Augmented renal clearance is associated with inadequate antibiotic pharmacokinetic/pharmacodynamic target in Asian ICU population: a prospective observational study

Figures & data

Table 1 Demographic and clinical characteristics of enrolled patients

	Total patients (N=100)	ARC (N=46)	Non-ARC (N=54)	p-value
Age (years)	60 (47, 71)	52 (44, 69)	64 (55.75, 74)	0.02*
Age <50 years, n (%)	32 (32)	21 (46)	11 (20)	<0.01*
Height (cm)	164 (157, 170)	166 (157, 171)	162 (157, 168)	0.14
Weight (kg)	58.2 (49.6, 63.4)	55.25 (48.45, 71.225)	59.2 (50.1, 65.025)	0.54
Male sex, n (%)	66 (66)	29 (63)	37 (69)	0.57
Obese^a	6 (6)	3 (7)	3 (6)	0.84
BSA (m^2)	1.62 (1.48, 1.73)	1.60 (1.45, 1.80)	1.64 (1.51, 1.71)	0.74
SCr^# (mg/dL)	0.5 (0.4, 0.7)	0.4 (0.3, 0.525)	0.6 (0.5, 0.725)	<0.01*
CLCr2hr (mL/min/1.73 m^2)	124 (87, 180)	180 (141, 235)	90 (74, 112)	<0.01*
CLCr8hr (mL/min/1.73 m^2)	126 (105, 178)	180 (147, 242)	106 (96, 120)	<0.01*
CLCr24hr (mL/min/1.73 m^2)	126 (103, 173)	177 (143, 215)	104 (88, 117)	<0.01*
GFRCG (mL/min/1.73 m^2)	124 (91, 175)	174 (132, 220)	97 (78, 124)	<0.01*
GFRMDRD (mL/min/1.73 m^2)	168 (119, 226)	220 (168, 319)	127 (103, 172)	<0.01*
GFRCKDEPI (mL/min/1.73 m^2)	113 (99, 133)	129 (116, 147)	100 (89, 116)	<0.01*
Underlying disease
Charlson comorbidity index	5 (3.25,7)	5.5 (3, 7.25)	5 (3.75, 6)	0.36
Cardiovascular disease	14 (14)	4 (9)	10 (19)	0.16
Chronic liver disease	16 (16)	8 (17)	8 (15)	0.73
Diabetes mellitus	13 (13)	3 (7)	10 (19)	0.08
Malignancy	37 (37)	17 (37)	20 (37)	0.18
Neurological disease	6 (6)	2 (4)	4 (7)	0.50
APACHE II score*	19 (14, 24.75)	18 (14, 25)	19.5 (14.75, 24.25)	0.51
SOFA score^#	5 (4, 7.75)	5 (3, 7)	6 (4, 8)	0.09
Ventilator use	88 (88)	43 (93)	45 (83)	0.12
Vasopressor use	15 (15)	6 (13)	9 (17)	0.61
Loop diuretic use	25 (25)	7 (15)	18 (33)	0.04*
Admission category
Respiratory failure	82 (82)	39 (85)	43 (80)	0.50
Pneumonia	90 (90)	41 (89)	49 (90)	0.79
Shock	15 (15)	6 (13)	9 (16)	0.61
Postoperative	2 (2)	1 (2)	1 (2)	0.90
Stroke	1 (1)	0 (0)	1 (2)
ICU mortality	25 (25)	10 (22)	15 (28)	0.49
Antibiotic use
Piperacillin/tazobactam	26	12	14
Cefepime	9	2	7
Meropenem	27	12	15

Notes: ^aObesity is defined as BMI >30, *24 hrs before intensive care unit admission, ^#On the date of enrollment.

Abbreviations: ARC, augmented renal clearance; APACHE II, Acute Physiologic Assessment and Chronic Health Evaluation; BSA, body surface area; S_Cr, serum creatinine; SOFA, Sequential Organ Failure Assessment; CL_Cr2hr, creatinine clearance through 2 h urine collection; CL_Cr8hr, creatinine clearance through 8 h urine collection; CL_Cr24hr, creatinine clearance through 24 h urine collection; GFR_CG, glomerular filtration rate through Cockcroft-Gault Method; GFR_MDRD, glomerular filtration rate through Modification of Diet in Renal Disease; GFR_CKD-EPI, glomerular filtration rate through Chronic Kidney Disease Epidemiology Collaboration.

Table 2 Multivariate logistic regression analysis with ARC as the dependent variable

	Odds ratio (95% CI)	p-value
Univariate
Age <50 (years)	3.28 (1.36–7.92)	0.008*
Obese	1.19 (0.23–6.18)	0.839
Loop diuretic use	0.36 (0.13–0.96)	0.041*
Ventilator use	2.87 (0.72–11.30)	0.132
Vasopressor use	0.75 (0.25–2.29)	0.614
APACHE II score	0.99 (0.93–1.04)	0.580
SOFA score	0.87 (0.74–1.02)	0.092*
CCI	1.08 (0.93–1.26)	0.321
Multivariate
Age <50 (years)	4.02 (1.54–10.51)	0.005*
Loop diuretic use	0.32 (0.11, 0.93)	0.036*
SOFA score	0.82 (0.68–0.99)	0.04*
Hosmer–Lemeshow goodness of fit, p=0.88

Note: *p<0.05.

Abbreviations: APACHE II, Acute Physiologic Assessment and Chronic Health Evaluation; CCI, Charlson comorbidity index; SOFA, Sequential Organ Failure Assessment.

Figure 1 Targets of pharmacokinetic and pharmacodynamic attainment. *p<0.05. (A) piperacillin/tazobactam, (B) cefepime, (C) meropenem, (D) all β-lactam.

Figure 2 Correlations among measured creatinine clearances and various estimated glomerular filtration rates. (A) CL_Cr2hr vs CL_Cr24hr. (B) CL_Cr8hr vs CL_Cr24hr. (C) GFR_CG vs CL_Cr24hr. (D) GFR_MDRD vs CL_Cr24hr. (E) GFR_CKD-EPI vs CL_Cr24hr.

Figure 3 Measurement of bias and agreement among measured creatinine clearances and various estimated glomerular filtration rates. (A) CL_Cr2hr vs CL_Cr24hr. (B) CL_Cr8hr vs CL_Cr24hr. (C) GFR_CG vs CL_Cr24hr. (D) GFR_MDRD vs CL_Cr24hr. (E) GFR_CKD-EPI vs CL_Cr24hr.

Table 3 Performance of various formulas of eGFR estimation to predict ARC using the receiver operating curve

	AUC (95% CI)	Cutoff values	Sensitivity (%)	Specificity (%)	PPV (%)	NPV (%)
GFRCG	0.87 (0.80–0.94)	130.5	78.3	85.2	81.8	82.1
GFRMDRD	0.84 (0.76–0.91)	180.5	67.4	85.2	78.3	74.5
GFRCKD-EPI	0.84 (0.77–0.92)	118.5	73.9	83.3	79	78.9

Abbreviations: eGFR, estimated glomerular filtration rate; AUC, area under the curve; PPV, positive predictive value; NPV, negative predictive value; GFR_CG, glomerular filtration rate through Cockcroft-Gault Method; GFR_MDRD, glomerular filtration rate through Modification of Diet in Renal Disease; GFR_CKD-EPI, glomerular filtration rate through Chronic Kidney Disease Epidemiology Collaboration.