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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: 31 August 2026 | Viewed by 21542

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Special Issue Editor

Prof. Dr. Yukihiro Hamada

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Guest Editor

Department of Pharmacy, Kochi Medical School Hospital, Nankoku, Kochi, Japan
Interests: clinical PK/PD; TDM; pharmacometrics
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Special Issue Information

Dear Colleagues,

In recent years, the increase in antimicrobial-resistant bacteria has become a global threat. While we look forward to the development of new antimicrobial agents, it is important to maximize the use of existing agents. To this end, successful utilization of PK/PD and TDM can be expected to improve clinical outcomes. Therefore, the main theme of this Special Issue is all approaches to AMR control in the areas of PK/PD, TDM, application, and AST activities. Manuscripts on other approaches to the proper use of antimicrobial agents for AMR control are also welcome.

Prof. Dr. Yukihiro Hamada
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 250 words) can be sent to the Editorial Office for assessment.

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

pharmacokinetics/pharmacodynamics
therapeutic drug monitoring
antimicrobial resistant
AI
antimicrobial stewardship

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Published Papers (7 papers)

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Research

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24 pages, 3276 KB

Open AccessArticle

Advanced Biosensing Strategies for Last-Line Antibiotics Vancomycin, Colistin, Daptomycin and Meropenem: Comparative Analysis of Electrochemical and Optical Detection Methods

by Vivian Garzon, Daniel G.-Pinacho, J.-Pablo Salvador, M.-Pilar Marco and Rosa-Helena Bustos

Antibiotics 2026, 15(4), 327; https://doi.org/10.3390/antibiotics15040327 - 24 Mar 2026

Viewed by 422

Abstract

Background/Objectives: In the area of pharmacology and clinical research, it is necessary to use versatile technologies able to quantify last-line antibiotic molecules with high specificity and sensitivity. This article describes the development of two types of immunosensors based on amperometric and surface plasmon resonance (SPR) measurements and their applicability in the measurement/assessment of therapeutic drug monitoring (TDM) of four last-line antibiotics such as vancomycin, colistin, daptomycin and meropenem in human plasma. In this study, ligand immobilization by preconcentration assays, sensor surface regeneration, determination of sensitivity and correlation of plasma sample quantification results by HPLC were considered. Results: In the case of the electrochemical biosensor the IC50 values obtained were 3.49 μg/L for vancomycin (VAN), 5.44 μg/L for colistin (COL), 0.82 μg/L for meropenem (MER) and 5.10 μg/L for daptomycin (DAP). For the SPRi biosensor the LODs achieved were 19 ng/mL for VAN, 9 μg/L for COL, 12 μg/L for MER and 12.3 μg/L for DAP. Finally, both electrochemical biosensor and the SPRi optical biosensor showed that for the four antibiotics the standard deviations were less than 10% with respect to the HPLC results, with ranges for VAN between ~5–6 µg/mL, for COL ~0.2–0.7 µg/mL, for MER ~4.5–5.5 µg/mL and for DAP ~0.09–0.65 µg/mL. Conclusions: These kinds of biosensors provide a precise and sensitive strategy, together with real-time determination, to quantify last-line antibiotics, with working ranges like those shown by robust techniques such as HPLC and great potential for the clinic. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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13 pages, 1142 KB

Open AccessArticle

Unbound and Periprostatic Adipose Tissue Cefazolin Pharmacokinetics in Robotic-Assisted Radical Prostatectomy

by Toshiaki Komatsu, Yuki Takahashi, Yoko Takayama, Yuto Akamada, Masaomi Ikeda, Hideyasu Tsumura, Daisuke Ishii, Kazumasa Matsumoto, Masatsugu Iwamura, Hirotsugu Okamoto, Hideaki Hanaki and Katsuya Otori

Antibiotics 2026, 15(2), 181; https://doi.org/10.3390/antibiotics15020181 - 6 Feb 2026

Viewed by 621

Abstract

Background/Objectives: This study aimed to describe the population pharmacokinetics of cefazolin (CFZ) using unbound serum and periprostatic adipose tissue concentrations and to optimize dosing regimens for patients undergoing robotic-assisted radical prostatectomy (RARP). Methods: We investigated the population pharmacokinetics of CFZ using 295 unbound serum and 67 periprostatic adipose tissue samples from 67 individuals. CFZ concentrations were determined in all samples. A nonlinear mixed-effects model was developed. The pharmacodynamic target was defined as maintaining unbound trough and periprostatic adipose tissue concentrations exceeding the minimum inhibitory concentration (MIC) against methicillin-susceptible Staphylococcus aureus (MSSA) for over 90% of the dosing interval (MIC₉₀; 0.5 mg/L). Results: Systemic clearance of unbound CFZ was significantly associated with creatinine clearance (CLcr). In patients with normal renal function, simulations showed that a 1 g CFZ infusion over 15 min maintained unbound concentrations exceeding the MSSA MIC₉₀ for >90% of the 3 h interval after the initial dose. Notably, in patients with mild renal impairment (CLcr ≤ 80 mL/min), a 5 h dosing interval also achieved a >90% probability of maintaining the target CFZ concentration. Conclusions: The simulations demonstrated that the probability of target attainment of >90% was maintained for up to 5 h in patients with mild renal impairment (CLcr ≤ 80 mL/min). These findings provide a pharmacokinetic rationale suggesting that the standard additional dose may not be necessary for this subgroup; however, future clinical studies are needed to validate safety and efficacy. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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14 pages, 1422 KB

