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• Estimation of Renal Function for Antibiotic Dosing Decision

  Adina Fésüs

  Zsanett Szilágyi

  Ghazal Mohammadi Khabbaz

  Attila Vaskó

  Views:

  25

  Background: Accurate renal function assessment is essential for appropriate antibiotic dosing in critically ill patients. However, different estimation equations may yield discrepant results, potentially leading to dosing errors and suboptimal clinical outcomes.

  Objectives: To compare antibiotic dosing appropriateness based on renal function estimated using Cockcroft–Gault (CG), MDRD, and CKD-EPI equations, and to evaluate associated clinical outcomes in ICU patients with pneumonia-associated sepsis.

  Methods: In this single-center retrospective observational study, 229 adult ICU patients were included. Renal function was estimated using CG, MDRD, and CKD-EPI equations. Antibiotic dosing was classified as appropriate or inappropriate according to SPC and local guidelines. Clinical outcomes, including 30-day mortality/survival, and length of stay (LOS) were analyzed.

  Results: Based on CKD-EPI and MDRD, 57.2% and 55.5% of patients received appropriate dosing, respectively. However, 7.4% of patients considered appropriately dosed by these equations were reclassified as inappropriately dosed using CG. While mean renal function values were similar across equations (~67 mL/min), median values differed by approximately 20 mL/min (CG: 74 mL/min vs. CKD-EPI/MDRD: 52 and 50 mL/min), leading to clinically relevant reclassification. Inappropriate dosing was associated with older age and higher comorbidity burden. Piperacillin/tazobactam was most frequently underdosed, whereas clarithromycin, cefepime, and amikacin were commonly overdosed. Patients with inappropriate dosing had longer hospital LOS (median 14 vs. 11 days) and ICU-LOS (9 vs. 6 days), and showed worse survival, although 30-day mortality differences were not significant.

  Conclusions: The choice of renal function equation significantly impacts antibiotic dosing decisions. CG-based assessment may better identify dosing inaccuracies, and inappropriate dosing is associated with worse clinical outcomes. Optimized, individualized dosing strategies are warranted in critically ill patients.

   

• Toward synthesis of thioglycosyl-phosphonate analogues of lipid ll

  Viktor Kelemen

  Milán Csiszár

  Anikó Borbás

  Views:

  254

  Although a multitude of epidemics have already been eradicated with the use of modern antibiotics, in the 20th century, a new and increasingly serious phenomenon has arisen - the resistance against antibiotic therapies, necessiting the need for the development of novel antibiotic compounds. Transglycosylases are key enzymes in the biosynthesis of the bacterial cell wall, and currently there is no approved drug in human use against them, so they are an excellent target for further antibiotic development. During our research, the main goal was to synthesize compounds that are structurally similar to lipid ll, the substrate of bacterial transglycosylases, however, with significant modifications, such as the incorporation of an α-thioglycosidic unit instead of the α-O-glycosidic bond and an alkylphosphonate unit instead of the pyrophosphate part, making the molecules suitable to act as enzyme inhibitors. The key step of our work is the stereoselective construction of the 1,2-cis-α-thioglycosidic bond by photoinitiated thiol ene coupling reaction. ln this paper, the novel synthesis route is described which can be applied to furnish different lipid ll analogues, on example synthesis of a D-glucose derivative.