Pharmacokinetic and Antibiotic Dosing for Intensive Care Unit 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: closed (31 March 2024) | Viewed by 9929

Special Issue Editor

Department of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Fukuyama-shi, Hiroshima 7290292, Japan
Interests: antibiotics; pharmacokinetics-pharmacodynamics; therapeutic drug monitoring; population pharmacokinetics analysis

Special Issue Information

Dear Colleagues,

Critically ill intensive care patients, particularly those with severe sepsis and septic shock, are at risk of antibiotic failure and secondary infections associated with incorrect antibiotic use. Optimizing antibiotic dosing through prolonged infusions can be beneficial in intensive care populations with altered pharmacokinetics. The use of a drug administration plan and therapeutic drug monitoring (TDM) based on pharmacokinetics (PK) analysis is important for the effective use of antibiotics to treat infections. We focused on antibiotic dosing in intensive care unit (ICU) patients from the viewpoint of PK. PK analysis utilizes the restrictive information that is obtained by a clinic to the maximum, and it allows to provide adequate antibiotic therapy. This Special Issue seeks manuscript submissions that further our understanding of PK and antibiotic dosing in ICU patients.          

Authors are invited to submit manuscripts of original preclinical and clinical research within their area of interest including (but not limited) to the topics highlighted below:

  1. Antibiotic optimization on continuous renal replacement therapy or extracorporeal membrane oxygenation therapy
  2. Population pharmacokinetics analysis of antibiotics
  3. Clinical antibiotic stewardship in the ICU
  4. Antibiotics dosing considering bacterial susceptibility

Dr. Yuhki Sato
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

  • antibiotics
  • pharmacokinetics-pharmacodynamics
  • therapeutic drug monitoring
  • population pharmacokinetics analysis
  • bacterial susceptibility

Published Papers (4 papers)

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Research

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10 pages, 3102 KiB  
Article
No Sequestration of Commonly Used Anti-Infectives in the Extracorporeal Membrane Oxygenation (ECMO) Circuit—An Ex Vivo Study
by Hendrik Booke, Benjamin Friedrichson, Lena Draheim, Thilo Caspar von Groote, Otto Frey, Anka Röhr, Kai Zacharowski and Elisabeth Hannah Adam
Antibiotics 2024, 13(4), 373; https://doi.org/10.3390/antibiotics13040373 - 19 Apr 2024
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Abstract
Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates [...] Read more.
Patients undergoing extracorporeal membrane oxygenation (ECMO) often require therapy with anti-infective drugs. The pharmacokinetics of these drugs may be altered during ECMO treatment due to pathophysiological changes in the drug metabolism of the critically ill and/or the ECMO therapy itself. This study investigates the latter aspect for commonly used anti-infective drugs in an ex vivo setting. A fully functional ECMO device circulated an albumin–electrolyte solution through the ECMO tubes and oxygenator. The antibiotic agents cefazolin, cefuroxim, cefepime, cefiderocol, linezolid and daptomycin and the antifungal agent anidulafungin were added. Blood samples were taken over a period of four hours and drug concentrations were measured via high-pressure liquid chromatography (HPLC) with UV detection. Subsequently, the study analyzed the time course of anti-infective concentrations. The results showed no significant changes in the concentration of any tested anti-infectives throughout the study period. This ex vivo study demonstrates that the ECMO device itself has no impact on the concentration of commonly used anti-infectives. These findings suggest that ECMO therapy does not contribute to alterations in the concentrations of anti-infective medications in severely ill patients. Full article
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8 pages, 217 KiB  
Article
The Impact of Antibiotics Administration on Mortality for Time in Sepsis and Septic Shock Patients including Possible Reasons for Delayed Administration in Malaysia
by Ann L. Arulappen, Monica Danial, Ling Wei Ng and Jui Chang Teoh
Antibiotics 2022, 11(9), 1202; https://doi.org/10.3390/antibiotics11091202 - 05 Sep 2022
Cited by 3 | Viewed by 1679
Abstract
The 2017 Surviving Sepsis Campaign guidelines endorse a focus on the rapidity of treatment once sepsis has been identified, with a strong recommendation for the administration of antimicrobial drugs within one hour; however, the quality of the supporting evidence is evaluated as moderate. [...] Read more.
The 2017 Surviving Sepsis Campaign guidelines endorse a focus on the rapidity of treatment once sepsis has been identified, with a strong recommendation for the administration of antimicrobial drugs within one hour; however, the quality of the supporting evidence is evaluated as moderate. This study was conducted for six months prospectively at a single center in an intensive care unit (ICU) from March 2020 to August 2020. All the patients, regardless of their age and gender, admitted into ICU who had their first episode of sepsis or septic shock concomitantly started on a broad-spectrum antibiotic given intravenously. For patients who had multiple episodes of sepsis throughout the study period, data from the very first episode of the sepsis were included in this study. Of all the 78 patients, only 38 (48.7%) received the antibiotics prescribed within an hour. The compliance rate as per the Surviving Sepsis Campaign was only 51.3%, which accounted for 40 patients. The overall survival rate was 60.3%. This study revealed that delayed antibiotics administration (more than an hour) significantly affects mortality. Full article
13 pages, 2387 KiB  
Article
Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update
by Giuseppe Balice, Claudio Passino, Maria Grazia Bongiorni, Luca Segreti, Alessandro Russo, Marianna Lastella, Giacomo Luci, Marco Falcone and Antonello Di Paolo
Antibiotics 2022, 11(7), 914; https://doi.org/10.3390/antibiotics11070914 - 07 Jul 2022
Cited by 5 | Viewed by 1556
Abstract
Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during [...] Read more.
Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol. Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM. The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence of creatinine clearance on drug clearance and of sex on distribution volume. After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages. For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S. aureus, S. pneumoniae and E. faecium was 95.77%, 99.99% and 68%, respectively. According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risks. Full article
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Review

