β-Lactam antimicrobials: what have you done for me lately?

Abstract

The "perpetual challenge of infectious diseases" is no better exemplified than by the phenomena of rapid emergence and spread of bacterial resistance. Although β-lactam antimicrobials have thus far been a mainstay of the therapeutic armamentarium for treatment of severe infections, their preeminent position has been challenged by an onslaught of resistance mechanisms in major nosocomial and community-acquired pathogens, including modification of penicillin-binding proteins, production of β-lactamases, overexpression of efflux pumps, and loss of porins. Given this formidable array of resistance mechanisms facing patients and their physicians, one can reasonably ask if there is hope for the future of β-lactams.