J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 16, Number 7-8, August 2024, pages 325-334

Impact of the First Twenty-Four-Hour Area Under the Concentration-Time Curve/Minimum Inhibitory Concentration of Vancomycin on Treatment Outcomes in Patients With Methicillin-Resistant Staphylococcus aureus Bacteremia

↓ Figure 1. Flowchart depicting patient selection in this study. AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration; VCM: vancomycin; MRSA: methicillin-resistant Staphylococcus aureus.

↓ Figure 2. Receiver operating characteristic (ROC) curve and early positive response. (a) The ROC curve used to determine the cutoff value of the first 24-h AUC/MIC of vancomycin for early positive response. The analysis identified an AUC/MIC of 309.7 µg·h/mL, represented by an AUC value of 0.754, sensitivity of 76.5%, and specificity of 69.4%. (b)The early positive response rate in the < 300 and ≥ 300 groups. Values are presented as numbers (%). AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration.

↓ Figure 3. Effectiveness of VCM therapy. The panels show the treatment efficacy rate (a), 30-day survival (b), and time to clinical and bacteriological improvement (c). Values are presented as numbers (%), and time to clinical and bacteriological improvement is presented as median (interquartile range). AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration; VCM: vancomycin.

↓ Figure 4. ROC curve for achieving first 24-h AUC/MIC ≥ 300 µg·h/mL. The figure presents the ROC curve used to determine the optimal dose of VCM to achieve a first 24-h AUC/MIC ≥ 300 µg·h/mL. The analysis identified an optimal VCM dose of 27.8 mg/kg, represented by an AUC value of 0.735, sensitivity of 68.4%, and specificity of 87.5%. VCM: vancomycin; AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration; ROC: receiver operating characteristic.

↓ **Table 1.** Number of Cases in Each AUC/MIC Range
First 24-h AUC/MIC (µg·h/mL)	N
AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration.
100 - 199	2 (2.9%)
200 - 299	30 (42.9%)
300 - 399	23 (32.9%)
400 - 499	15 (21.4%)
Total number of cases (n)	70
Median of AUC/MIC (µg·h/mL)	312.9

↓ Table 1. Number of Cases in Each AUC/MIC Range

First 24-h AUC/MIC (µg·h/mL)

AUC/MIC: area under the concentration-time curve/minimum inhibitory concentration.

100 - 199

2 (2.9%)

200 - 299

30 (42.9%)

300 - 399

23 (32.9%)

400 - 499

15 (21.4%)

Total number of cases (n)

Median of AUC/MIC (µg·h/mL)

312.9

↓ **Table 2.** Characteristics of the Patients Included in This Study
Clinical background	First 24-h AUC/MIC (µg·h/mL)	P value
Values are presented as number (%) or median (interquartile range). AUC: area under the concentration-time curve; AUC_{0 - 24 h}: AUC on day 1; AUC_{24 - 48 h}: AUC on day 2; AUC_ss: AUC at steady state; BT: body temperature; Ccr: creatinine clearance; CRP: C-reactive protein; MIC: minimum inhibitory concentration; SCr: serum creatinine; VCM: vancomycin; WBC: white blood cell.
Male sex (n (%))	21 (65.6)	25 (65.8)	0.988
Age (years)	69.5 (60.0 - 78.0)	70.5 (67.8 - 80.5)	0.285
Body weight (kg)	50.6 (38.5 - 56.1)	53.0 (43.6 - 61.5)	0.183
Comorbidities (n (%))
Heart failure	11 (34.3%)	15 (39.5%)	0.660
Malignancy	9 (28.1%)	8 (21.1%)	0.492
Diabetes	5 (15.6%)	7 (18.4%)	0.757
Aspiration pneumonia	7 (21.9%)	5 (13.2%)	0.335
Digestive disorders	1 (3.1%)	2 (5.3%)	0.660
Suspected origin of infection (n (%))			0.966
Catheter-related bloodstream infections	17 (53.1)	18 (47.4)
Skin and soft tissue infections	6 (18.8)	6 (15.8)
Urinary tract infections	2 (6.3)	2 (5.3)
Bacterial pneumonia	2 (6.3)	2 (5.3)
Pyogenic spondylitis	2 (6.3)	3 (7.9)
Unknown	1 (3.1)	3 (7.9)
Others	2 (6.3)	4 (10.5)
Laboratory data before VCM therapy
BT (°C)	37.9 (37.7 - 38.3)	37.9 (37.4 - 39.2)	0.981
WBC (× 10³/µL)	11.6 (9.1 - 15.1)	14.5 (9.8 - 19.9)	0.299
CRP (mg/dL)	14.6 (7.9 - 19.8)	11.7 (10.0 - 15.8)	0.396
SCr (mg/dL)	0.7 (0.6 - 0.9)	0.8 (0.7 - 1.0)	0.101
Ccr (mL/min)	65.0 (45.5 - 76.1)	61.4 (40.4 - 73.8)	0.465
Concomitant antimicrobial agent			0.511
Carbapenem	3 (9.4)	5 (13.2)
Penicillin/β-lactamase inhibitor	0 (0)	3 (7.9)
Third and fourth generation cephalosporin	3 (9.4)	2 (6.3)
Quinolone	0 (0)	0 (0)
Nothing	26 (81.3)	28 (73.7)
VCM therapy
MIC ≤ 1 µg/mL (n (%))	32 (100)	38 (100)	1.000
Initial trough concentration (µg/mL)	9.0 (6.7 - 10.0)	14.1 (10.9 - 18.7)	< 0.001
Dose of first day (mg/kg)	22.4 (18.1 - 27.4)	30.4 (22.8 - 35.4)	0.001
AUC_{0 - 24 h} (µg·h/mL)	268.2 (241.0 - 286.5)	385.7 (346.9 - 418.3)	< 0.001
AUC_{24 - 48 h} (µg·h/mL)	366.6 (315.1 - 406.5)	509.0 (388.1 - 588.7)	< 0.001
AUC_ss (µg·h/mL)	449.4 (420.3 - 501.8)	512.0 (422.6 - 541.0)	0.085

