en Anti-microbial agents, resistance and treatment protocols Anti-microbial agents, resistance and treatment protocols Original article Original article <span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span lang="EN-IN" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Introduction</span></span></b><span lang="EN-IN" style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">: 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&#39;s PK/PD. <b>Methods</b>: 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. <b>Results</b>: 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], <i>P</i>=0.467; 1.67 [0.31-8.90], <i>P</i>=0.548; 0.13 [0.001-19.5], <i>P</i> = 0.428, respectively). Hospital readmission rates within 90 days (OR [95% CI] = 1.05 [0.12-9.10], <i>P</i>=0.964) and duration of hospital stay (Beta coefficient = 1.55, <i>P</i>=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], <i>P</i>=0.004). <b>Conclusion</b>: 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.</span></span></span></span></span> <div id="gtx-trans" style="position: absolute; left: 332px; top: 328.5px;"><div class="gtx-trans-icon"></div></div> Multi-drug resistant Gram-negative infections, Colistin, Dosage regimen, Nephrotoxicity, Acute kidney injury (AKI) events 50 58 http://jommid.pasteur.ac.ir/browse.php?a_code=A-10-451-3&slc_lang=en&sid=1 Mohammed Valiyakath Hydross v.hmohammed11@gmail.com 0000-0002-7836-1872 No Department of Clinical Pharmacy, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India Sameer Abdul Samad sameerinvogue@gmail.com 0000-0001-7521-938X Yes 2Department of Infectious Diseases, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India; NHS Dumfries and Galloway Royal Infirmary, Scotland, United Kingdom Mahesh Balakrishna Savitri mahi.balakrishna@gmail.com No Department of Critical Care, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India Ashish Datt Upadhyay aduaiims@gmail.com 0000-0002-5957-5429 No Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India