Therapeutic Drug Monitoring of Antimicrobials

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 (15 April 2022) | Viewed by 21790

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
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Special Issue Information

Dear Colleagues,

Several recent guidelines and position papers defined dose optimization as a priority for antimicrobial research in special patient populations such as critically ill patients. Therapeutic drug monitoring (TDM) is the most commonly recommended strategy to evaluate exposure and adapt dosing in critically ill patients. TDM can be used as such, or can be integrated in dosing nomograms or dosing software to optimize antimicrobial exposure, and ultimately, clinical outcome.

Whereas TDM was previously mainly performed out of concern for toxicity, there is currently a shift towards antimicrobial TDM for efficacy. For many antimicrobials, although a clear therapeutic range has been defined, the clinical benefit of TDM remains unclear. For some antimicrobials, such as most antivirals, the merit of TDM-based dose optimization is still to be defined. Several issues need to be addressed before broader antimicrobial TDM can be implemented in routine clinical ICU practice. Therefore, we encourage the submission of all papers that refine our understanding of antimicrobial TDM and its potential benefit in both adult and pediatric patients. 

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 such as—but not limited to—critically ill patients, children, neonates, obese patients, hematological patients, patients with cystic fibrosis, etc.

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 (6 papers)

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Editorial

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3 pages, 199 KiB  
Editorial
Editorial for the Special Issue: “Therapeutic Drug Monitoring of Antimicrobials”
by Matthias Gijsen and Karel Allegaert
Antibiotics 2022, 11(6), 815; https://doi.org/10.3390/antibiotics11060815 - 17 Jun 2022
Viewed by 1578
Abstract
A recent guideline [...] Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)

Research

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14 pages, 680 KiB  
Article
Clinical Efficacy and Safety of Vancomycin Continuous Infusion in Patients Treated at Home in an Outpatient Parenteral Antimicrobial Therapy Program
by Lore Thijs, Charlotte Quintens, Lotte Vander Elst, Paul De Munter, Melissa Depypere, Willem-Jan Metsemakers, Georges Vles, Astrid Liesenborghs, Jens Neefs, Willy E. Peetermans and Isabel Spriet
Antibiotics 2022, 11(5), 702; https://doi.org/10.3390/antibiotics11050702 - 23 May 2022
Cited by 6 | Viewed by 2327
Abstract
Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of [...] Read more.
Vancomycin is commonly used in outpatient parenteral antimicrobial therapy (OPAT) of Gram-positive infections. Therapeutic drug monitoring and adverse event monitoring pose a challenge. Outcome data of vancomycin in OPAT (vOPAT) are limited. The study aim was to report the safety and efficacy of a structured vOPAT program implemented in the University Hospitals Leuven. The program provides continuous elastomeric infusion of vancomycin at home with biweekly follow-up at the outpatient clinic. Demographics, clinical, biochemical and treatment parameters, target attainment parameters and clinical outcomes were recorded. An e-survey was conducted to assess patient satisfaction. Thirty-five vOPAT episodes in 32 patients were included. During 206 follow-up consultations, 203 plasma concentration measurements were registered with a median vancomycin plasma concentration of 22.5 mg/L (range 6.6–32.0). The majority of concentrations (68.5%) were within the therapeutic range (20.0–25.0 mg/L). Adverse event rates, including drug- (5.7%) and catheter-related (5.7%) events, were low. For 32 vOPAT episodes, a clinical cure rate of 100% was observed. All patients who completed the e-survey were satisfied with their vOPAT course. These findings show that a structured vOPAT program with rigorous follow-up provides safe and effective ambulatory treatment of patients with vancomycin in continuous infusion. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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9 pages, 936 KiB  
Article
Validation and Application of an HPLC-UV Method for Routine Therapeutic Drug Monitoring of Dalbavancin
by Ute Chiriac, Heike Rau, Otto R. Frey, Anka C. Röhr, Sabrina Klein, Anna L. Meyer and Benedict Morath
Antibiotics 2022, 11(5), 541; https://doi.org/10.3390/antibiotics11050541 - 19 Apr 2022
Cited by 9 | Viewed by 3334
Abstract
Dalbavancin is emerging as a promising alternative in the ambulant treatment of gram-positive infections that require long-term antibiotic treatment such as osteomyelitis, prosthetic joint infections, and endocarditis. The aim of the current study was to develop and validate a simple, rapid, and cost-effective [...] Read more.
Dalbavancin is emerging as a promising alternative in the ambulant treatment of gram-positive infections that require long-term antibiotic treatment such as osteomyelitis, prosthetic joint infections, and endocarditis. The aim of the current study was to develop and validate a simple, rapid, and cost-effective high-performance liquid chromatography–ultraviolet spectrometry (HPLC–UV) method for the quantification of dalbavancin. Sample clean-up included a protein precipitation protocol, followed by chromatographic separation on a reverse phase HPLC column (C-18) with gradient elution of the mobile phase. Quantification was performed with the internal standard (caffeine) method. Linear relationships between peak area responses and drug concentrations were obtained in the range of 12.5–400 mg/L. The variation coefficient of precision and the bias of accuracy (both inter- and intraday) were less than 10%. The limit of quantification (LOQ) was 12.5 mg/L. The simple and reliable HPLC–UV assay described is a powerful tool for routine therapeutic drug monitoring (TDM) of dalbavancin in human serum in clinical laboratories. With a total process time of approximately 20 min, it allows for accurate and selective quantification up to the expected pharmacokinetic peak concentrations. The method was successfully used to analyze subsequent serum samples of three patients and showed good performance in monitoring serum levels. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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10 pages, 711 KiB  
Article
Validation of Vancomycin Area under the Concentration—Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections
by Takashi Ueda, Yoshio Takesue, Kazuhiko Nakajima, Kaoru Ichiki, Kaori Ishikawa, Kumiko Yamada, Toshie Tsuchida, Naruhito Otani, Yoshiko Takahashi, Mika Ishihara, Shingo Takubo, Hiroki Ikeuchi, Motoi Uchino, Toshimi Kimura, Kazuaki Matsumoto, Kazutaka Oda and Takeshi Kimura
Antibiotics 2022, 11(1), 96; https://doi.org/10.3390/antibiotics11010096 - 13 Jan 2022
Cited by 19 | Viewed by 2745
Abstract
Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected [...] Read more.
Area under the concentration–time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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Review

