Risk factors of colistin safety according to administration routes: Intravenous and aerosolized colistin.

Kyoung Lok Min,Jae Song Kim,Soo Hyun Kim,Sun Mi Jung,Eun Sun Son,Min Jung Chang,Andrea Ballotta

doi:10.1371/journal.pone.0207588

Kyoung Lok Min, Jae Song Kim + Show 5 more

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https://doi.org/10.1371/journal.pone.0207588

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Abstract

BackgroundNephrotoxicity of intravenous (IV) colistin has impeded its clinical use; aerosolized (AS) colistin may be an alternative, but safety data are lacking. Therefore, this study aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors associated with IV and AS colistin administration.MethodsA retrospective study was performed in a tertiary referral hospital. Data were collected before and after colistin administration between October 2012 and April 2016. Exclusion criteria were as follows: age less than 18 years, previous colistin administration, concurrent use of IV and AS colistin, dialysis before colistin use, and colistin use for less than 3 days. We compared AKI incidence following administration of IV versus AS colistin and analyzed risk factors for colistin-associated nephrotoxicity.ResultsA total of 464 patients were enrolled (n = 311, IV group; n = 153, AS group). Incidence of AKI was significantly higher in the IV group (IV vs AS, 20.26% vs 7.84%, p-value < 0.001). Duration of colistin use (OR 1.033, 95% CI 1.009–1.058, p-value 0.008) and presence of chronic kidney disease (OR 2.710, 95% CI 1.348–5.448, p-value 0.005) were associated with nephrotoxicity. There were no significant risk factors associated with AS colistin.ConclusionsAlthough AS colistin was not associated with any significant risk factors for nephrotoxicity, duration of colistin use and baseline kidney function may affect AS colistin-associated nephrotoxicity.

Highlights

Incidence of infections with multidrug-resistant gram-negative (MDR G (-)) pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter, has risen
Duration of colistin use and presence of chronic kidney disease were associated with nephrotoxicity
AS colistin was not associated with any significant risk factors for nephrotoxicity, duration of colistin use and baseline kidney function may affect AS colistin-associated nephrotoxicity

Summary

Introduction

Incidence of infections with multidrug-resistant gram-negative (MDR G (-)) pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter, has risen. These infections represent a threat to public health because these gram-negative bacteria are resistant to commonly used antibiotics such as antipseudomonal penicillins and cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, and carbapenems [1]. Use of colistin has declined since the 1970s due to adverse side effects and development of less-toxic antibiotics [4,5]. Many peer-reviewed studies have examined colistin-induced nephrotoxicity.[6,7,8,9,10,11,12]. Colistin induces nephrotoxicity through increased tubular epithelial cell membrane permeability. This study aimed to evaluate the incidence of acute kidney injury (AKI) and risk factors associated with IV and AS colistin administration

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