Skipper England (flagangle8)
To characterise the in vitro activity of imipenem/relebactam (IMR) against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa, including those isolates demonstrating resistance to piperacillin/tazobactam and meropenem, in hospitalized patients within the Asia-Pacific region. During the period of 2017 through 2020, the SMART global surveillance program included the participation of 49 clinical labs distributed across nine countries in the Asia-Pacific region, resulting in the collection of 26,783 NME and 6,383 P. aeruginosa specimens. By employing the CLSI broth microdilution method, minimum inhibitory concentrations (MICs) were determined, and their interpretation was guided by the CLSI M100 (2021) breakpoints. From a collection of isolates, subsets representing the period 2017 to 2020 displayed lactamase genes. OprD sequencing was performed on molecularly characterized P. aeruginosa samples obtained in 2020. NME's susceptibility to various agents revealed amikacin as the most potent, with a remarkable 979% susceptibility rate, while IMR (958%), meropenem (954%), and imipenem (926%) also showed significant activity. In NME isolates resistant to piperacillin/tazobactam (n=4070), 761% displayed susceptibility to IMR. The national rates exhibited a wide spectrum, from 975% in New Zealand to 506% in Vietnam. NME samples indicated metallo-lactamase (MBL) positivity in 27% of cases, 9% harbored OXA-48-like carbapenemases (MBL-negative), and 7% exhibited KPC (MBL-negative) positivity. Against P. aeruginosa, amikacin's efficacy reached 940% susceptibility and IMR 903%, demonstrating their high activity, while 712% of isolates displayed imipenem susceptibility. P. aeruginosa demonstrated MBL positivity in 43% of the instances examined. The oprD gene was absent in 703% (90/128) of IMR-insensitive P. aeruginosa strains. In the 2017-2020 period, a significant proportion, 96% of NME and 90% of P. aeruginosa, from the Asia-Pacific region, demonstrated susceptibility to IMR. In nations where the prevalence of MBL carriage was lower, there was a greater proportion of individuals displaying susceptibility to IMR, as measured by the IMR percentage. From 2017 through 2020, 96% of NME and 90% of P. aeruginosa samples collected from the Asia-Pacific region displayed susceptibility to the IMR agent. In nations with lower prevalence of multi-drug-resistant bacteria, the proportion of infants susceptible to IMR was observed to be greater. Against multidrug-resistant (MDR) Gram-negative bacterial (GNB) infections, colistin (COL) stands as the last resort. Yet, the growing number of bacteria resistant to colistin (COL-R) represents a serious concern for public well-being. This research introduces a strategy that proposes to restore COL activity by uniting farnesol (FAR), exhibiting anti-inflammatory and anti-tumor characteristics, with COL. In vivo and in vitro studies examined the collaborative effect of FAR and COL on COL-R GNB. The COL-FAR combination exhibited a remarkable synergistic antibacterial effect, a finding corroborated by checkerboard assays, time-kill analyses, and LIVE/DEAD bacterial cell viability assays. COL-FAR, as observed through crystal violet staining and scanning electron microscopy, effectively prevented the formation of biofilms and removed established mature biofilms. The cytotoxicity assay for FAR at 64 g/mL did not demonstrate any cytotoxic effects on the RAW2647 cell culture. Live infection experiments on Galleria mellonella showcased that COL-FAR improved the survival rate and reduced bacterial density in a mouse thigh infection model. These outcomes point to COL-FAR's possible efficacy in managing infections caused by COL-R GNB. Aging's intricacies, and the most beneficial methodologies for its scientific exploration Employing a series of queries that probe diverse viewpoints on senescence, we explore how Drosophila melanogaster data, spanning organismal, tiss
