A review of the mechanisms of action and resistance of antimicrobial agents.

Over the past 60 years, the introduction of new antibiotics has been matched by the development of new mechanisms of resistance by the bacteria. Current antibiotics act at a variety of sites within the target bacteria, including the cross-linking enzymes in the cell wall (beta-lactams), various ribosomal enzymes (macrolides, tetracyclines and aminoglycosides), nucleic acid polymerases (quinolones and rifampin) and folate synthesis (sulphas and trimethoprim). Four major mechanisms of resistance have been shown. Target site alterations, such as changes to the penicillin-binding protein, are common. Inactivation of antimicrobials, as by penicillinases or the new carbapenemases, is often seen. Some bacteria such as Pseudomonas aeruginosa can produce alterations in cell wall permeability that deny access to antimicrobials during the course of therapy. Finally, newly described efflux mechanisms pump the antimicrobial out of the cell before it can reach its target site.