Research Article: Combination of AS and Mefloquine Inhibits Carbapenem-Resistant Pseudomonas aeruginosa in vitro and in vivo
Abstract:
Pseudomonas aeruginosa is one of the common G?-opportunistic pathogens in hospital-acquired infection. It may cause a variety of infectious diseases, including pneumonia, septicemia, and urinary tract infection. Frequently used antibiotics for the treatment of P. aeruginosa include ?-lactams such as cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, aminoglycosides (gentamicin, tobramycin), and fosfomycin. However, due to the irrational use of antibiotics, the spread of resistant plasmids, and various other factors, multidrug resistance (MDR) and extensively drug-resistant (XDR) P. aeruginosa have emerged and widely spread across the world,, posing a serious threat to public health. According to the report on antibiotic resistance issued by the United States Centers for Disease Control and Prevention (CDC) in , anti-microbial pathogens caused more than . million infections and more than deaths every year. In fact, as early as , the World Health Organization (WHO) listed CRPA as a “key” group in urgent need of new antibiotics. Recently, the CDC reported an outbreak of XDR-P. aeruginosa carrying VIM-GES-CRPA, which involved states and resulted in various types of infections, including eyes, bloodstream, urinary tract, and respiratory system. This situation has drawn great concerns not only to the medical community but also to the governments around the world. Thus, a novel treatment strategy is urgently needed. In recent years, researchers have tried to explore additional therapeutics for CRPA for clinical use. Several new combinations of ?-lactamase inhibitors have been introduced for clinical applications, including meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam. These antibiotics might be toxic, especially to the patients with renal failure. At the same time, long-term use of antibiotics might expand the development of drug resistance and dysbiosis of homeostasis. In addition, new antibiotics have been investigated to treat refractory bacteria including CRPA. However, the development of new drugs requires a lot of manpower and material resources and has a long cycle. Explorations for treatment options besides antibiotic therapy, including inhibition of quorum sensing and biofilm formations as well as bacteriophage therapy, are under investigations. On the other hand, the reuse of old drugs has been tried to solve the current problems.– A small molecule of AS is a fully synthesized organic compound containing tellurium, which has the activity of immune regulation and can induce the secretion of cytokines such as interleukins and cluster stimulating factors in human lymphocyte proliferation., It could also be used to treat malignant tumors, autoimmune diseases, viral infections, and other disorders.– In addition, AS showed antibacterial activity. In the sepsis mouse model of cecal ligation and puncture, AS could improve the survival rate of animals. Furthermore, recent studies demonstrated that AS had promising antibacterial activity against a variety of bacteria in vitro and in vivo, including Enterobacter cloacae, carbapenem-resistant Acinetobacter baumannii, colistin-resistant Klebsiella pneumoniae, etc.,– but the antibacterial effect of CRPA is still unclear. Although the above research showed a potential choice of AS for carbapenem-resistant bacteria, we noted that the minimum inhibitory concentration (MIC) of AS to CRPA was as high as ?g/mL, which was not far from its % cytotoxicity level ( ?g/mL). A high dose of AS will bring unsafe results. Therefore, further improvement of the antibacterial activity of AS would be needed.
Introduction:
Pseudomonas aeruginosa is one of the common G ? -opportunistic pathogens in hospital-acquired infection. It may cause a variety of infectious diseases, including pneumonia, septicemia, and urinary tract infection. Frequently used antibiotics for the treatment of P. aeruginosa include ?-lactams such as cefepime, ceftazidime, piperacillin-tazobactam, aztreonam, aminoglycosides (gentamicin, tobramycin), and fosfomycin. However, due to the irrational use of antibiotics, the spread of resistant plasmids, and various…
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