Individualized Vancomycin Dosing with Therapeutic Drug Monitoring and Pharmacokinetic Consultation Service: A Large-Scale Retrospective Observational Study

Figures & data

Figure 1 Study design and patient population.

Abbreviations: TDM, therapeutic drug monitoring; PK, pharmacokinetic; ASHP, American Society of Health-System Pharmacists; ICU, intensive care unit; VIN, vancomycin induced nephrotoxicity; PKCS, pharmacokinetic consultation service; MRSA, methicillin resistant Staphylococcus aureus.

Table 1 Characteristics and Vancomycin Trough Concentration in Patients Who Underwent Vancomycin Therapeutic Drug Monitoring

Characteristics	Total	Without PKCS	With PKCS	P value
Total number of patients, n	2412	1884 (78.1%)	528 (21.9%)
Total no. of vancomycin concentration measurements, n	12846	9702 (75.5%)	3144 (24.5%)
Age, median (IQR), years	61 (46–71)	60 (46–71)	63 (49–72)	0.022
Age < 18 years, n (%)	264 (10.9%)	208 (11.0%)	56 (10.6%)	0.778
Male, n (%)	1473 (61.1%)	1153 (61.2%)	320 (60.6%)	0.805
Hospitalized patient, n (%)	2411 (99.9%)
Department, n (%)
Surgical department^a	666 (27.6%)	445 (23.6%)	221 (41.9%)
Hemato-oncology	529 (21.9%)	481 (25.5%)	48 (9.1%)
Critical care medicine	292 (12.1%)	228 (12.1%)	64 (12.1%)
Pediatrics	206 (8.5%)	167 (8.9%)	39 (7.4%)
Others	719 (29.8%)	563 (29.9%)	156 (29.5%)
No. of measurements per patient, median (IQR), n	3 (2–7)	3 (2–6)	4 (2–7)	<0.001
Vancomycin concentration, median (IQR), ㎍/mL	14.7 (10.9–18.3)	14.5 (10.8–18.1)	15.2 (11.3–18.6)	<0.001
Subtherapeutic, n (%)	2610 (20.3%)	2046 (21.1%)	564 (17.9%)	<0.001
Therapeutic, n (%)	8173 (63.6%)	6144 (63.3%)	2029 (64.5%)	0.229
Supratherapeutic, n (%)	2063 (16.1%)	1512 (15.6%)	551 (17.5%)	0.009

Notes:^aSurgical department includes general surgery, neurosurgery, plastic surgery and thoracic surgery. Significant values are indicated in bold.

Abbreviations: PKCS, pharmacokinetic consultation service; IQR, interquartile range.

