The influence of severe hypoalbuminemia on the half-life of vancomycin in elderly patients with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia

Figures & data

Table 1 Characteristics of patients with Methicillin-resistant Staphylococcus aureus pneumonia in this study

Characteristic	Severe hypoalbuminemia (n=23)	Non-severe hypoalbuminemia (n=71)	P-value
Age (years)	82.7 ± 1.4 (75–97)	82.6 ± 0.7 (75–99)	0.933a
Male (%)	17 (74%)	46 (65%)	0.161b
Body weight (kg)	41.8 ± 2.2 (28–72)	43.3 ± 1.1 (27–67)	0.526a
Serum creatinine (mg/dL)	0.8 ± 0.1 (0.2–2.1)	0.7 ± 0.1 (0.2–2.5)	0.348a
Charlson Comorbidity Index	2.9 ± 0.5 (1–10)	2.5 ± 0.2 (0–10)	0.475a
Albumin (g/dL)	2.1 ± 0.1 (1.4–2.4)	3.0 ± 0.1 (2.5–3.6)	<0.001a
Combination antibiotic therapy	12 (52%)	40 (56%)	0.570b
Diagnosis
Pneumonia/pneumonia and sepsis	21/2	55/16	0.143b
Infection severity
Mild	4 (17%)	9 (13%)	0.428b
Moderate	3 (13%)	25 (35%)	<0.001b
Severe	16 (70%)	37 (52%)	0.009b

Notes: Data are presented as the mean ± standard (range) error or the number of subjects (%).

a P-values determined using the Student’s t-test;

b P-values determined using the χ² test.

Table 2 Vancomycin pharmacokinetic/pharmacodynamic parameters between severe hypoalbuminemia and non-severe hypoalbuminemia patients with methicillin-resistant Staphylococcus aureus pneumonia

PK/PD parameters	Severe hypoalbuminemia (n=23)	Non-severe hypoalbuminemia (n=71)	P-value
Cmax (μg/mL)	26.8 ± 1.8 (11–44)	25.7 ± 1.0 (12–40)	0.606a
Trough concentration (μg/mL)	10.9 ± 1.3 (2.7–23)	9.0 ± 0.7 (1.6–23)	0.179a
AUC/MIC (μg × h/mL)	426.3 ± 43 (150–789)	340.1 ± 14.0 (167–784)	0.066b
<250 (μg × h/mL)	6 (26%)	11 (15%)	0.113c
250–450 (μg × h/mL)	8 (35%)	54 (76%)	<0.001c
>450 (μg × h/mL)	9 (39%)	6 (9%)	<0.001c
Vd (L)	64.0 ± 1.1 (51–71)	62.3 ± 0.7 (50–95)	0.223a
T1/2 (hours)	33.2 ± 5.4 (15–135)	24.9 ± 1.6 (10–68)	0.049a
CLr (mL/minute)	33.7 ± 3.7 (4.8–58.7)	40.7 ± 2.1 (7.9–91.2)	0.101a
Single dose (mg)	774 ± 51 (400–1,250)	815 ± 27 (350–1,250)	0.456a
Daily dose (mg/kg/day)	19.5 ± 1.6 (6.9–34.5)	20.4 ± 1.2 (3.4–63.1)	0.658a
Dose interval (hours)	25.0 ± 1.7 (12–48)	26.5 ± 1.5 (12–72)	0.509b

Notes: Data are presented as the mean ± standard error (range) or the number of subjects (%).

a P-values determined using the Student’s t-test;

b P-values determined using the Welch test;

c P-values determined using the χ² test.

Abbreviations: AUC, area under the concentration curve; CLr, renal clearance; C_max, peak concentration; MIC, minimum inhibitory concentration; PD, pharmacodynamic; PK, pharmacokinetic; T_1/2, half-life of VCM; VCM, vancomycin; Vd, volume of distribution.

Figure 1 Twenty-eight-day mortality according to stratification of the vancomycin AUC/MIC values in severe hypoalbuminemia and non-severe hypoalbuminemia groups. (A) AUC/MIC <250 μg × h/ml, (B) AUC/MIC = 250–450 μg × h/ml, and (C) AUC/MIC >450 μg × h/ml. P-values were determined using χ² tests. The AUC values of 250–450 and >450 μg × h/mL were significantly associated with 28-day mortality in patients with severe hypoalbuminemia (**P < 0.001), while AUC values of <250 μg × h/ml were not (P = 0.143).

Abbreviations: AUC, area under the concentration curve; MIC, minimum inhibitory concentration.

Table 3 Adverse effects of vancomycin between severe hypoalbuminemia and non-severe hypoalbuminemia patients

Characteristic	Severe hypoalbuminemia (n=23)	Non-severe hypoalbuminemia (n=71)	P-value
Nephrotoxicity	6 (26%)	6 (8%)	<0.001
Liver dysfunction	0 (0%)	3 (4%)	0.245

Notes: Data are presented as the number of subjects (%). P-values were determined using the χ² test.

Figure 2 Percentage of nephrotoxicity after VCM administration in the severe hypoalbuminemia and non-severe hypoalbuminemia groups.

Notes: P-values were determined using χ² tests. The percentage of nephrotoxicity in severe hypoalbuminemia group was significantly higher than that in the non-severe hypoalbuminemia group for AUC/MIC values of >450 μg × h/ml (**P < 0.001), whereas the percentage of nephrotoxicity in the non-severe hypoalbuminemia group was significantly higher than in the severe hypoalbuminemia group for AUC/MIC values of <250 μg × h/ml (**P < 0.001).
Abbreviations: AUC, area under the concentration curve; MIC, minimum inhibitory concentration; VCM, vancomycin.