Quantification of Antibiotic Concentration at the Site of Infection: Analytical Challenges and Current Practices

BACKGROUND: Quantifying antibiotic concentrations at infection sites is challenging because of invasive sampling and complex matrices. Despite limited knowledge, target-site data are crucial for optimizing dosing, minimizing resistance, ensuring safer strategies, and reducing toxicity risks through adequate target attainment. METHODS: This review aims to provide an overview of the most commonly reported challenges associated with quantifying target-site concentrations of antibiotics. Antibiotics were selected as the focus because of their use in hospital and outpatient settings. An extensive literature search was conducted using Embase.com. After title and abstract screening of 828 articles, 398 articles were included for full-text screening, and 72 were included based on relevance to analytical challenges in target-site quantification. Reported challenges were categorized in subgroups: sampling difficulties, sample heterogeneity, unavailability of free drug concentrations, drug complexities, and others. RESULTS: Direct measurement of antibiotic concentrations at infection sites is constrained by invasive procedures and complex analytical methods. Key challenges include sampling heterogeneity, difficulty in obtaining samples, and the lack of free drug concentration data. Several opportunities have been proposed to address these challenges. CONCLUSIONS: We recommend updating international validation guidelines to include standardized tissue sampling protocols, encouraging the commercial sectors to develop reference standards and blank materials for alternative matrices, and promoting the use of minimally invasive techniques, such as microneedle biosensors, to improve the accuracy and safety of target-site quantification. These advances offer promising avenues to enhance antimicrobial therapy optimization despite current.