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17 pages, 1304 KiB  
Review
Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients—A Narrative Review
by Jan Stašek, Filip Keller, Veronika Kočí, Jozef Klučka, Eva Klabusayová, Ondřej Wiewiorka, Zuzana Strašilová, Miroslava Beňovská, Markéta Škardová and Jan Maláska
Antibiotics 2023, 12(3), 568; https://doi.org/10.3390/antibiotics12030568 - 13 Mar 2023
Cited by 5 | Viewed by 5573
Abstract
Beta-lactam antibiotics remain one of the most preferred groups of antibiotics in critical care due to their excellent safety profiles and their activity against a wide spectrum of pathogens. The cornerstone of appropriate therapy with beta-lactams is to achieve an adequate plasmatic concentration [...] Read more.
Beta-lactam antibiotics remain one of the most preferred groups of antibiotics in critical care due to their excellent safety profiles and their activity against a wide spectrum of pathogens. The cornerstone of appropriate therapy with beta-lactams is to achieve an adequate plasmatic concentration of a given antibiotic, which is derived primarily from the minimum inhibitory concentration (MIC) of the specific pathogen. In a critically ill patient, the plasmatic levels of drugs could be affected by many significant changes in the patient’s physiology, such as hypoalbuminemia, endothelial dysfunction with the leakage of intravascular fluid into interstitial space and acute kidney injury. Predicting antibiotic concentration from models based on non-critically ill populations may be misleading. Therapeutic drug monitoring (TDM) has been shown to be effective in achieving adequate concentrations of many drugs, including beta-lactam antibiotics. Reliable methods, such as high-performance liquid chromatography, provide the accurate testing of a wide range of beta-lactam antibiotics. Long turnaround times remain the main drawback limiting their widespread use, although progress has been made recently in the implementation of different novel methods of antibiotic testing. However, whether the TDM approach can effectively improve clinically relevant patient outcomes must be proved in future clinical trials. Full article
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