Validated preclinical mouse model for therapeutic testing against multidrug-resistant Pseudomonas aeruginosa strains was written by Warawa, Jonathan M.;Duan, Xiaoxian;Anderson, Charles D.;Sotsky, Julie B.;Cramer, Daniel E.;Pfeffer, Tia L.;Guo, Haixun;Adcock, Scott;Lepak, Alexander J.;Andes, David R.;Slone, Stacey A.;Stromberg, Arnold J.;Gabbard, Jon D.;Severson, William E.;Lawrenz, Matthew B.. And the article was included in Microbiology Spectrum in 2022.Recommanded Product: 78110-38-0 This article mentions the following:
The rise in infections caused by antibiotic-resistant bacteria is outpacing the development of new antibiotics. The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a group of clin. important bacteria that have developed resistance to multiple antibiotics and are commonly referred to as multidrug resistant (MDR). The medical and research communities have recognized that, without new antimicrobials, infections by MDR bacteria will soon become a leading cause of morbidity and death. Therefore, there is an ever-growing need to expedite the development of novel antimicrobials to combat these infections. Toward this end, we set out to refine an existing mouse model of pulmonary Pseudomonas aeruginosa infection to generate a robust preclin. tool that can be used to rapidly and accurately predict novel antimicrobial efficacy. This refinement was achieved by characterizing the virulence of a panel of genetically diverse MDR P. aeruginosa strains in this model, by both 50% LD (LD50) anal. and natural history studies. Further, we defined two antibiotic regimens (aztreonam and amikacin) that can be used as comparators during the future evaluation of novel antimicrobials, and we confirmed that the model can effectively differentiate between successful and unsuccessful treatments, as predicted by in vitro inhibitory data. This validated model represents an important tool in our arsenal to develop new therapies to combat MDR P. aeruginosa strains, with the ability to provide rapid preclin. evaluation of novel antimicrobials and support data from clin. studies during the investigational drug development process. IMPORTANCE The prevalence of antibiotic resistance among bacterial pathogens is a growing problem that necessitates the development of new antibiotics. Preclin. animal models are important tools to facilitate and speed the development of novel antimicrobials. Successful outcomes in animal models not only justify progression of new drugs into human clin. trials but also can support FDA decisions if clin. trial sizes are small due to a small population of infections with specific drug-resistant strains. However, in both cases the preclin. animal model needs to be well characterized and provide robust and reproducible data. Toward this goal, we have refined an existing mouse model to better predict the efficacy of novel antibiotics. This improved model provides an important tool to better predict the clin. success of new antibiotics. In the experiment, the researchers used many compounds, for example, 2-((((Z)-1-(2-Aminothiazol-4-yl)-2-(((2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid (cas: 78110-38-0Recommanded Product: 78110-38-0).
2-((((Z)-1-(2-Aminothiazol-4-yl)-2-(((2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl)amino)-2-oxoethylidene)amino)oxy)-2-methylpropanoic acid (cas: 78110-38-0) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Recommanded Product: 78110-38-0
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica