Safety of high-dose daptomycin in patients with severe renal impairment

Figures & data

Table 1 Demographic characteristics of patients with renal impairment who received daptomycin therapy

Demographic characteristics	All patients, N=164	High dose, N=37 (≥9 mg/kg)	Standard dose, N=127 (<9 mg/kg)	P-value
Male	87 (53.0)	20 (54.1)	67 (52.8)	0.889
Age (years), range	68.1±16.5 (19.8–93.9)	68.3±15.5	68.0±16.8	0.937
Elderly ≥65 years old	102 (62.2)	24 (64.9)	78 (61.4)	0.704
ICU admission	107 (65.2)	23 (62.2)	84 (66.1)	0.655
Mean body weight (kg)	58.5±11.9 (36.3–103.1)	53.2±10.2	60.0±12.0	<0.001
Obesity (BMI >30)a	10 (6.1)	1 (2.7)	9 (7.4)	0.459
Types of renal failure
CLCr <30 mL/min	27 (16.5)	6 (16.2)	21 (16.5)	0.963
Dialysis (iHD/SLED/PD)	101 (61.6)	25 (67.6)	76 (59.8)	0.395
CRRT	13 (7.9)	0 (0.0)	13 (10.2)	0.042
AKI	23 (14.0)	6 (16.2)	17 (13.4)	0.663
Mean dose (mg/kg)	8.0±2.3	10.8±2.5	7.1±1.4	<0.001
Duration (days), median (IQR)	12.5 (11)	13 (11)	12 (11)	0.343
Type of infections
Bloodstream infection	91 (55.5)	27 (73.0)	64 (50.4)	0.015
Skin and soft tissue infection	17 (10.4)	0 (0.0)	17 (13.4)	0.014
Urinary tract infection	21 (12.8)	2 (5.4)	19 (15.0)	0.166
Infective endocarditis	4 (2.4)	1 (2.7)	3 (2.4)	1.000
Septic arthritis	5 (3.0)	1 (2.7)	4 (3.1)	1.000
Intra-abdominal infection	17 (10.4)	5 (13.5)	12 (9.4)	0.540
Empirical use	9 (5.5)	2 (5.4)	7 (5.5)	1.000
Dose frequency
QD	13 (7.9)	6 (16.2)	7 (5.5)	0.076
QOD	129 (78.7)	29 (78.4)	100 (78.7)	0.962
TIW	22 (13.4)	2 (5.4)	20 (15.7)	0.168
Creatine kinase follow-up	108 (65.9)	25 (67.6)	83 (65.4)	0.803
Number of CK follow-ups per weekb	0.8±1.2	0.7±0.8	0.8±1.3	0.946
Prior antibiotic use	105 (64.0)	30 (81.1)	75 (59.1)	0.014
Seizure or surgery during therapy	28 (17.1)	6 (16.2)	22 (17.3)	0.875
Concurrent drugc	15 (9.1)	3 (8.1)	12 (9.4)	1.000
Concurrent antibiotic therapy	132 (80.5)	32 (86.5)	100 (78.7)	0.295
β-Lactams	128 (78.0)	31 (83.8)	97 (76.3)	0.338
Gentamicin	3 (1.8)	1 (2.7)	2 (1.6)	0.538
Rifampin	12 (7.3)	6 (16.2)	6 (4.7)	0.029
Co-trimoxazole	12 (7.3)	6 (16.2)	6 (4.7)	0.029

Notes: Data are presented as number (%) or mean±SD (range) unless stated otherwise.

a BMI was available in 158 patients;

b Calculated by the number of CK measurement/duration (days) ×7;

c Statins, fibrate, or colchicine.

Abbreviations: AKI, acute kidney injury; BMI, body mass index; CK, creatine kinase; CL_Cr, creatinine clearance; CRRT, continuous renal replacement therapy; ICU, intensive care unit; iHD, intermittent hemodialysis; IQR, interquartile range; PD, peritoneal dialysis; QD, every 24 h; QOD, every 48 h; SLED, sustained low-efficiency dialysis; TIW, thrice per week.

Table 2 Characteristics of the patients who had creatine kinase elevation

Patient	Age (years)/sex	Renal failure	Indication (microbe)	Dose (mg/kg)	Dosing frequency	Treatment duration (days)	CK level (U/L)		Muscle symptoms	Action	Recovery
							Baseline	Peak
1	74.9/F	CKD	Bacteremia (MRSA)	10.7	QOD	21	15	2,895	Nil	Stop	Yes
2	55/M	SLED	Bacteremia (VRE)	7.6	QOD	8	53	2,801	NA	Stop	Yes
3	36.7/M	iHD	Bacteremia (MRSA)	9.8	QOD	31	–	1,449	NA	Closely monitor	Yes
4	78.4/F	iHD	Empirical therapy (−)	9.3	QOD	11	10	1,939	Muscle soreness	Stop	Yes
5	38.9/F	AKI	Skin and soft tissue infection (−)	8.3	QOD	13	23	4,697	Muscle soreness	Stop	Yes
6	76.6/F	AKI	Septic arthritis (−)	10.2	QD	7	23	1,299	Myalgia	Stop	Yes

Abbreviations: AKI, acute kidney injury; CK, creatine kinase; CKD, chronic kidney disease; iHD, intermittent hemodialysis; MRSA, methicillin-resistant Staphylococcus aureus; NA, not available, because of intubation and poor consciousness; QD, every 24 h; QOD, every 48 h; SLED, sustained low-efficiency dialysis; VRE, vancomycin-resistant enterococci.

Table 3 Possible factors contributing to creatine kinase elevation

Variables	Elevation of creatine kinase level, N (%)		P-value
	No, 158 (96.3)	Yes, 6 (3.7)
Dosage (mg/kg)			0.024
≥9	33 (89.2)	4 (10.8)
<9	125 (98.4)	2 (1.6)
Dosing frequency			0.484
QD	12 (92.3)	1 (7.7)
QOD	124 (96.1)	5 (3.9)
TIW	22 (100)	0 (0.0)
Concurrent drugsa			0.443
Yes	14 (93.3)	1 (6.7)
No	144 (96.6)	5 (3.4)

Note:

a Statin, fibrate, or colchicine.

Abbreviations: QD, every 24 h; QOD, every 48 h; TIW, thrice per week.

Table 4 Demographic characteristics of patients with and without CK measurement

Demographic characteristics	CK unavailable, N=56	CK available, N=108	P-value
Male	30 (53.6)	57 (52.8)	0.923
Age (years), range	66.3±16.2	69.0±16.6	0.305
Elderly ≥65 years old	31 (55.4)	71 (65.7)	0.193
ICU admission	36 (64.3)	71 (65.7)	0.853
Mean body weight (kg)	58.6±12.2	58.5±11.9	0.983
Obesity (BMI >30)a	4 (7.1)	6 (5.6)	0.736
Types of renal failure
CLCr <30 mL/min	15 (26.8)	12 (11.1)	0.010
Dialysis (iHD/SLED/PD)	26 (46.4)	75 (69.4)	0.004
CRRT	6 (10.7)	7 (6.5)	0.370
AKI	9 (16.1)	14 (13.0)	0.587
Mean dose (mg/kg)	8.0±2.9	7.9±1.9	0.611
Duration (days), median (IQR)	7 (6)	15 (13.75)	0.001
Dose frequency
QD	7 (12.5)	6 (5.6)	0.135
QOD	43 (76.8)	86 (79.6)	0.673
TIW	6 (10.7)	16 (14.8)	0.465
High dose (≥9 mg/kg)	12 (21.4)	25 (23.1)	0.803
Prior antibiotic use	35 (62.5)	70 (64.8)	0.770
Seizure or surgery during therapy	5 (8.9)	23 (21.3)	0.046
Concurrent drugb	8 (14.3)	7 (6.5)	0.100
Concurrent antibiotic therapy	44 (78.6)	88 (81.5)	0.656
β-Lactams	42 (75.0)	86 (79.6)	0.497
Gentamicin	3 (5.4)	0 (0.0)	0.038
Rifampin	5 (8.9)	7 (6.5)	0.546
Co-trimoxazole	2 (3.6)	10 (9.3)	0.224

Notes: Data are presented as number (%) or mean±SD (range) unless stated otherwise.

a BMI was available in 158 patients;

b Statins, fibrate, or colchicine.

Abbreviations: AKI, acute kidney injury; BMI, body mass index; CK, creatine kinase; CL_Cr, creatinine clearance; CRRT, continuous renal replacement therapy; ICU, intensive care unit; iHD, intermittent hemodialysis; IQR, interquartile range; PD, peritoneal dialysis; QD, every 24 h; QOD, every 48 h; SLED, sustained low efficiency dialysis; TIW, thrice per week.