title: Acute kidney injury during colistin therapy: a prospective study in patients with extensively-drug resistant Acinetobacter baumannii infections.
abstract: The study aimed to prospectively assess incidence and risk factors for colistin-associated nephrotoxicity. This is a secondary analysis of a multicentre, randomized clinical trial, comparing efficacy and safety of colistin versus the combination of colistin plus rifampicin in severe infections due to extensively drug-resistant (XDR) Acinetobacter baumannii. The primary end point was acute kidney injury (AKI) during colistin treatment, assessed using the AKI Network Criteria, and considering death as a competing risk. A total of 166 adult patients without baseline kidney disease on renal replacement therapy were studied. All had life-threatening infections due to colistin-susceptible XDR A. baumannii. Patients received colistin intravenously at the same initial dose (2 million international units (MIU) every 8 h) with predefined dose adjustments according to the actual renal function. Serum creatinine was measured at baseline and at days 4, 7, 11, 14 and 21 (or last day of therapy when discontinued earlier). Outcomes assessed were 'time to any kidney injury' (AKI stages 1-3) and 'time to severe kidney injury' (considering only AKI stages 2-3 as events). When evaluating overall mortality, AKI occurrence was modelled as a time-dependent variable. AKI was observed in 84 patients (50.6%, stage 1 in 40.4%), with an incidence rate of 5/100 person-days (95% CI 4-6.2). Risk estimates of AKI at 7 and 14 days were 30.6% and 58.8%. Age and previous chronic kidney disease were significantly associated with any AKI in multivariable analysis. Neither 'any' nor 'severe AKI' were associated with on-treatment mortality (p 0.32 and p 0.54, respectively). AKI occurs in one-third to one-half of colistin-treated patients and is more likely in elderly patients and in patients with kidney disease. As no impact of colistin-associated AKI on mortality was found, this adverse event should not represent a reason for withholding colistin therapy, whenever indicated.
authors.affiliation: Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Durante-Mangoni
authors.affiliation: Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Andini
authors.affiliation: Medical Statistics, Department of Medicine and Public Health, University of Naples S.U.N., Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Signoriello
authors.affiliation: Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cavezza
authors.affiliation: Anaesthesia and Intensive Care Unit, AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Murino
authors.affiliation: Anaesthesia and Intensive Care Unit, AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Buono
authors.affiliation: Anaesthesia and Intensive Care Unit, AORN Cardarelli, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Cristofaro
authors.affiliation: Anaesthesia and Intensive Care Unit, AORN Cardarelli, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Taglialatela
authors.affiliation: Infectious Diseases Division, S. Maria Misericordia University Hospital, Udine, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bassetti
authors.affiliation: Intensive Care Unit, Emergency Department, AOU Pisana, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Malacarne
authors.affiliation: 2nd Infectious Diseases Division, National Institute for Infectious Diseases 'L. Spallanzani', Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Petrosillo
authors.affiliation: Anaesthesia and Intensive Care Unit, AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Corcione
authors.affiliation: Infectious Diseases Division, San Martino University Hospital and University of Genoa, Genoa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Viscoli
authors.affiliation: Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Naples, Italy. Electronic address: riccardo.utili@unina2.it.
authors.forename: R
authors.initials: R
authors.lastname: Utili
authors.affiliation: Medical Statistics, Department of Medicine and Public Health, University of Naples S.U.N., Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Gallo
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D003091:Colistin / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D012293:Rifampin; D003091:Colistin
keywords: Acinetobacter baumannii; Colistin; Extensively-drug-resistant; Nephrotoxicity; Nosocomial infection; Risk factors