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24 pages, 1084 KiB  
Review
Ways to Improve Insights into Clindamycin Pharmacology and Pharmacokinetics Tailored to Practice
by Laura Armengol Álvarez, Greet Van de Sijpe, Stefanie Desmet, Willem-Jan Metsemakers, Isabel Spriet, Karel Allegaert and Jef Rozenski
Antibiotics 2022, 11(5), 701; https://doi.org/10.3390/antibiotics11050701 - 21 May 2022
Cited by 11 | Viewed by 6381
Abstract
Given the increase in bacterial resistance and the decrease in the development of new antibiotics, the appropriate use of old antimicrobials has become even more compulsory. Clindamycin is a lincosamide antibiotic approved for adults and children as a drug of choice for systemic [...] Read more.
Given the increase in bacterial resistance and the decrease in the development of new antibiotics, the appropriate use of old antimicrobials has become even more compulsory. Clindamycin is a lincosamide antibiotic approved for adults and children as a drug of choice for systemic treatment of staphylococcal, streptococcal, and gram-positive anaerobic bacterial infections. Because of its profile and high bioavailability, it is commonly used as part of an oral multimodal alternative for prolonged parenteral antibiotic regimens, e.g., to treat bone and joint or prosthesis-related infections. Clindamycin is also frequently used for (surgical) prophylaxis in the event of beta-lactam allergy. Special populations (pediatrics, pregnant women) have altered cytochrome P450 (CYP)3A4 activity. As clindamycin is metabolized by the CYP3A4/5 enzymes to bioactive N-demethyl and sulfoxide metabolites, knowledge of the potential relevance of the drug’s metabolites and disposition in special populations is of interest. Furthermore, drug–drug interactions derived from CYP3A4 inducers and inhibitors, and the data on the impact of the disease state on the CYP system, are still limited. This narrative review provides a detailed survey of the currently available literature on pharmacology and pharmacokinetics and identifies knowledge gaps (special patient population, drug–drug, and drug–disease interactions) to describe a research strategy for precision medicine. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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24 pages, 467 KiB  
Review
Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?
by Daniela Baracaldo-Santamaría, Juan David Cala-Garcia, Germán José Medina-Rincón, Luis Carlos Rojas-Rodriguez and Carlos-Alberto Calderon-Ospina
Antibiotics 2022, 11(5), 645; https://doi.org/10.3390/antibiotics11050645 - 12 May 2022
Cited by 10 | Viewed by 3915
Abstract
Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. [...] Read more.
Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring of Antimicrobials)
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