(527) Beta-Lactam TDM in Critically Ill Patients With Unstable Renal Function

Introduction: Sepsis is common in critically ill patients and the mortality is high. Antibiotics are a fundamental therapy for sepsis. However, the pharmacokinetic/pharmacodynamic (PK/PD) in critically ill patients are commonly altered and the current standard antibiotic dosing regimen was developed in healthy individuals, which may not be appropriate for use among the critically ill population. Further, acute kidney injury (AKI), both in progression or in the phase of recovery along with increased urine output (U/O), significantly affects the elimination of antibiotics and in the meantime, changes the volume of distribution, which further increases the difficulty in estimating the possibility of achieving the target attainment. Therefore, beta-lactam therapeutic drug monitoring (TDM) is recommended by international guidelines to ensure maximum efficacy and minimum safety issues. This study examines the proportion of target attainment achieved by empirical antibiotic dosing regimens during renal impairment.

Methods: This is a prospective observational study. Adults who receive piperacillin/tazobactam, cefepime, or meropenem at ICU who develop AKI, as defined by the KDIGO criteria are eligible for the study. The trough level is obtained after eligible patients receive at least 3 doses of beta-lactam. Serum creatinine, daily U/O, 8-hour urine collection, and cystatin C are obtained for renal function estimation. For a patient with AKI who is in the phase of kidney function recovery, the blood samples will be collected if U/O is more than 0.5 mL/kg/day. If a patient receives renal replacement therapy (RRT), the blood samples will be drawn at least 48 hours apart from the completion of the RRT session.

Results: This study is in the active enrollment stage. The primary objective is to assess the probability of target attainment of beta-lactam. From the preliminary results of 23 evaluable data, at least 80% of patients were able to reach the PK/PD target of 100% T>4xMIC. However, all of the patients had cefepime trough levels in the toxic range.

Conclusions: Beta-lactam TDM is important to identify possible harm in critically ill patients who have AKI. A further investigation may help clinicians find the more appropriate beta-lactam dosing adjustment in critically ill patients who develop AKI.