Article Figures & Data
Figures
- FIG 1
Distribution of vancomycin concentrations at the end of the loading dose (T1), at 12 h (T2), and at 24 h after the onset of therapy (T3). The shaded zone indicates target drug concentrations, assessed at T2 and T3.
- FIG 2
Distribution of vancomycin concentrations at 24 h after the onset of therapy (T3), according to different creatinine clearance values measured from daily urine collection. The shaded zone indicates target drug concentrations. Chi-square analysis for trend yielded a P value of 0.02. Lowercase letters a, b, and c above data indicate significant differences. Individual analyses showed significant differences (P < 0.05) from vancomycin concentrations at a creatinine clearance of <25 ml/min (a), 25 to 50 ml/min (b), or 51 to 80 ml/min (c).
- FIG 3
Vancomycin concentrations at different time points in the three groups, according to the differences in creatinine clearances measured using the Cockcroft-Gault formula or daily urinary excretion (see Materials and Methods). Two-way analysis of variance was performed (P = 0.02); an asterisk indicates differences at a specific time point according to the Bonferroni post hoc analysis.
Tables
- TABLE 2
Characteristics of patients
Characteristica Value for patientsb (n = 107) Age (yr) 59 (48–71) No. of men/women 77/30 Body wt (kg) 75 (65–85) Body mass index (kg/m2) 24 (22–28) No. (%) with comorbidities COPD/asthma 19 (18) Heart disease 24 (22) Diabetes 23 (21) Chronic renal disease 31 (29) Liver cirrhosis 7 (6) Cancer 17 (16) Corticosteroids 34 (32) Other immunosuppressive agents 25 (23) Organ transplantation 17 (16) No. (%) with medical admission 69 (64) APACHE II score on ICU admission 19 (13–25) SOFA score at the onset of therapy 6 (4–9) No. (%) with septic shock at the onset of therapy 57 (53) No. (%) on mechanical ventilation at the onset of therapy 58 (54) ICU mortality (no. [%]) 24 (22) - TABLE 3
Characteristics of infections
Infectiona No. (%) of patients (n = 107) Lung 47 (44) Abdominal 12 (11) Urinary 8 (7) Skin or soft tissue 8 (7) Catheter related 7 (6) Neurological 5 (5) Primary bacteremia 18 (17) MRSA 10 MRSE 10 Enterococcus faecium 4 ↵a MRSA, methicillin-resistant Staphylococcus aureus; MRSE, methicillin-resistant Staphylococcus epidermidis.
- TABLE 4
Pharmacokinetic and pharmacodynamic characteristics of therapy
Characteristica Value for patientsb Vancomycin concn (mg/liter) At 4 h (T1) 44 (37–49) At 12 h (T2) 25 (21–32) At 24 h (T3) 22 (19–28)c On day 2 26 (22–30)d AUC0–24 (mg · h/liter) 771 (644–905) Drug clearance from 0 to 24 h (mg · h/liter) 3.0 (2.1–3.8) CG-CrCL (ml/min) 94 (56–140) uCrCl (ml/min) 82 (43–157) ↵a CG-CrCL, creatinine clearance according to the Cockcroft-Gault formula; uCrCL, creatinine clearance determined from urinary elimination.
↵b Data are presented as medians (25th to 75th percentiles). A total of 107 patients were evaluated except where otherwise indicated.
↵c A total of 105 patients were evaluated.
↵d A total of 56 patients were evaluated.
