ABSTRACT :
Aims : Imipenem is a widely used antibiotic for the treatment of
critically ill patients with severe infections. Here, we present a
translational pharmacokinetic/pharmacodynamic
mathematical model to assessf T>MIC and evaluate the clinical
outcomes of imipenem treatment in critically ill patients.
Methods : Critically ill patients with severe infections were
included in our study. Blood samples at different time points were
collected after imipenem plasma concentration reached a steady statein vivo . A one-compartment model was used for pharmacokinetic
profiles. PK/PD parameters were calculated separately with or without a
mathematical model. Clinical results were mainly defined as the
microbiological results. The resolution of fever and the decrease in PCT
and WBC levels were also considered.
Results : A total of 54 patients were enrolled in our study. Thef T>MIC calculated by the
mathematical model was 67.26±39.96%, and thef T>MIC was 73.75±23.11% without the
model. The PK/PD parameters
calculated between the two groups were not significantly different.
Regarding clinical outcomes, 35 (64.3%) patients were defined as having
clinical success. The f T>MIC was
83.33±12.90% in the clinical success group and 59.42±19.11% in the
clinical failure group. The f T>MICwas significantly different between the two groups (p=0.022). Based on
the regimens, the PCT level decreased to at least 20% of the peak level
and the WBC level decreased during the first 3 days when patients’f T>MIC was greater than 70%.
Conclusion : The pharmacokinetic mathematical model may be used
for PK/PD parameter evaluation. To treat critically ill patients,
achieving f T>MIC greater than 70%
may be necessary.
KEY WORDS : Imipenem; PK/PD; antimicrobial; critically ill
patients