Table 2 Characteristics of the Patients Enrolled for VIN Assessment

	Non-PKCS (n=146)	% or IQR	PKCS (n=134)	% or IQR	P value
Incidence of VIN, n (%)	5	3%	8	6%	0.398
Duration of vancomycin therapy, days	6	4–8	9	5–15	<0.001
Daily dose of vancomycin^a, mg/kg/day	33	27–41	34	26–40	0.724
Male, n (%)	76	52%	83	62%	0.095
Age, years	63	54–72	67	54–73	0.212
No. of races other than East Asian, n (%)	1	1%	0	0%	N/A
Weight, kg	64	54–72	61	54–67	0.169
BMI^a, kg/m^2	24	21–27	20	18–22	<0.001
Obesity (BMI>30kg/m^2), n (%)	15	10%	2	1%	0.002
Target trough
10–15 ㎍/mL, n (%)	81	55%	64	48%	0.197
15–20 ㎍/mL, n (%)	65	45%	70	52%
Renal Function
Serum creatinine, mg/dL	0.78	0.61–0.96	0.75	0.56–0.98	0.348
Baseline eGFR, mL/min/1.73 m^2	90	74–104	95	77–105	0.41
≥90	72	49%	81	60%	0.062
60–89	52	36%	35	26%	0.086
<60	22	15%	18	13%	0.696
Renal replacement therapy, n (%)	11	8%	7	5%	0.431
Final eGFR, mL/min/1.73 m^2	93	73–107	90	67–104	0.698
Co-morbidities
Malignancy, n (%)	52	36%	41	31%	0.373
Cardiovascular, n (%)	20	14%	26	19%	0.198
Pulmonary, n (%)	5	3%	1	1%	0.216
Central nervous system, n (%)	2	1%	4	3%	0.431
Gastrointestinal, n (%)	13	9%	9	7%	0.497
Diabetes, n (%)	37	25%	24	18%	0.132
Site of Infection
Respiratory, n (%)	9	6%	15	11%	0.133
Blood stream, n (%)	24	16%	15	11%	0.065
Skin and soft tissue, n (%)	27	18%	39	29%	0.367
Central nervous system, n (%)	7	5%	9	7%	0.489
Bone/Joint, n (%)	25	17%	29	22%	0.338
Intra-abdominal, n (%)	22	15%	15	11%	0.339
Ear, nose and throat, n (%)	22	15%	7	5%	0.007
Urinary tract, n (%)	2	1%	4	3%	0.431
Surgical prophylaxis, n (%)	8	5%	1	1%	0.037
Positive culture result^b
MRSA, n (%)	28	19%	30	22%	0.417
MRCNS, n (%)	7	5%	18	13%	0.011
MSSA, n (%)	3	2%	2	1%	1
Enterococcus sp., n (%)	12	8%	14	10%	0.521
Other gram positives^c, n(%)	4	3%	9	7%	0.156
Empirical use	27	18%	20	15%	0.33
Concurrent nephrotoxic agents^d	72	49%	84	63%	0.024
Piperacillin/tazobactam, n (%)	42	29%	52	39%	0.758
Furosemide, n (%)	36	25%	40	30%	0.329
ACE inhibitor or ARBs, n (%)	6	4%	3	2%	0.504
Aminoglycosides, n (%)	2	1%	6	4%	0.158
Vasopressin, n (%)	2	1%	1	1%	1
Initial CRP^e, mg/dL	3.8 (n=130)	1.3–9.0	5.7 (n=132)	1.7–10.4	0.105
Initial WBC count^e, /mL	7.3 (n=134)	5.3–10.3	8 (n=133)	5.9–11.3	0.15

Notes:^aAll of the values were described in the median with interquartile range (IQR) given their non-normal distribution except for daily dose and BMI which followed normal distribution and was described in mean with range and compared with an independent sample t-test. ^bInfection with two microorganisms indicated for vancomycin existed (11 cases in PKCS group). ^cOther gram positives include Streptococcus species, Corynebacterium species, Propionibacterium acnes, and Bacillus cereus. ^dPatients using two or more concurrent nephrotoxic agents existed (19 cases in PKCS group, 19 cases in non-PKCS group). ^ePatients without the result of CRP and WBC count existed. Significant values are indicated in bold.

Abbreviations: VIN, vancomycin induced nephrotoxicity; PKCS, pharmacokinetic consultation service; IQR, interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate; MRSA, methicillin resistant Staphylococcus aureus; MRCNS, methicillin resistant coagulase negative Staphylococcus; MSSA, methicillin susceptible Staphylococcus aureus; ACE inhibitor, Angiotensin-converting enzyme inhibitor; ARBs, Angiotensin II receptor blockers; CRP, C-reactive protein; WBC, white blood cell.

Table 3 Logistic Regression Analysis for Vancomycin Induced Nephrotoxicity

Covariate		Univariate		Multiple
		OR (95% CI)	P value	OR (95% CI)	P value
Group (PKCS)		1.79 (0.57–5.62)	0.318
Duration of vancomycin therapy (day)		1.01 (0.65–1.07)	0.864
Daily dose of vancomycin		1.00 (0.96–1.04)	0.94
Male		0.32 (0.10–1.07)	0.064	0.327 (0.10–1.11)	0.072
Age		1.01 (0.96–1.05)	0.782
BMI		0.96 (0.83–1.11)	0.569
Target trough (15–20 ㎍/mL)		0.66 (0.21–2.07)	0.474
Baseline eGFR		1.01 (0.99–1.04)	0.319
Comorbidities
Malignancy		0.89 (0.27–2.97)	0.848
Diabetes		0.64 (0.14–2.97)	0.57
Site of infection
Respiratory		2.03 (0.42–9.72)	0.378
Skin and soft tissue		2.96 (0.96–9.13)	0.06	2.55 (0.81–8.08)	0.111
Central nervous system		1.4 (0.17–11.50)	0.754
Bone/Joint		0.34 (0.04–2.65)	0.301
Positive Culture result
MRSA		0.97 (0.21–4.55)	0.973
MRCNS		3.34 (0.86–13.0)	0.083	2.95 (0.72–12.04)	0.131
Initial CRP		0.98 (0.88–1.07)	0.611
Initial WBC count		0.93 (0.80–1.09)	0.369
Concurrent nephrotoxic agent		1.29 (0.41–4.04)	0.666
Piperacillin/tazobactam		0.87 (0.26–2.92)	0.827
Furosemide		1.73 (0.55–5.45)	0.353

Note: Significant values are indicated in bold.

