolini GM, Sanguinetti M, Sarti M, Scarparo C, Tumbarello M, Venditti M, Viale P, Bassetti M, Luzzaro F, Menichetti F, Stefani S, Tinelli M. Diagnosis and management of infections caused by multidrug-resistant bacteria: guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), the Italian Society of Anti-Infective Therapy (SITA), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Association of Clinical Microbiologists (AMCLI) and the Italian Society of Microbiology (SIM). Int J Antimicrob Agents 2022; 60:106611. [PMID: 35697179 DOI: 10.1016/j.ijantimicag.2022.106611] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 05/12/2022] [Accepted: 05/29/2022] [Indexed: 02/08/2023]
Abstract
Management of patients with infections caused by multidrug-resistant organisms is challenging and requires a multidisciplinary approach to achieve successful clinical outcomes. The aim of this paper is to provide recommendations for the diagnosis and optimal management of these infections, with a focus on targeted antibiotic therapy. The document was produced by a panel of experts nominated by the five endorsing Italian societies, namely the Italian Association of Clinical Microbiologists (AMCLI), the Italian Group for Antimicrobial Stewardship (GISA), the Italian Society of Microbiology (SIM), the Italian Society of Infectious and Tropical Diseases (SIMIT) and the Italian Society of Anti-Infective Therapy (SITA). Population, Intervention, Comparison and Outcomes (PICO) questions about microbiological diagnosis, pharmacological strategies and targeted antibiotic therapy were addressed for the following pathogens: carbapenem-resistant Enterobacterales; carbapenem-resistant Pseudomonas aeruginosa; carbapenem-resistant Acinetobacter baumannii; and methicillin-resistant Staphylococcus aureus. A systematic review of the literature published from January 2011 to November 2020 was guided by the PICO strategy. As data from randomised controlled trials (RCTs) were expected to be limited, observational studies were also reviewed. The certainty of evidence was classified using the GRADE approach. Recommendations were classified as strong or conditional. Detailed recommendations were formulated for each pathogen. The majority of available RCTs have serious risk of bias, and many observational studies have several limitations, including small sample size, retrospective design and presence of confounders. Thus, some recommendations are based on low or very-low certainty of evidence. Importantly, these recommendations should be continually updated to reflect emerging evidence from clinical studies and real-world experience.
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Affiliation(s)
- Giusy Tiseo
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
| | - Gioconda Brigante
- Clinical Pathology Laboratory, ASST Valle Olona, Busto Arsizio, Italy
| | - Daniele Roberto Giacobbe
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; Clinica Malattie Infettive, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | | | - Floriana Gona
- Emerging Bacterial Pathogens Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Marco Falcone
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy
| | - Maddalena Giannella
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Paolo Grossi
- Infectious and Tropical Diseases Unit, Department of Medicine and Surgery, University of Insubria-ASST-Sette Laghi, Varese, Italy
| | - Federico Pea
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; SSD Clinical Pharmacology, Department for Integrated Infectious Risk Management, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gian Maria Rossolini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, and Microbiology and Virology Unit, Careggi University Hospital, Florence, Italy
| | - Maurizio Sanguinetti
- Microbiology Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Università Cattolica del Sacro Cuore, Largo 'A. Gemelli', Rome, Italy
| | - Mario Sarti
- Clinical Microbiology Laboratory, University of Modena and Reggio Emilia, Modena, Italy
| | - Claudio Scarparo
- Clinical Microbiology Laboratory, Angel's Hospital, AULSS3 Serenissima, Mestre, Venice, Italy
| | - Mario Tumbarello
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Mario Venditti
- Policlinico 'Umberto I', Department of Public Health and Infectious Diseases, 'Sapienza' University of Rome, Rome, Italy
| | - Pierluigi Viale
- Infectious Diseases Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Matteo Bassetti
- Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; Clinica Malattie Infettive, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Francesco Luzzaro
- Clinical Microbiology and Virology Unit, A. Manzoni Hospital, Lecco, Italy
| | - Francesco Menichetti
- Infectious Diseases Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliera Universitaria Pisana, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
| | - Stefania Stefani
- Medical Molecular Microbiology and Antibiotic Resistance Laboratory (MMARLab), Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Catania, Italy
| | - Marco Tinelli
- Infectious Diseases Consultation Service, IRCCS Istituto Auxologico Italiano, Milan, Italy
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Downs AM, Gerson J, Leung KK, Honeywell KM, Kippin T, Plaxco KW. Improved calibration of electrochemical aptamer-based sensors. Sci Rep 2022; 12:5535. [PMID: 35365672 PMCID: PMC8976050 DOI: 10.1038/s41598-022-09070-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 02/24/2022] [Indexed: 12/22/2022] Open
Abstract
Electrochemical aptamer-based (EAB) sensors support the real-time, high frequency measurement of pharmaceuticals and metabolites in-situ in the living body, rendering them a potentially powerful technology for both research and clinical applications. Here we explore quantification using EAB sensors, examining the impact of media selection and temperature on measurement performance. Using freshly-collected, undiluted whole blood at body temperature as both our calibration and measurement conditions, we demonstrate accuracy of better than ± 10% for the measurement of our test bed drug, vancomycin. Comparing titrations collected at room and body temperature, we find that matching the temperature of calibration curve collection to the temperature used during measurements improves quantification by reducing differences in sensor gain and binding curve midpoint. We likewise find that, because blood age impacts the sensor response, calibrating in freshly collected blood can improve quantification. Finally, we demonstrate the use of non-blood proxy media to achieve calibration without the need to collect fresh whole blood.
