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.