Polymixins derivatives: Lower hydrophobicity, higher therapeutic index. Polymyxins have been lifesaving drugs, particularly in treating multidrug-resistant Gram-negative infections. However, their clinical utility is hampered by significant safety concerns, particularly nephrotoxicity. Around 50-60% of patients receiving polymyxins experience dose-limiting adverse effects, most commonly involving the kidneys . Renal complications are especially dangerous in critically ill patients with comorbidities , underscoring the urgent need for polymyxin derivatives with improved safety profiles.