↓ Table 2. Characteristics of the Patients Included in This Study

Clinical background

First 24-h AUC/MIC (µg·h/mL)

P value

< 300 (n = 32)

≥ 300 (n = 38)

Values are presented as number (%) or median (interquartile range). AUC: area under the concentration-time curve; AUC_{0 - 24 h}: AUC on day 1; AUC_{24 - 48 h}: AUC on day 2; AUC_ss: AUC at steady state; BT: body temperature; Ccr: creatinine clearance; CRP: C-reactive protein; MIC: minimum inhibitory concentration; SCr: serum creatinine; VCM: vancomycin; WBC: white blood cell.

Male sex (n (%))

21 (65.6)

25 (65.8)

0.988

Age (years)

69.5 (60.0 - 78.0)

70.5 (67.8 - 80.5)

0.285

Body weight (kg)

50.6 (38.5 - 56.1)

53.0 (43.6 - 61.5)

0.183

Comorbidities (n (%))

Heart failure

11 (34.3%)

15 (39.5%)

0.660

Malignancy

9 (28.1%)

8 (21.1%)

0.492

Diabetes

5 (15.6%)

7 (18.4%)

0.757

Aspiration pneumonia

7 (21.9%)

5 (13.2%)

0.335

Digestive disorders

1 (3.1%)

2 (5.3%)

0.660

Suspected origin of infection (n (%))

0.966

Catheter-related bloodstream infections

17 (53.1)

18 (47.4)

Skin and soft tissue infections

6 (18.8)

6 (15.8)

Urinary tract infections

2 (6.3)

2 (5.3)

Bacterial pneumonia

2 (6.3)

2 (5.3)

Pyogenic spondylitis

2 (6.3)

3 (7.9)

Unknown

1 (3.1)

3 (7.9)

Others

2 (6.3)

4 (10.5)

Laboratory data before VCM therapy

BT (°C)

37.9 (37.7 - 38.3)

37.9 (37.4 - 39.2)

0.981

WBC (× 10³/µL)

11.6 (9.1 - 15.1)

14.5 (9.8 - 19.9)

0.299

CRP (mg/dL)

14.6 (7.9 - 19.8)

11.7 (10.0 - 15.8)

0.396

SCr (mg/dL)

0.7 (0.6 - 0.9)

0.8 (0.7 - 1.0)

0.101

Ccr (mL/min)

65.0 (45.5 - 76.1)

61.4 (40.4 - 73.8)

0.465

Concomitant antimicrobial agent

0.511

Carbapenem

3 (9.4)

5 (13.2)

Penicillin/β-lactamase inhibitor

0 (0)

3 (7.9)

Third and fourth generation cephalosporin

3 (9.4)

2 (6.3)

Quinolone

0 (0)

Nothing

26 (81.3)

28 (73.7)

VCM therapy

MIC ≤ 1 µg/mL (n (%))

32 (100)

38 (100)

1.000

Initial trough concentration (µg/mL)

9.0 (6.7 - 10.0)

14.1 (10.9 - 18.7)

< 0.001

Dose of first day (mg/kg)

22.4 (18.1 - 27.4)

30.4 (22.8 - 35.4)

0.001

AUC_{0 - 24 h} (µg·h/mL)

268.2 (241.0 - 286.5)

385.7 (346.9 - 418.3)

< 0.001

AUC_{24 - 48 h} (µg·h/mL)

366.6 (315.1 - 406.5)

509.0 (388.1 - 588.7)

< 0.001

AUC_ss (µg·h/mL)

449.4 (420.3 - 501.8)

512.0 (422.6 - 541.0)

0.085