comparative efficacy of twice and thrice daily colistin administration in critically ill patients battling multi-drug resistant gram-negative infections: an observational study

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 9 million international units (miu) of colistin in 151 critically ill patients with multidrug-resistant gram-negative infections. propensity score matching with a 1:5 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 125 patients, and twice-daily dosing in 26 patients. a total of 73 patients were included in the final analysis after propensity score matching. the 28-day mortality rates, clinical cure rates, and microbiological failure rates were comparable between the two groups (odds ratio (or) [95% confidence-interval (ci)] = 0.48 [0.07-3.46], p=0.467; 1.67 [0.31-8.90], p=0.548; 0.13 [0.001-19.5], p = 0.428, respectively). hospital readmission rates within 90 days (or [95% ci] = 1.05 [0.12-9.10], p=0.964) and duration of hospital stay (beta coefficient = 1.55, p=0.683) were also comparable between the two groups. the incidence of nephrotoxicity-related aki events during colistin therapy was significantly lower with the 4.5 miu twice-daily regimen (or [95% ci] = 0.04 [0.004-0.35], p=0.004). 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.