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Affiliation(s)
- Alex M Downs
- Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.,Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Julian Gerson
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Kaylyn K Leung
- Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.,Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Kevin M Honeywell
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Tod Kippin
- Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.,The Neuroscience Research Institute and Department of Molecular Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, 93106, USA
| | - Kevin W Plaxco
- Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA. .,Center for Bioengineering, University of California Santa Barbara, Santa Barbara, CA, 93106, USA. .,Department of Chemistry and Biochemistry, University of California Santa Barbara, Santa Barbara, CA, 93106, USA.
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Vancomycin Therapeutic Drug Monitoring (TDM) and Its Association with Clinical Outcomes: A Retrospective Cohort. J Infect Public Health 2022; 15:589-593. [DOI: 10.1016/j.jiph.2022.04.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 03/13/2022] [Accepted: 04/17/2022] [Indexed: 01/05/2023] Open
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38
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Koch BCP, Muller AE, Hunfeld NGM, de Winter BCM, Ewoldt TMJ, Abdulla A, Endeman H. Therapeutic Drug Monitoring of Antibiotics in Critically Ill Patients: Current Practice and Future Perspectives With a Focus on Clinical Outcome. Ther Drug Monit 2022; 44:11-18. [PMID: 34772892 DOI: 10.1097/ftd.0000000000000942] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 10/23/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Early initiation of antibiotics is essential for ameliorating infections in critically ill patients. The correct dosage of antibiotics is imperative to ensure their adequate exposure. Critically ill patients have altered pharmacokinetic parameters and are often infected by less susceptible microorganisms. Differences in drug disposition are not considered with standard doses of antibiotics. This can lead to suboptimal antibiotic exposure in critically ill patients. To overcome this problem of suboptimal dosing, therapeutic drug monitoring (TDM) is a strategy commonly used to support individualized dosing of antibiotics. It is routinely used for vancomycin and aminoglycosides in clinical practice. In recent years, it has become apparent that TDM may also be used in other antibiotics. METHODS This review summarizes the evidence for TDM of antibiotics in critically ill patients, focuses on clinical outcomes, and summarizes possibilities for optimized TDM in the future. RESULTS AND CONCLUSION After reviewing the literature, we can conclude that general TDM implementation is advised for glycopeptides and aminoglycosides, as evidence of the relationship between TDM and clinical outcome is present. For antibiotics, such as beta-lactams, fluoroquinolones, and linezolid, it seems rational to perform TDM in specific patient cases. TDM involving other antibiotics is supported by individual cases, specifically to decrease toxicity. When focusing on future possibilities to improve TDM of antibiotics in critically ill patients, implementation of model-informed precision dosing should be investigated because it can potentially streamline the TDM process. The logistics of TDM, such as turnaround time and available equipment, are challenging but may be overcome by rapid bioanalytical techniques or real-time monitoring of drug concentrations through biosensors in the future. Education, clinical information on targets, and clinical outcome studies are other important factors that facilitate TDM implementation.
