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Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics of Drugs".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 7867

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Special Issue Editor

Prof. Dr. Toshimi Kimura

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Guest Editor

Department of Pharmacy, Juntendo University Hospital, Tokyo 113-0033, Japan
Interests: pharmacometrics; TDM; infectious disease; pediatrics; oncology

Special Issue Information

Dear Colleagues,

The incomplete attainment of recommended antibiotics PK/PD parameters are associated with the treatment failure of infection disease and emergence of antimicrobial resistant bacteria. Blood concentration monitoring of antibiotics and appropriate dosing regimen based on PK/PD can help improving clinical outcomes, reducing adverse drug reactions, and decreasing spread of antimicrobial resistance in patients with critical infections. TDM of Aminoglycosides and Glycopeptides are very popular and Beta-lactams optimization such as meropenem in complex infections have become necessary to monitor the concentrations. Recently, TDM strategy directed towards personalized medicine and Model-informed precision dosing (MIPD) of antibiotics is rapidly evolving TDM fields. Near future MIPD comprised PBPK model will be more advanced therapy options that support the treatment of infectious patients with complicated backgrounds.

In this Special Issue of Antibiotics, we aim to publish highlighted clinical evidence on optimization of a dosage regimen by TDM and the concept of MIPD as below:

Therapeutic index of blood or tissue concentration of any antibiotics based on efficacy and toxicity in human.
Improvement of clinical outcome or antimicrobial resistance by TDM interventions.
Systematic reviews/meta-analysis within TDM/MIPD fields
Population pharmacokinetics and pharmacodynamics of antibiotics in special populations such as pediatrics
Applied to antibiotics treatment based on mechanism-based pharmacokinetics and pharmacodynamics in human.

Prof. Dr. Toshimi Kimura
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

TDM
MIPD
PBPK
antibiotics
PK/PD
dose optimization

Published Papers (5 papers)

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Research

Jump to: Review

11 pages, 848 KiB

Open AccessArticle

Therapeutic Drug Monitoring of Dalbavancin in Real Life: A Two-Year Experience

by Dario Cattaneo, Marta Fusi, Marta Colaneri, Chiara Fusetti, Camilla Genovese, Riccardo Giorgi, Maddalena Matone, Stefania Merli, Francesco Petri and Andrea Gori

Antibiotics 2024, 13(1), 20; https://doi.org/10.3390/antibiotics13010020 - 24 Dec 2023

Cited by 1 | Viewed by 1281

Abstract

Dalbavancin is a long-acting lipoglycopeptide that is registered for the treatment of acute bacterial skin and skin structure infections, and it is also increasingly used for infections that require prolonged antibiotic treatment. Here, we present the results from the first 2 years of a service set up in December 2021 for the therapeutic drug monitoring (TDM) of dalbavancin in clinical settings. In particular, we compared the trough concentration (Cmin) to maximum concentration (Cmax) in patients with osteoarticular infections receiving prolonged treatment with dalbavancin. Log-linear regression models were used to estimate the timing of dalbavancin administration with the goal of maintaining Cmin concentrations of >8 mg/L in the two TDM-based strategies. From December 2021 to November 2023, 366 TDMs of dalbavancin from 81 patients were performed. The Cmin and Cmax concentrations of dalbavancin ranged from 4.1 to 70.5 mg/L and from 74.9 to 995.6 mg/L, respectively. With log-linear regression models, we estimated that each injection should be administered every 42–48 days to maintain the Cmin concentrations. Out of the 81 patients, 37 received at least three doses of dalbavancin for the treatment of osteoarticular infections. Despite there being no significant differences in the days of dalbavancin treatment (130 ± 97 versus 106 ± 102 days), the patients in the Cmax-based TDM group received a significantly lower number of dalbavancin injections (5.2 ± 1.8 versus 7.3 ± 2.6 injections, p = 0.005), and they were administered over a longer period of time (40 ± 10 versus 29 ± 14 days, p = 0.013) than in the Cmin-based TDM group. In conclusion, Cmax-based TDM was associated with a significant reduction in the inter-individual variability of dalbavancin concentrations and lower drug dosing frequency than those of Cmin-based TDM. This approach could, therefore, favor a more rational and targeted use of dalbavancin in patients requiring prolonged treatment. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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13 pages, 580 KiB

