Abx hydrophilic and lipophilic drugs

hydrophilic agents

Beta-lactams

Aminoglycosides

Glycopeptides

Daptomycin

Polymyxins

lipophilic agents

Quinolones

Macrolides

Rifampin

Linezolid

Tetracyclines

hydrophilic agents characteristics

small Vd -> less tissue penetration

mostly renally cleared -> drug accumulation and SE can occur if not dose adjusted

low intracellular concentrations -> not active against atypical (intracellular) pathogens

poor bioavailability -> IV:PO not 1:1

lipophilic agents characteristics

large Vd -> better tissue penetration

mostly hepatically metabolized -> potential for hepatotoxicity and DDIs

achieve higher intracellular concentrations

excellent bioavailability -> IV:PO is often 1:1

Cmax:MIC (concentration-dependent)

aminoglycosides, quinolones, daptomycin

Cmax:MIC goal

high peak (more killing), low trough (less toxicity)

dosing strategies: large dose, long interval

AUC:MIC (exposure dependent) goal

exposure over time

dosing strategies are variable

AUC:MIC (exposure-dependent) antibiotics

vancomycin, macrolides, tetracyclines, polymyxins

Time > MIC (time-dependent) goal

maintain drug goal > MIC for most of the dosing interval

dosing: shorter dosing interval, extended or continuous infusions

time > MIC antibiotics

beta lactams (PCNs, cephalosporins, carbapenems)