Removal of common antimicrobial agents by sustained low-efficiency dialysis

• Published in: Antimicrobial agents and chemotherapy 2024-03, Vol.68 (3), p.e0157923
• Main Authors: Hudson, Joanna Q, Hilgers, Madelyn N, Gosmanova, Elvira O
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Adult; Aged; Anti-Bacterial Agents; Cefepime - therapeutic use; Clinical Therapeutics; Critical Illness; Daptomycin - therapeutic use; Female; Humans; Hybrid Renal Replacement Therapy; Male; Meropenem - therapeutic use; Middle Aged; Pharmacology; Piperacillin, Tazobactam Drug Combination - therapeutic use; Renal Dialysis; Retrospective Studies; Vancomycin - therapeutic use
• ISSN: 0066-4804; 1098-6596; 1098-6596
• DOI: 10.1128/aac.01579-23

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin-tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for 8 hours during SLED (on-SLED). Arterial samples were collected every 2 hours for up to 6 hours while not receiving SLED (off-SLED) for the calculation of SLED clearance, half-life ( ) on-SLED and off-SLED, and the fraction of removal by SLED ( ). Twenty-one patients completed the study: 52% male, mean age (±SD) 53 ± 13 years, and mean weight of 98 ± 30 kg. Eighty-six percent had AKI, and 4 patients were receiving cefepime, 3 daptomycin, 10 meropenem, 6 piperacillin-tazobactam, and 13 vancomycin. The average SLED time was 7.3 ± 1.1 hours, and the mean ultrafiltration rate was 95 ± 52 mL/hour (range 10-211). The on-SLED was substantially lower than the off-SLED for all antimicrobials, and the SLED varied between 44% and 77%. An 8-hour SLED session led to significant elimination of most antimicrobials evaluated. If SLED is performed, modification of the dosing regimen is warranted to avoid subtherapeutic concentrations.