Open AccessArticle

Long-Term Suppressive Therapeutic-Drug-Monitoring-Guided Dalbavancin Therapy for Cardiovascular Prosthetic Infections

by Altea Gallerani, Milo Gatti, Andrea Bedini, Stefania Casolari, Gabriella Orlando, Cinzia Puzzolante, Erica Franceschini, Marianna Menozzi, Antonella Santoro, Nicole Barp, Sara Volpi, Alessandra Soffritti, Federico Pea, Cristina Mussini and Marianna Meschiari

Antibiotics 2023, 12(11), 1639; https://doi.org/10.3390/antibiotics12111639 - 19 Nov 2023

Cited by 2 | Viewed by 1540

Abstract

Dalbavancin represents a promising treatment for cardiovascular prosthetic infections due to its prolonged half-life, bactericidal activity, large spectrum of activity, and excellent biofilm penetration. However, the use of dalbavancin in this setting is limited, and only a few cases have performed therapeutic drug monitoring (TDM) analysis to optimize dosage in suppressive treatments longer than 4 weeks. Our retrospective case series reports the use of dalbavancin in a small cohort of patients with cardiovascular prosthetic infections (cardiac implantable electronic device infections (CEDIs), prosthetic valve endocarditis (PVE), prosthetic vascular graft infections (PVGIs)) treated with dalbavancin as sequential therapy. From May 2019 to May 2023, 14 patients were included: eight cases of PVE (57.1%), seven cases of PVGI (50%), three cases of CEDI (21.4%), and four cases with overlap of infection sites (28.6%). The main pathogen was Staphylococcus aureus (35.7%). Prosthesis replacement was obtained in four patients (28.6%). The median time between symptom onset and the end of treatment was 15 weeks (IQR 7–53), with a median duration of dalbavancin therapy of 8 weeks (IQR 1 to 45 weeks) and 3.5 doses per patient. Among patients managed with TDM-guided strategy, dalbavancin infusion intervals ranged from 4 to 9 weeks. The median length of follow-up was 65 weeks (IQR 23 to 144 weeks). Clinical success was achieved in 10 cases (76.9%); all clinical failures occurred in patients with the implant retained. Among patients monitored by TDM, clinical success was 87.5% vs. 60% in patients treated without TDM. Because of pharmacokinetic individual variability, dalbavancin TDM-guided administration could improve clinical outcomes by individualizing dosing and selecting dosing intervals. This case series seems to suggest a promising role of long-term suppressive dalbavancin treatment for difficult-to-treat cardiovascular prosthesis infection, also with limited surgical indications. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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13 pages, 1750 KiB

Open AccessArticle

Dosing Optimization of Posaconazole in Lung-Transplant Recipients Based on Population Pharmacokinetic Model

by Eliška Dvořáčková, Martin Šíma, Andrea Zajacová, Kristýna Vyskočilová, Tereza Kotowski, Kateřina Dunovská, Eva Klapková, Jan Havlín, Robert Lischke and Ondřej Slanař

Antibiotics 2023, 12(9), 1399; https://doi.org/10.3390/antibiotics12091399 - 1 Sep 2023

