Serum concentrations and pharmacokinetics of linezolid in critically ill patients dialyzed by ADVanced Organ Support compared to conventional continuous renal replacement therapy.

BACKGROUND

Dosing of antibiotics proves to be both crucial and especially challenging in critically ill patients due to extracorporeal therapies. In this exploratory study, we compared the influence of the albumin based ADVanced Organ Support (ADVOS) system to conventional continuous venovenous hemodialysis (CVVHD) on linezolid serum concentrations.

METHODS

A total of 14 critically ill patients (8 ADVOS, 6 CVVHD) receiving linezolid 600 mg twice daily were analyzed, comprising 22 measurement cycles. Machine clearance was calculated by pre- and post-filter concentrations; total and patient clearance were estimated by area under the curve (AUC) calculations. Linezolid pharmacokinetics were evaluated by Cmin and estimated AUC24, considering target ranges. All parameters were compared between dialysis types.

RESULTS

Machine clearance was significantly higher in ADVOS than in CVVHD (median 3.4 vs. 1.6 L/h, p < 0.001), accounting for a higher share of total clearance (38.1% vs. 18.2%). Total clearance (9.3 vs. 10.4 L/h) and patient clearance (6.7 vs. 8.4 L/h) did not differ significantly, nor did AUC24 (250.9 vs. 221.2 mg·h/L) or Cmin (4.6 vs. 4.0 mg/L). A substantial proportion of subtherapeutic serum concentrations was observed in both groups (45.5% by AUC24 and 31.8% by Cmin).

CONCLUSION

This in-vivo study provides real-life data of linezolid levels in ICU-patients treated with conventional CVVHD and ADVOS. The high occurrence of subtherapeutic serum concentrations and a significant difference in dialysis capacities depending on dialysis type indicate the necessity of a tailored therapeutic drug monitoring approach in this vulnerable population.