Host Biomarkers and Antibiotic Tissue Penetration in Sepsis: Insights from Moxifloxacin.

Abstract

Background and objective: Sepsis-induced pathophysiological changes may lead to pharmacokinetic variability which alters antibiotic concentrations at the host infection site. This poses a challenge in clinical practice, as sufficient antibiotic concentrations in tissue are necessary to effectively eradicate bacterial pathogens. In this exploratory study, we aimed to evaluate the potential of routinely used laboratory biomarkers to predict subcutaneous and muscle tissue penetration of moxifloxacin in septic patients.

Methods: We retrospectively analyzed data from 10 septic patients included in a pharmacokinetic study, in which moxifloxacin concentrations in subcutaneous adipose and muscle tissues were measured with microdialysis. We correlated the tissue-to-plasma ratio and protein binding with various clinical biomarkers.

Results: Our results revealed significant correlations for CRP, LDH, BUN, GPT, and total protein with moxifloxacin subcutaneous penetration, and BUN, GOT, and GPT with muscle penetration. Notably, all biomarkers except CRP correlated negatively with tissue penetration. Moreover, we found a positive correlation between moxifloxacin protein binding and total plasma proteins and albumin.

Conclusion: Biomarker tissue correlations suggest that the penetration of moxifloxacin into tissues is a complex process influenced by factors like inflammation, tissue integrity, liver function, protein levels, and renal function. Understanding these interactions might help optimize antibiotic dosing strategies.