Risk factors for acute kidney injury in patients treated with polymyxin B or colistin methanesulfonate sodium
Introduction
The increased incidence of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa, mainly determined by the dissemination of carbapenemase-producing strains, has led to the re-emergence of polymyxins in clinical practice since they are the last-resort treatment against most infections by these organisms [1], [2].
The bactericidal effect of polymyxins has been shown to be most associated with the unbound (free) area under the concentration–time curve to minimum inhibitory concentration ratio (fAUC/MIC), which emphasises the importance of achieving adequate exposures to these drugs [3]. However, nephrotoxicity is the main dose-limiting adverse effect both of polymyxin B (PMB) and colistin [administered as the prodrug colistin methanesulfonate sodium (CMS)], with rates of acute kidney injury (AKI) ranging from 30% to 60% in recent studies using standardised definitions [4], [5], [6], [7], [8], [9], [10], [11], [12], [13].
There is no clear evidence of increased renal toxicity of one polymyxin compared with the other. In fact, there are only two studies comparing both drugs regarding toxicity: one has found no difference between them [14] and the other has demonstrated a higher incidence of toxicity with CMS [9]. The aim of this study was to assess risk factors for AKI in a cohort of patients at the same institution treated with PMB and CMS, with particular focus on the potential differences between each polymyxin.
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Patients and study design
This was a retrospective cohort study carried out at Hospital Universitário Evangélico de Curitiba, a 700-bed tertiary care teaching hospital in Curitiba, Brazil. Patients were enrolled using the hospital's pharmacy database from January 2009 to January 2011. Inclusion criteria were patients receiving intravenous PMB or CMS for ≥48 h. Exclusion criteria were patients <18 years old and patients receiving renal replacement therapy at the beginning of treatment. PMB or CMS were prescribed according
Patient characteristics
A total of 132 patients were included in the study. Most patients were male (80; 60.6%) and the mean ± standard deviation (S.D.) age was 46.5 ± 21.5 years. Most patients (82; 62.1%) had no co-morbidities, with a median [interquartile range (IQR)] Charlson score of 0 (0.5–2.5). In total, 56 patients (42.4%) were admitted for trauma (n = 41) or burns (n = 15), and 72 (54.5%) were surgical patients including 67 (50.8%) admitted for emergency surgery; other less frequent conditions were cardiovascular
Discussion
This study evaluated the incidence of and risk factors for AKI in a cohort of patients treated with polymyxins mostly composed by young adults with baseline normal creatinine levels and few co-morbidities. The overall incidence of AKI during therapy (25.8%) may be considered low in comparison with other studies evaluating AKI through a standardised criteria, especially considering that most patients in the current cohort treated with PMB and all patients treated with CMS received relatively
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