title: Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.
abstract: BACKGROUND
  Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia.
  
  
  METHODS
  A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria.
  
  
  RESULTS
  Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy.
  
  
  CONCLUSIONS
  The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.
authors.affiliation: 1 Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Elefritz
authors.affiliation: 1 Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Karri A
authors.initials: KA
authors.lastname: Bauer
authors.affiliation: 2 Division of Acute Care Surgery, Department of Surgery, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Jones
authors.affiliation: 3 Division of Infectious Diseases, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA.|4 Department of Clinical Epidemiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Mangino
authors.affiliation: 5 Center for Biostatistics, The Ohio State University, Columbus, OH, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Porter
authors.affiliation: 1 Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors.forename: Claire V
authors.initials: CV
authors.lastname: Murphy
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003091:Colistin / Q000009:adverse effects / Q000627:therapeutic use*; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000188:drug therapy* / Q000382:microbiology; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin
keywords: colistimethate sodium; colistin; intensive care unit; multidrug resistance; nephrotoxicity; pneumonia