Abstract
Pseudomonas aeruginosa (PA), a Gram-negative bacterium, has a high detection rate in hospital-acquired infections. Recently, the frequent appearance of multidrug-resistant (MDR) PA strain with high morbidity and mortality rates has aggravated the difficulty in treating infectious diseases. Due to its multiple resistance mechanisms, the commonly used antibiotics have gradually become less effective. Qiguiyin decoction (QGYD) is a clinically experienced prescription of Chinese herbal medicine, and its combined application with antibiotics has been confirmed to be effective in the clinical treatment of MDR PA infection, which could be a promising strategy for the treatment of drug-resistant bacterial infections. However, the mechanism of QGYD restoring antibiotics susceptibility to MDR PA remains unclear. In the present study, we investigated the effects of QGYD and levofloxacin (LEV) singly or in combination on MDR PA-induced pneumonia rat models. Further analysis was carried out in the serum differential expression profiles of inflammatory cytokines by cytokine antibody array. Besides, the lung TLR4/MyD88/NF-κB signaling pathway was detected by RT-qPCR. Our results showed that based on the treatment of MDR PA-infected rat model with LEV, the combination of QGYD improved the general state and immune organ index. Furthermore, it moderately increased the expressions of proinflammatory cytokines including IL-1β, IL-6, and TNF-α in the early stage of infection and decreased their release rapidly in the later stage, while regulated the same phase change of anti-inflammatory cytokine IL-10. In addition, the adhesion molecule ICAM-1 was significantly downregulated after QGYD combined with LEV treatment. Moreover, the mRNA expressions of TLR4, MyD88, NF-κB, and ICAM-1 were significantly downregulated. These results indicated that the mechanism of QGYD restoring LEV susceptibility to MDR PA was related to its regulation of inflammatory cytokines and the TLR4/MyD88/NF-κB signaling pathway, which provides theoretical support for the clinical application of QGYD combined with LEV therapy to MDR PA infection.
Highlights
Pseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria that cause hospital-acquired infections, with strong pathogenicity and increasing clinical isolation rate [1]
These results suggested that the development of pneumonia caused by MDR PA infection was accompanied with the activation of inflammatory immune response in rats
The results showed that compared with the Model group, the drug intervention could improve the general state of MDR PA-infected rats and significantly inhibit the body weight loss and the increase of lung W/D (P < 0:01) and SI (P < 0:05) caused by MDR PA infection; in addition, the improving effect of Qiguiyin decoction (QGYD)-LEV was superior to that of LEV or QGY alone, as shown in Table 2 and Figures 1 and 2
Summary
Pseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria that cause hospital-acquired infections, with strong pathogenicity and increasing clinical isolation rate [1]. Levofloxacin (LEV) used to be an effective antibiotic against PA infection [2]. With its extensive clinical application, PA has been increasingly resistant to LEV [3,4,5,6]. The combination of multiple antibiotics, nor continuous replacement of antibiotics can effectively control drug-resistant PA infection. BioMed Research International frequently with high infection and mortality rates, which poses a great challenge to clinical anti-infection treatment. It is urgent to find a more effective therapeutic strategy
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