The threat of antibiotic resistance in Gram-negative pathogenic bacteria: beta-lactams in peril!
Beta-lactam antibiotics are the cornerstone of our antibiotic armamentarium. By inhibiting bacterial cell wall synthesis, they are highly effective against Gram-positive and Gram-negative bacteria. Unfortunately, bacteria have evolved sophisticated resistance mechanisms to combat the lethal effects of beta-lactam antibiotics. Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae are all able to evade killing by penicillins, cephalosporins and carbapenems. This multi-drug resistant phenotype that challenges health care workers worldwide is caused by an array of resistance determinants. These include altered expression of outer membrane proteins and efflux pumps, along with an increasing arsenal of beta-lactamases. Future strategies in beta-lactam design must take into account the complex nature of resistance in Gram-negative pathogens.
Thomson
Jodi M
JM
Department of Pharmacology, Case Western Reserve University School of Medicine Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106, USA.
Bonomo
Robert A
RA
D040981:Acinetobacter baumannii / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000378:metabolism; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases