(1057) Precision Medicine in Sepsis: Carbapenem Therapeutic Drug Monitoring in the Burn ICU

Introduction: Burn injured patients demonstrate alterations in pharmacokinetics (PK). A method to improve PK parameters is to use therapeutic drug monitoring (TDM) for precise dosing of antibiotics in the treatment of sepsis. This case report describes serum and tissue TDM for dosing of carbapenems in a burn injured patient with acute renal failure.

Description: A 58 year old woman, 59 kg, assaulted by immolation resulted in 45% total body surface area burn involving face, neck, chest, abdomen, four extremities. On day 4, wound changes prompted 0.25% sodium hypochlorite topical care. Fever, hypotension, and arrhythmias followed prompting cultures (blood, bronchoalveolar lavage (BAL)), chest X-Ray and broad spectrum antibiotics per hospital antibiogram. 24 hours later, patient progressed to acute renal failure requiring renal replacement. Blood and BAL grew Pseudomonas aeruginosa (Minimum Inhibitory Concentration (MIC) < 1 ug/mL) and ESBL Klebsiella pneumoniae (MIC < 1 ug/mL); meropenem continued for 16 days. Initial serum meropenem level was obtained after 2 g dose over 30 minutes with peak of 77 ug/mL and trough level of 44 ug/mL. Meropenem TDM was obtained at steady state - 82 ug/mL. Lung aspirate was obtained for TDM with peak of 62 ug/mL. The patient had resolution of sepsis markers, pressors weaned and ventilation improved.

Discussion: Carbapenems are time above MIC dependent for antimicrobial killing. When serum concentrations fall beneath MIC, bacterial proliferation occurs immediately1,2 MIC thresholds for a 1 g / 2 g dose of meropenem are 112 ug/mL and >200 ug/mL. The significant decrease in serum peak concentrations in the burn patient could be due to increased clearance due to CRRT, less albumin binding of the drug, loss of the drug via the wound bed or increased volume of distribution (Vd) from third spacing of the free-unbound drug. In contrast, tissue penetration was observed with excellent mucosal MIC of 62 ug/mL (literary bronchial MIC range between 1.3 to 11.1 ug/mL).3,4 So, despite our reduced serum peak concentration after loading, adequate steady state and elevated tissue level penetration correlated well with resolution of sepsis. This is a case utilizing TDM for precision dosing of antibiotics in the treatment of sepsis in a critical burn patient with acute renal failure.