ABSTRACT: Optimal Treatment of Ceftazidime-Avibactam and Aztreonam-Avibactam Against Bloodstream Infections or Lower respiratory tract Infections Caused by extensively drug-resistance or pan drug-resistance (XDR/PDR) Pseudomonas aeruginosa
Project description:Using in vitro directed evolution, we show that mismatch repair-deficient Pseudomonas aeruginosa can engage novel resistance mechanisms to ceftazidime-avibactam.
Project description:To explore the mechanism of drug resistance, most works focused on resistance associated genetic mutations, whereas concerns for resistance related gene expression are relatively low. Here a global expression analysis was performed between a reference strain H37Rv and two clinical extensively drug-resistant (XDR) strains with three anti-TB drug exposures {isoniazid (INH), capreomycin (CAP), rifampicin (RIF)}
Project description:Pseudomonas aeruginosa is a major cause of infection in hospitalised patients, with a large genome which makes it highly versatile and resistant to most antimicrobial agents. Ceftazidime-avibactam (CZA) offers an alternative treatment, but resistance is quickly evolving. There is limited knowledge on the exact resistance mechanisms to this drug, or on cross-resistance to meropenem (MEM). This laboratory experiment aimed to decipher these mechanisms in order to provide guidance for the best treatment choice in meropenem pre-treated P. aeruginosa infections. Six clinical isolates of P. aeruginosa were subjected to multistep resistance selection in sub inhibitory concentrations of CZA and MEM. MICs were also determined in the presence of the efflux pump inhibitor phenyl-Arginine-β-Naphthylamide (PAβN). Molecular analyses were performed by whole genome sequencing, whole -gene- and -protein expression profiles. CRISPR/Cas9 genome editing was performed using a two-plasmid method for selected mutations
Project description:Extensively drug resistant tuberculosis (XDR-TB) showed many different characteristics including the extreme drug resistance versus the drug sensitive clinical isolates (DS-TB), to know better about the reasons we used the tuberculosis host cells named as THP-1 (one kind of the macrophage cells) to be infected by the XDR-TB and DS-TB.DS strain A36 and the XDR strain B42 and was typical and selected by our lab. Then the total RNA of infected or uninfected THP-1 cells was extract and purified for the analysis by the chip (22K Human Genome chip representing the 21522 ORF of human with the oligonucleotide probe of 70 mer from CapitalBio Corp., Beijing, China). The results reflected the different expressed genes involved in apoptosis, secreted cytokines and signal pathway and so on. Those results might indicate the how the XDR-TB cause the pathogenesis.
2009-04-04 | GSE15539 | GEO
Project description:Ceftazidime-avibactam Resistance in Klebsiella pneumoniae
Project description:To explore the mechanism of drug resistance, most works focused on resistance associated genetic mutations, whereas concerns for resistance related gene expression are relatively low. Here a global expression analysis was performed between a reference strain H37Rv and two clinical extensively drug-resistant (XDR) strains with three anti-TB drug exposures {isoniazid (INH), capreomycin (CAP), rifampicin (RIF)} Strains were grown in Middlebrook 7H9 broth supplemented with ADC, 0.05% Tween 80 and 0.2% glycerol to an OD600 of 0.5-0.6, and then respectively treated with control (water), 10×MIC INH, 1×MIC RIF and CAP for 6hr.
Project description:Ceftazidime-Avibactam Resistance Development following Ceftazidime-Avibactam-based therapy in critically-ill patients with infections caused by KPC-producing Klebsiella pneumoniae
