Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 3, 2025
Appropriate antifungal therapy is a major determinant of survival in critically ill patients with invasive fungal disease. We sought to describe whether contemporary dosing antifungals achieves therapeutic exposures patients. In prospective, open-label, multicenter pharmacokinetic study, intensive care unit (ICU) prescribed azoles, echinocandins, or polyene for treatment prophylaxis disease were enrolled. Blood samples collected on two occasions, three taken during single interval each occasion. Total concentrations centrally measured using validated chromatographic methods. Pharmacokinetic parameters estimated noncompartmental Antifungal adequacy was assessed predefined PK/PD targets. included 339 from 30 ICUs across 12 countries. Median age 62 (interquartile range [IQR], 51-70) years, median APACHE II score 22 (IQR, 17-28), and 61% males. primarily (80.8%). Fluconazole the most frequently (40.7%). The common indication intra-abdominal infection (30.7%). Fungi identified 45% patients, which only 26% had minimum inhibitory concentration available. Target attainment higher receiving (> 80% drugs). For treatment, low target noted voriconazole (57.1%), posaconazole (63.2%), micafungin (64.1%) amphotericin B (41.7%). This study highlights varying degrees agents While significant proportion achieved targets, wide variability subtherapeutic persist. ClinicalTrials.gov Identifier: NCT03136926, 2017-04-21.
Language: Английский
Citations
4Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis
Intensive Care Medicine Experimental, Journal Year: 2025, Volume and Issue: 13(1)
Published: Jan. 18, 2025
CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It primarily used in critically ill patients with sepsis and related conditions, including cytokine storms systemic inflammatory responses. Up to now, there no evidence nor recommendation the use of CS filters (22). There limited clinical data on effect plasma concentrations beta-lactams. We aimed evaluate statistical impact post-filter CKRT-CS setting antibiotics meropenem piperacillin patients. Patients admitted intensive care unit (ICU) who received prolonged infusion or CS-combined CKRT were included this retrospective analysis. TDM (therapeutic drug monitoring) samples collected at three different points. The differences antibiotic between Pre, Intra, Post statistically compared total isolated contributions removal. CS, combined clearance (CL) values calculated. hypothesis was that would have clinically relevant levels. 207 taken from 24 requiring beta-lactam antibiotics. Among these, 129 samples, 78 samples. A decrease both levels observed Pre Post, median relative difference >15% (meropenem: Pre-Intra 34.8%, Pre-Post 35.8%; piperacillin: 41.1%, 34.7%), indicating significant exposures. No Intra removal via filter. Changes CL attributed minimal, differing by ≤8.60% clearance. application does not appear significantly affect
Language: Английский
Citations
2Validating Low‐Dose Iohexol as a Marker for Glomerular Filtration Rate by In Vitro and In Vivo Studies
Clinical and Translational Science, Journal Year: 2025, Volume and Issue: 18(2)
Published: Feb. 1, 2025
ABSTRACT Clearance of an intravenous iohexol dose 3235 mg is used to assess glomerular filtration rate (GFR), although systematic assessment its pharmacokinetic (PK) properties incomplete. The objectives the present investigations were (i) potential interactions with important drug transporters, and (ii) whether a 259 could replace current standard dose. In vitro, we evaluated inhibits or transported by renal transporters (hOAT1/3, hOCT2, hMATE1/2K) other (hOATP1B1/3, hOCT1, hMDR1) using cell‐based vesicle‐based systems. vivo, conducted clinical trial 12 volunteers administration single doses (“reference”) (“test”) changeover design. Plasma urine samples collected up 24 h postdose. We assessed linearity pharmacokinetics bioequivalence approach population PK analysis characterize profile. Our in vitro findings indicate that neither substrate nor significant inhibitor suggesting it unlikely participate transporter‐mediated drug–drug vivo. trial, test/reference ratio for plasma clearance, calculated as divided area under concentration–time curve, was 1.01 (90% confidence interval 0.968–1.05), confirming linearity. Population further supported these results, showing no effect on clearance negligible nonrenal iohexol. Low‐dose suitable marker precise GFR measurement, even when coadministered drugs.
Language: Английский
Citations
1Optimizing ICU antifungal therapy: overcoming pharmacokinetic limitations with combination strategies
Intensive Care Medicine, Journal Year: 2025, Volume and Issue: unknown
Published: March 10, 2025
Language: Английский
Citations
1Adverse Drug Reactions Relevant to Drug Resistance and Ineffectiveness Associated with Meropenem, Linezolid, and Colistin: An Analysis Based on Spontaneous Reports from the European Pharmacovigilance Database
Antibiotics, Journal Year: 2023, Volume and Issue: 12(5), P. 918 - 918
Published: May 16, 2023
Antimicrobial resistance is considered one of the major threats to public health and an important factor that influences patient's outcome in intensive care unit. Pharmacovigilance can help raise awareness potential drug (DR) or ineffectiveness (DI) through adverse reaction reports are submitted different spontaneous reporting systems. Based on Individual Case Safety Reports from EudraVigilance, we conducted a descriptive analysis reactions associated with meropenem, colistin, linezolid, focus DR DI. Of total (ADRs) reported for each analyzed antibiotic by 31 December 2022, between 2.38-8.42% 4.15-10.14% were related DI, respectively. A disproportionality was evaluate frequency relevant DI antibiotics compared other antimicrobials. collected data, this study underlines importance post-marketing safety monitoring raising warning signal regarding antimicrobial resistance, thereby potentially contributing reduction treatment failure setting.
