Evaluation of the Efficacy and Safety of N-Acetylcysteine Versus Alpha-Lipoic Acid on the Occurrence and Severity of Colistin-Induced Nephrotoxicity in Critically Ill Patients

Detailed Summary

Healthcare- associated infections that caused by multi-drug-resistant Gram-negative bacteria (MDR G-ve) represent the most important problem that face the critically ill patients in the ICU. The available broad-spectrum antibiotics as penicillin, fluoroquinolones, aminoglycosides, and β-lactams fail to overcome these aggressive organisms. Accordingly, this led to the reconsideration of old drugs such as polymyxin B and polymyxin E (also known as colistin) that were previously considered to be too toxic for clinical use in the treatment of MDR G-ve bacteria. Colistin can be used as monotherapy or in combination with other antibiotics as high dose tigecycline, carbapenem or high-dose ampicillin/sulbactam. Colistin associated acute kidney injury (CA-AKI) is the frequently observed side effect in ICU patients treated with colistin that may lead to cessation of treatment. Accordingly, it is important to monitor renal functions prior to and during colistin treatment to detect the early signs of renal injury and minimize long term renal dysfunction. Inflammation with release of reactive oxygen species (ROS) can lead to renal tubular cells apoptosis. Several animal studies proved the beneficial effect of the concomitant use of antioxidants as N-acetylcysteine, alpha lipoic acid in preventing or attenuating colistin induced nephrotoxicity by their potent antioxidant effects Therefore, a clinical trial will be carried out to evaluate the efficacy and safety of N-acetylcysteine versus Alpha-lipoic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients.

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