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Affiliation(s)
- Birgit C P Koch
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Anouk E Muller
- Department of Medical Microbiology, Haaglanden Medical Center, The Hague, the Netherlands
- Department of Medical Microbiology & Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, the Netherlands; and
| | - Nicole G M Hunfeld
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, the Netherlands
- Department of Adult Intensive Care, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Brenda C M de Winter
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Tim M J Ewoldt
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, the Netherlands
- Department of Adult Intensive Care, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Alan Abdulla
- Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, the Netherlands
| | - Henrik Endeman
- Department of Adult Intensive Care, Erasmus MC, University Medical Center Rotterdam, the Netherlands
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Ewoldt TMJ, Abdulla A, Hunfeld NGM, Muller AE, Gommers D, Polinder S, Koch BCP, Endeman H. Health Care Costs of Target Attainment for Beta-Lactam Antibiotics in Critically Ill Patients: A Retrospective Analysis of the EXPAT Study. Ther Drug Monit 2022; 44:224-229. [PMID: 33770020 PMCID: PMC8746885 DOI: 10.1097/ftd.0000000000000891] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/23/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Optimizing beta-lactam antibiotic treatment is a promising method to reduce the length of intensive care unit (ICU) stay and therefore reduce ICU costs. We used data from the EXPAT trial to determine whether beta-lactam antibiotic target attainment is a cost determinant in the ICU. METHODS Patients included in the EXPAT trial were divided into target attainment and target nonattainment based on serum antibiotic levels. All hospital costs were extracted from the hospital administration system and categorized. RESULTS In total, 79 patients were included in the analysis. Target attainment showed a trend toward higher total ICU costs (€44,600 versus €28,200, P = 0.103). This trend disappeared when correcting for ICU length of stay (€2680 versus €2700). Renal replacement therapy was the most important cost driver. CONCLUSIONS Target attainment for beta-lactam antibiotics shows a trend toward higher total costs in ICU patients, which can be attributed to the high costs of a long stay in the ICU and renal replacement therapy.
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Affiliation(s)
| | | | | | - Anouk E. Muller
- Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands
- Department of Medical Microbiology, Haaglanden Medical Center, The Hague, the Netherlands; and
| | | | - Suzanne Polinder
- Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands
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40
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Kim Y, Kim S, Park J, Lee H. Clinical Response and Hospital Costs of Therapeutic Drug Monitoring for Vancomycin in Elderly Patients. J Pers Med 2022; 12:jpm12020163. [PMID: 35207653 PMCID: PMC8875716 DOI: 10.3390/jpm12020163] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 01/01/2022] [Accepted: 01/03/2022] [Indexed: 12/04/2022] Open
Abstract
Cost-effectiveness analysis has been widely used to assess and compare the costs and benefits of a clinical service. The cost-effectiveness of vancomycin therapeutic drug monitoring (TDM) has not been studied in the elderly, who are susceptible to vancomycin-induced adverse effects. This study was performed to evaluate if vancomycin TDM is cost-effective in elderly patients in the Republic of Korea. Using the electronic medical records at a tertiary university hospital, we performed a retrospective observational study to evaluate the cost-effectiveness of vancomycin TDM in 850 elderly patients who underwent vancomycin TDM with an appropriate, recommended dosing regimen and 1094 elderly patients who did not. Cost-effectiveness variables such as clinical outcomes and medical expenses were evaluated using univariate and multivariate analyses. The TDM group spent significantly less than the non-TDM group per patient for total medical expenses (by USD 841.40) and medication expenses (by USD 16.70). However, no significant difference was noted between the TDM and non-TDM groups in clinical outcomes such as microbiological cure, prevention of nephrotoxicity, or reduced mortality, irrespective of admission to the intensive care unit. Vancomycin TDM in elderly patients was associated with economic benefits, but not with better clinical outcomes.
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Affiliation(s)
- Yun Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
- Hanyang Medicine-Engineering-Bio Collaborative & Comprehensive Center for Drug Development (MEBC), Hanyang University, Seoul 04763, Korea
| | - Soohyun Kim
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea;
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03087, Korea
| | - Jinsook Park
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
| | - Howard Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea; (Y.K.); (J.P.)
- Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03080, Korea;
- Center for Convergence Approaches in Drug Development, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 03087, Korea
- Advanced Institute of Convergence Technology, Suwon-si 16229, Korea
- Correspondence: ; Tel.: +82-2-3668-7602
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41
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Chen M, Lee C, Gnyra M, Wong M. Vancomycin area under the curve/minimum inhibitory concentration and trough level concordance–evaluation on an urban health unit. Ther Adv Infect Dis 2022; 9:20499361221140368. [DOI: 10.1177/20499361221140368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 11/04/2022] [Indexed: 12/02/2022] Open
Abstract
Background: A vancomycin AUC/MIC (area under the curve/minimum inhibitory concentration) of 400–600 mg•h/L is associated with improved clinical outcomes for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. Currently, there are still limited studies evaluating the relationship between vancomycin trough and AUC. Objectives: To evaluate the correlation between vancomycin trough and AUC/MIC and determine if trough-guided monitoring is an adequate predictor of AUC/MIC in the Urban Health population at St Paul’s Hospital. Methods: This was a retrospective chart review of 29 patients from November 2019 to February 2021. Patient demographics and laboratory data were collected from electronic medical records. The two-level equation-based approach was used to calculate AUC/MIC. The proportion of AUC/MIC values within target (400–600 mg•h/L) despite subtherapeutic troughs, and the proportion of AUC/MIC values supratherapeutic when trough is within target (15–20 mg/L) were the primary endpoints. Main Results: Fifty-seven sets of levels were collected and 75% of vancomycin troughs and AUC24 were found to be discordant. When trough was 10–14.9 mg/L, AUC24 was > 400 mg•h/L in 94% of cases and when trough was 15–20 mg/L, AUC24 was > 600 mg•h/L in 69% of cases. There was a moderate correlation between vancomycin trough and AUC24h ( R2 = 0.57; p < 0.001). Conclusion: A vancomycin trough between 15 and 20 mg/L may result in an AUC/MIC greater than necessary for clinical efficacy. Considering these findings and the practical concerns of AUC-guided monitoring, a modest reduction in target troughs to prevent vancomycin toxicity warrants clinical consideration and further evaluation.
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Affiliation(s)
- Maggie Chen
- Pharmacy Department, Vancouver General Hospital, Vancouver, BC, Canada
| | - Colin Lee
- Pharmacy Department, St. Paul’s Hospital, Vancouver, BC, Canada
| | - Michelle Gnyra
- Pharmacy Department, St. Paul’s Hospital, Vancouver, BC, Canada
| | - Michelle Wong
- Pharmacy Department, St. Paul’s Hospital, 1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada
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42
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PBPK Modeling and Simulation and Therapeutic Drug Monitoring: Possible Ways for Antibiotic Dose Adjustment. Processes (Basel) 2021. [DOI: 10.3390/pr9112087] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Pharmacokinetics (PK) is a branch of pharmacology present and of vital importance for the research and development (R&D) of new drugs, post-market monitoring, and continued optimizations in clinical contexts. Ultimately, pharmacokinetics can contribute to improving patients’ clinical outcomes, helping enhance the efficacy of treatments, and reducing possible adverse side effects while also contributing to precision medicine. This article discusses the methods used to predict and study human pharmacokinetics and their evolution to the current physiologically based pharmacokinetic (PBPK) modeling and simulation methods. The importance of therapeutic drug monitoring (TDM) and PBPK as valuable tools for Model-Informed Precision Dosing (MIPD) are highlighted, with particular emphasis on antibiotic therapy since dosage adjustment of antibiotics can be vital to ensure successful clinical outcomes and to prevent the spread of resistant bacterial strains.
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43
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A personalised approach to antibiotic pharmacokinetics and pharmacodynamics in critically ill patients. Anaesth Crit Care Pain Med 2021; 40:100970. [PMID: 34728411 DOI: 10.1016/j.accpm.2021.100970] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 07/26/2021] [Accepted: 08/14/2021] [Indexed: 01/01/2023]
Abstract
Critically ill patients admitted to intensive care unit (ICU) with severe infections, or those who develop nosocomial infections, have poor outcomes with substantial morbidity and mortality. Such patients commonly have suboptimal antibiotic exposures at routinely used antibiotic doses related to an increased volume of distribution and altered clearance due to their underlying altered physiology. Furthermore, the use of extracorporeal devices such as renal replacement therapy and extracorporeal membrane oxygenation in these group of patients also has the potential to alter in vivo drug concentrations. Moreover, ICU patients are likely to be infected with less-susceptible pathogens. Therefore, one potential contributing cause to the poor outcomes observed in critically ill patients may be related to subtherapeutic antibiotic exposures. Newer concepts include the clinician considering optimised dosing based on a blood antibiotic exposure defined by pharmacokinetic modelling and therapeutic drug monitoring, combined with a knowledge of the antibiotic penetration into the site of infection, thereby achieving optimal bacterial killing. Such optimised dosing is likely to improve patient outcomes. The aim of this review is to highlight key aspects of antibiotic pharmacokinetics and pharmacodynamics (PK/PD) in critically ill patients and provide a PK/PD approach to tailor antibiotic dosing to the individual patient.
