Amoxicillin-Clavulanate Dosing in the Intensive Care Unit: The Additive Effect of Renal Replacement Therapy in a...

Dosing of amoxicillin-clavulanic acid in critical illness is difficult as β-lactam pharmacokinetics are altered by physiological changes and therapies initiated in the intensive care unit such as renal replacement therapy (RRT). Successful treatment relies on sustaining a free antibiotic concentration above the minimum inhibitory concentration of the target pathogen (fT>MIC). We present a case of a patient treated with amoxicillin-clavulanic acid (1.2 g for 8 h) for an aspiration pneumonia. Dosing in this case was complicated by the necessity for RRT to treat a drug overdose with carbamazepine, despite normal native renal function. Antibiotic concentrations taken at steady state revealed a clearance of 14.6 L/h and a low fT>MIC (<40%). Analysis of the urine drug concentration suggested that 48% of clearance was via the native kidneys. This case illustrates that careful consideration of antibiotic dose and frequency is required in critically ill patients receiving RRT and highlights the need for further research in this patient group. In future similar cases, we would consider a dose of 2.2 g 6- or 8-hourly with early therapeutic drug monitoring.