Table 4.

Patho-physiological changes and their effects on antibiotic PK.

Changes	Effect on Drug PK
Impaired absorption	Reduced bioavailability of orally administered antibiotics
Hypoalbuminemia	Increased Vd and clearance of highly bound (>80%) antibiotics with increased risk of failing to attain PK/PD targets
Obesity	Increased Vd and changes in hepatic metabolism and renal excretion, especially in hydrophilic antimicrobials (e.g., β-lactams, vancomycin). Lack of specific dosing recommendations for antibiotics in obese patients
Renal failure	Impaired clearance of hydrophilic antibiotics with augmented risk of joining over-therapeutic plasma concentrations and undergoing drug-related toxicity (β-lactams, aminoglycosides)
Hyperfiltration	Increased clearance of hydrophilic antibiotics with increased risk of reaching sub-therapeutic plasma concentrations (β-lactams)
Modified fluid balance (increased capillary leakage)	Increasing extracellular fluid volume causing the augmentation of the drug Vd and reducing plasma drug concentrations, particularly in case of the hydrophilic antibiotics with low Vd (aminoglycosides, β-lactams)
Clearance related to CVVH (DF)	CRRT (continuous renal replacement therapy) is associated with increased Vd and clearance of hydrophilic antibiotics