In the last 15 years, varieties of plasmid-mediated β-lactamases have been identified in

Gram-negative bacteria, one of which includes the extended-spectrum β-lactamases (ESBL)

(Liebana et al., 2013). Among the β-lactamases, ESBL are known as enzymes that can hydrolyze
extended-spectrum (third genereation) cephalosporins (e.g., cefotaxime, ceftriaxone, ceftazidime,
and cefepime) and monobactams (e.g., aztreonam) but do not affect cephamycins (e.g., cefoxitin
and cefotetan) or carbapenems (e.g., meropenem or imipenem). Class A ESBLs mainly include
TEM, SHV, CTX-M, VEB, and GES enzymes (Coque et al., 2008; Pitout & Laupland, 2008;
Center of Disease Control and Prevention, 2010).

ESBL testing is performed for epidemiological purposes because ESBL-resistance genes

transmit rapidly. After the prevalence of ESBLs such as SHV-1 and TEM-1, the ESBL family of
cefotaxime β-lactamases (CTX) have increased in frequency around the world (Woerther, Burdet,
Chachaty, & Adremont, 2013; D’Andrea, Arena, Pallechi, & Rossolini, 2013). CTX-M β-
lactamases form a non-homogenous complex group of enzymes and can be divided into five
clusters according to amino acid sequence, with each genotype of CTX-M having different
hydrolysis reactions to β-lactam antibiotics. Unlike other ESBLs, CTX-M did not originate from
mutations of plasmid mediated enzymes but through the mobilization of chromosomal bla genes
of Kluyvera spp into mobile genetic elements, which greatly inhibited the action of cefotaxime
compared to ceftazidime (Cantón, 2008).

CTX-M genes have become the most common ESBL genes due to their mobilization and
dissemination mechanisms, namely insertion sequences (e.g., ISEcpl, IS26, and ISCR1), integrons,
transposons, and plasmids (Bush & Fisher, 2011; Coque, Baquero, & Cantón, 2008). CTX-M-1
was first reported in Munich, Germany from a cefotaxime-resistant but ceftazidime-susceptible
Escherichia coli isolate recovered from the ear of a 4-month-old child with otitis media.
Succeeding enzymes were grouped under the CTX-M family due to their preferential hydrolytic
activity against cefotaxime. CTX-M enzymes were initially detected in Enterobacteriaciae,
including Escherichia coli, Klebsiella pneumoniae and Salmonella spp. but have increased in
prevalence among non-Enterobacteriaciae Gram-negative bacilli such as Pseudomonas
aeruginosa and Stenotrophomonas maltophila (Cantón, González-Alba, & Galán, 2012).
According to a study conducted by Tacão, Correia, and Henriques (2012), cefotaxime-resistant
strains recovered were identified as Pseudomonas spp. (i.e., P. fluorescens & P. putida),
Enterobacteriaciae such as Escherichia coli and Enterobacter spp., and Aeromonas spp.

Bush, K., Fisher, J.F. (2011). Epidemiological expansion, structural studies, and clinical
challenges of new beta-lactamases from Gram-negative bacteria. Annu. Rev.
Microbiol. 65, 455–478

Cantón, R. (2008). Epidemiology and evolution of β-lactamases, in Evolutionary Biology of

Bacterial and Fungal Pathogens, Washington: ASM Press, 249–270.
Cantón, R., González-Alba, J. M., & Galán, J.C. (2012). CTX-M Enzymes: Origin and Diffusin.
Front Microbiol. 3, 110. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC3316993/#fn1

Center for Disease Control and Prevention (2010). Healthcare-associated Infections. Retrieved
from https://www.cdc.gov/hai/settings/lab/lab_esbl.html.

Coque T. M., Baquero F., Cantón R. (2008). Increasing prevalence of ESBL-producing

Enterobacteriaceae in Europe. Euro Surveill.

D’Andrea, M.M., Arena, F., Pallecchi, L., & Rossolini, G.M. (2013). CTX-M-type beta-
lactamases: a successful story of antibiotic resistance. Int J Med Microbiol. 303, 05–17.

Liebana, E., Carattoli, A., Coque, T.M., Hasman, H., Magiorakos, A., Mevius, D. et al. (2013).
Public health risks of enterobacterial isolates producing extended-spectrum β-lactamases or
AmpC g-lactamases in food and food- producing animals: An EU perspective of
epidemiology, analytical methods, risk factors, and control options. Food Safety, 56,
1030-1037.

Pitout, J. D. & Laupland, K. B. (2008). Extended-spectrum β-lactamase-producing

Enterobacteriaceae: an emerging public-health concern. Lancet Infect. 159–
16610.1016/S1473-3099(08)70041-0

Tacão, M., Correia, A., & Henriques, I. (2012). Resistance to Broad-Spectrum Antibiotics in
Aquatic Systems: Anthropogenic Activities Modulate the Dissemination of blaCTX-M-Like
Genes. Appl Environ Microbiol. 78(12), 4134-4140. Retrieved from https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC3370516/

Woerther, P.L., Burdet, C., Chachaty, E., & Andremont, A. (2013). Trends in human fecal
carriage of extended-spectrum beta-lactamases in the community: toward the
globalization of CTX-M. Clin Microbiol. 26, 744-758.