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 efficac...

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Main Authors: Mohammed Valiyakath Hydross1, Sameer Abdul Samad2, 5*, Mahesh Balakrishna Savitri3, Ashish Datt Upadhyay4
Format: Article
Language:English
Published: Pasteur Institute of Iran 2024-03-01
Series:Journal of Medical Microbiology and Infectious Diseases
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author Mohammed Valiyakath Hydross1
Sameer Abdul Samad2, 5*
Mahesh Balakrishna Savitri3
Ashish Datt Upadhyay4
author_facet Mohammed Valiyakath Hydross1
Sameer Abdul Samad2, 5*
Mahesh Balakrishna Savitri3
Ashish Datt Upadhyay4
author_sort Mohammed Valiyakath Hydross1
collection DOAJ
description 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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spelling doaj-art-a2a0049bce4e4c8a8ccd789f2ca69c062025-08-20T03:52:52ZengPasteur Institute of IranJournal of Medical Microbiology and Infectious Diseases2345-53492345-53302024-03-01121505810.61186/JoMMID.12.1.50Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational StudyMohammed Valiyakath Hydross10https://orcid.org/0000-0002-7836-1872Sameer Abdul Samad2, 5*1https://orcid.org/0000-0001-7521-938XMahesh Balakrishna Savitri32Ashish Datt Upadhyay43https://orcid.org/0000-0002-5957-54291Department of Clinical Pharmacy, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India2Department of Infectious Diseases, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India; 5NHS Dumfries and Galloway Royal Infirmary, Scotland, United Kingdom3Department of Critical Care, Aster Malabar Institute of Medical Sciences, Calicut, Kerala, India4Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, IndiaIntroduction: 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.multi-drug resistant gramnegative infectionscolistindosage regimennephrotoxicityacute kidney injury (aki) events
spellingShingle Mohammed Valiyakath Hydross1
Sameer Abdul Samad2, 5*
Mahesh Balakrishna Savitri3
Ashish Datt Upadhyay4
Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
Journal of Medical Microbiology and Infectious Diseases
multi-drug resistant gramnegative infections
colistin
dosage regimen
nephrotoxicity
acute kidney injury (aki) events
title Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
title_full Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
title_fullStr Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
title_full_unstemmed Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
title_short Comparative Efficacy of Twice and Thrice Daily Colistin Administration in Critically Ill Patients Battling Multi-Drug Resistant Gram-Negative Infections: An Observational Study
title_sort comparative efficacy of twice and thrice daily colistin administration in critically ill patients battling multi drug resistant gram negative infections an observational study
topic multi-drug resistant gramnegative infections
colistin
dosage regimen
nephrotoxicity
acute kidney injury (aki) events
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AT maheshbalakrishnasavitri3 comparativeefficacyoftwiceandthricedailycolistinadministrationincriticallyillpatientsbattlingmultidrugresistantgramnegativeinfectionsanobservationalstudy
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