title: Pharmacogenomic influence on sepsis outcome in critically ill patients.
abstract: In infectious and inflammatory diseases, pharmacogenetics affects treatment efficacy and toxicity. Moreover, recent studies suggest its important role in predicting the clinical outcome of sepsis. Our aim was to investigate the influence of single nucleotide polymorphisms (SNPs) in genes which we supposed to be involved in linezolid elimination upon sepsis outcome. Fourteen ICU-admitted patients in therapy with intravenous linezolid (600mg q12h) were enrolled and classified into three groups: group 0 for sepsis, 1 for severe sepsis and 2 for septic shock. Genotyping for SNPs in MDR1 3435 rs1045642 C>T, 2677 rs2032582 G>T and 1236 rs1128503 C>T, MRP2 -24 rs717620 G>A and 1249 rs2273697 G>A, MRP4 *879 rs1059751 T>C and 3348 rs1751034 T>C, BCRP1 421 rs2231142 C>A and 1194+928 rs13120400 T>C, -127 rs4149170 G>A and OCT1 480 rs683369 C>G genes was done using real-time PCR allelic discrimination assay. The Mann-Whitney statistical test was used to analyse variables. MDR1 2677 (p= 0.012), MRP2 1249 (p= 0.038), MRP4 *879 (p= 0.032) and 3348 SNPs significantly influenced the sepsis score. Our study, despite its limited sample size, could be decisive for early sepsis prediction and may improve the management of critically ill patients.
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Allegra
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Fatiguso
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Corcione
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Favata
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ariaudo
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pagani
authors.affiliation: Department of Surgical Sciences, University of Turin, City of Health and Science, Molinette Hospital, Turin, Italy.
authors.forename: Vito Marco
authors.initials: VM
authors.lastname: Ranieri
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: De Rosa
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Department of Medical Sciences, Unit of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D016638:Critical Illness / Q000401:mortality; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007558:Italy; D000069349:Linezolid / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid