Epidemiology of β-Lactamase-Producing Pathogens

Abstract

β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in Staphylococcus aureus challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. Critical β-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major β-lactamase families include plasmid-mediated extended-spectrum β-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-β-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from β-lactam use continues, multiple β-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 β-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.

Keywords: ESBL; beta-lactamase; carbapenemase; epidemiology; resistance.

FIG 1

Generic structures of β-lactams most important in clinical medicine. Structures include penicillin (1), cephalosporin (2), carbapenem (3), and monobactam (4).

FIG 2

Schematic showing the interaction of β-lactam antibiotics with β-lactam interactive proteins in Gram-negative bacteria.

FIG 3

Prevalence of penicillinase (blaZ)-producing staphylococci from global sources. Data for the years 1946 to 1980 were from references and . Data for the years 2011 to 2017 include studies from Trinidad and Tobago (88), Kuwait (89), China (90), and the United States (91), with the range of percentages shown by the error bars.

FIG 4

Distribution of KPC-positive Enterobacteriaceae and P. aeruginosa collected in 2012 to 2014 from surveillance data. (Republished from reference .)

FIG 5

Global distribution of metallo-β-lactamase-positive Enterobacteriaceae and P. aeruginosa, including NDM-type enzymes collected from 2012 to 2014 from surveillance. (Republished from reference 287).

FIG 6

Coproduction of carbapenemases in the same organism. Data for production of KPC β-lactamases, OXA-48-type β-lactamases, and NDM β-lactamases with other carbapenemases were compiled from Table 2.

FIG 7

Surveillance of carbapenem-producing Enterobacteriaceae in Canada. Data were provided with the permission of Michael Mulvey, Public Health Agency of Canada.