title: Glyburide is anti-inflammatory and associated with reduced mortality in melioidosis.
abstract: BACKGROUND
  Patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. Glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. This K(ATP)-channel blocker and broad-spectrum ATP-binding cassette (ABC) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infection.
  
  
  METHODS
  We studied a cohort of 1160 patients with gram-negative sepsis caused by a single pathogen (Burkholderia pseudomallei), 410 (35%) of whom were known to have diabetes. We subsequently studied prospectively diabetics with B. pseudomallei infection (n = 20) to compare the gene expression profile of peripheral whole blood leukocytes in patients who were taking glyburide against those not taking any sulfonylurea.
  
  
  RESULTS
  Survival was greater in diabetics than in nondiabetics (38% vs 45%, respectively, P = .04), but the survival benefit was confined to the patient group taking glyburide (adjusted odds ratio .47, 95% confidence interval .28-.74, P = .005). We identified differential expression of 63 immune-related genes (P = .001) in patients taking glyburide, the sum effect of which we predict to be antiinflammatory in the glyburide group.
  
  
  CONCLUSIONS
  We present observational evidence for a glyburide-associated benefit during human melioidosis and correlate this with an anti-inflammatory effect of glyburide on the immune system.
authors.affiliation: Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. gavin.koh@gmail.com
authors.forename: Gavin C K W
authors.initials: GC
authors.lastname: Koh
authors.forename: Rapeephan R
authors.initials: RR
authors.lastname: Maude
authors.forename: M Fernanda
authors.initials: MF
authors.lastname: Schreiber
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Wiersinga
authors.forename: Vanaporn
authors.initials: V
authors.lastname: Wuthiekanun
authors.forename: Sue J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Weera
authors.initials: W
authors.lastname: Mahavanakul
authors.forename: Wipada
authors.initials: W
authors.lastname: Chaowagul
authors.forename: Wirongrong
authors.initials: W
authors.lastname: Chierakul
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Nicholas P J
authors.initials: NP
authors.lastname: Day
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Peacock
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016957:Burkholderia pseudomallei / Q000302:isolation & purification; D015331:Cohort Studies; D005260:Female; D005905:Glyburide / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008554:Melioidosis / Q000188:drug therapy* / Q000401:mortality*; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D005905:Glyburide