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: 30 November 2024 | Viewed by 12675
Special Issue Editor
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:
- Antibiotic optimization on continuous renal replacement therapy or extracorporeal membrane oxygenation therapy
- Population pharmacokinetics analysis of antibiotics
- Clinical antibiotic stewardship in the ICU
- 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
Planned Papers
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Title: Meropenem disposition in neonatal and pediatric extracorporeal membrane oxygenation: a retrospective study
Authors: Pavla Pokorná (1,2,4), Danica Michaličková (1), Dick Tibboel (2,5) Jonas Berner (2,3,4),
Affiliation: Affiliations:
1. Institute of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
2. Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and
General University Hospital, Prague, Czech Republic
3. Department of Physiology and Pharmacology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
4. Pediatric Perioperative medicine and intensive care, Astrid Lindgren Children´s Hospital, Karolinska University Hospital, Stockholm, Sweden
5. Department of Paediatric Surgery, Erasmus Medical Center Sophia Children’s Hospital, Rotterdam, The Netherlands
Abstract: Introduction: Meropenem is a broad-spectrum antibiotic commonly used to treat serious infections in the pediatric population treated with extracorporeal membrane oxygenation (ECMO). It is known that ECMO may affect the drug's pharmacokinetics (PK) by altering the drug's clearance (CL), volume of distribution (Vd). There are limited data on ECMO influence on PK of meropenem in neonates and children undergoing ECMO. Therefore, the aim of this study was to describe PK of meropenem in critically ill neonates and children undergoing ECMO.
Methodology: Data from therapeutic drug monitoring (TDM) were available from 45 critically ill patients (median (interquartile range, IQR), body weight (BW): 7.88 (3.62 – 11.97) kg; postnatal age (PNA) at start of therapy: 3 (0 – 465)) days) treated with meropenem. In total 38 patients received veno-venous (VV) or veno-arterial (VA) ECMO. There were 152 available plasma concentrations ranging from 0.68 to 75 mg/L, of whom 94 were collected during ECMO treatment. Population PK analysis was performed using NONMEM V7.4.0. The following covariates were tested: maturation variables: BW, PNA; disease status: laboratory values, including serum creatinine, serum urea, serum albumin, total bilirubin, blood pH, aspartate transaminase, and alanine transaminase; concomitant therapy: use of diuretics, inotropes, as well as use of continuous renal replacement therapy (CRRT); ECMO variables: on/off ECMO, duration of ECMO treatment, ECMO flow rate and speed. Monte Carlo dosing simulations were performed using Simulx (Lixoft, France) for short-term infusion (0.5, and 3 h) of 20mg/kg and 40 mg/kg of meropenem every 8 h (q8h) and continuous regimen of 60 and 120 mg/kg/day for patients with a typical individual with BW of 7.88 on and off CRRT during 7 days. Probability of target attainment (PTA) was assessed for 40% and 100% fT% > MIC for MIC= 1, 2, 4, 8, 16, 32 mg/L.
Results: Observed meropenem plasma concentrations were best described by a one-compartment model with log-normally distributed intra-individual variability (IIV) on CL and Vd. A proportional residual error model provided the best description of residual variability. BW was found to be a significant covariate for Vd and CL; adding CRRT as a binary covariate (i.e., on/off) on Vd resulted in a statistically significant improvement of the model fit. In the final model, CL and Vd for a typical patient of the median BW of 7.88 kg that was off CRRT were 1.09 L/hr (RSE = 8%)) and 3.98 L (14%), respectively. CRRT was found to increase Vd approximately 2 times. According to simulations, none of the regimens achieved PTA for 100% fT% > MIC for any MIC, whereas PTA for 40% fT% > MIC was achieved for MICs up to 4 mg/L.
Conclusion: ECMO does not affect the PK of meropenem in the neonatal and pediatric cohort, but CRRT use increases Vd. BW is a significant covariate for CL and Vd. Further larger studies should confirm these results.