With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment reg...With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.展开更多
Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which...Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.展开更多
文摘With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.
文摘Pseudomonas aeruginosa is an opportunistic pathogen that contributes to high morbidity and mortality. MexAB-OprM is the main efflux pump among the Resistance-Nodulation-Division family multi-drug effiux systems, which contribute greatly to the multidrug resistance of P. aeruginosa. Effiux pump inhibitors （EPIs） of MexAB-OprM could enhance the activity of the antibiotics effiuxed by MexAB-OprM, and thus they might be useful in the clinic as antibacterial synergistic agents. In this work, a new EPI of MexAB-OprM, KL-0153, was discovered by screening of a small molecular library. Its inhibition of MexAB-OprM was confirmed by assays of synergistic activity and EB accumulation. The activity of KL-0153 was shown to be synergistic with antibiotics effiuxed by MexAB-OprM when they were tested against strains expressing MexAB-OprM, especially so for the strains that express MexAB-OprM at high levels. KL-0153 showed more activity than the positive drug carbonyl cyanide m-chlorophenylhydrazone in the EB accumulation assay. It cannot be neglected that KL-0153 has significant liver and kidney toxicity. However, KL-0153 may be a lead comoound for the research and development of new tvoes of EPIs.
