title: Impact of colistin plasma levels on the clinical outcome of patients with infections caused by extremely drug-resistant Pseudomonas aeruginosa.
abstract: Colistin has a narrow therapeutic window with nephrotoxicity being the major dose-limiting adverse effect. Currently, the optimal doses and therapeutic plasma levels are unknown.
  
  
  
  Prospective observational cohort study, including patients infected by colistin-susceptible P. aeruginosa treated with intravenous colistimethate sodium (CMS). Clinical data and colistin plasma levels at steady-state (Css) were recorded. The primary and secondary end points were clinical cure and 30-day all-cause mortality.
  
  
  
  Ninety-one patients were included. Clinical cure was observed in 72 (79%) patients. The mean (SD) Csswas 1.49 (1.4) mg/L and 2.42 (1.5) mg/L (p = 0.01) in patients who achieved clinical cure and those who not, respectively. Independent risk factors for clinical failure were male sex (OR 5.88; 95% CI 1.09-31.63), APACHE II score (OR 1.15; 95% CI 1.03-1.27) and nephrotoxicity at the EOT (OR 9.13; 95% CI 95% 2.06-40.5). The 30-day mortality rate was 30.8%. Risk factors for 30-day mortality included the APACHE II score (OR 1.98; 95% CI 1-1.20), the McCabe score (OR 2.49; 95% CI 1.14-5.43) and the presence of nephrotoxicity at the end of treatment (EOT) (OR 3.8; 95% CI 1.26-11.47).
  
  
  
  In this series of patients with infections caused by XDR P. aeruginosa infections, Cssis not observed to be related to clinical outcome.
authors.affiliation: Infectious Disease Service, Hospital del Mar, Barcelona, Spain. lsorli@parcdesalutmar.cat.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. lsorli@parcdesalutmar.cat.|Universitat Autònoma de Barcelona, Barcelona, Spain. lsorli@parcdesalutmar.cat.|CEXS-Universitat Pompeu Fabra, Barcelona, Spain. lsorli@parcdesalutmar.cat.
authors.forename: Luisa
authors.identifier: 0000-0001-9562-514X
authors.initials: L
authors.lastname: Sorlí
authors.affiliation: Pharmacy Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Luque
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.|Laboratori de Referència de Catalunya, Prat de Llobregat, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Segura
authors.affiliation: Pharmacy Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Campillo
authors.affiliation: Infectious Disease Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.|CIBERES, Madrid, Spain.
authors.forename: Milagro
authors.initials: M
authors.lastname: Montero
authors.affiliation: Infectious Disease Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Erika
authors.initials: E
authors.lastname: Esteve
authors.affiliation: Infectious Disease Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
authors.forename: Sabina
authors.initials: S
authors.lastname: Herrera
authors.affiliation: InfectiousDiseaseUnit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.|Institut d'Investigació Biomèdica Sant Pau, Barcelona, Spain.|CIBERES, Madrid, Spain.
authors.forename: Natividad
authors.initials: N
authors.lastname: Benito
authors.affiliation: Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.|Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain.|CIBERES, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Alvarez-Lerma
authors.affiliation: Pharmacy Service, Hospital del Mar, Barcelona, Spain.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.|CIBERES, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Grau
authors.affiliation: Infectious Disease Service, Hospital del Mar, Barcelona, Spain. jhorcajada@parcdesalutmar.cat.|Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. jhorcajada@parcdesalutmar.cat.|Intensive Care Unit, Hospital del Mar, Barcelona, Spain. jhorcajada@parcdesalutmar.cat.|Universitat Autònoma de Barcelona, Barcelona, Spain. jhorcajada@parcdesalutmar.cat.|CEXS-Universitat Pompeu Fabra, Barcelona, Spain. jhorcajada@parcdesalutmar.cat.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Horcajada
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011552:Pseudomonas Infections / Q000097:blood* / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin
keywords: Colistin; Extremely drug-resistant; Mortality; Nephrotoxicity; Plasma concentration; Pseudomonas aeruginosa