Renal Dosing of Antibiotics: Are We Jumping the Gun?

Abstract

Antibiotic renal dose adjustments are determined in patients with stable chronic kidney disease and may not translate to patients in late-phase trials and practice. Ceftolozane/tazobactam, ceftazidime/avibactam, and telavancin all carry precautionary statements for reduced clinical response in patients with baseline creatinine clearance of 30-50 mL/min, potentially due to unnecessary dose reduction in the setting of acute kidney injury (AKI). In this review, we discuss the regulatory landscape for antibiotics eliminated by the kidney and highlight the importance of the first 48 hours of therapy. Using a clinical database, we identified AKI on admission in a substantial proportion of patients with pneumonia (27.1%), intraabdominal (19.5%), urinary tract (20.0%), or skin and skin structure infections (9.7%) that resolved by 48 hours in 57.2% of cases. We suggest that deferred renal dose reduction of wide therapeutic index antibiotics could improve outcomes in patients with infectious diseases.

Keywords: acute kidney injury; creatinine clearance; kidney function; precision medicine; regulatory science.