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.