Acinetobacter baumannii is an opportunistic pathogen associated with nosocomial and community infections of great clinical relevance. Its ability to rapidly develop resistance to antimicrobials, especially carbapenems, has re-boosted the prescription and use of polymyxins. However, the emergence of strains resistant to these antimicrobials is becoming a critical issue in several regions of the world because very few of currently available antibiotics are effective in these cases. This review summarizes the most up-to-date knowledge about chromosomally encoded and plasmid-mediated polymyxins resistance in A. baumannii. Different mechanisms are employed by A. baumannii to overcome the antibacterial effects of polymyxins. Modification of the outer membrane through phosphoethanolamine addition, loss of lipopolysaccharide, symmetric rupture, metabolic changes affecting osmoprotective amino acids, and overexpression of efflux pumps are involved in this process. Several genetic elements modulate these mechanisms, but only three of them have been described so far in A. baumannii clinical isolates such as mutations in pmrCAB, lpxACD, and lpsB. Elucidation of genotypic profiles and resistance mechanisms are necessary for control and fight against resistance to polymyxins in A. baumannii, thereby protecting this class for future treatment.
The use of antimicrobials represents one of the most successful ways of chemotherapy in the medical clinic. These drugs were responsible for the control of several infectious diseases, which have been considered as the main cause of mortality and morbidity throughout the history of the humanity. [1] However, infectious diseases remain a major challenge to human health. Currently, it is estimated that about 1 billion people are diagnosed with mycoses annually, and more than 1.5 million die from complications of invasive fungal diseases. [2] Furthermore, infectious diarrhea and pneumonia account for 40% of child deaths worldwide, especially in underdeveloped regions. [3] Over the past 40 years, only two classes of antibiotics effective against Gram-negative bacteria have been approved for clinical use (e.g., oxazolidinones and cyclic lipopeptides) and the development of new antimicrobials in the future seems unpromising. [3] Currently, there is a scarce therapeutic arsenal for the treatment of fungal infections and the development of new antifungal drugs conflicts with the difficulty of finding compounds which are specific for fungal cells. [4] Similar situation happens with the development of new antivirals. Since viruses are obligate intracellular parasites, finding a drug that has an action against the virus but does not interfere with the basal functions of the cells is pointed out as the main challenge. [5] In this regard, considering the 15 largest companies in the pharmaceutical industry, only 5 of their drugs in the clinical or preclinical research phase are anti-infective agents. [3] The alarming increase in the microorganism's resistance to the currently available antimicrobials, caused mainly by the long-term exposure to subinhibitory concentrations of these
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.