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Open AccessReview

Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment

1
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, No.2 Yuanmingyuan West Road, Beijing 100193, China
2
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3
Department of Pharmacology & Therapeutics, Faculty of Medicine, School of Biomedical Sciences, Dentistry and Health Sciences, the University of Melbourne, Parkville 3052, Australia
*
Authors to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 506; https://doi.org/10.3390/antiox9060506
Received: 5 April 2020 / Revised: 31 May 2020 / Accepted: 3 June 2020 / Published: 9 June 2020
The emergence of antimicrobial resistance in Gram-negative bacteria poses a huge health challenge. The therapeutic use of polymyxins (i.e., colistin and polymyxin B) is commonplace due to high efficacy and limiting treatment options for multidrug-resistant Gram-negative bacterial infections. Nephrotoxicity and neurotoxicity are the major dose-limiting factors that limit the therapeutic window of polymyxins; nephrotoxicity is a complication in up to ~60% of patients. The emergence of polymyxin-resistant strains or polymyxin heteroresistance is also a limiting factor. These caveats have catalyzed the search for polymyxin combinations that synergistically kill polymyxin-susceptible and resistant organisms and/or minimize the unwanted side effects. Curcumin—an FDA-approved natural product—exerts many pharmacological activities. Recent studies showed that polymyxins–curcumin combinations showed a synergistically inhibitory effect on the growth of bacteria (e.g., Gram-positive and Gram-negative bacteria) in vitro. Moreover, curcumin co-administration ameliorated colistin-induced nephrotoxicity and neurotoxicity by inhibiting oxidative stress, mitochondrial dysfunction, inflammation and apoptosis. In this review, we summarize the current knowledge-base of polymyxins–curcumin combination therapy and discuss the underlying mechanisms. For the clinical translation of this combination to become a reality, further research is required to develop novel polymyxins–curcumin formulations with optimized pharmacokinetics and dosage regimens. View Full-Text
Keywords: polymyxin B; colistin; curcumin; oxidative stress; mitochondrial dysfunction polymyxin B; colistin; curcumin; oxidative stress; mitochondrial dysfunction
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MDPI and ACS Style

Dai, C.; Wang, Y.; Sharma, G.; Shen, J.; Velkov, T.; Xiao, X. Polymyxins–Curcumin Combination Antimicrobial Therapy: Safety Implications and Efficacy for Infection Treatment. Antioxidants 2020, 9, 506.

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