Clinician decision-making for polymyxin dosing in critically ill patients with renal impairment: a qualitative study

Polymyxin remain essential last-line agents for the treatment of multidrug-resistant gram-negative infections in critically ill patients. However, dosing polymyxin B and colistin in patients with renal impairment is clinically challenging due to complex pharmacokinetics, fluctuating renal function, toxicity concerns and limited implementation of therapeutic drug monitoring. While pharmacokinetic and guideline-based recommendations exist, little is known about how clinicians navigate these complexities in real-world practice. We conducted an inductive qualitative study using semi-structured interviews with physicians involved in the management of critically ill patients with severe gram-negative infections. Participants were purposively sampled from critical care, nephrology, infectious diseases and general medicine. Interviews explored experiences and decision-making related to polymyxin selection, dosing adjustments, renal dysfunction, renal replacement therapy, safety monitoring and institutional influences. Transcripts were analysed using a constructivist grounded theory approach, following iterative coding, constant comparison and theme development. Coding and analysis were performed using ATLAS.ti software. Reporting adhered to the COREQ checklist. Seventeen physicians were interviewed. Analysis yielded six interrelated themes: 1. Clinical determinants of polymyxin selection, 2. Individualized and adaptive dosing practices, 3. Renal dysfunction and renal replacement therapy-related uncertainty, 4. Safety-driven decision-making, 5. Monitoring, diagnostic, and evidence limitations, and vi. Institutional and system-level influences. Clinicians described polymyxin dosing as a dynamic experience-driven process requiring continuous reassessment and risk-benefit negotiation. Renal function variability, lack of therapeutic drug monitoring, and absence of standardized institutional protocols contributed to cautious and heterogenous dosing practices, particularly in patients receiving dialysis. Polymyxin dosing in critically ill patients with renal impairment is shaped by complex clinical judgement, safety concerns and systemic constraints rather than rigid adherence to dosing algorithms. These findings highlight a gap between pharmacokinetic evidence and bedside practice and underscore the need for pragmatic, context-appropriate dosing guidance, multidisciplinary stewardship support and decision-support tools to optimize polymyxin use in high-risk populations.