Antimicrobial dosing considerations in critically ill patients with acute kidney injury: A review

Table 1 Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antibiotics

Antibiotics	PK/PD index	PK profile	Renal clearance (%)	Suggested CKRT dosing
β-lactam (prolonged infusion strategies should be used with drug/brand specific stability data)
Aztreonam	%T > MIC	MW: 435[100]; PB: 56%; Vd: 0.15-0.18 L/kg	60-70	2 g every 8 hours
Cefepime	%T > MIC	MW: 481; PB: 20%; Vd: 0.3 L/kg	85	2 g every 8-12 hours
Ceftazidime	%T > MIC	MW: 547; PB < 10%; Vd: 0.28-0.4 L/kg	60-85	2 g every 8 hours
Imipenem/cilastatin	%T > MIC	MW: 317/380; PB: 20/40%; Vd: 0.22-0.24 L/kg	20-70/60	500 mg every 6-8 hours
Meropenem	%T > MIC	MW: 383; PB: 2%; Vd: 0.35 L/kg	70	1-2 g every 8 hours
Piperacillin-tazobactam	%T > MIC	MW: 518/300; PB: 26-33/31%-32%; Vd: 0.24/0.40 L/kg	75-90/65	4.5 g every 8 hours
Novel agents BL/BLI (prolonged infusion strategies should be used with drug/brand specific stability data)
Cefiderocol	%T > MIC	MW: 752; PB: 40%-60%; Vd: 18 L	90	1.5 g every 12 hours to 2 g every 8 hours[17]
Ceftazidime-avibactam	%T > MIC	MW: 637/265; PB: < 10%; Vd: 14-17 L	80-90	1.25 g every 8 hours
Ceftolozane-tazobactam	%T > MIC	MW: 765/322; PB: 16%-21%; Vd: 13-18 L	66	1.5 g every 8 hours, 1.5-3 g every 8 hours[17]
Imipenem-relebactam	%T > MIC	MW: 317/366; PB: 20%; Vd: 24 L	63	1.25 g single dose, followed by 0.75 g every 6 hours
Meropenem-vaborbactam	%T > MIC	MW: 437/297; PB: 2%; Vd: 19 L	40-60	2 g every 8 hours
Aminoglycosides (aminoglycosides dosing recommendations are in the context of systemic gram-negative infections)
Amikacin	Cmax/MIC	MW: 586; PB: 0%-11%; Vd: 0.22-0.5 L/kg	95	15-25 mg/kg every 48 hours with TDM; 25 mg/kg every 48 hours combined with TDM[50]
Gentamicin	Cmax/MIC	MW: 478; PB: < 30%; Vd: 0.36 L/kg	95	3-5 mg/kg every 24-48 hours with TDM; 7 mg/kg every 24 hours with high dose of 40 mL/kg/hour CKRT dose[53]
Glycopeptides
Vancomycin	AUC24/MIC	MW: 1448; PB: 55%; Vd: 0.47-1.1 L/kg	90-100	Load 20-25 mg/kg followed by 7.5-10 mg/kg every 12 hours with AUC monitoring[58]
Fluoroquinolones
Ciprofloxacin	AUC24/MIC	MW: 331; PB: 20-40%; Vd: 2.5 L/kg	50-70	400 mg IV every 8-12 hours
Levofloxacin	AUC24/MIC	MW: 361; PB: 24-38; Vd: 1.1-1.5 L/kg	67-87	750 mg IV once followed by 750 mg IV every 24 hours with effluent flow rates > 20 mL/kg/hour[11]
Lipopeptides
Daptomycin	AUC24/MIC	MW: 1620; PB: 90%-93%; Vd: 0.1-0.13 L/kg	78	6 mg/kg every 24 hours; 8-10 mg/kg every 24 hours[49,61]

Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antibiotics[17,25,98,99]. PK: Pharmacokinetic; PD: Pharmacodynamic; CKRT: Continuous kidney replacement therapy; MIC: Minimum inhibitory concentration; MW: Molecular weight; Vd: Volume of distribution; PB: Protein binding; BL/BLI: Β-lactam/β-lactamase inhibitor; C_max: Maximal plasma concentration; TDM: Therapeutic drug monitoring; AUC24/MIC: 24-hour area under the concentration time curve to minimum inhibitory concentration; AUC: Area under the curve.

