Therapeutic Drug Monitoring of Antimicrobials - 2nd Volume

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

Deadline for manuscript submissions: closed (1 February 2023) | Viewed by 7692

Special Issue Editors

1. Clinical Pharmacology and Pharmacotherapy, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, 3000 Leuven, Belgium
2. Pharmacy Department, University Hospitals Leuven, 3000 Leuven, Belgium
Interests: antibiotic therapy; dose optimization; pk/pd; antimicrobial tdm; augmented renal clearance; extracorporeal membrane oxygenation; critically ill
Special Issues, Collections and Topics in MDPI journals
1. Department of Development and Regeneration, KU Leuven, Leuven, Belgium
2. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
3. Department of Clinical Pharmacy, Erasmus Medical Center, Rotterdam, The Netherlands
Interests: perinatal pharmacology; neonatal clinical pharmacology; PBPK in special populations; newborn; infant; lactation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, several therapeutic drug monitoring (TDM)-based strategies have been suggested to optimize antibacterial and antifungal dosing in special patient populations. Nevertheless, a few obstacles still need to be addressed before TDM-based dosing strategies can be deployed widely in routine clinical practice.

Volume 1 of this Special Issue addressed suboptimal exposure to antibiotics and antifungals and knowledge on their pharmacokinetic/pharmacodynamic relationship in special patient populations. In these studies, recommendations and areas for further research have been identified. Additionally, for many antimicrobials, the link between exposure and clinical outcome remains to be confirmed. The topic of this Special Issue therefore remains of utmost relevance to the overarching topic of this journal. Consequently, we intend to keep this Special Issue open for submissions as a tool to communicate and interact between clinical researchers.

In the present volume 2 of this Special Issue, papers that further refine our understanding of antimicrobial TDM and its potential benefits in both adult and pediatric patients are welcomed. In particular, papers addressing the potential clinical benefit of antimicrobial TDM-based dose optimization and those addressing antiviral TDM-based dose optimization strategies are welcome, as these constitute major gaps in the current literature.

This Special Issue welcomes all types of submissions (original research papers, short communications, reviews, case reports and perspectives) related to antimicrobial TDM in special patient populations, including but not limited to critically ill patients, children, neonates, obese patients, hematological patients, and patients with cystic fibrosis.

Dr. Matthias Gijsen
Prof. Dr. Karel Allegaert
Guest Editors

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
  • antimicrobial
  • dose optimization
  • pharmacokinetics and pharmacodynamics
  • antibiotic
  • personalised dosing
  • critically ill patients

Published Papers (4 papers)

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Research

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16 pages, 1283 KiB  
Article
Evaluation of Dosing Guidelines for Gentamicin in Neonates and Children
Antibiotics 2023, 12(5), 810; https://doi.org/10.3390/antibiotics12050810 - 25 Apr 2023
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Abstract
Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in [...] Read more.
Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children’s Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8–12 mg/L for neonates and 15–20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials - 2nd Volume)
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10 pages, 1374 KiB  
Article
External Validation of the Augmented Renal Clearance Predictor in Critically Ill COVID-19 Patients
Antibiotics 2023, 12(4), 698; https://doi.org/10.3390/antibiotics12040698 - 03 Apr 2023
Cited by 2 | Viewed by 1091
Abstract
The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in [...] Read more.
The ARC predictor is a prediction model for augmented renal clearance (ARC) on the next intensive care unit (ICU) day that showed good performance in a general ICU setting. In this study, we performed a retrospective external validation of the ARC predictor in critically ill coronavirus disease 19 (COVID-19) patients admitted to the ICU of the University Hospitals Leuven from February 2020 to January 2021. All patient-days that had serum creatinine levels available and measured creatinine clearance on the next ICU day were enrolled. The performance of the ARC predictor was evaluated using discrimination, calibration, and decision curves. A total of 120 patients (1064 patient-days) were included, and ARC was found in 57 (47.5%) patients, corresponding to 246 (23.1%) patient-days. The ARC predictor demonstrated good discrimination and calibration (AUROC of 0.86, calibration slope of 1.18, and calibration-in-the-large of 0.14) and a wide clinical-usefulness range. At the default classification threshold of 20% in the original study, the sensitivity and specificity were 72% and 81%, respectively. The ARC predictor is able to accurately predict ARC in critically ill COVID-19 patients. These results support the potential of the ARC predictor to optimize renally cleared drug dosages in this specific ICU population. Investigation of dosing regimen improvement was not included in this study and remains a challenge for future studies. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials - 2nd Volume)
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Review

