Clinical Information

The Check-MDR CT103XL panel, which is performed on bacterial isolates, detects 27 genes associated with antimicrobial resistance in Gram-negative bacilli.

Antibiotic resistance is evolving as a result of use and overuse of antibacterial agents. Characterizing the molecular mechanisms of antimicrobial resistance can be helpful to explain unusual phenotypic susceptibility profiles or for epidemiologic purposes. A myriad of beta-lactamase enzymes may be found in Gram-negative bacteria; these enzymes hydrolyze (break down) the beta-lactam ring of beta-lactam antibiotics, destroying their antibacterial activity. A single bacterial isolate may carry 1 or more genes that code for the production of a beta-lactamase enzyme. Beta-lactamases can be on the chromosome or on plasmids and may be classified as extended-spectrum beta-lactamases (ESBLs), AmpCs, and carbapenemases, among other types.

ESBLs are beta-lactamases with an expanded substrate profile and are typically plasmid-borne. They are capable of hydrolyzing first-, second-, third- and fourth-generation cephalosporins, penicillins, and monobactams. TEM, SHV, and CTX-M genes are the most clinically prevalent.

-TEM and SHV subtypes are derived from the parental sequences by point mutations resulting in amino acid substitutions, which allow the enzymes to hydrolyze a wide range of beta-lactam antibiotics.

-CTX-M genes originate from Kluyvera species and can be separated into 5 different groups based on their amino acid sequence: CTX-M-1, CTX-M-2, CTX-M-9, CTX-M-8, and CTX-M-25.

-VEB, PER, BEL, and GES genes are less common.

AmpC cephalosporinases hydrolyze almost all beta-lactam antibiotics including penicillins, cephalosporins, and monobactams and may be chromosomally- or plasmid-encoded. Several Enterobacteriaceae carry a chromosomal copy of an AmpC gene.

-Plasmid-encoded AmpC genes may be shared among bacteria. Plasmid-encoded AmpC genes may produce a higher amount of beta-lactamase as compared to chromosomally-encoded AmpC genes; knowing the mechanism may be useful in assessing treatment. An AmpC gene detected in a species that does not have a chromosomal AmpC (see table above) suggests that the gene is plasmid-encoded.

Carbapenemases show general resistance to all beta-lactam antibiotics including the beta-lactam-beta-lactamase inhibitor combinations and elevated or complete resistance against carbapenem antibiotics. In addition, isolates harboring carbapenemases often have additional beta-lactamase genes and genes for resistance to quinolones and aminoglycosides.

-Klebsiella pneumoniae Carbapenemase (KPC) is a plasmid-encoded carbapenemase first identified in Klebsiella pneumoniae isolates in North America. KPC has since spread to many parts of the world and can be found in several species of the Enterobacteriaceae.

-New Delhi Metallo-beta-lactamase (NDM) was first reported in 2009 from a patient of Indian origin in Sweden. It is prevalent in the Indian subcontinent, but has spread worldwide.

-The oxacillinase group consists of 10 members, of which OXA-48 and OXA-181 are the most prevalent variants. OXA-48 occurs predominantly in Enterobacteriaceae, originated from Shewanella species, and is most prevalent in Europe and the North African subcontinent. Another grouping of OXA-type carbapenemases are found in Acinetobacter species and consists of 3 type members, OXA-23, OXA-24, and OXA-58. Each type has several subtypes.

-VIM, a metallo-beta-lactamase, was first found in 1997 in a Pseudomonas aeruginosa isolate in Verona. It may be found in Enterobacteriaceae and includes at least 38 variants of which the DNA sequences may differ significantly.

-IMP, a metallo-beta-lactamase, was detected in Japan in 1990 (IMP-1) in Pseudomonas aeruginosa. It may be found worldwide in Enterobacteriaceae and includes at least 44 members with varying gene sequences.

-GIM-1 and SPM-1, also metallo-beta-lactamases, are less frequently found carbapenemases. GIM-1 originated in Germany and has been found in Pseudomonas aeruginosa, Enterobacteriaceae, and Acinetobacter spp. SPM-1 producing Pseudomonas aeruginosa is endemic in Brazilian hospitals where it has been associated with numerous outbreaks.

-GES gene family consists of both ESBL-types and carbapenemase types.

Content was based on the Check-MDR CT103XL User Manual and reproduced with permission by Wouter de Levita of Check-Points, 2016.