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44
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Ferreira A, Martins H, Oliveira JC, Lapa R, Vale N. PBPK Modeling and Simulation of Antibiotics Amikacin, Gentamicin, Tobramycin, and Vancomycin Used in Hospital Practice. Life (Basel) 2021; 11:life11111130. [PMID: 34833005 PMCID: PMC8620954 DOI: 10.3390/life11111130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/20/2021] [Accepted: 10/22/2021] [Indexed: 12/22/2022] Open
Abstract
The importance of closely observing patients receiving antibiotic therapy, performing therapeutic drug monitoring (TDM), and regularly adjusting dosing regimens has been extensively demonstrated. Additionally, antibiotic resistance is a contemporary concerningly dangerous issue. Optimizing the use of antibiotics is crucial to ensure treatment efficacy and prevent toxicity caused by overdosing, as well as to combat the prevalence and wide spread of resistant strains. Some antibiotics have been selected and reserved for the treatment of severe infections, including amikacin, gentamicin, tobramycin, and vancomycin. Critically ill patients often require long treatments, hospitalization, and require particular attention regarding TDM and dosing adjustments. As these antibiotics are eliminated by the kidneys, critical deterioration of renal function and toxic effects must be prevented. In this work, clinical data from a Portuguese cohort of 82 inpatients was analyzed and physiologically based pharmacokinetic (PBPK) modeling and simulation was used to study the influence of different therapeutic regimens and parameters as biological sex, body weight, and renal function on the biodistribution and pharmacokinetic (PK) profile of these four antibiotics. Renal function demonstrated the greatest impact on plasma concentration of these antibiotics, and vancomycin had the most considerable accumulation in plasma over time, particularly in patients with impaired renal function. Thus, through a PBPK study, it is possible to understand which pharmacokinetic parameters will have the greatest variation in a given population receiving antibiotic administrations in hospital context.
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Affiliation(s)
- Abigail Ferreira
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;
| | - Helena Martins
- Departament of Pathology, Clinical Chemistry Service, Centro Hospitalar Universitário do Porto (CHUP), 4099-001 Porto, Portugal; (H.M.); (J.C.O.)
| | - José Carlos Oliveira
- Departament of Pathology, Clinical Chemistry Service, Centro Hospitalar Universitário do Porto (CHUP), 4099-001 Porto, Portugal; (H.M.); (J.C.O.)
| | - Rui Lapa
- LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal;
| | - Nuno Vale
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
- Correspondence: ; Tel.: +351-220426537
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45
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Bang JY, Kang HI, Lee HJ, Chong YP, Hong SK, Lee EK, Choi BM, Noh GJ. Development of a new pharmacokinetic model for target-concentration controlled infusion of vancomycin in critically ill patients. Clin Exp Pharmacol Physiol 2021; 49:202-211. [PMID: 34596258 DOI: 10.1111/1440-1681.13597] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 09/15/2021] [Accepted: 09/27/2021] [Indexed: 11/28/2022]
Abstract
The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions). In total, 197 serum concentration measurements from 22 patients were used to characterise the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.
