Effectiveness of Beta-Lactams Adjusted Based on Cystatin C for Treatment of Gram-Negative Infections

Introduction: Gram-negative infections cause significant morbidity and mortality in critically ill adult patients. Serum creatinine (SCr) as a marker of drug clearance can be unreliable in these patients leading to imprecise antibiotic dosing. Cystatin C estimated glomerular filtration rate (eGFR) may be advantageous when there are discrepancies with SCr-guided dose adjustments. This study aims to evaluate the clinical effectiveness of utilizing cystatin C eGFR in critically ill patients to renally dose antibiotics for treatment of gram-negative bacteremia, pneumonia, or urinary tract infections.


Methods: This was a retrospective, single-center, cohort study. Adult medical intensive care unit (ICU) patients were eligible for inclusion if they used cystatin C eGFR for cefepime, piperacillin-tazobactam, or meropenem dose adjustments, had one positive culture (blood, respiratory, or urinary) for a gram-negative organism(s) or were treated for pneumonia based off clinical signs and symptoms. The primary outcome was treatment failure, defined as: escalation of antibiotics after 48 hours; mortality due to sepsis prior to treatment course completion; or re-initiation of antibiotics within 48 hours of completion. Safety outcomes included acute kidney injury (AKI) incidence, confirmed Clostridioides difficile infection, and suspected beta-lactam encephalopathy.


Results: From June 1, 2022, to June 30, 2024, 337 patients were assessed for inclusion and 19 patients were included. Four patients (21.1%) met the primary outcome of treatment failure. Three out of these 4 patients expired prior to treatment completion. One patient restarted antibiotics within 48 hours. ICU mortality occurred more often in the treatment failure group than in the treatment success group (100% vs 33%, p=0.033). One AKI occurred in the treatment success group (6.7%). Three patients in the treatment success group (20%) were tested for C. difficile, but none met confirmed C. difficile infection criteria. There were no incidences of beta-lactam encephalopathy.


Conclusions: Antibiotic dose adjustments with cystatin C eGFR resulted in a low rate of treatment failure. Cystatin C eGFR may be a safer and more reliable strategy to dose antibiotics in chronically critically ill patients, in whom SCr may no longer be a dependable marker of renal function.