The currently recommended gonococcal therapies are rapidly losing efficacy and;therefore,novel options for treatment are urgently required to ensure future treatment remains available.Here we investigated the suscepti...The currently recommended gonococcal therapies are rapidly losing efficacy and;therefore,novel options for treatment are urgently required to ensure future treatment remains available.Here we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic acid.These isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin,antimicrobials that are currently recommended as a first-line dual therapy.Although official susceptibility breakpoints have not been established,all gonococcal isolates appeared to be susceptible to fusidic acid,with the majority of isolates displaying a minimal inhibitory concentration(MIC)of 0.25 or 0.5mg/L.Overall,the MIC90 was 0.5mg/L,with a MIC range of 0.08-2mg/L.Importantly,no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was observed.Further analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations(4MIC).In conclusion,fusidic acid displayed consistent antimicrobial activity against N.gonorrhoeae and,given the absence of cross-resistance with ceftriaxone and azithromycin,might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.展开更多
The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future.To deal with these“new challenges”,scientists tend to re-pick up“old antibiotics”.Fusid...The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future.To deal with these“new challenges”,scientists tend to re-pick up“old antibiotics”.Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria,especially Staphylococci,and represent the only triterpene-derived antibiotic class in clinical setting.These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades.Isolation,characterization,biological evaluation,as well as chemical modifications of fusidane-type antibiotics are increasingly being reported.Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways,but also for expanding their structural diversity.Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid.This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021.The informative structure-activity relationship is also highlighted.展开更多
基金This work was supported by the Zhejiang Provincial Natural Science Foundation of China(grant number LR16H190001).
文摘The currently recommended gonococcal therapies are rapidly losing efficacy and;therefore,novel options for treatment are urgently required to ensure future treatment remains available.Here we investigated the susceptibility of 379 contemporary clinical Neisseria gonorrhoeae isolates from China for susceptibility to fusidic acid.These isolates include numerous multidrug-resistant strains with resistance or reduced susceptibility against ceftriaxone and/or azithromycin,antimicrobials that are currently recommended as a first-line dual therapy.Although official susceptibility breakpoints have not been established,all gonococcal isolates appeared to be susceptible to fusidic acid,with the majority of isolates displaying a minimal inhibitory concentration(MIC)of 0.25 or 0.5mg/L.Overall,the MIC90 was 0.5mg/L,with a MIC range of 0.08-2mg/L.Importantly,no correlation between fusidic acid susceptibility and susceptibility to ceftriaxone or azithromycin was observed.Further analysis of gonococcal survival curves indicated that fusidic acid was only mildly bactericidal at the highest tested concentrations(4MIC).In conclusion,fusidic acid displayed consistent antimicrobial activity against N.gonorrhoeae and,given the absence of cross-resistance with ceftriaxone and azithromycin,might be interesting for further evaluation of single or dual antimicrobial therapies in combination with ceftriaxone or azithromycin.
基金supported by the National Natural Science Foundation of China(Nos.81903494 and 81903483)。
文摘The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future.To deal with these“new challenges”,scientists tend to re-pick up“old antibiotics”.Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria,especially Staphylococci,and represent the only triterpene-derived antibiotic class in clinical setting.These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades.Isolation,characterization,biological evaluation,as well as chemical modifications of fusidane-type antibiotics are increasingly being reported.Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways,but also for expanding their structural diversity.Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid.This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021.The informative structure-activity relationship is also highlighted.
