Table 1.

Relevant factors that can influence antimicrobial pharmacokinetics in patients receiving renal replacement therapy

Patient-specific factors
Critical illness	Vd ↑
	CL ↑ or ↓ based on renal function or RRT settings
Residual renal function	CL ↑ compared to anuric patients
Hypoalbuminemia	Free drug concentrations ↑
	CL ↑ for highly protein bound drugs
	Vd ↑
Drug-specific factors
Solubility	Hydrophilic drugs more likely to be affected by RRT-related CL
	Lipophilic drugs potentially affected by membrane adsorption
Molecular weight	CL ↑ for low molecular weight drugs
	This may not be a major determinant of drug removal due to the use of high flux hemofilters with large pore size
Protein binding	CL ↑ for low protein bound drugs
Electric charge	CL ↑ for anionic antibiotics (e.g. cefotaxime and ceftazidime) compared to cationic antibiotics (e.g. aminoglycosides) retained in plasma by negatively charged molecules like albumin (Gibbs–Donnan effect)
PK/PD target	RRT-related CL influences maintenance dose for time-dependent antibiotics (e.g. 100%fT>1–4 × MIC)
	RRT-related CL influences dosing frequency for concentration-dependent antibiotics (Cmax/MIC)
	RRT-related CL influences maintenance dose and/or dosing frequency for time- and concentration-dependent antibiotics (AUC/MIC)
RRT-specific factors
RRT modality: Continuous versus Intermittent	Variable elimination rates depending on intra and inter-dialytic phases for IHD
	Relatively constant drug CL depending on RRT intensity for CRRT
RRT technique: Convective versus Diffusive	Higher CL of high molecular weight drugs with convection technique
	Combining convection and diffusion (i.e. CVVHDF) often results in greater drug CL than by convection or diffusion alone at equal RRT doses
Effluent flow rate	Higher CRRT effluent rates resulting in higher CL
Blood flow rate	CL ↑ with high blood flow rate
	Negligible clinical impact for CRRT
Dilution mode	CL ↓ in pre-dilution mode
	Negligible clinical impact
Membrane type/adsorption	Polyacrylonitrile membranes more likely to be associated with drug adsorption (e.g. amikacin, levofloxacin, echinocandins in particular)
	Saturable effect
Hemofilter life span	CL ↓ over time unless circuit components are replaced regularly
Down time	CL ↓ if prolonged circuit downtime

AUC area under the concentration–time curve, CL clearance, C_max maximal drug concentration during a dosing interval, CRRT continuous renal replacement therapy, CVVHDF continuous veno-venous hemodiafiltration, IHD intermittent hemodialysis, MIC minimum inhibitory concentration, RRT renal replacement therapy, PK/PD pharmacokinetic/pharmacodynamics, V_d volume of distribution