Open AccessArticle

Preclinical Study of Pharmacokinetic/Pharmacodynamic Analysis of Tebipenem Using Monte Carlo Simulation for Extended-Spectrum β-Lactamase-Producing Bacterial Urinary Tract Infections in Japanese Patients According to Renal Function

by Fumiya Ebihara, Takumi Maruyama, Hidefumi Kasai, Mitsuru Shiokawa, Nobuaki Matsunaga and Yukihiro Hamada

Antibiotics 2025, 14(7), 648; https://doi.org/10.3390/antibiotics14070648 - 26 Jun 2025

Cited by 2 | Viewed by 1891

Abstract

Background/Objectives: The increasing prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing organisms poses a significant clinical challenge worldwide due to limited oral treatment options. Tebipenem (TBPM), an oral carbapenem antibiotic, is currently approved only for pediatric use in Japan, with no adult indication established. International studies have shown promising results for ESBL-producing infections, but optimal dosing regimens for Japanese adults with varying renal function have not been established. This study aimed to determine the optimal TBPM dosing regimens for ESBL-producing Enterobacterales UTIs in Japanese patients stratified by renal function, providing evidence for potential adult approval applications in Japan. Methods: Monte Carlo simulations (MCSs) were performed using pharmacokinetic parameters derived from clinical trials in Japanese subjects. Various dosing regimens were evaluated across different creatinine clearance (CCR) ranges and minimum inhibitory concentrations (MICs). The pharmacokinetic/pharmacodynamic target was set at fAUC_0–24/MIC·1/tau ≥ 34.58, with a ≥90% probability of target attainment (PTA) considered optimal. Results: For patients with severe renal impairment (CCR < 30 mL/min), 150 mg q12 h achieved a >90% PTA against ESBL-producing organisms with an MIC of 0.03 mg/L. For moderate-to-severe renal impairment (30 ≤ CCR < 50 mL/min) and moderate renal impairment (50 ≤ CCR < 80 mL/min), 300 mg q8 h maintained a >90% PTA. For normal renal function (CCR ≥ 80 mL/min), 600 mg q8 h was required to achieve the target PTA. Conclusions: This first Japanese PK/PD analysis of TBPM in ESBL-producing UTIs provides evidence-based dosing recommendations across various renal function levels. TBPM, with appropriate renal-adjusted dosing, may offer an effective oral treatment option for patients who have traditionally required hospitalization for parenteral therapy. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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13 pages, 1474 KB

Open AccessArticle

Rapid Therapeutic Drug Monitoring of Voriconazole Based on High-Performance Liquid Chromatography: A Single-Center Pilot Study in Outpatients

by Satoru Morikawa, Yusuke Yagi, Moemi Okazaki, Narika Yanagisawa, Tomoaki Ishida, Kohei Jobu, Takumi Maruyama, Takahiro Kato, Miyuki Matsushita, Yu Arakawa, Yuka Yamagishi and Yukihiro Hamada

Antibiotics 2025, 14(5), 474; https://doi.org/10.3390/antibiotics14050474 - 8 May 2025

Cited by 1 | Viewed by 1933

Abstract

Background/Objectives: Voriconazole (VRCZ) use requires accurate monitoring to avoid suboptimal drug levels and adverse effects. In addition, the appearance of resistant fungal strains is a problem that needs attention. Blood concentration measurement is the monitoring technique of choice; however, it is slow, limiting its clinical application. This study aimed to evaluate the clinical utility of rapid therapeutic drug monitoring (TDM) for VRCZ using high-performance liquid chromatography with ultraviolet detection (HPLC-UV) compared to conventional outsourced liquid chromatography–tandem mass spectrometry (LC-MS/MS) testing in outpatient care. Methods: VRCZ blood concentrations were measured using HPLC-UV and LC-MS/MS. Reporting times, accuracy, and clinical outcomes were assessed for outpatients receiving VRCZ treatment. Safety was monitored for renal, hepatic, and visual toxicities. Results: HPLC-UV significantly reduced reporting times (0.433 h vs. 74.3 h, p < 0.001), and Deming’s regression analyses showed a strong correlation with LC-MS/MS results (Pearson’s r = 0.988). Bland–Altman analysis showed an average difference of 0.025 μg/mL between HPLC-UV and LC-MS/MS. Prospective monitoring of three outpatients revealed no adverse events, enabling safe and effective VRCZ dosing. Conclusions: Rapid VRCZ TDM using HPLC-UV is a cost-effective and feasible approach for outpatient care, significantly improving reporting times and patient safety. Further studies and cross-facility collaboration are needed to expand its application. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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12 pages, 1643 KB