Abbreviations: OR, odds ratio; CI, confidence interval; PKCS, pharmacokinetic consultation service; BMI, body mass index; eGFR, estimated glomerular filtration rate;MRSA, methicillin resistant Staphylococcus aureus; MRCNS, methicillin resistant coagulase negative Staphylococcus; CRP, C-reactive protein; WBC, white blood cell.

Table 4 Target Trough Attainment and Baseline Characteristics of Enrolled Patient

	Non-PKCS (n=132)	% or IQR	PKCS (n=126)	% or IQR	P value
Target trough attainment rate, n (%)	79	60%	94	75%	0.012
Time to initial target trough^a, days	3.6	2.5–5.2	4.2*	2.3–5.8	0.43
Total trough concentration, ㎍/mL	15.3	11.5–18.3	16.2	12.8–19.2	0.001
Subtherapeutic, n (%)	206	34%	261	27%	0.004
Therapeutic, n (%)	201	33%	371	39%	0.028
Supratherapeutic, n (%)	199	33%	328	34%	0.588
Mean trough^b, ㎍/mL	14.8	8.21–22.8	15.5	8.7–24.4	0.037
Subtherapeutic, n (%)	51	39%	39	31%	0.196
Therapeutic, n (%)	44	33%	55	44%	0.088
Supratherapeutic, n (%)	37	28%	32	25%	0.633
Maximum trough, ㎍/mL	18.7	16.7–21.4	20.9	17.1–24.5	0.001
Subtherapeutic, n (%)	31	23%	15	12%	0.015
Therapeutic, n (%)	32	24%	25	20%	0.394
Supratherapeutic, n (%)	69	52%	86	68%	0.009
Final trough, ㎍/mL	16.5	13.6–18.3	16.7	13.4–19.1	0.412
Subtherapeutic, n (%)	41	31%	28	22%	0.109
Therapeutic, n (%)	42	32%	55	44%	0.005
Supratherapeutic, n (%)	49	37%	43	34%	0.616
Patient characteristics
Male, n (%)	70	53%	77	61%	0.21
Age, years	65	55–74	67	55–72	0.271
BMI (kg/m^2)	24	22–27	19	18–23	<0.001
Target trough 15–20 mg/L, n (%)	59	45%	66	52%	0.217
Baseline eGFR, mL/min/1.73 m^2	87	74–101	93	81–107	0.398
Concurrent nephrotoxic agent use^c, n (%)	63	48%	77	61%	0.031
Initial CRP^d	3.5	1.1–8.7	5.8	1.7–10.4	0.04
Initial WBC count^d	7.1	5.1–10.0	8	5.9–11.3	0.088
Duration of vancomycin therapy, days	8	6–11	11	7–17	<0.001
Daily dose of vancomycin, mg/kg/day	34	28–40	33	26–41	0.61
Incidence of VIN, n (%)	7	5%	8	6%	0.72

Notes:^aTime to target attainment was compared between PKCS group patients who received their first PKCS within 72 h from the start of vancomycin therapy and achieved target trough (n=79) and non-PKCS group patients who achieved target trough (n=67). ^bSince mean trough concentration followed a normal distribution, it was described in mean with range and compared via independent sample t-test. ^cPatients using two or more concurrent nephrotoxic agents existed (19 cases in PKCS group, 18 cases in non-PKCS group). ^dPatients without the result of CRP and WBC count existed. Significant values are indicated in bold.

Abbreviations: PKCS, pharmacokinetic consultation service; IQR, interquartile range; BMI, body mass index; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; WBC, white blood cell; VIN, vancomycin induced nephrotoxicity.

