Impact of augmented renal clearance on piperacillin and meropenem exposure in critically ill adult burn patients: A prospective observational study

BACKGROUND: Burn patients in the intensive care unit (ICU) are at high risk for pharmacokinetic variability, particularly due to augmented renal clearance (ARC), which can compromise β-lactam antibiotic exposure. We aimed to assess the association of ARC with β-lactam target attainment in a burn ICU population. METHODS: We conducted a prospective observational study between 2023 and 2025 in a tertiary burn ICU. Adult patients treated with meropenem or piperacillin/tazobactam were included and had undergone daily drug level and renal function assessments. Plasma drug levels were quantified by high-performance liquid chromatography (HPLC), renal function was assessed using creatinine clearance based on urine creatinine measurement with ARC defined as creatinine clearance > 130 mL/min. Pharmacodynamic target attainment (TA) was defined as 100% ƒT > MIC against both EUCAST breakpoint and isolate-specific MICs. Antibiotic level measurements with concomitant ARC were compared with those without ARC using Fisher's exact test. RESULTS: Of 85 screened patients, 24 received study antibiotics, yielding 84 samples paired with estimated creatinine clearance and minimum inhibitory concentrations (MICs). Target attainment was significantly higher without ARC: 100.0% vs. 71.4% for 100% ƒT > MIC using isolate MICs (OR 0.019 [0.001-0.38], p < 0.001) and 74.6% vs. 38.1% for 100% ƒT > MIC using breakpoint MICs (OR 0.21 [0.07-0.60], p = 0.004). Exploratory analyses indicated preserved renal function and lower organ failure scores were linked to subtherapeutic levels. CONCLUSIONS: ARC was frequent in critically ill burn patients and was associated with significantly reduced β-lactam target attainment. Although isolate-specific MIC targets were usually achieved, breakpoint-based thresholds were frequently subtherapeutic. Further research is needed to clarify the role of therapeutic drug monitoring and ARC in this high-risk population.