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Affiliation(s)
- Ji-Yeon Bang
- Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Il Kang
- University of Ulsan College of Medicine, Seoul, Korea
| | - Hak-Jae Lee
- Division of Acute Care Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyung Hong
- Division of Acute Care Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun-Kyung Lee
- Department of Statistics, Ewha Womans University, Seoul, Korea
| | - Byung-Moon Choi
- Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gyu-Jeong Noh
- Departments of Anesthesiology and Pain Medicine, Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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46
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Brasier N, Osthoff M, De Ieso F, Eckstein J. Next-Generation Digital Biomarkers for Tuberculosis and Antibiotic Stewardship: Perspective on Novel Molecular Digital Biomarkers in Sweat, Saliva, and Exhaled Breath. J Med Internet Res 2021; 23:e25907. [PMID: 34420925 PMCID: PMC8414294 DOI: 10.2196/25907] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/25/2021] [Accepted: 05/24/2021] [Indexed: 01/18/2023] Open
Abstract
The internet of health care things enables a remote connection between health care professionals and patients wearing smart biosensors. Wearable smart devices are potentially affordable, sensitive, specific, user-friendly, rapid, robust, lab-independent, and deliverable to the end user for point-of-care testing. The datasets derived from these devices are known as digital biomarkers. They represent a novel patient-centered approach to collecting longitudinal, context-derived health insights. Adding automated, analytical smartphone applications will enable their use in high-, middle-, and low-income countries. So far, digital biomarkers have been focused primarily on accelerometer data and heart rate due to well-established sensors originating from the consumer market. Novel emerging smart biosensors will detect biomarkers (or compounds) independent of a lab and noninvasively in sweat, saliva, and exhaled breath. These molecular digital biomarkers are a promising novel approach to reduce the burden from 2 major infectious diseases with urgent unmet needs: tuberculosis and infections with multidrug resistant pathogens. Active tuberculosis (aTbc) is one of the deadliest diseases from an infectious agent. However, a simple and reliable test for its detection is still missing. Furthermore, inappropriate antimicrobial use leads to the development of antimicrobial resistance, which is associated with high mortality and health care costs. From this perspective, we discuss the innovative approach of a noninvasive and lab-independent collection of novel biomarkers to detect aTbc, which at the same time may additionally serve as a scalable therapeutic drug monitoring approach for antibiotics. These molecular digital biomarkers are next-generation digital biomarkers and have the potential to shape the future of infectious diseases.
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Affiliation(s)
- Noe Brasier
- Department of Digitalization & ICT, University Hospital Basel, Basel, Switzerland.,Institute for Translational Medicine, ETH Zurich, Zurich, Switzerland
| | - Michael Osthoff
- Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Fiorangelo De Ieso
- Department of Digitalization & ICT, University Hospital Basel, Basel, Switzerland.,Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
| | - Jens Eckstein
- Department of Digitalization & ICT, University Hospital Basel, Basel, Switzerland.,Division of Internal Medicine, University Hospital Basel, Basel, Switzerland
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47
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Hirai T, Hanada K, Iwamoto T, Itoh T. Involvement of the effect of renal hypoperfusion medications on vancomycin trough concentration: A secondary analysis using a retrospective observational data. Basic Clin Pharmacol Toxicol 2021; 129:376-384. [PMID: 34396691 DOI: 10.1111/bcpt.13646] [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] [Received: 04/15/2021] [Revised: 07/09/2021] [Accepted: 08/11/2021] [Indexed: 12/14/2022]
Abstract
This study examined the association between vancomycin (VCM) trough concentration and confounding factors including renal hypoperfusion medications which include angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, loop/thiazide diuretics, or non-steroidal anti-inflammatory drugs. This secondary analysis included patients aged >15 years who were administered VCM intravenously between June 2015 and August 2017 at the Tokyo Women's Medical University Medical Center East. We investigated predictors for three (initial, mean, and final) dose-normalized VCM trough concentration (dose-normalized VCMtrough ) as outcome using a multiple linear regression analysis. In total, 208 patients were analysed (use of loop/thiazide diuretics: 48 [23%]). Multiple linear regression analysis revealed that the initial dose-normalized VCMtrough was negatively correlated with estimated glomerular filtration rate (eGFR) (p = 0.028) and positively correlated with the use of loop/thiazide diuretics (p = 0.003). Meanwhile, there was a positive correlation between the mean dose-normalized VCMtrough and age (p = 0.023). The mean dose-normalized VCMtrough was negatively correlated with eGFR (p < 0.001) and serum albumin (p < 0.001). The final dose-normalized VCMtrough was positively associated with age (p = 0.034) and negatively associated with eGFR (p = 0.032) and serum albumin (p = 0.007). Clinicians should closely monitor VCM trough concentration while receiving VCM and loop/thiazide diuretics.
