Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia

Figures & data

Table 1 Characteristics of study patients with methicillin-resistant Staphylococcus aureus pneumonia

Characteristic	Survivors (n = 62)	Nonsurvivors (n = 32)	P-value
Age (years)	83.0 ± 6.2 (75–99)	81.8 ± 5.2 (75–93)	0.162a
Gender (male/female)	39/23	24/8	0.171b
Body weight (kg)	43.1 ± 9.2 (27–70)	42.5 ± 9.4 (28–72)	0.388a
Serum creatinine (mg/dL)	0.7 ± 0.4 (0.2–2.5)	0.8 ± 0.4 (0.2–2.1)	0.145a
Charlson comorbidity index	2.4 ± 1.8 (0–8)	3.1 ± 2.5 (1–10)	0.089b
Combination antibiotic therapy	32 (51.6%)	20 (63%)	0.216b
Diagnosis Pneumonia/Pneumonia and sepsis	48/14	28/4	0.185b
Infection severity
Mild	9	4	0.004c,*
Moderate	25	3
Severe	28	25

Notes:

a P-values were determined by the Student’s t-test

b Fisher’s Exact test

c Chi-square test

* P < 0.01, survivors versus nonsurvivors. Data are presented as the mean ± standard (range) deviation or the number of subjects (percentage).

Table 2 Pharmacokinetic and pharmacodynamic parameters for vancomycin between surviving and nonsurviving patients with methicillin-resistant Staphylococcus aureus pneumonia

PK/PD parameters	Survivors (n = 62)	Nonsurvivors (n = 32)	P-value
Cmax (μg/mL)	24.5 ± 8.2	25.5 ± 8.0	0.378
Trough concentration (μg/mL)	9.2 ± 8.2	10.0 ± 5.8	0.266
AUC (μg*h/mL)	344 ± 95.8	394.7 ± 209.9	0.104
Vd (L)	62.3 ± 6.6	63.6 ± 4.1	0.129
T1/2 (hours)	26.5 ± 13.1	31.5 ± 23.2	0.064
CLr (mL/min)	40.8 ± 16.9	35.5 ± 18.9	0.094
Daily dose (mg/kg/day)	20.9 ± 10.6	18.8 ± 6.6	0.119
Dose interval (hours)	26.5 ± 13.3	25.5 ± 7.8	0.322

Notes:P-values were determined by the Student’s t-test. Data were presented as the mean ± standard deviation.

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

Figure 1 Twenty-eight-day mortality according to stratification of vancomycin trough concentrations and AUC values. Data were presented as percentages. P values were determined by χ² tests. Stratification of vancomycin trough concentrations revealed no statistically significant relationship with 28-day mortality at any of the breakpoints evaluated (P = 0.603 [A]). However, AUC values of 250–350 μg*h/mL and 350–450 μg*h/mL were associated with significantly lower 28-day mortality than AUC values <250 and >450 μg*h/mL (P < 0.001 [B]).

Abbreviation: AUC, area under the concentration curve.

Table 3 Risk factors for mortality after treatment of methicillin-resistant Staphylococcus aureus pneumonia with vancomycin

Variable	Univariate analysis			Multivariate analysis
	Odds ratio	95% CI	P-value	Odds ratio	95% CI	P-value
Age	0.983	0.881–1.097	0.763
Nephrotoxicity	2.570	0.420–15.734	0.307	2.544	0.421–15.371	0.309
Infection severity	1.021	0.268–3.889	0.976
Charlson comorbidity index	1.236	0.924–1.654	0.154	1.236	0.941–1.625	0.128
Combination antibiotic therapy	0.745	0.195–2.852	0.667
Nonoptimal AUC (<250, >450 μg*h/mL)	25.377	5.791–111.203	< 0.001	23.156	6.814–78.687	< 0.001

Note: Hosmer–Lemeshow test, P = 0.134.

Abbreviations: AUC, area under the concentration curve; CI, confidence interval.

Table 4 Adverse effects of vancomycin among survivors and nonsurvivors

Adverse effect	Survivors (n = 62)	Nonsurvivors (n = 32)	P-value
Nephrotoxicity	3 (4.8%)	9 (28%)	0.003*
Liver dysfunction	3 (4.8%)	0 (0%)	0.282
Skin rash	2 (3.2%)	1 (3.2%)	0.718

Notes:P-values were determined by Fisher’s Exact test

* P < 0.01, survivors versus nonsurvivors. Data are presented as the number of subjects (percentage).