Removal of common antimicrobial agents by sustained low-efficiency dialysis

Abstract

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 (t_1/2) on-SLED and off-SLED, and the fraction of removal by SLED (f_D). 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 t_1/2 on-SLED was substantially lower than the off-SLED t_1/2 for all antimicrobials, and the SLED f_D 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.

Keywords: antimicrobials; end-stage kidney disease; kidney; pharmacokinetics; sustained low-efficiency dialysis.

Fig 1

Meropenem concentration vs time profile (patient #16). Meropenem concentrations measured during both on-SLED and off-SLED study periods.

Fig 2

Antimicrobial clearance reported for IHD, CKRT, and SLED (6–17). SLED data from this study. Antimicrobials: C= cefepime (6, 7), D=daptomycin (8, 9), M=meropenem (10, 11), P= piperacillin (12, 13), T=tazobactam (13, 14), and V=vancomycin (15, 16). ^*Meropenem clearance by IHD reported for a low flux filter.

Fig 3

Suggested antimicrobial dosing regimens for SLED performed daily.^{* *}Base dosing on the estimated kidney function of the patient on non-SLED days. ^**Extended infusion method may be used. Higher doses may be warranted depending on severity of infection and source. BFR, blood flow rate; DFR, dialysate flow rate; LD, loading dose; SLED, sustained low efficiency dialysis; TDM, therapeutic drug monitoring.