The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from me...The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.展开更多
Collective syntheses of A.baumannii CPS K43,K47 and K88 repeating units have been accomplished via a newα-glycosylation method with GlcN_(3) as donors,which features:1)mild reaction conditions,2)good to high yields,3...Collective syntheses of A.baumannii CPS K43,K47 and K88 repeating units have been accomplished via a newα-glycosylation method with GlcN_(3) as donors,which features:1)mild reaction conditions,2)good to high yields,3)excellent stereoselectivities.The synthetic route also highlights an orthogonal one-pot coupling strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates for stereoselective constructions of both 1,2-trans and 1,2-cis glycosidic bonds,precluding the issues of aglycone transfer.展开更多
Background:With various changes implemented such as perioperative antibiotics for tangential excision,this retrospective study reviews the infection profile of burn patients at Singapore's only centralized burns u...Background:With various changes implemented such as perioperative antibiotics for tangential excision,this retrospective study reviews the infection profile of burn patients at Singapore's only centralized burns unit.Worldwide,the appearance of multidrug-resistant(MDR)strains of Acinetobacter baumanni(A.baumanni)continues to worsen patient outcomes.This study also surveys the role of blood cultures in burns at our unit.Methods:Four hundred fifty-two burn patients admitted to the unit between 2011 and 2013,and with cultures performed,were included in the study.The yields of various cultures were evaluated and 2684 samples were amassed,of which 984(36.7%)were positive.Patient variables for predictors of MDR A.baumanni infection acquisition and bacteremia were evaluated through multivariate analyses.Results:Pseuodomonas aeruginosa(P.aeruginosa)(67 patients)was the most common organism in those with total body surface area(TBSA)burn<20%while MDR A.baumanni(39 patients)was most prevalent in those with TBSA burn≥20%.We found a yield of 1.1%positive blood cultures for TBSA burn<20%and a yield of 18.6%positive cultures in TBSA burn≥20%.The median time between surgery and bacteremia was 6.5 days(range-18 to 68 days,interquartile range 4.5);2.9 and 8.8%of bacteremic episodes occurred within 24 and 48 h,respectively.This is a decrease from a predeceasing study(45.3%for 24 h and 60%for 48 h).Multivariate analysis revealed that length of hospital stay and TBSA burn≥20%were predictors of MDR A.baumanni infection and positive blood cultures.Conclusions:MDR A.baumanni infection burdens patient management,especially in those with TBSA burn≥20%and longer hospital stay.Prophylactic antibiotics may reduce perioperative bacteremia,but their role in MDR infections needs to be evaluated.The role of blood cultures in TBSA burn<20%needs reconsideration.展开更多
基金supported by the Nanjing Infectious Disease Clinical Medical Center,Innovation center for infectious disease of Jiangsu Province(NO.CXZX202232)the Leading Talent Project of Jiangsu Province Traditional Chinese Medicine(NO.SLJ0216)+4 种基金the Nanjing Health science and Technology Development Special fund Project(NO.YKK20102)the General Program of Jiangsu Commission of Health(NO.M2021088)the Nanjing Health science and Technology Development General Project(NO.YKK21121)the 2023 Nanjing Second Hospital Talent Support Project Grant(RCZD23003)the Jiangsu Province Postgraduate Research and Practice Innovation Program(KYCX24_2176).
文摘The treatment of Acinetobacter baumannii(A.baumannii)poses significant clinical challenges due to its multidrug/pan-drug resistance.In this study,we isolated a broad-spectrum lytic A.baumannii phage,named P425,from medical wastewater,targeting nine multidrug-resistant A.baumannii(MDRAB)with diverse capsular types.Biological characterization revealed that P425 maintains activity at pH range of 3–12 and temperature range of 4–50℃.It resists UV irradiation for 20 minutes,and had an optimal multiplicity of infection(OMOI)is 0.00001.The adsorption kinetics showed that P425 achieves>90%within 10 minutes of incubation,and the one-step growth curve indicated a 10-min latent period,with a burst size of 184 PFU/cell.The genome sequencing results indicated that it harbors a double-stranded DNA genome of 40,583 bp with a GC content of 39.39%.Intergenomic similarity analysis classified it as a novel species within the Friunavirus genus,while electron microscopy results showed that it belongs to the Podoviridae family.Notably,P425 exhibits potent 24-h in vitro inhibitory activity against MDRAB,and demonstrates synergistic effect at an MOI of 0.001 when combined with five classes of antibiotics targeting distinct antimicrobial mechanisms.Safety evaluations confirmed the absence of cytotoxicity,hemolytic activity,or systemic toxicity both in vitro and in vivo.In mouse infection models,P425 can significantly improve the survival rates of mice infected with Ab25(ST1791/KL101).When co-administered with levofloxacin,it achieved 100%protection against mortality and promoted immune recovery.Collectively,P425 is a prospective lytic phage that could offer novel strategies for combating MDRAB infections.
基金supports from National Natural Science Foundation of China(22322110)the CAS Pioneer Hundred Talents Program(No.2017-128)+1 种基金Yunnan Province Science and Technology Department(202305AH340005)the Young Talents Project of High-level Talent Introduction Program of Yunnan Province are greatly acknowledged。
文摘Collective syntheses of A.baumannii CPS K43,K47 and K88 repeating units have been accomplished via a newα-glycosylation method with GlcN_(3) as donors,which features:1)mild reaction conditions,2)good to high yields,3)excellent stereoselectivities.The synthetic route also highlights an orthogonal one-pot coupling strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates for stereoselective constructions of both 1,2-trans and 1,2-cis glycosidic bonds,precluding the issues of aglycone transfer.
文摘Background:With various changes implemented such as perioperative antibiotics for tangential excision,this retrospective study reviews the infection profile of burn patients at Singapore's only centralized burns unit.Worldwide,the appearance of multidrug-resistant(MDR)strains of Acinetobacter baumanni(A.baumanni)continues to worsen patient outcomes.This study also surveys the role of blood cultures in burns at our unit.Methods:Four hundred fifty-two burn patients admitted to the unit between 2011 and 2013,and with cultures performed,were included in the study.The yields of various cultures were evaluated and 2684 samples were amassed,of which 984(36.7%)were positive.Patient variables for predictors of MDR A.baumanni infection acquisition and bacteremia were evaluated through multivariate analyses.Results:Pseuodomonas aeruginosa(P.aeruginosa)(67 patients)was the most common organism in those with total body surface area(TBSA)burn<20%while MDR A.baumanni(39 patients)was most prevalent in those with TBSA burn≥20%.We found a yield of 1.1%positive blood cultures for TBSA burn<20%and a yield of 18.6%positive cultures in TBSA burn≥20%.The median time between surgery and bacteremia was 6.5 days(range-18 to 68 days,interquartile range 4.5);2.9 and 8.8%of bacteremic episodes occurred within 24 and 48 h,respectively.This is a decrease from a predeceasing study(45.3%for 24 h and 60%for 48 h).Multivariate analysis revealed that length of hospital stay and TBSA burn≥20%were predictors of MDR A.baumanni infection and positive blood cultures.Conclusions:MDR A.baumanni infection burdens patient management,especially in those with TBSA burn≥20%and longer hospital stay.Prophylactic antibiotics may reduce perioperative bacteremia,but their role in MDR infections needs to be evaluated.The role of blood cultures in TBSA burn<20%needs reconsideration.
