Epidemiology of beta-Lactamase-Producing Pathogens

beta-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of beta-lactam-inactivating beta-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, beta-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all beta-lactam-containing antibiotics. Critical beta-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major beta-lactamase families include plasmid-mediated extended-spectrum beta-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases now appearing globally, with geographic preferences for specific variants. CTX-M enzymes include the most common ESBLs that are prevalent in all areas of the world. In contrast, KPC serine carbapenemases are present more frequently in the Americas, the Mediterranean countries, and China, whereas NDM metallo-beta-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from beta-lactam use continues, multiple beta-lactamases per organism are increasingly common, including pathogens carrying three different carbapenemase genes. These organisms may be spread throughout health care facilities as well as in the community, warranting close attention to increased infection control measures and stewardship of the beta-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.