Mechanisms of Resistance to β-Lactam Antibiotics

Chapter 62 Mechanisms of Resistance to β-Lactam Antibiotics Douglas S. Kernodle, Douglas S. KernodleSearch for more papers by this author Douglas S. Kernodle, Douglas S. KernodleSearch for more papers by this author Book Editor(s):Vincent A. Fischetti, Vincent A. FischettiSearch for more papers by this authorRichard P. Novick, Richard P. NovickSearch for more papers by this authorJoseph J. Ferretti, Joseph J. FerrettiSearch for more papers by this authorDaniel A. Portnoy, Daniel A. PortnoySearch for more papers by this authorJulian I. Rood, Julian I. RoodSearch for more papers by this author First published: 03 March 2006 https://doi.org/10.1128/9781555816513.ch62 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onFacebookTwitterLinked InRedditWechat Summary The introduction of penicillin into clinical use in 1941 had a profound impact on the treatment of diseases caused by gram-positive pathogens. Antibiotic degradation by ß-lactamase and alterations in penicillin-binding membrane proteins remain the major mechanisms by which gram-positive pathogens express resistance to ß-lactam antibiotics. The penicillin-interactive enzymes involved in cell wall biosynthesis are specialized acyl serine transferases localized on the outer face of the cytoplasmic membrane. The strong antibacterial efficacy of β-lactams, combined with their low toxicity for eukaryotic cells, has helped to make them the most highly developed class of antibacterial agents in clinical use. The resistance phenotype in β-lactamase-producing gram-positive bacteria differs from that observed with gram-negative species and is associated with an inoculum effect in which the MIC depends upon the number of bacteria tested. Around 95% of Staphylococcus aureus isolates recovered from clinical specimens produce ß-lactamase. The production of large amounts of ß-lactamase in isolates possessing the normal penicillin-sensitive penicillin-binding proteins (PBPs) has been associated with borderline susceptibility to the antistaphylococcal penicillins. External factors such as temperature, osmolality, and light influence the proportion of the bacterial cell population that exhibits resistance. Most penicillin-resistant clinical isolates exhibit a PBP pattern more complex than just a combination of point mutations. In clinical isolates, tolerance appears to be more prevalent among gram-positive than gram-negative species. Gram-Positive Pathogens, Second Edition RelatedInformation