Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study

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Hydross Mohammed Valiyakath; Samad Sameer Abdul; Savitri Mahesh Balakrishna; Upadhyay Ashish Datt

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Journal Paper

Paper Information

Journal: Journal of Medical Microbiology and Infectious Diseases Year:2024 | Volume:12 | Issue:1 Page(s): 50-58

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Title

Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study

Author(s)

Hydross Mohammed Valiyakath | Samad Sameer Abdul | Savitri Mahesh Balakrishna | Upadhyay Ashish Datt | Issue Writer Certificate

Keywords

Multi-drug resistant Gram-negative infectionsQ4

ColistinQ4

Dosage regimenQ4

NephrotoxicityQ4

Acute kidney injury (AKI) eventsQ4

Abstract

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

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