Table 5 Logistic Regression Analysis for Target Trough Attainment

Covariate	Univariate		Multiple
	OR (95% CI)	P value	OR (95% CI)	P value
Group (PKCS)	1.97 (1.16–3.35)	0.012	1.80 (1.05–3.11)	0.034
Duration of vancomycin therapy	1.22 (1.13–1.32)	<0.001
BMI	0.99 (0.93–1.05)	0.71
Target trough (15–20 ㎍/mL)	0.82 (0.49–1.38)	0.455
Baseline eGFR	1.00 (0.99–1.01)	0.835
Concurrent nephrotoxic agent use	1.78 (1.05–3.00)	0.032	1.65 (0.97–2.82)	0.064
Initial CRP	1.01 (0.97–1.06)	0.556
Initial WBC	1.01 (0.96–1.07)	0.654

Note: Significant values are indicated in bold.

Abbreviations: OR, odds ratio; CI, confidence interval; PKCS, pharmacokinetic consultation service; BMI, body mass index; eGFR, estimated glomerular filtration rate; CRP, C-reactive protein; WBC, white blood cell.

Figure 2 Cumulative percentage of target trough attainment by time. Percentage of the patients who attained target trough was determined at three time periods (<3 days, 3–<5days, and ≥5days).

Abbreviation: PKCS, pharmacokinetic consultation service.

Table 6 Characteristics of Patients Enrolled for Clinical Outcome Assessment

	Non-PKCS (n=51)	% or IQR	PKCS (n=61)	% or IQR	P value
Treatment failure rate, n (%)	6	12%	6	10%	0.742
Duration of vancomycin therapy, days	7	5–12	12	8–17	0.008
Daily dose of vancomycin^a, mg/kg/day	33	28–38	30	20–38	0.569
Incidence of VIN, n (%)	2	4%	5	8%	0.452
Target trough attainment rate, n (%)	37	73%	48	79%	0.449
Time to initial target trough^b, days	3.7	2.9–5.2	3.9	2.3–6.4	0.965
No. of trough measurement per week	4.2	3.5–5.3	3.9	3.3–4.9	0.205
No. of dose adjustment per week	1.2	0.0–1.8	1.6	0.9–2.0	0.054
Patient Characteristics
Male, n (%)	26	51%	38	62%	0.228
Age^a, years	61	26–83	62	29–83	0.58
Race other than East Asian, n (%)	0	0%	1	2%	N/A
Weight, kg	64	41–94	61	37–91	0.341
BMI^a, kg/m^2	24	20–26	20	18–21	<0.001
Obesity (BMI>30kg/m^2), n (%)	6	12%	1	2%	0.046
Target trough 15–20 ㎍/㎖, n (%)	14	27%	26	43%	0.095
Baseline eGFR, mL/min/1.73 m^2	94	74–108	96	80–109	0.343
Renal replacement therapy, n (%)	2	4%	6	10%	0.287
Final eGFR, mL/min/1.73 m^2	2	4%	6	10%	0.287
Co-morbidities
Malignancy, n (%)	24	47%	27	44%	0.767
Cardiovascular, n (%)	3	6%	10	16%	0.137
Pulmonary, n (%)	1	2%	0	0%	N/A
Central nervous system, n (%)	1	2%	3	5%	0.624
Gastrointestinal, n (%)	5	10%	5	8%	1
Diabetes, n (%)	11	22%	9	15%	0.348
Site of Infection
Respiratory, n (%)	1	2%	7	11%	0.069
Bloodstream, n (%)	6	12%	4	7%	0.508
Skin and soft tissue, n (%)	11	22%	18	30%	0.339
Central nervous system, n (%)	2	4%	6	10%	0.287
Bone/Joint, n (%)	5	10%	7	11%	1
Intra-abdominal, n (%)	9	18%	10	16%	0.86
Ear, nose, and throat, n (%)	15	29%	6	10%	0.008
Urinary tract, n (%)	2	4%	3	5%	1
Positive culture result^c	25	49%	28	46%	0.742
MRSA, n (%)	7	14%	14	23%	0.213
MRCNS, n (%)	3	6%	2	3%	0.658
MSSA, n (%)	11	22%	13	21%	0.974
Enterococcus sp., n (%)	3	6%	7	11%	0.342
Other gram positives^d, n(%)	9	18%	10	16%	0.86
Concurrent nephrotoxic agents^e	25	49%	35	57%	0.377
Piperacillin/tazobactam, n (%)	14	27%	24	39%	0.186
Furosemide, n (%)	10	20%	13	21%	0.824
ACE inhibitor or ARBs, n (%)	3	6%	1	2%	0.329
Aminoglycosides, n (%)	0	0%	2	3%	N/A
Vasopressin, n (%)	0	0%	0	0%	N/A
Initial CRP^f, mg/dL	1.7	0.4–5.0 (n=40)	3.6	1.4–7.3 (n=60)	0.031
Initial WBC count^f,/mL	6.7	4.7–9.0 (n=43)	7.2	5.1–10.4 (n=60)	0.286

