Table 3.

Plasma and epithelial lining fluid concentrations of β-lactams in critically ill patients

Antibacterial agent	Dosage regimen	Patients [n]	Sampling time [h]a	ELF to plasma ratio based on AUC	Plasma concentration [µg/mL]b	ELF concentration [µg/mL]b	References
Piperacillin/tazobactam	Piperacillin 4 g IV over 30 min q8h (q12h if CLCR < 20 mL/min)	16	Between 7.88 and 148.33c	0.49d	Range: 5.26–241.62	Range: 0.14–295.43	[47]
	Tazobactam 0.5 g IV over 30 min q8h (q12h if CLCR < 20 mL/min)	16	Between 7.88 and 148.33c	1.21d	Range: 3.24–33.90	Range: 0.62–62.48
Ceftazidime	Intermittent infusion: 20 mg/kg IV over 30 min q8h	17	44e	ND	95 and 6f	6.0	[50]
	CI: 20 mg/kg IV over 30 min loading dose, followed by 60 mg/kg/day IV CI	17	44e	ND	27.0	12.0
Cefiderocol	2 g IV (1.5 g if renally impaired) over 3 h q8h (q6h if CLCR >120 mL/min) for 6–9 doses	7	1	ND	60.3g	NC	[52]
		7	3		80.8g	7.63g,h
		7	5		56.3g	10.4g,i
		7	7		44.6g	NC
Ceftolozane/tazobactam	Ceftolozane 2 g IV over 1 h q8h if CLCR >50 mL/min (1 g IV over 1 h q8h if CLCR 30–50 mL/min; 500 mg IV over 1 h q8h if CLCR 15–29 mL/min) for 4–6 doses	5	1	0.50j	NR	NR	[53]
		5	2		NR	NR
		5	4		NR	NR
		4	6		NR	NR
		3	8		NR	NR
	Tazobactam 1 g IV over 1 h q8h if CLCR >50 mL/min (500 mg IV over 1 h q8h if CLCR 30–50 mL/min; 250 mg IV over 1 h q8h if CLCR 15–29 mL/min) for 4–6 doses	5	1	0.62k	NR	NR
		5	2		NR	NR
		5	4		NR	NR
		4	6		NR	NR
		3	8		NR	NR
Meropenem	2 g or 500 mg IV over 3-h infusion q8h or 1 g IV over 30 min q8h	17	NR	0.25l	NR	NR	[55]
Meropenem	1 g IV over 30 min q8h	5	0	0.20m	NR	NR	[56]
		5	0.5		NR	NR
		5	1		NR	NR
		5	3		NR	NR
		5	4		NR	NR
		5	6		NR	NR
	1 g IV over 3 h q8h	5	0	0.29m	NR	NR
		5	1		NR	NR
		5	3		NR	NR
		5	4		NR	NR
		5	6		NR	NR
Meropenem	Loading dose of 2 g IV over 15 min followed by 3 g/day CI	15	0	0.32m	12.9	NC	[57]
		15	1.5		13.4	NC
		15	3		13.3	NC
		15	6		11.7	3.9
		15	8		12.3	NC
	Loading dose of 2 g IV over 15 min followed by 6 g/day IV CI	15	0	0.36m	23.0	NC
		15	1.5		23.9	NC
		15	3		21.4	NC
		15	6		22.4	6.6
		15	8		18.9	NC
Doripenem	500 mg IV over 1 h	2	0	0.29	NR	NR	[58]
		2	2		NR	NR
		2	4		NR	NR
		2	6		NR	NR
	500 mg IV over 4 h	2	0	0.21	NR	NR
		2	2		NR	NR
		2	4		NR	NR
		2	6		NR	NR

ELF epithelial lining fluid, AUC area under the concentration-time curve, IV intravenously, CL_CR creatinine clearance, CI continuous intravenous infusion, ND not determined, NC no samples collected at this time, NR not reported, qxh every x hours

^aSampling time after the last dose

^bValues expressed as median

^cSample collection occurred throughout therapy

^dMedian value for the ratio of AUC in ELF to AUC in unbound plasma, assuming 30% protein binding in plasma

^eSampling time was at steady-state (44 h after starting therapy)

^fMaximum and minimum ceftazidime concentration, respectively

^gValues expressed as geometric mean

^hFour patients had an ELF concentration at 3 h

ⁱThree patients had an ELF concentration at 5 h

^jBased on the ratio of AUC₈ in ELF to AUC₈ in unbound plasma, assuming 21% protein binding in plasma

^kBased on the ratio of AUC₈ in ELF to AUC₈ in unbound plasma, assuming 30% protein binding in plasma

^lMedian value for the ratio of AUC in ELF to AUC in total plasma

^mBased on the ratio of AUC₂₄ in ELF to AUC₂₄ in total plasma

ⁿCalculated from the reported values of AUC₈ in ELF and total plasma