.jpg "Benjamin August, PharmD, BCCCP photo")
Benjamin August, PharmD, BCCCP
Critical Care Pharmacist
Henry Ford Hospital
Detroit, MI
Disclosure information not submitted.
Nicholas Pauley, PharmD
PGY2 Solid Organ Transplant Pharmacy Resident
Henry Ford Hospital, United States
Disclosure information not submitted.
Meagan Conrath, PharmD
PGY2 Solid Organ Transplant Pharmacy Resident
Massachusetts General Hospital, United States
Disclosure information not submitted.
Joseph Johnson, PharmD, BCCCP
Critical Care Pharmacist
Henry Ford Hospital, United States
Disclosure information not submitted.
Zachary Smith, PharmD, BCPS, BCCCP,
Critical Care Pharmacist
Henry Ford Hospital
Detroit, Michigan, United States
Disclosure information not submitted.
Title: Early Antipseudomonal Beta-Lactam Renal Dose Adjustment in Sepsis and Acute Kidney Injury
INTRODUCTION/HYPOTHESIS: Recommendations for dose reductions in beta-lactams due to renal impairment are made by manufacturers based on pharmacokinetic studies in chronic kidney disease (CKD), but not in those with acute kidney injury (AKI). Many patients with sepsis experience transient AKI that resolves upon fluid resuscitation. Early creatinine clearance (CrCl) estimates may not correspond to actual renal function and lead to insufficient dosing in sepsis. The purpose of this investigation was to characterize antibiotic dosing in patients with sepsis and AKI.
Methods: This was an IRB approved, retrospective, observational study of patients with AKI and sepsis or septic shock treated with cefepime, piperacillin-tazobactam, or meropenem who were admitted to the intensive care unit (ICU) at a large academic center from 1/1/2018 to 12/31/2019. AKI was defined using KDIGO criteria. Patients with KDIGO stage 3a CKD or higher, receiving dialysis, or lacking daily serum creatinine were excluded. The primary outcome was the percentage of patients on maximal dose therapy on each study day. The observation period began on the first ICU admission day and continued through the third ICU admission day. Conservative versus maximal dosing was defined by an institutional protocol based on CrCl, which was calculated with the last creatinine of the day. Secondary endpoints included percentage of patients with resolution of AKI per KDIGO criteria by the end of the study period. Descriptive statistics were used for statistical analysis.
Results: 245 patients were screened and 37 were included in the analysis. A total of 62% of patients were male and 51% required vasopressors over the study period. For the primary outcome on study day 1, 2, and 3, the percentage of patients on maximal dose therapy was 68%, 76%, and 89%, respectively. All patients received cefepime or piperacillin-tazobactam and each accounted for about half of therapies administered. A total of 67.5% suffered in-hospital mortality. Approximately half of patients experienced AKI resolution by the end of day 3.
Conclusions: Nearly one-third of patients with sepsis and AKI received less than maximal dose antipseudomonal beta-lactam therapy at the end of their first ICU admission day. Further research is needed to optimize early antimicrobial dosing in sepsis with AKI.