title: High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy? A preliminary study.
abstract: BACKGROUND
  Gram-negative bacteria susceptible only to colistin (COS) are emerging causes of severe nosocomial infections, reviving interest in the use of colistin. However, consensus on the most effective way to administer colistin has not yet been reached.
  
  
  METHODS
  All patients who had sepsis due to COS gram-negative bacteria or minimally susceptible gram-negative bacteria and received intravenous colistimethate sodium (CMS) were prospectively enrolled. The CMS dosing schedule was based on a loading dose of 9 MU and a 9-MU twice-daily fractioned maintenance dose, titrated on renal function. For each CMS course, clinical cure, bacteriological clearance, daily serum creatinine clearance, and estimated creatinine clearance were recorded.
  
  
  RESULTS
  Twenty-eight infectious episodes due to Acinetobacter baumannii (46.4%), Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (7.2%) were analyzed. The main types of infection were bloodstream infection (64.3%) and ventilator-associated pneumonia (35.7%). Clinical cure was observed in 23 cases (82.1%). Acute kidney injury developed during 5 treatment courses (17.8%), did not require renal replacement therapy, and subsided within 10 days from CMS discontinuation. No correlation was found between variation in serum creatinine level (from baseline to peak) and daily and cumulative doses of CMS, and between variation in serum creatinine level (from baseline to peak) and duration of CMS treatment.
  
  
  CONCLUSIONS
  Our study shows that in severe infections due to COS gram-negative bacteria, the high-dose, extended-interval CMS regimen has a high efficacy, without significant renal toxicity.
authors.affiliation: Anesthesia and Intensive Care Unit, Department of Emergeny and Organ Transplantion, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy. dalfino@tiscali.it
authors.forename: Lidia
authors.initials: L
authors.lastname: Dalfino
authors.forename: Filomena
authors.initials: F
authors.lastname: Puntillo
authors.forename: Adriana
authors.initials: A
authors.lastname: Mosca
authors.forename: Rosa
authors.initials: R
authors.lastname: Monno
authors.forename: Maria Luigia
authors.initials: ML
authors.lastname: Spada
authors.forename: Sara
authors.initials: S
authors.lastname: Coppolecchia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Miragliotta
authors.forename: Francesco
authors.initials: F
authors.lastname: Bruno
authors.forename: Nicola
authors.initials: N
authors.lastname: Brienza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016638:Critical Illness; D003428:Cross Infection / Q000188:drug therapy*; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; C004691:colistinmethanesulfonic acid; D003091:Colistin