Mohammed Valiyakath Hydross - Department of Clinical Pharmacy, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India
Sameer Abdul Samad - ۲Department of Infectious Diseases, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India; NHS Dumfries and Galloway Royal Infirmary, Scotland, United Kingdom
Mahesh Balakrishna Savitri - Department of Critical Care, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India
Ashish Datt Upadhyay - Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India

Introduction: Colistin, a polymyxin antibiotic often reserved for treatment of multidrug-resistant Gram-negative infections, exhibits a narrow therapeutic index. Careful consideration of the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of colistin is essential to maximize its efficacy and minimize toxicity. Both thrice-daily and twice-daily administration regimens have been employed, with critically ill patients posing unique challenges regarding colistin's PK/PD. Methods: This retrospective observational study compared the mortality rates, cure rates, length of hospital stay, nephrotoxicity, and readmission rates associated with thrice-daily and twice-daily administration of a fixed total daily dose of ۹ million international units (MIU) of colistin in ۱۵۱ critically ill patients with multidrug-resistant Gram-negative infections. Propensity score matching with a ۱:۵ case-control ratio was performed using XLSTAT software (by Addinsoft), and outcomes were analysed using logistic regression analysis. Results: Thrice-daily dosing of colistin was recorded in ۱۲۵ patients, and twice-daily dosing in ۲۶ patients. A total of ۷۳ patients were included in the final analysis after propensity score matching. The ۲۸-day mortality rates, clinical cure rates, and microbiological failure rates were comparable between the two groups (Odds ratio (OR) [۹۵% confidence-interval (CI)] = ۰.۴۸ [۰.۰۷-۳.۴۶], P=۰.۴۶۷; ۱.۶۷ [۰.۳۱-۸.۹۰], P=۰.۵۴۸; ۰.۱۳ [۰.۰۰۱-۱۹.۵], P = ۰.۴۲۸, respectively). Hospital readmission rates within ۹۰ days (OR [۹۵% CI] = ۱.۰۵ [۰.۱۲-۹.۱۰], P=۰.۹۶۴) and duration of hospital stay (Beta coefficient = ۱.۵۵, P=۰.۶۸۳) were also comparable between the two groups. The incidence of nephrotoxicity-related AKI events during Colistin therapy was significantly lower with the ۴.۵ MIU twice-daily regimen (OR [۹۵% CI] = ۰.۰۴ [۰.۰۰۴-۰.۳۵], P=۰.۰۰۴). Conclusion: Twice-daily colistin administration significantly reduces the risk of nephrotoxicity-related AKI events compared to thrice-daily administration in critically ill patients with multidrug-resistant Gram-negative infections.

Multi-drug resistant Gram-negative infections, Colistin, Dosage regimen, Nephrotoxicity, Acute kidney injury (AKI) events