Antimicrobial drug resistance and antibiosis

Effective antimicrobial agents are essential for the management of some bacterial infections in human and veterinary medicine and the increased prevalence of resistance is of major concern to health professionals and UK governments. The threat is particularly acute due to a lack of new antibiotics in development and the spread of multidrug resistant (MDR) organisms. Four recent high level reports document the extent of the issue: ESPAUR — English surveillance programme for antimicrobial utilisation and resistance (2014) (ESPAUR, 2015); Antimicrobial Resistance Empirical and Statistical Evidence-Base — Department of Health Antimicrobial Resistance Strategy Analytical Working group (2015) (Charlett et al, 2015); One Health Report (2015) (Hopkins and Muller-Pebody, 2015); and Tackling Drug-Resistant Infections Globally: final report and recommendations (O'Neill, 2016).

Antimicrobial resistance (AMR) is either inherent or acquired. Inherent or intrinsic resistance is the ability of all members of a bacterial species to resist the action of an antimicrobial agent because of structural or functional characteristics. Generally this is associated with an inability of the drug to bind to a target or to enter bacteria, efficient export of a drug out of bacteria, or the presence of enzymes that inactivate the drug (Table 1). Acquired resistance refers to the development of resistance in bacteria through spontaneous gene mutations or acquisition of plasmids carrying resistance genes from other bacteria. A recent study of 1000 year old Incan mummies identified antibiotic resistance genes, including beta-lactamases, penicillin-binding proteins, and resistance to fosfomycin, chloramphenicol, aminoglycosides, macrolides, quinolones, tetracycline and vancomycin demonstrating resistance genes were present long before antibiotics were discovered (Santiago-Rodriguez et al, 2015). The use of antimicrobial agents selects for these naturally occurring resistant bacteria.