Background: The aims of this study were to describe pharmacokinetic/pharmacodynamic target attainment in intensive care unit (ICU) patients treated with continuously infused -lactam antibiotics, their associated covariates, and the impact of dosage adjustment.
Methods: This prospective, observational, cohort study was performed in three ICUs. Four -lactams were continuously infused, and therapeutic drug monitoring (TDM) was performed at days 1, 4, and 7. The primary pharmacokinetic/pharmacodynamic target was an unbound -lactam plasma concentration four times above the bacteria's minimal inhibitory concentration during the whole dosing interval. The demographic and clinical covariates associated with target attainment were evaluated.
Results: A total of 170 patients were included (426 blood samples). The percentages of empirical -lactam underdosing at D1 were 66% for cefepime, 43% for cefotaxime, 47% for ceftazidime, and 14% for meropenem. Indexed creatinine clearance was independently associated with treatment underdose if increased (adjusted odds ratio per unit, 1.01; 95% CI, 1.00 to 1.01; = 0.014) or overdose if decreased (adjusted odds ratio per unit, 0.95; 95% CI, 0.94 to 0.97; < 0.001). Pharmacokinetic/pharmacodynamic target attainment was significantly increased after -lactam dosage adjustment between day 1 and day 4 vs. no adjustment (53.1% vs. 26.2%; = 0.018).
Conclusions: This study increases our knowledge on the optimization of -lactam therapy in ICU patients. A large inter- and intra-patient variability in plasmatic concentrations was observed, leading to inadequate exposure. A combined indexed creatinine clearance and TDM approach enables adequate dosing for better pharmacokinetic/pharmacodynamic target attainment.
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http://dx.doi.org/10.3390/antibiotics12081289 | DOI Listing |
Pediatr Infect Dis J
October 2024
From the Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine.
Background: Rates of carbapenem-resistant Acinetobacter baumannii are rising in Thailand. Although high-dose (HD) sulbactam is recommended for treating carbapenem-resistant A. baumannii infections, data on plasma sulbactam concentrations in children are limited.
View Article and Find Full Text PDFJAC Antimicrob Resist
December 2024
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.
Background: Sulbactam is an effective therapy for infections. Previous sulbactam pharmacokinetics/pharmacodynamics (PK/PD) analyses established exposure efficacy targets in plasma against pneumonia. Herein, we established sulbactam efficacy targets in epithelial lining fluid (ELF).
View Article and Find Full Text PDFJ Antimicrob Chemother
December 2024
Facultés de Médecine et de Pharmacie de Lyon, Univ Lyon, Université Claude Bernard Lyon 1, Lyon, France.
Background And Objectives: Cefiderocol approved dosages are based on a prolonged infusion (PI) of 3 h that may not be adequate in all settings The objective of this study was to identify alternative cefiderocol dosage regimens based on short infusion (SI) or continuous infusion (CI).
Methods: We performed 1000-patient pharmacokinetic/pharmacodynamic (PK/PD) simulations based on a reference population model. Drug penetration into the epithelial lining fluid (ELF) was considered for pneumonia.
Rev Esp Anestesiol Reanim (Engl Ed)
December 2024
Departamento de Farmacia, Clínica Universidad de Navarra, Pamplona, Universidad de Navarra, Spain.
Introduction: The independent association of vancomycin with Acute Kidney Injury (AKI) in the critically ill patient with sepsis or septic Shock is controversial. The aim of this study was to evaluate the incidence of AKI in a cohort of patients with sepsis or septic Shock with an adequate and strict monitoring of vancomycin, guided by the area under the concentration-time curve in relation to the minimum inhibitory concentration (AUC/MIC ratio).
Material And Methods: Retrospective cohort study on 106 patients admitted to the ICU with a diagnosis of sepsis or septic shock with vancomycin treatment, consecutively from January 2017 to December 2019.
Neurol Ther
December 2024
Axoltis Pharma, Bioparc Laennec, 60 Avenue Rockefeller, 69008, Lyon, France.
Introduction: Blood-brain barrier (BBB) integrity is fundamental to brain homeostasis, enabling control of substance exchange and safeguarding neurons against harmful toxins, pathogens, and immune cells that lead to dysregulation and inflammation involved in ageing and neurodegenerative diseases (NDD). The cyclized peptide NX210c is a thrombospondin type 1 repeat analogue derived from subcommissural organ-spondin. It exerts beneficial effects in animal models of NDD owing to its effects on neurons and endothelial cells.
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