colistin and Renal-Insufficiency--Chronic

Colistin (polymyxin E) is a mainly concentration-dependent bactericidal antimicrobial active against multidrug-resistant Gram-negative bacteria. After being abandoned over the past 30 years due to its neuro- and nephrotoxicity, colistin has been reintroduced recently as a last-resort drug for the treatment of multidrug-resistant Gram-negative bacteria infections in combination with other antimicrobials. Unfortunately, although renal toxicity is a well-known dose-related adverse effect of colistin, relatively few studies are currently available on its peculiar pharmacodynamic/pharmacokinetic properties in clinical settings at high risk for drug accumulation, such as acute or chronic kidney disease. In these specific contexts, the risk for underdosing is also substantial because colistin can be easily removed by dialysis/hemofiltration, especially when the most efficient modalities of renal replacement therapy (RRT) are used in critically ill patients. For this reason, recent recommendations in patients undergoing RRT have shifted toward higher dosing regimens, and therapeutic drug monitoring is advised. This review aims to summarize the main issues related to chemical structure, pharmacodynamics/pharmacokinetics, and renal toxicity of colistin. Moreover, recent data and current recommendations concerning colistin dosing in patients with reduced kidney function, with special regard to those receiving RRT such as dialysis or hemofiltration, are also discussed.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Drug Monitoring; Humans; Kidney; Kidney Diseases; Practice Guidelines as Topic; Renal Insufficiency, Chronic; Renal Replacement Therapy

The use of colistin for multi-drug resistant (MDR) infections has led to an increase of colistin-associated acute kidney injury (AKI). Nevertheless, information on long-term renal prognosis is scarce. We aimed to determine the predictors of chronic kidney disease (CKD) in survivors of MDR-infections with colistin-associated AKI.. A retrospective cohort of patients with colistin-associated AKI was compared with controls (survivors of severe infections who developed AKI matched by age, sex, diabetes, vancomycin exposure, and baseline kidney function). The primary outcome was the development of CKD after 6months of follow-up.. From 2011 to 2015, 122 patients with MDR infections received colistin. Among 72 survivors, 29 (40%) had colistin-associated AKI. After 6months, 22 of them (75%) progressed to CKD (G3 in 21/22) compared with 16 (27%) in 58 controls (P<0.001). Independent predictors of progression to CKD were colistin use [odds ratio (OR): 8.86; 95% CI: 2.8-27.8] and age (OR: 1.04, 95% CI: 1.01-1.07). In patients exposed to colistin, a total dose of colistin >5g was an independent predictor of progression to CKD (OR: 14.1, 95% CI: 2.6-75.7).. Colistin-associated AKI had a substantial risk for the latter development CKD, and consequently, these patients should be tightly monitored.

Topics: Acute Kidney Injury; Adult; Aged; Anti-Bacterial Agents; Cohort Studies; Colistin; Female; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Mexico; Middle Aged; Prevalence; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Staphylococcal Infections; Survivors; Young Adult