{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brennan-Krohn T"],"funding":["HHS | National Institutes of Health","NICHD NIH HHS","NIAID NIH HHS"],"pagination":["e00873-18"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6153801"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["62(10)"],"pubmed_abstract":["Resistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistant <i>Enterobacteriaceae</i> (CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistant <i>Enterobacteriaceae</i> isolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens."],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae."],"pmcid":["PMC6153801"],"funding_grant_id":["T32 AI007061","U19AI110818","K08 AI132716","K08AI132716","T32 HD055148","T32HD055148","UM1 AI104681","T32AI007061","U19 AI110818"],"pubmed_authors":["Kirby JE","Pironti A","Brennan-Krohn T"],"additional_accession":[]},"is_claimable":false,"name":"Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae.","description":"Resistance to colistin, a polypeptide drug used as an agent of last resort for the treatment of infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria, including carbapenem-resistant <i>Enterobacteriaceae</i> (CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistant <i>Enterobacteriaceae</i> isolates, 15 of which were also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and the activities of those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the 4 most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in the checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative bacterial outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Oct","modification":"2026-06-14T04:19:56.839Z","creation":"2026-06-14T03:09:07.897Z"},"accession":"S-EPMC6153801","cross_references":{"pubmed":["30061285"],"doi":["10.1128/AAC.00873-18","10.1128/aac.00873-18"]}}