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Affiliation(s)
- Toshinori Hirai
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, Tsu, Japan
| | - Kazuhiko Hanada
- Department of Pharmacometrics and Pharmacokinetics, Meiji Pharmaceutical University, Tokyo, Japan
| | - Takuya Iwamoto
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, Tsu, Japan
| | - Toshimasa Itoh
- Department of Pharmacy, Tokyo Women's Medical University Medical Center East, Tokyo, Japan
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48
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Hamilton F, Albur M, Noel A, MacGowan AP. Comment on: The case for 'conservative pharmacotherapy'. J Antimicrob Chemother 2021; 76:2489-2491. [PMID: 33993247 DOI: 10.1093/jac/dkab153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- F Hamilton
- Bristol Centre for Antimicrobial Chemotherapy (BCARE), North Bristol NHS Trust, Bristol, UK.,MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK
| | - M Albur
- Bristol Centre for Antimicrobial Chemotherapy (BCARE), North Bristol NHS Trust, Bristol, UK
| | - A Noel
- Bristol Centre for Antimicrobial Chemotherapy (BCARE), North Bristol NHS Trust, Bristol, UK
| | - A P MacGowan
- Bristol Centre for Antimicrobial Chemotherapy (BCARE), North Bristol NHS Trust, Bristol, UK
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49
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He N, Su S, Ye Z, Du G, He B, Li D, Liu Y, Yang K, Zhang X, Zhang Y, Chen X, Chen Y, Chen Z, Dong Y, Du G, Gu J, Guo D, Guo R, Hu X, Jiao Z, Li H, Liu G, Li Z, Lv Y, Lu W, Miao L, Qu J, Sun T, Tong R, Wang L, Wang M, Wang R, Wen A, Wu J, Wu X, Xu Y, Yang Y, Yang F, Zhan S, Zhang B, Zhang C, Zhang H, Zhang J, Zhang J, Zhang J, Zhang W, Zhao L, Zhao L, Zhao R, Zhao W, Zhao Z, Zhou W, Zeng XT, Zhai S. Evidence-based Guideline for Therapeutic Drug Monitoring of Vancomycin: 2020 Update by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. Clin Infect Dis 2021; 71:S363-S371. [PMID: 33367582 DOI: 10.1093/cid/ciaa1536] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. METHODS Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. RESULTS We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. CONCLUSIONS We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.
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Affiliation(s)
- Na He
- Department of Pharmacy, Peking University Third Hospital, Beijing, China.,School of Pharmaceutical Science, Peking University, Beijing, China
| | - Shan Su
- Department of Pharmacy, Peking University Third Hospital, Beijing, China.,School of Pharmaceutical Science, Peking University, Beijing, China
| | - Zhikang Ye
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada
| | - Guanhua Du
- Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Bei He
- Department of Respiratory Medicine, Peking University Third Hospital, Beijing, China
| | - Dakui Li
- Department of Pharmacy, Peking Union Medical College Hospital, Beijing, China
| | - Youning Liu
- Department of Respiratory and Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.,Chinese GRADE Center, Lanzhou, China
| | - Xianglin Zhang
- Department of Pharmacy, China-Japan Friendship Hospital, Beijing, China
| | - Yingyuan Zhang
- Institute of Antibiotics, Huashan Hospital affiliated with Fudan University, Shanghai, China
| | - Xiao Chen
- Department of Pharmacy, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yaolong Chen
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.,Chinese GRADE Center, Lanzhou, China
| | - Zhigang Chen
- Clinical Trial Center of Beijing Jishuitan Hospital, Beijing, China
| | - Yalin Dong
- Department of Pharmacy, First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
| | - Guang Du
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jian Gu
- Department of Pharmacy, Peking University People's Hospital, Beijing, China
| | - Daihong Guo
- Drug Security Center, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Ruichen Guo
- Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, China
| | - Xin Hu
- Department of Pharmacy, Beijing Hospital, Beijing, China
| | - Zheng Jiao
- Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Huande Li
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - Gaolin Liu
- Department of Pharmacy, Shanghai First People's Hospital, Shanghai, China
| | - Zhiping Li
- Department of Pharmacy, National Children's Medical Center/Children's Hospital of Fudan University, Shanghai, China
| | - Yuan Lv
- Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China
| | - Wei Lu
- School of Pharmaceutical Science, Peking University, Beijing, China
| | - Liyan Miao
- Department of Pharmacy, First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jieming Qu
- Department of Respiratory and Critical Care Medicine, Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tieying Sun
- Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology, Beijing, China
| | - Rongsheng Tong
- Department of Pharmacy, Sichuan Provincial People's Hospital, Chengdu, China
| | - Li Wang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Minggui Wang
- Institute of Antibiotics, Huashan Hospital affiliated with Fudan University, Shanghai, China
| | - Rui Wang
- Laboratory of Clinical Pharmacology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Aidong Wen
