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10.1021/acsinfecdis.6b00035 http://scihub22266oqcxt.onion/10.1021/acsinfecdis.6b00035 C5300747!5300747!27626100     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 296.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 296.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 296.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       ACS+Infect+Dis 2016 ; 2 (7): 478-88 Nephropedia Template TP {{tp|p=27626100|t=2016. An ?unlikely? pair: The antimicrobial synergy of polymyxin B in combination with the cystic fibrosis trans-membrane conductance regulator drugs KALYDECO and ORKAMBI |pdf=|usr=}}{{27626100}} gab.com Text An unlikely pair: The antimicrobial synergy of polymyxin B in combination with the cystic fibrosis trans-membrane conductance regulator drugs KALYDECO and ORKAMBI JO: ACS Infect Dis http://www.kidney.de/pget.php?&tw=1&pmid=27626100 #FOAvip Novel combination therapies are desperately needed for combating lung infections caused by bacterial ?superbugs?. This study aimed to investigate synergistic antibacterial activity of polymyxin B in combination with the cystic fibrosis (CF) drugs KALYDECO? (ivacaftor) and ORKAMBI? (ivacaftor+lumacaftor) against Gram-negative pathogens that commonly colonize the CF lung, in particular the problematic Pseudomonas aeruginosa. The in vitro synergistic activity of polymyxin B combined with ivacaftor or lumacaftor was assessed using checkerboard and static time-kill assays against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa isolates from the lungs of CF patients. Polymyxin B, ivacaftor or lumacaftor were ineffective when used individually against polymyxin-resistant (MIC, ? 4 mg/L) isolates. However, when used together the combination of clinically-relevant concentrations of polymyxin B (2 mg/L) combined with ivacaftor (8 mg/L) or ivacaftor (8 mg/L)+lumacaftor (8 mg/L) and displayed synergistic killing activity against polymyxin-resistant P. aeruginosa isolates as demonstrated by 100-fold decrease in the bacterial count (CFU/mL) after 24 h. The combinations also displayed excellent antibacterial activity against P. aeruginosa under CF relevant conditions in a sputum medium assay. The combination of lumacaftor (alone) with polymyxin B showed additivity against P. aeruginosa.The potential antimicrobial mode of action of the combinations against P. aeruginosa was investigated using different methods. Treatment with the combinations induced cytosolic GFP release from P. aeruginosa cells and showed permeabilizing activity in the nitrocefin assay, indicating damage to both the outer and inner Gram-negative cell membranes. Moreover, scanning and transmission electron micrographs revealed that the combinations produce outer membrane damage to P. aeruginosa cells that is distinct from the effect of each compound per se. Ivacaftor was also shown to be a weak inhibitor of the bacterial DNA gyrase and topoisomerase IV with no effect on either human type I or type II? topoisomerases. Lumacaftor displayed the ability to increase the cellular production of damaging reactive oxygen species.In summary, the combination of polymyxin B with KALYDECO? or ORKAMBI? exhibited synergistic activity against highly polymyxin-resistant P. aeruginosa CF isolates and can be potentially useful for otherwise untreatable CF lung infections. Twit Text FOAVip An unlikely pair: The antimicrobial synergy of polymyxin B in combination with the cystic fibrosis trans-membrane conductance regulator drugs KALYDECO and ORKAMBI ????ACS Infect Dis http://www.kidney.de/pget.php?&tw=1&pmid=27626100 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27626100 #FOAvip English Wikipedia <ref>{{Cite pmid|27626100}}</ref> An ?unlikely? pair: The antimicrobial synergy of polymyxin B in combination with the cystic fibrosis trans-membrane conductance regulator drugs KALYDECO and ORKAMBI #MMPMID27626100 Schneider EK; Azad MA; Han ML; Zhou Q(; Wang J; Huang JX; Cooper MA; Doi Y; Baker MA; Bergen PJ; Muller MT; Li J; Velkov T ACS Infect Dis 2016[Jul]; 2 (7): 478-88 PMID27626100show ga Novel combination therapies are desperately needed for combating lung infections caused by bacterial ?superbugs?. This study aimed to investigate synergistic antibacterial activity of polymyxin B in combination with the cystic fibrosis (CF) drugs KALYDECO? (ivacaftor) and ORKAMBI? (ivacaftor+lumacaftor) against Gram-negative pathogens that commonly colonize the CF lung, in particular the problematic Pseudomonas aeruginosa. The in vitro synergistic activity of polymyxin B combined with ivacaftor or lumacaftor was assessed using checkerboard and static time-kill assays against a panel of polymyxin-susceptible and polymyxin-resistant P. aeruginosa isolates from the lungs of CF patients. Polymyxin B, ivacaftor or lumacaftor were ineffective when used individually against polymyxin-resistant (MIC, ? 4 mg/L) isolates. However, when used together the combination of clinically-relevant concentrations of polymyxin B (2 mg/L) combined with ivacaftor (8 mg/L) or ivacaftor (8 mg/L)+lumacaftor (8 mg/L) and displayed synergistic killing activity against polymyxin-resistant P. aeruginosa isolates as demonstrated by 100-fold decrease in the bacterial count (CFU/mL) after 24 h. The combinations also displayed excellent antibacterial activity against P. aeruginosa under CF relevant conditions in a sputum medium assay. The combination of lumacaftor (alone) with polymyxin B showed additivity against P. aeruginosa.The potential antimicrobial mode of action of the combinations against P. aeruginosa was investigated using different methods. Treatment with the combinations induced cytosolic GFP release from P. aeruginosa cells and showed permeabilizing activity in the nitrocefin assay, indicating damage to both the outer and inner Gram-negative cell membranes. Moreover, scanning and transmission electron micrographs revealed that the combinations produce outer membrane damage to P. aeruginosa cells that is distinct from the effect of each compound per se. Ivacaftor was also shown to be a weak inhibitor of the bacterial DNA gyrase and topoisomerase IV with no effect on either human type I or type II? topoisomerases. Lumacaftor displayed the ability to increase the cellular production of damaging reactive oxygen species.In summary, the combination of polymyxin B with KALYDECO? or ORKAMBI? exhibited synergistic activity against highly polymyxin-resistant P. aeruginosa CF isolates and can be potentially useful for otherwise untreatable CF lung infections. äAn ?unlikely? pair: The antimicrobial synergy of polymyxin B in combin(epmc).pdf DeepDyve Pubget Overpricing