Open AccessArticle

Association between Extended Meropenem Regimen and Achievement of Aggressive PK/PD in Patients Receiving Continuous Renal Replacement Therapy for Septic AKI

by Shinya Chihara, Tomoyuki Ishigo, Satoshi Kazuma, Kana Matsumoto, Kunihiko Morita and Yoshiki Masuda

Antibiotics 2024, 13(8), 755; https://doi.org/10.3390/antibiotics13080755 - 11 Aug 2024

Cited by 1 | Viewed by 3440

Abstract

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated. The 100% fT > 4 × MIC for a pathogen with an MIC of 0.5 mg/L was 89%, and that for a pathogen with an MIC of 2 mg/L was 56%. The mean steady-state trough concentration of meropenem was 11.9 ± 9.0 mg/L and the maximum steady-state trough concentration was 29.2 mg/L. Simulations using Bayesian estimation showed the probability of achieving 100% fT > 4 × MIC for up to an MIC of 2 mg/L for the administered administration via continuous infusion at 3 g/24 h. We found that an aggressive PK/PD could be achieved up to an MIC of 0.5 mg/L with a meropenem regimen of 1 g infused every 8 h over 3 h for patients receiving CRRT for septic AKI. In addition, the risk of reaching the toxicity range with this regimen is low. In addition, if the MIC was 1–2 mg/L, the simulation results indicated that aggressive PK/PD can be achieved by continuous infusion at 3 g/24 h without increasing the daily dose. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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Review

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18 pages, 513 KB

Open AccessReview

Physiologically Based Pharmacokinetic Modeling of Antibiotics in Children: Perspectives on Model-Informed Precision Dosing

by Ryota Tanaka, Kei Irie and Tomoyuki Mizuno

Antibiotics 2025, 14(6), 541; https://doi.org/10.3390/antibiotics14060541 - 24 May 2025

Cited by 3 | Viewed by 5254

Abstract

The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs’ physicochemical properties with anatomical and physiological data to predict PK behavior. In pediatric populations, PBPK modeling accounts for developmental changes in organ function, making it particularly useful for optimizing antibiotic dosing across different age groups, from neonates to adolescents. In recent decades, PBPK modeling has been widely applied to predict antibiotic disposition in pediatric patients for various clinical and research purposes. Model-informed precision dosing (MIPD) is an evolving approach that enhances traditional therapeutic drug monitoring by integrating multiple information sources into a mathematical framework. By incorporating PBPK modeling, MIPD could offer a more optimized antibiotic dosing that accounts for PK/PD parameters at the site of infection, improving therapeutic outcomes while minimizing toxicity. This review summarizes currently published pediatric PBPK modeling studies on antibiotics, covering various objectives such as evaluating drug–drug interactions, PK/PD analyses in targeted tissues, predicting PK in specific populations (e.g., maternal/fetal, renal impairment, obesity), and PK predictions for preterm neonates. Based on these reports, the review discusses the implications of PBPK modeling for MIPD in pediatric antibiotic therapy. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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18 pages, 1048 KB

Open AccessReview

Artificial Intelligence and Machine Learning Applications to Pharmacokinetic Modeling and Dose Prediction of Antibiotics: A Scoping Review

by Iria Varela-Rey, Enrique Bandín-Vilar, Francisco José Toja-Camba, Antonio Cañizo-Outeiriño, Francisco Cajade-Pascual, Marcos Ortega-Hortas, Víctor Mangas-Sanjuan, Miguel González-Barcia, Irene Zarra-Ferro, Cristina Mondelo-García and Anxo Fernández-Ferreiro

Antibiotics 2024, 13(12), 1203; https://doi.org/10.3390/antibiotics13121203 - 10 Dec 2024

Cited by 11 | Viewed by 6876

Abstract

Background and Objectives: The use of artificial intelligence (AI) and, in particular, machine learning (ML) techniques is growing rapidly in the healthcare field. Their application in pharmacokinetics is of potential interest due to the need to relate enormous amounts of data and to the more efficient development of new predictive dose models. The development of pharmacokinetic models based on these techniques simplifies the process, reduces time, and allows more factors to be considered than with classical methods, and is therefore of special interest in the pharmacokinetic monitoring of antibiotics. This review aims to describe the studies that use AI, mainly oriented to ML techniques, for dose prediction and analyze their results in comparison with the results obtained by classical methods. Furthermore, in the review, the techniques employed and the metrics to evaluate the precision are described to improve the compression of the results. Methods: A systematic search was carried out in the EMBASE, OVID, and PubMed databases and the results obtained were analyzed in detail. Results: Of the 13 articles selected, 10 were published in the last three years. Vancomycin was monitored in seven and none of the studies were performed on new antibiotics. The most used techniques were XGBoost and neural networks. Comparisons were conducted in most cases against population pharmacokinetic models. Conclusions: AI techniques offer promising results. However, the diversity in terms of the statistical metrics used and the low power of some of the articles make the overall assessment difficult. For now, AI-based ML techniques should be used in addition to classical population pharmacokinetic models in clinical practice. Full article

(This article belongs to the Special Issue Clinical Pharmacokinetics, Pharmacodynamics, and/or TDM of Antimicrobial Agents)

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