RESULTS——CASE PRESENTATION
A 44-year-old female was diagnosed with SAP in February 2018 because of her clinical manifestations (abdominal pain, nausea, emesis and fever), imaging work-up (ultrasound and computed tomography) and laboratory parameters (serum amylase and lipase to be three times of the upper limit) with Acute Physiology and Chronic Health Evaluation II (APACHE II) score of 12, Balthazar CT score of 6 and Marshall score of 3. Since hospital admission, she was constantly in fever with intermittently elevated white blood cell (WBC) and neutrophil percentage (N%). On February 28th, the patient’s WBC and N% rose to 30.17*10^9/L and 96% respectively, which can be explained with aggravation of infection. As she underwent trachea intubation because of hypoxemia on the same day, stress response or the effect of glucocorticoid after trachea intubation couldn’t be excluded. To control the infection better, the patient was operated percutaneous drainage and vancomycin was prescribed empirically on the basis of imipenem/cilastatin. The primary dosage regimen of vancomycin was 0.5g thrice daily, which was calculated using SHIONOGI-VCM-TDM S1-1[26] according to her age (44 year), weight (60 kg), and serum creatinine (89 µmol·L-1). On March 2nd, when vancomycin concentration was assumed to achieve steady state, we got the drainage and blood for vancomycin concentration measurement simultaneously. The sampling time was at 0.5 hours before administration and 1.5, 2, 3, 5, 7 hours after administration of the seventh dose. And the concentration was determined using chemiluminescent microparticle immunoassay assay (CMIA) method[27]. On March 12th, the patient’s temperature, WBC and N% returned to normal.
Figure 1 showed the result of vancomycin concentration in serum and pancreas tissue. It could be seen that the time to peak concentration (Tmax) of pancreas tissue fell behind Tmax of serum about 30 minutes, which means it took time for vancomycin to get through from serum to pancreas tissue. And we calculated the area under curve (AUC) of these two curves to estimate the amount of vancomycin in pancreas tissue by trapezoidal rule. The AUC0-8h of time-tissue concentration and time-serum concentration was 117 and 154 respectively. The ratio of the two was 76%, which means about 76% of vancomycin could move into pancreas tissue. Besides, the pharmacokinetic parameters were calculated using first-order conditional estimation method[28] with NONMEM version 7.3.0 software (ICON Development Solutions). One- and two-compartment models with first-order absorption and linear elimination were investigated to determine the optimal structural model. Because we only had one patient, the inter-individual variability was fixed as 0 and no covariate was retained in the final model. The two-compartment model was chosen finally as it well described the data. The results were shown in Table 1.