Introduction to Extended-Spectrum β-Lactamase (ESBL)

Written by : Mohd Azrul Hisham Ismail, Raja Mohd Fadhil Raja Abd Rahman, Rosniza Mohamad Hussain, and Hui-min Neoh

Date Publish : 23rd August 2023

UKM Medical Molecular Biology Institute (UMBI)

Introduction to Extended-Spectrum β-Lactamase (ESBL)

What is ESBL?

Extended-spectrum β-lactamase (ESBL) are enzymes that are produced by certain Gram-negative bacteria such as Enterobacteriaceae and Pseudomonas aeruginosa. ESBLs mediate resistance to penicillin, cephalosporins and monobactams, which belong to the group of β-lactams (Lim et al., 2009, Seenama et al., 2019), and bacteria carrying these enzymes can be found all over the world including Europe, North America, Asia (Storberg, 2014). β-lactams are a group of antibiotics that act on the cell wall of a bacterium via weakening of the cell wall structure, thus leading to cell lysis. ESBL are mostly found in clinically important gram negative bacteria such as Entrerobacteriaaceae species, K. pneumonia, K. oxytoca and E. coli. Bacteria such as Enterobacter spp., Salmonella spp., Morganella morganii, Proteus mirabilis, Serratia marcescens and Pseudomonas aeruginosa have also been shown to secrete ESBL but the production is low (Chaudhary & Aggarwal, 2004). Epidemiological studies have demonstrated the dissemination of ESBL-E. coli, which has become a worldwide alarm. Indeed, the ESBL enzymes have become a key component of horizontal gene transfers that contributes to the rapid dissemination of resistant bacterial strains (Hawkey et al., 2009).

This group of antibiotics include penicillins, cephalosporins, carbapanems and monobactems. ESBLs alter the structure of β-lactam antibiotics via hydrolysis of their β-lactam ring structure, rendering the drugs ineffective in killing their targeted bacteria. According to Tissera & Lee (2013), ESBLs that have been discovered to date target various spectrum of antibiotics such as penicillins and their complexes (e.g. amoxicillinclavulanate), monobactams (e.g. aztreonam), and even third generation cephalosporins (e.g. cefotaxime). Figure 1 shows the structure of β-lactam antibiotics.

Figure 1: Structure of β-lactam antibiotics (Bergšpica et al., 2020;ur Rahman et al., 2018)

Like many other infections, ESBL infections present with various clinical symptoms that depend on the infection site, such as cough and shortness of breath for lung infection, or burning pain and urinary problems for urinary type of infection. The clinical course of infections due to ESBL-carrying bacteria may be varied. The infection can be resolved easily such as the urinary tract infections (UTIs), or in some cases can be harmful that could lead to lethal sepsis (Chaudhary & Aggarwal, 2004). All ESBL infections should be managed carefully, as these infections can lead to worse clinical outcomes, higher mortality rates, longer hospital stays and pose economic burden compared to similar infections by ESBL non-producing bacteria. In addition, these drug-resistant bacteria could also be transmitted to other patients and lead to outbreaks that are difficult to manage and eradicate, due to limited treatment options.

ESBL research in UMBI

A recent study by Tan et al., (2021), Hospital Canselor Tuanku Mukhriz (HCTM), Universiti Kebangsaan reported on ESBL-producing bacterial species isolated from the hospital. UMBI’s Infectious Diseases Laboratory performs ESBL genotyping and is currently involved in a project lead by HCTM’s antimicrobial stewardship team to investigate the feasibility of ESBL genotyping for antibiotic prescription.

References

Bergšpica, I., Kaprou, G., A. Alexa, E., Prieto, M., & Alvarez-Ordóñez, A. (2020). Extended Spectrum β -Lactamase ( ESBL) Producing Escherichia coli in Pigs and Pork Meat in the European Union. Antibiotics, 9(10), 678. https://doi.org/https://doi.org/10.3390/antibiotics9100678

Chaudhary, U., & Aggarwal, R. (2004). Extended Spectrum β-Lactamases (ESBL) – an Emerging Threat to Clinical Therapeutics. Indian Journal of Medical Microbiology, 22(2), 75–80. https://doi.org/10.1016/S0255-0857(21)02884-X

Hawkey, P. M., Jones, A. M., Birmingham, B., Strategic, M., & House, M. (2009). The changing epidemiology of resistance. Journal of Antimicrobial Chemotherapy, 64(Suppl. 1), i3–i10. https://doi.org/10.1093/jac/dkp256

Lim, K., Yasin, R., Yeo, C., Puthucheary, S., & Thong, K. (2009). Characterization of Multidrug Resistant ESBL-Producing Escherichia coli Isolates from Hospitals in Malaysia. 2009. https://doi.org/10.1155/2009/165637

Seenama, C., Thamlikitkul, V., & Ratthawongjirakul, P. (2019). Multilocus sequence typing and bla ESBL characterization of extended-spectrum beta- lactamase-producing Escherichia coli isolated from healthy humans and swine in Northern Thailand. Infection and Drug Resistance, 12, 2201–2214.

Storberg, V. (2014). ESBL-producing Enterobacteriaceae in Africa – a non-systematic literature review of research published 2008–2012. Infection Ecology & Epidemiology, 4(1), 20342. https://doi.org/10.3402/iee.v4.20342

Tan, T. L., Wan, C., Ooi, K. S., Tan, S. T., Ahmad, N. S., Nasuruddin, D. N., Ithnin, A., Arifin, K. T., Heng, L. Y., Hassan, N. I., Gan, K., & Neoh, H. (2021). Comparison of sPLA2IIA performance with high ‑ sensitive CRP neutrophil percentage PCT and lactate to identify bacterial infection. Scientific Reports, 11, 11369. https://doi.org/10.1038/s41598-021-90894-0

Tissera, S., & Lee, S. M. (2013). Isolation of Extended Spectrum ß-lactamase (ESBL) Producing Bacteria from Urban Surface Waters in Malaysia. Malays J Med Sci., 20(3), 14–22.

ur Rahman, S., Ali, T., Ali, I., Khan, N. A., Han, B., & Gao, J. (2018). The Growing Genetic and Functional Diversity of Extended Spectrum Beta-Lactamases. BioMed Research International, 2018. https://doi.org/10.1155/2018/9519718