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Antibiotics
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Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients
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Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients

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 November 2025 | Viewed by 4384

Special Issue Editor

Prof. Dr. Young Ran Lee

E-Mail Website
Guest Editor
Department of Clinical Sciences, The Ben and Maytee Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, TX, USA
Interests: critical care; infectious diseases; anticoagulants; pharmacotherapy in the obese

Special Issue Information

Dear Colleagues,

Despite numerous therapeutic innovations, infection-related mortality in critically ill patients persists as a significant healthcare concern. Early initiation of antimicrobials is essential to improve the clinical outcomes of infections in critically ill patients. Additionally, correct dosage of antimicrobials is extremely important to ensure their adequate exposure. Therapeutic drug monitoring (TDM) is the most commonly recommended strategy to evaluate exposure and adapt dosing in critically ill patients.

This Special Issue welcomes all types of submissions (original research papers, short communications, reviews, case reports and perspectives) related to antimicrobial TDM in critically ill patients.

Prof. Dr. Young Ran Lee
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

  • therapeutic drug monitoring (TDM)
  • antibiotics
  • antimicrobials
  • pharmacokinetic
  • pharmacodynamic
  • critically ill

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Published Papers (4 papers)

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Research

18 pages, 2346 KB  
Article
TDM-Based Approach for Properly Managing Intravenous Isavuconazole Treatment in a Complex Case Mix of Critically Ill Patients
by Milo Gatti, Matteo Rinaldi, Riccardo De Paola, Antonio Siniscalchi, Tommaso Tonetti, Pierluigi Viale and Federico Pea
Antibiotics 2025, 14(8), 777; https://doi.org/10.3390/antibiotics14080777 - 1 Aug 2025
Viewed by 464
Abstract
Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study [...] Read more.
Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021–31 March 2025. Desired isavuconazole exposure was defined as trough concentrations (Cmin) of 1.0–5.1 mg/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole Cmin underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole Cmin was 3.5 mg/L (2.1–4.6 mg/L). Proportions of ECPAs with isavuconazole Cmin under- and overexposure were 4.2% (7/166) and 16.3% (27/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg/m2; p < 0.001). Trends of isavuconazole Cmin under- and overexposure changed over time, significantly decreasing the former (10.5% <7 days vs. 4.3% 7–28 days vs. 0.0% >28 days; p < 0.001) and increasing the latter (5.3% <7 days vs. 12.8% 7–28 days vs. 29.3% >28 days; p < 0.001). HTD occurred in 15/32 patients, most of whom (10/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)
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12 pages, 814 KB  
Article
Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series
by Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas and Jordi Riera
Antibiotics 2025, 14(6), 600; https://doi.org/10.3390/antibiotics14060600 - 12 Jun 2025
Viewed by 758
Abstract
Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in [...] Read more.
Background/Objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO. Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters—Area Under Curve (AUC0–24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T1/2), volume of distribution (Vd), and clearance (CL)—were estimated and compared with published data in non-ECMO populations. Results: Five patients were included. The median AUC0–24 was 227.3 µg·h/mL (IQR 182.4–311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727–832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5–3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure. Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)
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13 pages, 549 KB  
Article
Impact of Recovery from Febrile Neutropenia on Intra-Individual Variability in Vancomycin Pharmacokinetics in Pediatric Patients
by Yukie Takumi, Ryota Tanaka, Motoshi Iwao, Ryosuke Tatsuta and Hiroki Itoh
Antibiotics 2025, 14(6), 570; https://doi.org/10.3390/antibiotics14060570 - 2 Jun 2025
Viewed by 611
Abstract
Background/Objectives: The pharmacokinetics of vancomycin (VCM) in patients with febrile neutropenia (FN) are highly variable due to coexisting conditions such as systemic inflammatory response syndrome and augmented renal clearance. Upon hematopoietic recovery, VCM clearance (CLvcm) is expected to normalize, which contributes to intra-individual [...] Read more.
Background/Objectives: The pharmacokinetics of vancomycin (VCM) in patients with febrile neutropenia (FN) are highly variable due to coexisting conditions such as systemic inflammatory response syndrome and augmented renal clearance. Upon hematopoietic recovery, VCM clearance (CLvcm) is expected to normalize, which contributes to intra-individual variability. This study aimed to investigate the factors contributing to intra-individual variability in CLvcm among pediatric patients with FN. Methods: This retrospective, single-center study analyzed 33 pediatric patients (48 FN episodes) who met the inclusion criteria. CLvcm was estimated using Bayesian estimation based on the pediatric population pharmacokinetic model developed by Le et al., and standardized with allometrically scaled body weight. The change (Δ) in each clinical laboratory parameter or CLvcm was calculated as the difference between the values at the current and previous TDM within the same episode. Results: A total of 155 VCM TDM data points were analyzed. Intra-individual comparisons revealed that CLvcm decreased significantly in patients recovering from FN to a non-FN state (n = 18, p = 0.0285). Further analysis of intra-individual variability revealed that Δ CLvcm correlated significantly with Δ hemoglobin, Δ C-reactive protein, and Δ maximum daily body temperature, with the strongest correlation observed for Δ maximum daily body temperature (rs = 0.325, p = 0.001). Multivariate analysis confirmed Δ maximum daily body temperature as a significant factor influencing Δ CLvcm (B = 0.376, 95% CI: 0.074 to 0.678, p = 0.015). Conclusions: Maximum daily body temperature was identified as a factor influencing intra-individual variability in CLvcm in pediatric FN patients, particularly during the recovery process from FN to a non-FN state. The finding suggests that dose adjustment based on maximum daily body temperature may allow safe and effective VCM therapy in FN patients. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)
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9 pages, 578 KB  
Article
A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients
by Emory G. Johnson, Kayla Maki Ortiz, David T. Adams, Satwinder Kaur, Andrew C. Faust, Hui Yang, Carlos A. Alvarez and Ronald G. Hall 2nd
Antibiotics 2024, 13(9), 835; https://doi.org/10.3390/antibiotics13090835 - 2 Sep 2024
Viewed by 1812
Abstract
Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem’s activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or [...] Read more.
Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem’s activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study’s primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials in Critically Ill Patients)
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