The impact of an ex vivo paediatric renal replacement therapy circuit on antimicrobial concentrations

Critically ill children receiving continuous renal replacement therapy may experience sub-therapeutic concentrations for antimicrobials leading to treatment failure and antimicrobial resistant pathogens. The objective of this study was to determine whether antimicrobial concentrations are reduced by a paediatric continuous renal replacement therapy (CRRT).

An ex vivo closed continuous veno-venous haemodiafiltration was simulated for a 3 kg infant to assess antimicrobial clearance across three ultrafiltration rates (zero, low and high flux). Slow continuous ultrafiltration was used to assess antimicrobial adsorption and recovery over 240 minutes. Controls were included to account for spontaneous drug degradation. This study was conducted in a university research laboratory with no participants. Antimicrobial concentrations were measured using a validated HPLC-MS/MS method.

The antimicrobial filter clearance during high-flux filtration was significantly increased for fluconazole, piperacillin, tazobactam, vancomycin and voriconazole (P < 0.05). The antimicrobial recovery [mean (%)] at 240 minutes in the CRRT model was significantly different from baseline (time zero) for ampicillin 49%, fluconazole 76%, gentamicin (0%) meropenem 51%, piperacillin 54%, vancomycin 31% and voriconazole 47% (P < 0.05). A significant relationship was demonstrated between antimicrobial recovery and molecular charge (R2 = 0.58 P < 0.001) in the CRRT model; no relationships were reported for lipophilicity or protein binding.

The concentrations were reduced in >70% of the study antimicrobials in the ex vivo paediatric CRRT model, as a result of an increase in filter clearance during high-flux filtration or from drug-circuit adsorption. These findings suggests that antimicrobial dosing in critically ill children receiving CRRT requires assessment to determine whether antimicrobial concentrations are therapeutic.