Notes:^aAll of the values were described in median with interquartile range (IQR) given their non-normal distribution except for daily dose, age, and BMI which followed normal distribution, and was described in mean with range and compared with independent sample t-test. ^bTime to target attainment was compared between PKCS group patients who received their first PKCS within 72h from the start of vancomycin therapy and achieved target trough (n=36) and non-PKCS group patients who achieved target trough (n=37). ^cInfection with two microorganisms indicated for vancomycin existed (4 cases in PKCS group). ^dOther gram positives include Streptococcus species, Corynebacterium species, Propionibacterium acnes, and Bacillus cereus. ^ePatients using two or more concurrent nephrotoxic agents existed (5 cases in PKCS group, 4 cases in non-PKCS group). ^fPatients without the result of CRP and WBC count existed. Significant values are indicated in bold.

Abbreviations: PKCS, pharmacokinetic consultation service; IQR, interquartile range; VIN, vancomycin induced nephrotoxicity; N/A, not applicable; BMI, body mass index; eGFR, estimated glomerular filtration rate; MRSA, methicillin resistant Staphylococcus aureus; MRCNS, methicillin resistant coagulase negative Staphylococcus; MSSA, methicillin susceptible Staphylococcus aureus; ACE inhibitor, Angiotensin-converting enzyme inhibitor; ARBs, Angiotensin II receptor blockers; CRP, C-reactive protein; WBC, white blood cell.

Table 7 Logistic Regression Analysis for Treatment Failure Rate and Development of VIN in Patients with Positive Culture Result

	Treatment Failure				VIN
	Univariate		Multiple		Univariate		Multiple
Covariate	OR	P value	OR (95% CI)	P value	OR	P value	OR	P value
Group (PKCS)	1.22	0.743			2.19	0.362
Duration of vancomycin therapy	1.01	0.675			0.95	0.405
Daily dose of vancomycin	1.02	0.562			1.01	0.805
Target trough attainment	1.67	0.433
Time to initial target trough	0.67	0.003	0.64 (0.50–0.85)	0.002
BMI	1.12	0.225			0.94	0.582
Baseline eGFR	0.99	0.516			1.01	0.528
Renal replacement therapy	0.83	0.866			N/A	1
Malignancy	1.78	0.374			0.46	0.362
Diabetes	0.38	0.15	0.26 (0.04–1.98)	0.195	1.93	0.452
Skin and soft tissue infection	0.30	0.053	0.48 (0.07-3.37)	0.46	2.28	0.301
MRSA	0.61	0.422			0.83	0.807
MRSA MIC ≤0.5 mg/L	1.17	0.826			1.05	0.957
Initial CRP	0.96	0.385			1.03	0.702
Concurrent nephrotoxic agent use	0.20	0.044	N/A	1	5.67	0.114	N/A	1

Note: Significant values are indicated in bold.

Abbreviations: VIN, vancomycin induced nephrotoxicity; OR, odds ratio; CI, confidence interval; PKCS, pharmacokinetic consultation service; BMI, body mass index; eGFR, estimated glomerular filtration rate; MRSA, methicillin resistant Staphylococcus aureus; MIC, minimum inhibitory concentration; CRP, C-reactive protein; N/A, not applicable.

