ICU · Pharmacology

Antibiotic pharmacokinetics in critical illness

Also known as Antibiotic dosing in ICU · Augmented renal clearance (ARC) · Volume of distribution in sepsis · Beta-lactam therapeutic drug monitoring

Critical illness alters antibiotic pharmacokinetics (PK), often leading to sub-therapeutic levels and treatment failure. Key changes: (1) Increased volume of distribution (Vd) — capillary leak, fluid resuscitation, hypoalbuminaemia dilute water-soluble drugs (beta-lactams, aminoglycosides). (2) Augmented renal clearance (ARC) — young trauma/sepsis patients have increased renal blood flow → enhanced clearance of renally eliminated drugs → sub-therapeutic levels. (3) Organ failure — renal/hepatic impairment reduces clearance → accumulation → toxicity. (4) CRRT — removes drugs, need dose adjustment. (5) ECMO — sequesters drugs in circuit, increases Vd. Principles: give LOADING DOSE for severe infections (especially beta-lactams — target 4-5x MIC). Consider extended/continuous infusion for beta-lactams (time-dependent killing). Monitor levels (TDM) for vancomycin, aminoglycosides, beta-lactams.

Checked against its sources on 1 Oct 2026