Antibiotic Resistance: Mechanisms and Impact

Abstract

Bacterial multidrug resistance poses an enormous threat to the health of mankind and risks to push back the clock of human medicine to the preantibiotic era, when bacterial infections (eg, tuberculosis, syphilis, and staphylococcal infections of wounds) were almost untreatable and resulted in a huge death toll. Bacterial antibiotic resistance (AR) may be conferred by a plethora of mechanisms that can be grouped into three categories: (a) Modification or protection of the antibiotic target—This can occur (i) as a result of one or more mutations of the gene encoding the target (eg, fluoroquinolones resistance due to mutations of topoisomerase II); (ii) following an enzymatic process that chemically modifies structure and properties of the target (eg, macrolide resistance due to 23S rRNA methylation); or (iii) the physical removal of the inhibitor from its target (resistance to tetracycline by the intervention of ribosomal protection proteins). (b) Enzymatic inactivation of the antimicrobial drug (e.g. resistance to β‐lactam antibiotics upon hydrolysis of the β‐lactam ring by β‐lactamases). (c) Blocking the entrance of the antibiotic or promoting its extrusion by remodeling of the cellular membrane (eg, resistance to polymixins) or activation of cellular efflux pumps (eg, multidrug resistance). In this article, we review in some depth all these mechanisms of resistance to various types of antibiotics, describe the concerns of the world health organizations, the likely socioeconomical impact that AR will have in the future, and some possible actions that can be taken to cope with this global problem.