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23 pages, 1066 KiB  
Review
Pharmacokinetics of Antimicrobials in Children with Emphasis on Challenges Faced by Low and Middle Income Countries, a Clinical Review
Antibiotics 2023, 12(1), 17; https://doi.org/10.3390/antibiotics12010017 - 22 Dec 2022
Cited by 5 | Viewed by 2517
Abstract
Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism [...] Read more.
Effective antimicrobial exposure is essential to treat infections and prevent antimicrobial resistance, both being major public health problems in low and middle income countries (LMIC). Delivery of drug concentrations to the target site is governed by dose and pharmacokinetic processes (absorption, distribution, metabolism and excretion). However, specific data on the pharmacokinetics of antimicrobials in children living in LMIC settings are scarce. Additionally, there are significant logistical constraints to therapeutic drug monitoring that further emphasize the importance of understanding pharmacokinetics and dosing in LMIC. Both malnutrition and diarrheal disease reduce the extent of enteral absorption. Multiple antiretrovirals and antimycobacterial agents, commonly used by children in low resource settings, have potential interactions with other antimicrobials. Hypoalbuminemia, which may be the result of malnutrition, nephrotic syndrome or liver failure, increases the unbound concentrations of protein bound drugs that may therefore be eliminated faster. Kidney function develops rapidly during the first years of life and different inflammatory processes commonly augment renal clearance in febrile children, potentially resulting in subtherapeutic drug concentrations if doses are not adapted. Using a narrative review approach, we outline the effects of growth, maturation and comorbidities on maturational and disease specific effects on pharmacokinetics in children in LMIC. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials - 2nd Volume)
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Other

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12 pages, 567 KiB  
Brief Report
Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study
Antibiotics 2023, 12(3), 444; https://doi.org/10.3390/antibiotics12030444 - 23 Feb 2023
Cited by 1 | Viewed by 1245
Abstract
Introduction: Probability of target attainment (PTA) analysis using Monte Carlo simulations has become a mainstay of dose optimization. We highlight the technical and clinical factors that may affect PTA for beta-lactams. Methods: We performed a mini review in adults to explore factors relating [...] Read more.
Introduction: Probability of target attainment (PTA) analysis using Monte Carlo simulations has become a mainstay of dose optimization. We highlight the technical and clinical factors that may affect PTA for beta-lactams. Methods: We performed a mini review in adults to explore factors relating to cefepime PTA success and how researchers incorporate PTA into dosing decisions. In addition, we investigated, via simulations with a population pharmacokinetic (PK) model, factors that may affect cefepime PTA success. Results: The mini review included 14 articles. PTA results were generally consistent, given the differences in patient populations. However, dosing recommendations were more varied and appeared to depend on the definition of pharmacodynamic (PD) target, definition of PTA success and specific clinical considerations. Only 3 of 14 articles performed formal toxicological analysis. Simulations demonstrated that the largest determinants of cefepime PTA were the choice of PD target, continuous vs. intermittent infusion and creatinine clearance. Assumptions for protein binding, steady state vs. first dose, and simulating different sampling schemes may impact PTA success under certain conditions. The choice of one or two compartments had a minimal effect on PTA. Conclusions: PTA results may be similar with different assumptions and techniques. However, dose recommendation may differ significantly based on the selection of PD target, definition of PTA success and considerations specific to a patient population. Demographics and the PK parameters used to simulate time-concentration profiles should be derived from patient data applicable to the purpose of the PTA. There should be strong clinical rationale for dose selection. When possible, safety and toxicity should be considered in addition to PTA success. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials - 2nd Volume)
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