Are Antibiotics Appropriately Dosed in Critically Ill Patients with Augmented Renal Clearance? A Narrative Review

Table 2

A summary of key pharmacodynamic thresholds of antibiotics [4, 20, 49, 57].

Antibiotics	Bacterial killing characteristics^†	Pharmacodynamic indices^‡	Pharmacodynamic targets
Beta-lactams	a	% fT > MIC^§; % fT > 4  MIC (in critically ill patients)	Penicillin: 50%–60%; Cephalosporin: 60%–70%; Carbapenem: 40%–50%
Aminoglycosides	b	Cmax/MIC ratio	(i) Cmax/MIC ≥8–10; (ii) AUC0–24/MIC >70; (iii) Trough concentration: Amikacin < 2 mg/L; Gentamycin and tobramycin <0.5 mg/L
Fluoroquinolones	b	AUC0–24/MIC ratio^¥	Ciprofloxacin ≥125; Levofloxacin ≥80
Glycopeptides	c	AUC0–24/MIC ratio	Vancomycin: (i) AUC0–24/MIC 400; (ii) Trough concentrations between 10 and 20 mg/L; Teicoplanin: Trough concentration: (iii) Total between 20 and 60 mg/L; (iv) Unbound 1.5 mg/L
Linezolid	c	AUC0–24/MIC ratio; % fT > MIC	(i) AUC0–24/MIC = 80–120; (ii) fT > MIC >85%; (iii) Trough concentration between 2 and 10 mg/L
Colistin	c	AUC0–24/MIC ratio	Steady-state concentration 2 mg/L

^†Bacterial killing characteristics of antibiotics: a: time-dependent agents, b: concentration-dependent agents, and c: concentration- and time-dependent agents; ^‡pharmacodynamic indices: best parameters to predict the antibacterial activity of antibiotics and their correlation with clinical efficacy; ^§% fT > MIC: duration of time that the free drug plasma concentration remains above the minimum inhibitory concentration (MIC) of each pathogen; Cmax/MIC ratio: maximum concentration of antibiotic relative to the pathogen MIC; ^¥AUC0–24/MIC ratio: area under the plasma concentration-time curve over 24 hr relative to the pathogen MIC.