Cited by 2 | Viewed by 832

Abstract

Although posaconazole tablets show relatively low variability in pharmacokinetics (PK), the proportion of patients achieving the PK/PD target at the approved uniform dose for both prophylaxis and therapy is not satisfactory. The aim of this study was to develop a posaconazole population PK model in lung-transplant recipients and to propose a covariate-based dosing optimization for both prophylaxis and therapy. In this prospective study, 80 posaconazole concentrations obtained from 32 lung-transplant patients during therapeutic drug monitoring were analyzed using nonlinear mixed-effects modelling, and a Monte Carlo simulation was used to describe the theoretical distribution of posaconazole PK profiles at various dosing regimens. A one-compartment model with both linear absorption and elimination best fit the concentration–time data. The population apparent volume of distribution was 386.4 L, while an apparent clearance of 8.8 L/h decreased by 0.009 L/h with each year of the patient’s age. Based on the covariate model, a dosing regimen of 200 mg/day for prophylaxis in patients ˃60 years, 300 mg/day for prophylaxis in patients ˂60 years and for therapy in patients ˃60 years, and 400 mg/day for therapy in patients ˂60 years has been proposed. At this dosing regimen, the PK/PD target for prophylaxis and therapy is reached in 95% and 90% of population, respectively, representing significantly improved outcomes in comparison with the uniform dose. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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13 pages, 4354 KiB

Open AccessArticle

Altered Pharmacokinetics Parameters of Vancomycin in Patients with Hematological Malignancy with Febrile Neutropenia, a Bayesian Software Estimation

by Abdullah M. Alzahrani, Anjum Naeem, Aeshah AlAzmi, Alqassem Y. Hakami, Shahid Karim, Ahmed S. Ali, Fatemah Omer Kamel, Rami M. Alzhrani, Teaf S. Alkhaldi, Loujayne A. Maghrabi, Norah F. Alshehri and Yahya A. Alzahrani

Antibiotics 2023, 12(6), 979; https://doi.org/10.3390/antibiotics12060979 - 29 May 2023

Viewed by 1654

Abstract

The pharmacokinetics of vancomycin vary significantly between specific groups of patients, such as critically ill patients and patients with hematological malignancy (HM) with febrile neutropenia (FN). Recent evidence suggests that the use of the usual standard dose of antibiotics in patients with FN may not offer adequate exposure due to pharmacokinetic variability (PK). Therefore, the purpose of this study is to assess the effect of FN on AUC_0–24 as a key parameter for vancomycin monitoring, as well as to determine which vancomycin PK parameters are affected by the presence of FN using Bayesian software PrecisePK in HM with FN. This study was carried out in King Abdulaziz Medical City. All adult patients who were admitted to the Princess Norah Oncology Center PNOC between 1 January and 2017 and 31 December 2020, hospitalized and received vancomycin with a steady-state trough concentration measured before the fourth dose, were included. During the trial period, 297 patients received vancomycin during their stay at the oncology center, 217 of them meeting the inclusion criteria. Pharmacokinetic parameters were estimated for the neutropenic and non-FN patients using the precise PK Bayesian platform. The result showed that there was a significant difference (p < 0.05) in vancomycin clearance Cl_van, the volume of distribution at a steady-state V_dss, the volume of distribution for peripheral compartment V_dp, half-life for the elimination phase t½_β, and the first-order rate constant for the elimination process β in FN compared to non-FN patients. Furthermore, AUC_0–24 was lower for FN patients compared to non-FN patients, p < 0.05. FN has a significant effect on the PK parameters of vancomycin and AUC_0–24, which may require specific consideration during the treatment initiation. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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Review

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12 pages, 545 KiB

Open AccessReview

New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections

by Roland Nau, Jana Seele and Helmut Eiffert

Antibiotics 2024, 13(1), 58; https://doi.org/10.3390/antibiotics13010058 - 7 Jan 2024

Viewed by 1960

Abstract

Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections. The new glycopeptides dalbavancin, telavancin, and oritavancin are highly bound to plasma proteins. Although effective in animal models of meningitis, it is unlikely that they reach effective cerebrospinal fluid (CSF) concentrations after intravenous administration alone. The β-lactam/β-lactamase inhibitor combinations have the principal problem that both compounds must achieve adequate CSF concentrations. In the commercially available combinations, the dose of the β-lactamase inhibitor tends to be too low to achieve adequate CSF concentrations. The oxazolidinone tedizolid has a broader spectrum but a less suitable pharmacokinetic profile than linezolid. The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing. Generally, treatment of CNS infections should be intravenous, whenever possible, to avoid adverse effects of intraventricular therapy (IVT). An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring: Pharmacodynamics and Pharmacokinetics of Antibiotics in Clinical Care Settings)

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