Sýklalyfjaónæmi sérstaklega af Gram-neikvæðum bakteríum hefur næstum skapað kreppulíkar aðstæður. Nýja sýklalyfið Zosurabalpin (RG6006) lofar góðu. Það hefur reynst áhrifaríkt gegn lyfjaónæmum, Gram-neikvæðum bakteríum CRAB í forklínískum rannsóknum.
Antimicrobial resistance (AMR), driven mainly by the misuse and overuse of antimicrobials, is one of top public health risk.
Infections by Gram-negative bacteria are particularly concerning. It is not easy for most of sýklalyf to cross both inner and outer membranes present in this category of bacteria to enter the bacterial cells to show bactericidal actions. Also, Gram-negative bacteria have accumulated disproportionately high degree of sýklalyf mótstöðu.
Acinetobacter baumannii is a Gram-negative bacterium. Infection by one of its strains called ‘carbapenem-resistant Acinetobacter baumannii’ (CRAB) is hard to treat using available sýklalyf. There is an urgent need for an effective sýklalyf against CARB as mortality rate is high (about 40%-60%) which attributed largely to lack of an effective sýklalyf. A progress towards this goal has been reported.
Scientists have identified a novel class of sýklalyf namely, tethered macrocyclic peptides (MCPs) which are active against the Gram –ve bacteria A. baumannii including CARB by blocking transport of bacterial lipopolysaccharide from the inner membrane to the outer membrane.
Zosurabalpin (RG6006) er sýklalyf candidate belonging to ‘tethered macrocyclic peptides (MCPs)’ class. In pre-klínísk trials involving in vitro studies and in vivo studies on animal models, Zosurabalpin has been found to be effective against drug-resistant isolates of ‘carbapenem-resistant Acinetobacter baumannii’ (CRAB) from different regions. It successfully overcame sýklalyf-resistance mechanism of CARB suggesting Zosurabalpin hefur möguleika.
Hence, human klínísk trials have been initiated to check for safety and efficacy Zosurabalpin við að meðhöndla ífarandi sýkingar af völdum KRABBA.
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Tilvísanir:
- Zampaloni, C., Mattei, P., Bleicher, K. et al. A novel sýklalyf class targeting the lipopolysaccharide transporter. Nature (2024). https://doi.org/10.1038/s41586-023-06873-0
- Hawser S., et al 2023. Activity of the Novel Antibiotic Zosurabalpin (RG6006) against Klínísk Acinetobacter Isolates from China, Open Forum Infectious Diseases, Volume 10, Issue Supplement_2, December 2023, ofad500.1754, https://doi.org/10.1093/ofid/ofad500.1754
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