Continuous beta-lactam infusion in critically ill patients: the clinical evidence

Abdul-Aziz, Mohd H; Dulhunty, Joel M; Bellomo, Rinaldo; Lipman, Jeffrey; Roberts, Jason A

doi:10.1186/2110-5820-2-37

Annals of Intensive Care

Table 3 Antibiotic dosage and outcome data of previously published for CI vs. IB of beta-lactam antibiotics

From: Continuous beta-lactam infusion in critically ill patients: the clinical evidence

Study	Types of infection	Number of patients (APACHE score ^a)		Antibiotic dosage regimen		Concurrent PK/PD analysis	Clinical outcome measures	CI	IB	p value
Study	Types of infection	CI	IB	CI	IB	Concurrent PK/PD analysis	Clinical outcome measures	CI	IB	p value
Angus et al. [87]	Melioidosis	10 (15)	11 (21)	12 mg/kg LD, then 4 mg/kg every 1 hr	40 mg/kg every 8 hr	Yes	Mortality	20%	36.4%	0.89
Bodey et al. [89]	Pneumonia, UTI, septicemia and neutropenic fever	167 (ND)	162 (ND)	3 g LD, then 12 g/24 hr	3 g every 6 hr	No	Clinical cure	64.8%	56.5%	ND
Buck et al. [81]	Pneumonia, cholangitis and FUO	12 (ND)	12 (ND)	2 g LD then 8 g/24 hr^b	4 g every 8 hr^b	Yes	Clinical response	67%	67%	ND
Buijk et al. [52]	Intra-abdominal infections	12 (16)	6 (14)	1 g LD then 4.5 g/24 hr	1.5 g every 8 hr	Yes	Mortality	25%	33%	1.0
Georges et al. [80]	Pneumonia and septicemia	24 (45^c)	23 (44^c)	2 g/12 hrs twice daily	2 g every 12 hr	Yes	Mortality	12%	13%	ND^d
							Clinical cure	85%	67%	ND^d
							Duration of MV	24 ± 13	25.3 ± 10	ND^d
							LOS ICU	34 ± 17	40 ± 15	ND^d
Hanes et al. [86]	Pneumonia	17 (13)	14 (11)	2 g LD then 60 mg/kg every 24 hr	2 g every 8 hr	Yes	Duration of MV	22.9 ± 19.9	13.3 ± 6.1	0.16
							LOS ICU	26.8 ± 20.1	15.5 ± 5.9	0.11
							LOS Hospital	41.7 ± 30.5	28.7 ± 15.9	0.37
							Duration of leukocytosis	7.8 ± 7.3	11.3 ± 4.7	0.35
							Duration of pyrexia	7.9 ± 4.4	4.3 ± 2.5	0.06
Kojika et al. [82]	Abdominal abscess	5 (ND)	5 (ND)	0.5 g every 8 hr (over 3 hr)	0.5 g every 8 hr (over 30 min)	No	Mortality	20%	0%
Lagast et al. [88]	Septicemia	20 (ND)	25 (ND)	Day 1: 1 g LD then 3 g/24 hr Day 2 +: 4 g/24 hr	2 g every 12 hr	No	Mortality	25%	16%	ND
Lagast et al. [88]	Septicemia	20 (ND)	25 (ND)	Day 1: 1 g LD then 3 g/24 hr Day 2 +: 4 g/24 hr	2 g every 12 hr	No	Clinical cure	70%	80%	ND
Lau et al. [79]	Abdominal infections	81 (8)	86 (8)	2 g LD then 12 g/24 hr^e	3 g every 6 hr^e	No	Mortality	0.76%	2.6%
							Clinical cure	86.4%	88.4%	0.817
							Adverse events	89.2%	87.1%
Lubasch et al. [83]	Chronic bronchitis	41 (ND)	40 (ND)	2 g LD then 2 g/7 hr twice daily	2 g every 8 hr	Yes	Clinical cure	90.2%	90%	ND^d
Lubasch et al. [83]	Chronic bronchitis	41 (ND)	40 (ND)	2 g LD then 2 g/7 hr twice daily	2 g every 8 hr	Yes	Bacteriological cure	90.2%	87.5%	ND^d
Nicolau et al. [84]	Pneumonia	17 (14)	18 (16)	1 g LD then 3 g/24 hr^f	2 g every 8 hr^f	No	Clinical cure	41%	33%	0.592
							Duration of MV	7.9 ± 4.0	8.3 ± 4.3	0.97
							LOS ICU	8.5 ± 3.4	9.3 ± 4.0	0.691
							Time to defervescence	3.1 ± 2.1	5.2 ± 2.3	0.015
							WBC normalization	7.3 ± 3.0^g	5.5 ± 4.2^g	0.259
Pedeboscq et al. [85]	Gastrointestinal-related infections	3 (ND)	4 (ND)	12 g/24 hr	4 g every 8 hr	Yes	Mortality	0%	0%	ND
Rafati et al. [78]	Pneumonia, UTI, abdominal infections, SSI and septicemia	20 (16)	20 (14)	2 g LD then 8 g/24 hr	3 g every 6 hr	Yes	Mortality	30%	25%	0.72
							Decrease in illness severity			CI > IT^h
							Duration of pyrexia	2.4 ± 1.5	1.7 ± 0.7	0.08
							WBC normalization	75%	83%	ND
Roberts et al. [75]	Septicemia	29 (19)	28 (16)	0.5 g LD then 2 g/24 hr	Day 1: 2.5 g/24 hr Day 2: 2 g/24 hr	No	Mortality	10%	0%	0.25
							Clinical cureⁱ	52%	20%	0.04
							Duration of MV	4.3 ± 4.5	3.4 ± 4.1	0.33
							LOS ICU	10.8 ± 23.2	5.6 ± 6.0	0.29
							LOS hospital	42 ± 6.9	24 ± 2.1	0.34
Sakka et al. [77]	Pneumonia	10 (26)	10 (28)	1 g LD then 2 g/24 hr	1 g every 8 hr	Yes	Mortality	10%	20%	ND
Van Zanten et al. [76]	COPD exacerbations	40 (ND)	43 (ND)	1 g LD then 2 g/24 hr	1 g every 8 hr	Yes	Clinical cure	93%	93%	0.93

APACHE, Acute Physiology and Chronic Health Evaluation score; CI, continuous infusion; IB, intermittent bolus; PK/PD, pharmacokinetic/pharmacodynamic; UTI, urinary tract infection; FUO, fever of unknown origin; SSI, surgical site infection; COPD, chronic obstructive pulmonary disease; ND, not described; LD, loading dose; MV, mechanical ventilation; LOS, length of stay; ICU, intensive care unit; WBC, white blood cells.
^aValues are reported as mean.
^bDose reduction in renal dysfunction-if creatinine clearance 25–60 mL/min (CI group 6.75 g/24 hr; IT group 4.5 g q12hr); if creatinine clearance <25 mL/min (CI group 4.5 g/24 hr; IB group 4.5 g every 24 hr).
^cValues are SAPS II score.
^d P values for nonsignificance were not reported.
^eDose reduction in renal dysfunction-if creatinine clearance 20–40 mL/min (CI group 8 g-1 g/24 hr; IB group 2 g −0.25 g every 6 hr).
^fDose reduction in renal dysfunction-if creatinine clearance 31–50 mL/min (CI group 2.5 g/24 hr; IB group 2 g every 12 hr); if creatinine clearance 21–30 mL/min (CI group 2 g/24 hr; IB group 2 g every 24 hr).
^gx 10⁹/L.
^hSignificant difference in APACHE II scores on days 2, 3, and 4.
ⁱ A priori analysis.

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