Objective:To characterize two Achromobaeter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program.Methods:Nasopharyngeal swabs from 2 children under 1 year ...Objective:To characterize two Achromobaeter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program.Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR.Results:Two Achromobaeter xylosoxidans A8,closely related to Bordetella spp.were recovered from 2 patients diagnosed of pertussis,both carrying the ptxA gene and IS418 the pertussis toxin encoding gene.Subsequently,antibiotic susceptibility was evaluated by disk-diffusion method and by PCR.Conclusions:Although more detailed studies are needed,the present data highlight the possibility that Achromobaeter xylosoxidans.closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella,might also result in cases of whooping cough.Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.展开更多
Azithromycin(AZM),the most commonly prescribed antibiotic in the United States,is thought to have no activity against multidrugresistant Gram-negative pathogens such as Achromobacter xylosoxidans(AX)per standard minim...Azithromycin(AZM),the most commonly prescribed antibiotic in the United States,is thought to have no activity against multidrugresistant Gram-negative pathogens such as Achromobacter xylosoxidans(AX)per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth.Here we provide the first report of AZM bactericidal activity against carbapenemresistant isolates of AX,with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment.This pharmaceutical activity,evident in eukaryotic tissue culture media,is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood,serum,and neutrophils.Additionally,AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable bacteria.In an illustrative case,AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis,sternal osteomyelitis,and aortic graft infection.Our study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents,adversely affecting patient outcomes.We conclude that AZM merits further exploration in the treatment of drug-resistant AX infections.Novel approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered,especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality.展开更多
基金supported by Sanoti Aventis del Perua fellowship from the program 13.of the ISCIII(grant number:CES11/012)+1 种基金a PhD fellowship of the ISCIII(FI12/00561)a fellowship from CONCYTEC/FONDECYT
文摘Objective:To characterize two Achromobaeter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program.Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR.Results:Two Achromobaeter xylosoxidans A8,closely related to Bordetella spp.were recovered from 2 patients diagnosed of pertussis,both carrying the ptxA gene and IS418 the pertussis toxin encoding gene.Subsequently,antibiotic susceptibility was evaluated by disk-diffusion method and by PCR.Conclusions:Although more detailed studies are needed,the present data highlight the possibility that Achromobaeter xylosoxidans.closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella,might also result in cases of whooping cough.Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.
基金supported by the National Institute of Health grants K12-HD000850(to ERU),U54-HD090259(to GS and VN),1U01AI124316-01(to MK,GS,JP,and VN),and 1KL2TR001444(to MK).
文摘Azithromycin(AZM),the most commonly prescribed antibiotic in the United States,is thought to have no activity against multidrugresistant Gram-negative pathogens such as Achromobacter xylosoxidans(AX)per standard minimum inhibitory concentration testing in cation-adjusted Mueller Hinton Broth.Here we provide the first report of AZM bactericidal activity against carbapenemresistant isolates of AX,with a multifold decrease in minimum inhibitory concentration across 12 clinical isolates when examined under physiologic testing conditions that better recapitulate the in vivo human environment.This pharmaceutical activity,evident in eukaryotic tissue culture media,is associated with enhanced AZM intracellular penetration and synergistic killing with human whole blood,serum,and neutrophils.Additionally,AZM monotherapy inhibited preformed AX biofilm growth in a dose-dependent manner together with a reduction in viable bacteria.In an illustrative case,AZM in combination with piperacillin-tazobactam exerted clear therapeutic effects in a patient with carbapenem-resistant AX mediastinitis,sternal osteomyelitis,and aortic graft infection.Our study reinforces how current antimicrobial testing practices fail to recapitulate the host environment or host-pathogen interactions and may misleadingly declare complete resistance to useful agents,adversely affecting patient outcomes.We conclude that AZM merits further exploration in the treatment of drug-resistant AX infections.Novel approaches to antimicrobial susceptibility testing that better recapitulate the host environment should be considered,especially as infections caused by multidrug-resistant Gram-negative bacterial pathogens are expanding globally with high morbidity and mortality.