Resistance of Gram-Negative Bacilli to Antimicrobials

Abstract

Bacterial pathogens exist in extremely large numbers, and their growth rates are generally rapid. This results in relentless evolution toward drug resistance under the selective pressure applied by the use of antibiotics in medicine and agriculture. Antimicrobial resistance has severely impacted the effectiveness of our current armamentarium of antibiotics, and the evolution of resistance will continue for any new agents that are introduced into clinical use. An understanding of drug resistance is important to prolong the effectiveness of currently used antibiotics and to inform the development of new agents. This chapter discusses antibiotic resistance in Gram-negative pathogens, beginning with the intrinsic resistance engendered by their unique outer membrane combined with active efflux and extending to the broad range of mechanisms including upregulation of efflux, alterations of cell envelope, mutation of antibacterial target genes, antibiotic-modifying enzymes, and target-protection mechanisms that are found in this diverse group of organisms. Resistance is often multifactorial, and the cumulative effect of multiple mechanisms is highlighted. Examples of these themes are provided for a range of important antibiotic classes, and efforts to address current resistance mechanisms are examined.