- TABLE 5
Risk factors for insufficient or excessive serum vancomycin concentrations at 24 h of treatment (T3)
Characteristica Valueb for patients with vancomycin concns (mg/liter) of: P value (<20 vs >20 mg of vancomycin/liter)b Valuec for patients with vancomycin concns (mg/liter) of: P value (<30 vs >30 mg of vancomycin/liter)c <20 (n = 29) >20 (n = 78) <30 (n = 85) >30 (n = 22) Age 56 (37–68) 59 (49–71) 0.07 59 (47–72) 59 (46–70) 0.67 No. (%) male 23 (79) 54 (69) 0.31 63 (74) 14 (64) 0.35 Wt (kg) 56 (65–75) 59 (65–90) 0.007 75 (65–80) 80 (65–95) 0.12 Body mass index (kg/m2) 24 (22–26) 25 (15–27) 0.01 24 (22–28) 28 (24–30) 0.01 No. (%) with: Medical admission 20 (69) 49 (63) 0.56 54 (64) 15 (68) 0.69 Corticosteroids 7 (24) 27 (35) 0.31 28 (33) 6 (27) 0.58 Neutropenia 1 (3) 9 (12) 0.23 8 (9) 2 (9) 0.51 Organ transplant 2 (7) 15 (19) 0.17 15 (18) 2 (9) 0.51 Cancer 4 (14) 13 (17) 0.72 13 (15) 4 (18) 0.99 COPD/asthma 5 (17) 14 (18) 0.93 14 (17) 5 (23) 0.68 Diabetes 7 (24) 16 (21) 0.69 18 (21) 5 (23) 0.58 Heart disease 7 (24) 17 (22) 0.79 19 (22) 5 (23) 0.65 CKD 7 (24) 24 (31) 24 (28) 7 (32) Liver cirrhosis 0 (0) 6 (8) 0.99 5 (6) 2 (9) 0.81 APACHE II on admission 20 (15–23) 19 (13–24) 0.97 20 (14–23) 19 (13–23) 0.66 No. (%) in shock 17 (59) 41 (53) 0.63 46 (54) 12 (55) 0.97 No. (%) on mechanical ventilation 18 (62) 40 (51) 0.32 49 (58) 9 (41) 0.25 SOFA score on day 1 6 (3–9) 7 (4–10) 0.91 7 (4–9) 6 (4–10) 0.86 Daily dose of vancomycin (mg/kg) 36.8 (25–42.6) 28.2 (23.5–35.7) 0.19 33.8 (24.0–38.5) 25.8 (25.0–40.0) 0.98 Vancomycin concn (mg/liter) at T1 39 (33–45) 46 (40–50) 0.12 42 (33–47) 50 (46–59) 0.001 No. (%) with respiratory infection 15 32 0.32 39 (46) 8 (36) 0.86 uCrCL (ml/min) 138 (73–178) 64 (33–138) 0.13 97 (51–162) 52 (23–82) 0.02 ↵a CKD, chronic kidney disease; T1, end of loading dose infusion; uCrCL, creatinine clearance measured on daily urine excretion.
↵b Obtained by univariate analysis. Multivariate analysis found body mass index (odds ratio [95% confidence interval], 0.87 [0.78 to 0.96]) and uCrCL (1.01 [1.00 to 1.02]) to be predictive of insufficient drug concentrations.
↵c Obtained by univariate analysis. Multivariate analysis found body mass index (odds ratio [95% confidence interval], 1.15 [1.02 to 1.29]), the vancomycin concentration at T1 (1.06 [1.01 to 1.10]), and uCrCL (0.98 [0.97 to 0.99]) to be predictive of excessive drug concentrations.
- TABLE 6
Sensitivity, specificity, and positive and negative predictive values of vancomycin concentrations at T3 for predicting AUC0–24/MIC ratios of ≥400 at different MICsa
Vancomycin concn (mg/liter) at T3 and predictive measure Value (%) for predicting anAUC0–24/MIC ratio of ≥400 at a MIC (mg/liter) of: 0.5 1.0 1.5 2.0 ≥15 Sensitivity 95 96 100 100 Specificity 100 100 31 6 PPV 100 100 89 26 NPV 0 20 100 100 ≥20 Sensitivity 78 78 87 94 Specificity 100 100 75 37 PPV 100 100 95 57 NPV 0 4 50 88 ≥25 Sensitivity 37 37 43 70 Specificity 100 100 100 93 PPV 100 100 100 90 NPV 0 2 24 78 ≥30 Sensitivity 21 21 24 44 Specificity 100 100 100 100 PPV 100 100 100 100 NPV 0 1 19 67 ↵a T3, 24 h after the initiation of therapy; AUC0–24/MIC ratio, ratio between the area under the curve of drug concentrations over the first day of therapy and the MIC.