Table 2 Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antivirals

Antivirals	PK/PD index	PK profile	Renal clearance (%)	Suggested CKRT dosing
Acyclovir	No data	MW: 225; PB: 15%; Vd: 0.8 L/kg	62-91	5-10 mg/kg/dose IV every 12-24 hours (high-flux dialyzers and effluent flow rates of 20-25 mL/kg/hour)
Ganciclovir	No data	MW: 255; PB: 1%-2%; Vd: 0.7 L/kg	80-99	2.5 mg/kg/dose IV every 24 (induction dose)
Foscarnet	No data	MW: 300; PB: 14%-17%; Vd: 0.5 L/kg	28 as unchanged in the urine	30 mg/kg IV every 12 hour (CVVH; hemofiltration rate of 3000 mL/hour)[74]
Oseltamivir[75]	No data	Oseltamivir carboxylate; MW: 284.4; PB: 3%; Vd: 23 L	> 99	75 mg once a day (CVVHD; effluent flow rates used in the study (3300 ± 919 mL/hour)
Remdesivir	No data	MW: 602.6; PB: 88%-93.6%; Vd: Low tissue distribution	Remdesivir: 10; GS-441524: 49	200 mg IV loading dose, followed by 100 mg daily

Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antivirals[98,99]. PK: Pharmacokinetic; PD: Pharmacodynamic; CKRT: Continuous kidney replacement therapy; MW: Molecular weight; Vd: Volume of distribution; CVVHD: Continuous veno-venous hemodialysis; CVVH: Continuous veno-venous hemofiltration.

Table 3 Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antifungals

Antifungals	PK/PD index	PK profile	Renal clearance (%)	Suggested CKRT dosing
Echinocandins[99]
Anidulafungin	AUC24/MIC	MW: 1140.3; PB: > 99%; Vd: 30-50 L	< 1	No dosage adjustment necessary (poorly dialyzed)
Caspofungin	AUC24/MIC	MW: 1213.42; PB: 97%; Vd: 9.7 L	Approximately 1% of total dose as unchanged drug	No dosage adjustment necessary (poorly dialyzed)
Micafungin	AUC24/MIC	MW: 1292.26; PB: > 99%; Vd: 0.39 L/kg	< 1	No dosage adjustment necessary (poorly dialyzed)
Azoles
Fluconazole	AUC24/MIC	MW: 306; PB: 11%-12%; Vd: 0.6 L/kg	80%	For recommended dose of 400 mg once daily, to give 800 mg loading dose, followed by maintenance doses of 800 mg/day in 1 to 2 divided doses
Voriconazole	AUC24/MIC	MW: 349; PB: 58%; Vd: 4.6 L/kg	< 2	No dosing adjustment necessary
Isavuconazole	AUC24/MIC	MW: 437; PB: > 99%; Vd (IV): 450 L	< 1	No dosing adjustment necessary
Polyenes
Amphotericin B deoxycholate	Cmax/MIC	MW: 924; PB: 90%; Vd: 4 L/kg	< 5	No dosage adjustment necessary (unlikely dialyzed)

Pharmacokinetic/pharmacodynamic profiles and continuous kidney replacement therapy dosing recommendations for selected antifungals[98]. Drug dosing from UpToDate unless otherwise specified. Molecular weight units are in Daltons. PK: Pharmacokinetic; PD: Pharmacodynamic; CKRT: Continuous kidney replacement therapy; MIC: Minimum inhibitory concentration; MW: Molecular weight; Vd: Volume of distribution; C_max: Maximal plasma concentration; AUC24/MIC: 24-hour area under the concentration time curve to minimum inhibitory concentration.