Mechanistic and quantitative understanding of antibiotic resistance and adaptation of Escherichia coli under levofloxacin exposure
Abstract
Successful treatment of infectious diseases is increasingly challenging, as emergence and spread of bacterial adaptation and resistance mechanisms threaten the availability of efficacious treatment options. A prerequisite for bacterial eradication and prevention of adaptation and resistance is sufficient antibiotic exposure at target site, which can be obtained by dosing optimisation. For that purpose, a comprehensive understanding of the relationship between pharmacokinetics (PK) and pharmacodynamics (PD), i.e., between antibiotic exposure and effect, is crucial. Currently applied PK/PD parameters and target values are mainly based on the minimal inhibitory concentration (MIC). The informative value of this endpoint measurement is limited, but appropriate alternatives are currently lacking. A comprehensive understanding of exposure-effect relationships requires knowledge about relevant antibiotic resistance and bacterial adaptation mechanisms, which has substantially increased in the last years. However, a link between PK/PD relationships and the underlying mechanisms has not been established yet. Hence, the present thesis aimed to characterise, quantify, and mechanistically explain bacterial growth-kill behaviour over time. The model compound levofloxacin (LEV) and the bacterial species Escherichia coli (E. coli) were chosen for the case study, as life-threatening infections with fluoroquinolone resistant E. coli strains are of clinically relevant concern. To characterise…
Read the paper
Related studies
- Ferulic acid regulates the AKT/GSK-3β/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
- Photochemical behavior of levofloxacin
- Correlation Between Dissolution Profiles of Salt-Form Drugs in Biorelevant Bicarbonate Buffer and Oral Drug Absorption: Importance of Dose/ Fluid Volume Ratio
- Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides
- Synthesis of [11C]levofloxacin
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.