Table 8 Clinical Outcome Analysis of Patients with MRSA Infection

		Non-PKCS (n=25)	% or IQR	PKCS (n=28)	% or IQR	P value
Treatment failure rate, n (%)		5	20%	2	7%	0.234
Duration of vancomycin therapy, days		7	5–12	13	8–17	0.003
Daily dose of vancomycin^a, mg/kg/day		36	9–67	29	4–50	0.071
Incidence of VIN, n (%)		2	8%	1	4%	0.597
Target trough attainment rate, n (%)		18	72%	20	71%	0.963
Time to initial target trough^b, days		3.9	3.0–4.6	2.3	1.8–3.4	0.02
No. of trough measurement per day, n		3.9	2.7–4.7	3.9	3.1–4.9	0.748
No. of dose adjustment per week, n		1.4	0.0–1.9	1.6	0.8–2.1	0.219
Patient Characteristics
Initial CRP^c. mg/dL		1.1	0.3–3.5	3.3	1.3–6.8	0.076
Initial WBC count^c,/mL		6.9	4.9–9.0	8	5.4–12.1	0.138
Site of infection
Respiratory, n (%)		0	0%	3	11%	N/A
Blood stream, n (%)		4	16%	0	0%	N/A
Skin and Soft Tissue, n (%)		4	16%	10	36%	0.104
Central Nervous System, n (%)		0	0%	3	11%	N/A
Bone/Joint, n (%)		0	0%	3	11%	N/A
Intra-abdominal, n (%)		2	8%	3	11%	0.736
Ear, nose and throat, n (%)		15	60%	6	21%	0.004
MRSA MIC
≤0.5 mg/L, n (%)		17	68%	12	43%	0.114
1 mg/L, n (%)		6	24%	16	57%	0.015
2 mg/L, n (%)		2	8%	0	0%	N/A

Notes:^aAll of the values were described in median with interquartile range (IQR) given their non-normal distribution except for daily dose which followed normal distribution, and was described in mean with range and compared with independent sample t-test. ^bTime to target attainment was compared between PKCS group patients who received their first PKCS within 72 h from the start of vancomycin therapy and achieved target trough (n=15) and non-PKCS group patients who achieved target trough (n=18). ^cPatients without the result of CRP and WBC count existed. Significant values are indicated in bold.

Abbreviations: MRSA, methicillin resistant Staphylococcus aureus; PKCS, pharmacokinetic consultation service; IQR, interquartile range; VIN, vancomycin induced nephrotoxicity; MIC, minimum inhibitory concentration; CRP, C-reactive protein; WBC, white blood cell; N/A, not applicable.

Table 9 Comparison of Duration of Vancomycin Therapy Between Groups with or without the Possible Cause of Longer Duration of Therapy

		Duration of Vancomycin Therapy, Days, Median (IQR)	P value
Non-PKCS vs PKCS group		6.0 (4.0–8.25) vs 9.0 (5.0–15.0)	<0.001
Concurrent nephrotoxic agent use (no vs yes)		7.5 (5.0–13.8) vs 7.0 (4.3–11.0)	0.144
Target range (10–15 vs 15–20 mg/L)		7.0 (5.0–11.0) vs 7.0 (4.0–13.0)	0.958
Obesity (BMI ≤30 vs >30 kg/m2)		7.0 (5.0–12.0) vs 9.0 (4.5 vs 11.5)	0.713
Sex (Female vs Male)		7.0 (5.0–12.0) vs 7.0 (4.0–11.0)	0.671
Malignancy (No vs Yes)		7.0 (5.0–12.0) vs 7.0 (4.0–11.0)	0.302
DM (No vs Yes)		7.0 (4.0–11.0) vs 7.0 (5.0–13.0)	0.516
Site of infection (No vs Yes)
Skin and soft tissue		7.0 (4.0–12.0) vs 8.0 (5.0–12.3)	0.214
Bone and joint		7.0 (4.0–11.0) vs 8.5 (5.0–14.0)	0.006
Blood stream		7.0 (5.0–13.0) vs 4.5 (3.0–7.0)	<0.001
Respiratory		7.0 (5.0–11.8) vs 8.0 (4.3 vs 14.5)	0.691
Central Nervous System		7.0 (4.0–12.0) vs 7.5 (5.3 vs 22.3)	0.264
Empirical use (No vs Yes)		8.0 (5.0–13.5) vs 7.0 (4.0–11.0)	0.066
MRSA infection (No vs Yes)		7.0 (4.0–11.0) vs 8.5 (5.0–14.0)	0.053

Note: Significant values are indicated in bold.

Abbreviations: PKCS, pharmacokinetic consultation service; IQR, interquartile range; BMI, body mass index; MRSA, methicillin-resistant Staphylococcus aureus.