Late Breaking Original Research
Monday, October 14, 2024
01:00 PM–02:30 PM
Abstract
Introduction: Sulbactam-durlobactam is a novel, preferred antibiotic for the treatment of carbapenem-resistant
Acinetobacter baumannii-calcoaceticus (CRAB) infections. Current package labeling and drug databases do not provide dosing guidance for patients requiring continuous renal replacement therapy, but ex vivo studies suggest both drugs are freely cleared. Herein, we present the first pharmacokinetic assessment of sulbactam-durlobactam during continuous venovenous hemofiltration (CVVH) in a patient with CRAB bacteremia and ventilator-associated pneumonia (VAP).
Research Question or Hypothesis: What is the recommended dosing regimen for sulbactam-durlobactam during CVVH?
Study Design: In vivo pharmacokinetic analysis.
Methods: A 59-year-old patient (BMI 60kg/m2) with a prolonged hospitalization in the surgical ICU required CVVH and developed CRAB bacteremia secondary to VAP. Sulbactam-durlobactam 2g q4h infused over 3h was initiated based on ex vivo study guidance and the patient’s prescribed effluent dose. CVVH was performed via NxStage System One with a 1.6m2 polyethersulphone membrane filter. Effluent and blood flow rates were 6L/h and 250ml/min, respectively, with net hourly fluid removal rate of 25ml/h and no residual urine output. The sulbactam-durlobactam MIC for the isolate was determined by reference broth microdilution, and whole genome sequencing (WGS) was performed to characterize resistance mechanisms. Steady-state pre, post-filter blood, and effluent samples were collected on three different dosing intervals to characterize plasma exposure and estimate the sieving coefficient (SC).
Results: The sulbactam-durlobactam MIC was 4/4 mg/L (susceptible). WGS revealed PBP-1b and PBP-3 mutations. The sulbactam and durlobactam SC ranged from 0.59-0.78 and 0.59-0.66, respectively, across three different filters. The selected sulbactam-durlobactam dose achieved 100% T>MIC and resulted in microbiological cure with repeat blood cultures demonstrating CRAB clearance; however, the patient was later transitioned to comfort care.
Conclusion: Sulbactam-durlobactam monotherapy was associated with microbiologic clearance in a patient with CRAB bacteremia and VAP. An aggressive dosing regimen of 2g q4h consistent with the prescribed CVVH effluent rate was successful in achieving high T>MIC exposure in plasma.
Presenting Author
Wesley Kufel PharmDBinghamton University School of Pharmacy and Pharmaceutical Sciences
Authors
Aliaa Fouad Ph.D.
Hartford Hospital
Kathleen Hanrahan PharmD
Arnot Ogden Medical Center
Joseph Kuti PharmD, FCCP, FIDP
Hartford Hospital
Hanna Roenfanz Ph.D.
Hartford Hospital
Ryan Shields PharmD, MS
UPMC Presbyterian Hospital
Nabil Zeineddine MD
State University of New York Upstate Medical University