- Department of Pharmacy, Xijing Hospital, Xi'an, China
| | - Jiuhong Wu
- Department of Pharmacy, 306th Hospital of People's Liberation Army, Beijing, China
| | - Xin'an Wu
- Department of Pharmacy, Lanzhou University First Hospital, Lanzhou, China
| | - Yingchun Xu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yong Yang
- Department of Pharmacy, Sichuan Provincial People's Hospital, Chengdu, China
| | - Fan Yang
- Institute of Antibiotics, Huashan Hospital affiliated with Fudan University, Shanghai, China
| | - Siyan Zhan
- Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Bikui Zhang
- Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China
| | - Chao Zhang
- Department of Pharmacy, Beijing Tongren Hospital, Beijing, China
| | - Huizhi Zhang
- Nursing Department, Peking University Third Hospital, Beijing, China
| | - Jie Zhang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Jing Zhang
- Institute of Antibiotics, Huashan Hospital affiliated with Fudan University, Shanghai, China
| | - Jun Zhang
- Pharmacy Department, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wenting Zhang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Libo Zhao
- Department of Pharmacy, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Limei Zhao
- Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China
| | - Rongsheng Zhao
- Department of Pharmacy, Peking University Third Hospital, Beijing, China
| | - Wei Zhao
- Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhigang Zhao
- Pharmacy Department, Beijing Tiantan Hospital, Beijing, China
| | - Wei Zhou
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Xian-Tao Zeng
- Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Suodi Zhai
- Department of Pharmacy, Peking University Third Hospital, Beijing, China
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Roydhouse SA, Carland JE, Debono DS, Baysari MT, Reuter SE, Staciwa AJ, Sandhu APK, Day RO, Stocker SL. Accuracy of documented administration times for intravenous antimicrobial drugs and impact on dosing decisions. Br J Clin Pharmacol 2021; 87:4273-4282. [PMID: 33792079 DOI: 10.1111/bcp.14844] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 03/03/2021] [Accepted: 03/08/2021] [Indexed: 11/27/2022] Open
Abstract
AIMS Accurate documentation of medication administration time is imperative for many therapeutic decisions, including dosing of intravenous antimicrobials. The objectives were to determine (1) the discrepancy between actual and documented administration times for antimicrobial infusions and (2) whether day of the week, time of day, nurse-to-patient ratio and drug impacted accuracy of documented administration times. METHODS Patient and dosing data were collected (June-August 2019) for 55 in-patients receiving antimicrobial infusions. "Documented" and "actual" administration times (n = 660) extracted from electronic medication management systems and smart infusion pumps, respectively, were compared. Influence of the day (weekday/weekend), time of day (day/evening/night), nurse-to-patient ratio (high 1:1/low 1:5) and drug were examined. Monte Carlo simulation was used to predict the impact on dose adjustments for vancomycin using the observed administration time discrepancies compared to the actual administration time. RESULTS The median discrepancy between actual and documented administration times was 16 min (range, 2-293 min), with discrepancies greater than 60 minutes in 7.7% of administrations. Overall, discrepancies (median [range]) were similar on weekends (17 [2-293] min) and weekdays (16 [2-188] min), and for high (16 [2-157] min) and low nurse-to-patient ratio wards (16 [2-293] min). Discrepancies were smallest for night administrations (P < .05), and antimicrobials with shorter half-lives (P < .0001). The observed discrepancies in vancomycin administration time resulted in a different dose recommendation in 58% of cases (30% higher, 28% lower). CONCLUSIONS Overall, there were discrepancies between actual and documented antimicrobial infusion administration times. For vancomycin, these discrepancies in administration time were predicted to result in inappropriate dose recommendations.
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Affiliation(s)
- Stephanie A Roydhouse
- Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia
| | - Jane E Carland
- Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia
| | - Deborah S Debono
- Centre for Health Services Management, School of Public Health, The University of Technology Sydney, Sydney, Australia
| | - Melissa T Baysari
- Sydney School of Health Sciences, Charles Perkins Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
| | - Stephanie E Reuter
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Alice J Staciwa
- Pharmacy Department, St Vincent's Hospital Sydney, Sydney, Australia
| | - Anmol P K Sandhu
- Pharmacy Department, St Vincent's Hospital Sydney, Sydney, Australia
| | - Richard O Day
- Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia
| | - Sophie L Stocker
- Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital Sydney, Sydney, Australia.,St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.,Sydney Pharmacy School, The University of Sydney, Sydney, Australia
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