Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study.
BACKGROUND
Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy.


METHODS
A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach.


RESULTS
Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001).


CONCLUSIONS
In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Lidia
L
Dalfino
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Filomena
F
Puntillo
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Maria Josephine Mura
MJ
Ondok
Microbiology Section, Department of Interdisciplinary Medicine.
Adriana
A
Mosca
Department of Basic Medical Science, Neuroscience and Sense Organs, University "Aldo Moro" of Bari, Italy.
Rosa
R
Monno
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Sara
S
Coppolecchia
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Maria Luigia
ML
Spada
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Francesco
F
Bruno
Anesthesia and Intensive Care Unit, Department of Emergency and Organ Transplantation.
Nicola
N
Brienza
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D000931:Antidotes / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D032124:Blighia; D003091:Colistin / Q000008:administration & dosage* / Q000009:adverse effects*; D016638:Critical Illness; D005260:Female; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D018805:Sepsis / Q000188:drug therapy; D055815:Young Adult
D000900:Anti-Bacterial Agents; D000931:Antidotes; D001205:Ascorbic Acid; D003091:Colistin
acute kidney injury; ascorbic acid; colistimethate sodium; colistin; critically ill