Research Article AComparativeStudyofHigh-DoseColistinAdministrationforthe Management of Multidrug-Resistant Gram-Negative Infections in the ICU Monireh Ghazaein, 1 Majid Mokhtari, 2 Mehran Kouchek, 2 Mir-Mohammad Miri, 2 Reza Goharani, 2 and Mohammad Sistanizad 3,4 1 Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran 2 Department of Pulmonary and Critical Care Medicine, Imam Hossein Teaching and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran 3 Department of Clinical Pharmacy, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Prevention of Cardiovascular Disease Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Correspondence should be addressed to Mohammad Sistanizad; sistanizadm@sbmu.ac.ir Received 1 May 2020; Revised 12 July 2020; Accepted 31 July 2020; Published 21 August 2020 Academic Editor: Peter J. Weina Copyright © 2020 Monireh Ghazaein et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. e aim of this study was to assess the clinical and microbiological efficacy and toxicity of different high-dose regimens of colistin in the ICU patients with colistin-sensitive MDR Gram-negative infections. In this prospective, open label, randomized clinical trial, patients with clinical features of infection and positive culture for MDR colistin-sensitive Gram-negative bacteria were randomly allocated to receive colistin, 3 or 9 million units every 8 and 24 hours, (groups A and B), respectively. For each dose regimen, clinical and microbiological response, the rates of nephrotoxicity, and its risk factors were analyzed. Forty-three patients were enrolled, and 35 completed the study protocol, of whom 30 (88.2%) had ventilator-associated pneumonia (VAP) and 5 (14%) had bacteremia. Although there were no statistically significant differences in the clinical or microbiological response between the study groups, the microbiological response favored the divided dose group numerically (p � 0.40). Clinical response was achieved in 27 of 35 (77.1%) patients (p � 0.999). Twelve (34.28%) patients developed AKI during colistin treatment, 4 and 8 in groups A and B, respectively (p value �0.193). Significant risk factors for nephrotoxicity related to colistin were age, hyperbilirubinemia, and coadministration of other nephrotoxic agents. In multivariate regression analysis, the only independent risk factor for CMS- associated AKI was hyperbilirubinemia (p value �0.008). Although the clinical and microbiological responses to colistin ad- ministration were not statistically different in two groups, the microbiological response favored the divided dose regimen group numerically. We did not observe any significant safety concerns with high-dose colistin administration in this population. 1. Introduction e increasing global prevalence of microbial resistance to antibiotics is one of the main challenges facing modern medicine. e Infectious Diseases Society of America (IDSA) recognizes antimicrobial resistance as “one of the greatest threats to human health worldwide.” Multidrug-resistant (MDR) infections, defined as in- fections caused by the microbial pathogens resistant to two or more classes of antibiotics, has significant adverse effects on morbidity, mortality, and health economy which extend into all aspects of medicine [1]. e emergence of carba- penem-resistant Gram-negative bacteria is of particular concern, as there are limited therapeutic options available for effective treatment of these microorganisms in critically ill patients. is has led to the redeployment of the older and more toxic antibiotics, such as colistin (polymyxin E), which was discovered nearly 60 years ago. is antimicrobial agent is currently the mainstay of treatment for the resistant Gram- Hindawi Canadian Journal of Infectious Diseases and Medical Microbiology Volume 2020, Article ID 3403520, 8 pages https://doi.org/10.1155/2020/3403520