Language: Английский
Citations
17Development of Orally Active Anti-Inflammatory Agents: In Vivo and In Silico Analysis of Naphthalene-Chalcone Derivatives Based on 2-Acetyl-6-Methoxy Naphthalene
Chemical Physics Impact, Journal Year: 2024, Volume and Issue: 8, P. 100472 - 100472
Published: Jan. 11, 2024
Chalcone compounds are reported to have diverse biological activities such as antiviral, antimicrobial, antimalarial, antitumor, antifungal, anticancer, and so forth. Herewith, we wish report the in-vivo anti-inflammatory of previously synthesized naphthalene-chalcone hybrids from 2-Acetyl-6-Methoxy Naphthalene derivatives (C1-C25). All chalcones (C1-C25) were thoroughly characterized with standard spectroscopic techniques tested for their activities. The currently employed in-silico docking methodology uses 'Molegro Virtual Docker' a tool target proteins COX-1 (PDB ID: 1EQH) COX-2 1PXX). Molecular analysis suggested that compound C-24 exhibited higher score -117.495 kcal/mol than flurbiprofen -115.259 on target. To understand more about pharmacokinetics aspects, predicted theoretical ADME properties using 'QikProp, 2022' found all acceptable pharmacokinetic properties.
Language: Английский
Citations
7Pharmacokinetic Factors Associated With Early Meropenem Target Attainment in Pediatric Severe Sepsis
Pediatric Critical Care Medicine, Journal Year: 2024, Volume and Issue: unknown
Published: Aug. 20, 2024
To determine the frequency of early meropenem concentration target attainment (TA) in critically ill children with severe sepsis; to explore clinical, therapeutic, and pharmacokinetic factors associated TA; assess how fluid resuscitation volume status relate TA.
Language: Английский
Citations
5Pharmacokinetics and exposure–safety relationship of ciprofol for sedation in mechanically ventilated patients in the intensive care unit
CPT Pharmacometrics & Systems Pharmacology, Journal Year: 2024, Volume and Issue: 13(5), P. 823 - 836
Published: March 5, 2024
Abstract Ciprofol (HSK3486) is a newly developed, highly selective γ‐aminobutyric acid‐A (GABA A ) receptor potentiator that recently approved for new indication of sedation patients in the intensive care unit (ICU) China. This analysis aimed to characterize population pharmacokinetics (PopPKs) ciprofol and evaluate relationship exposure with hypotension mechanically ventilated ICU. total 462 subjects 3918 concentration measurements from two clinical trials ICU, four elective surgical patients, six healthy were used PopPK analysis. Exposure–safety was evaluated based on data gathered 112 (PKs) adequately described by three‐compartment linear disposition model first‐order elimination. Body weight, age, sex, blood sampling site (vein vs. arterial), study design (long‐term infusion short‐term infusion), patient (ICU non‐ICU) identified as statistically significant covariates PKs ciprofol. Within range ICU population, no meaningful association observed between incidence hypotension. These results support dosing regimen currently
Language: Английский
Citations
4A Randomized Noninferiority Trial to Compare Enteral to Parenteral Phosphate Replacement on Biochemistry, Waste, and Environmental Impact and Healthcare Cost in Critically Ill Patients With Mild to Moderate Hypophosphatemia*
Critical Care Medicine, Journal Year: 2024, Volume and Issue: 52(7), P. 1054 - 1064
Published: March 25, 2024
Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste.
Language: Английский
Citations
4Metformin for sepsis-associated AKI: a protocol for the Randomized Clinical Trial of the Safety and FeasibiLity of Metformin as a Treatment for sepsis-associated AKI (LiMiT AKI)
BMJ Open, Journal Year: 2024, Volume and Issue: 14(4), P. e081120 - e081120
Published: April 1, 2024
Introduction Acute kidney injury (AKI) is a common complication of sepsis associated with increased risk death. Preclinical data and observational human studies suggest that activation AMP-activated protein kinase, an ubiquitous master regulator energy can limit mitochondrial injury, metformin may protect against sepsis-associated AKI (SA-AKI) mortality. The Randomized Clinical Trial the Safety FeasibiLity Metformin as Treatment for (LiMiT AKI) aims to evaluate safety feasibility enteral in patients at developing SA-AKI. Methods analysis Blind, randomised, placebo-controlled clinical trial single-centre, quaternary teaching hospital USA. We will enrol adult (18 years age or older) within 48 hours meeting Sepsis-3 criteria, admitted intensive care unit, oral access. Patients be randomised 1:1:1 low-dose (500 mg two times per day), high-dose (1000 day) placebo 5 days. Primary outcome proportion metformin-associated serious adverse events. Feasibility assessment based on acceptability by clinicians, enrolment rate. Ethics dissemination This study has been approved Institutional Review Board. All surrogates provide written consent prior any intervention. widely available, inexpensive medication long track record safety, which if effective would accessible easy deploy. describe methods using Standard Protocol Items Trials framework discuss key design features methodological decisions. LiMiT investigate critically ill SA-AKI, preparation future large-scale efficacy study. Main results published soon available after final analysis. registration number NCT05900284 .
Language: Английский
Citations
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