Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study

Dalfino, Lidia; Puntillo, Filomena; Ondok, Maria Josephine Mura; Mosca, Adriana; Monno, Rosa; Coppolecchia, Sara; Spada, M.; Bruno, Francesco; Brienza, Nicola

doi:10.1093/cid/civ717

Cited by 90 publications

(85 citation statements)

References 43 publications

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“…or to minimize the use of polymyxins altogether (i.e., aminoglycoside use, novel combination therapy, drug development, etc.) (17)(18)(19). In this investigation, nephrotoxicity was reversible in only about 60% of non-cystic fibrosis patients by hospital discharge, highlighting the significant effect of this toxicity on patient outcomes.…”

Section: Discussionmentioning

confidence: 68%

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin

Crass

Rutter

Burgess

et al. 2017

Antimicrob Agents Chemother

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Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e., risk, injury, failure, loss, end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%, P ϭ 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%, P ϭ 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%, P Ͻ 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture.

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Section: Discussionmentioning

confidence: 68%

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin

Crass

Rutter

Burgess

et al. 2017

Antimicrob Agents Chemother

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“…Any consideration given to ceasing either polymyxin should recognize that polymyxin-associated AKI is usually mild to moderate and reversible (6) and balance risk to benefit in the light of the condition of the patient and the availability of other antimicrobial options. While concomitant administration of the antioxidant ascorbic acid has been shown to protect against colistin-induced nephrotoxicity in animals (50), clinical studies have provided contradictory findings (51,52), necessitating further examination.…”

Section: Discussionmentioning

confidence: 99%

Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B?

Zavascki

Nation

2017

Antimicrob Agents Chemother

168

120

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Nephrotoxicity is a common adverse effect of the clinically used polymyxins, colistin and polymyxin B. This adverse effect is dose limiting for both polymyxins, as the plasma polymyxin concentrations associated with renal damage overlap those required for antibacterial effect. Since development of acute kidney injury (AKI) during therapy is highly undesirable, it is extremely important to know whether there is any difference between the nephrotoxic potential of colistin (administered as its inefficient prodrug, colistimethate) and polymyxin B (administered as the active form). Both polymyxins are cytotoxic to renal tubular cells and are prone to cause nephrotoxicity in vivo because of the renal handling mechanisms that facilitate accumulation of these compounds in these cells, processes that are reviewed in this article. Also reviewed are the emerging data that strongly suggest significantly higher rates of AKI in patients treated with colistimethate compared to patients treated with polymyxin B. This finding may be due to differences in pharmacokinetics and renal handling mechanisms of colistimethate and formed colistin versus polymyxin B, and consequently the relative amount of polymyxin material delivered to tubular cells. A lower risk of AKI with polymyxin B is one of several potential advantages over colistimethate. The relative safety and efficacy of the two agents require closer examination in well-designed clinical studies.

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“…Colistin (COL) is still the most commonly used antibiotic regimen against carbapenem-resistant Gramnegative bacteria. However, COL often requires dose modifications based on decreased glomerular filtration rate (GFR) under therapy [2,3]. Acute kidney injury (AKI) is a frequent adverse effect of COL, with an incidence of 8-58%, particularly at high doses [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Nephrotoxicity is usually reversible but can sometimes result in chronic kidney disease (CKD) [6]. Oxidative stress plays an important role in the pathogenesis of COL-induced nephrotoxicity so the protective effects of antioxidative agents, such as ascorbic acid, lycopene, and N-acetylcysteine [NAC] have been investigated recently [2,7,8]. NAC is commonly used as a mucolytic agent, but it has powerful anti-inflammatory and antioxidant activities [9].…”

Section: Introductionmentioning

confidence: 99%

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study

Bozkurt

Sharma

Esen

2017

J Infect Dev Ctries

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Introduction: Colistin is associated with dose-dependent nephrotoxicity. N-acetylcycteine (NAC) may reduce the risk of concomitant acute kidney injury (AKI) due to its antioxidant properties. We report a retrospective cohort study evaluating the role of N-acetylcysteine (NAC) in the development of colistin (COL) associated nephrotoxicity. Methodology: A single centre retrospective cohort study was conducted in a university hospital between January 2014 and June 2015. Nephrotoxicity was defined and staged per the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. We evaluated the association between NAC use and COL-related nephrotoxicity by comparing the incidence of nephrotoxicity in patients receiving colistin with or without adjunctive NAC. Results: Forty-six patients received intravenous (IV) COL and 46 patients received IV NAC+COL. The cumulative COL doses did not differ between the two groups (p = 0.802). The initial creatinine value doubled in 29 (63%) patients undergoing NAC+COL therapy and in 27 (58.7%) patients in the COL group (p = 0.669). The median doubling time of baseline creatinine was 6 and 7 days in the NAC+COL and COL groups, respectively. The mean hospital stay, potentially nephrotoxic agent use, and mortality rates were statistically higher for the patients receiving NAC+COL (p < 0.005). Conclusions: The present study was not able to reveal any beneficial effect of NAC for patients undergoing COL therapy. The NAC+COL group had a higher baseline risk for development of AKI. However, the incidence of AKI was comparable between the groups. The results of the study would not solely exhibit the protective effect of adjunctive NAC therapy.

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Colistin-associated Acute Kidney Injury in Severely Ill Patients: A Step Toward a Better Renal Care? A Prospective Cohort Study

Abstract: 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.

Cited by 90 publications

References 43 publications

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin

Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin

Nephrotoxicity of Polymyxins: Is There Any Difference between Colistimethate and Polymyxin B?

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study

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