Mechanism of Qiguiyin Decoction Sensitizing Levofloxacin Against Multidrug-Resistant Pseudomonas aeruginosa Infection Based on PK-PD and Antibody Chip Technology
Abstract
Background: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection. Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD. Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as T max , t 1/2 , MRT, V d /F, CL/F and PD parameters such as MIC, AUC 0-24h /MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6,…
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