Selection

Usage of antibiotics in healthcare

In the presence of antibiotics, minor resistant bacterial populations have a selective growth advantage and proliferate while the others die out.

Inappropriate use or misuse of antibiotics could lead to selective amplification of resistant populations and is considered as one of the main reasons for the emergence of drug resistant bacterial pathogens. According to a report of the Centre for Disease Control (CDC) USA, around 50% of antibiotic prescriptions are considered unnecessary [1]. Use of antibiotics is higher among hospitalised patients with around 33% of all patients in Europe receiving at least one antimicrobial agent [2]. A close relationship between antibiotic usage and resistance levels is illustrated by the reduction in the levels of resistance achieved due to overall reduction of antibiotics in Europe [3]. Another factor leading to rapid spread of resistance is human-to-human transmission. This is shown by the rapid spread of MRSA clones in both hospitals and the community around the world. A recent whole genome sequencing study of MRSA from various regions around the UK identified several transmission clusters of the dominant MRSA clone within the community and hospitals [4].

Usage of antibiotics in livestock

Another area of greater importance is the use of antibiotics in animals, particularly in livestock. It is believed that use of antimicrobials in livestock as growth promoters and to treat infections drives the selection of resistant bacterial populations in animals [5]. Livestock has been proposed as a potential reservoir for drug-resistant bacteria that infect humans, which may involve the transfer of drug-resistant strains or resistance genes via mobile genetic elements such as plasmids. One Health genomic studies can shed light into the transmission of drug-resistant bacteria between animals and humans. A recent study has shown that E. coli causing bloodstream infections in UK patients are not acquired from livestock and that sharing of mobile elements between animals and humans is infrequent [6].

In addition, in some cases the resistance genes co-occur with heavy metal resistance genes on the same plasmid. Therefore, heavy metal contamination of the soil or its usage in animal farming also leads to co-selection of resistant bacterial cells. Further, the heavy metals are also used in agriculture as a fungicide or bactericide and can lead to selective enrichment of resistant populations.

References

1. Centres for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. Atlanta, 2013. http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf
2. https://www.ecdc.europa.eu/en/publications-data/antimicrobial-use-european-hospitals
3. Livermore DM, Hope R, Reynolds R, Blackburn R, Johnson AP, Woodford N. Declining cephalosporin and fluoroquinolone non-susceptibility among bloodstream Enterobacteriaceae from the UK: links to prescribing change? J Antimicrob Chemother 2013; 68: 2667–74.
4. Coll F, Harrison EM, Toleman MS, Reuter S, Raven KE, Blane B, Palmer B, Kappeler ARM, Brown NM, Török ME, Parkhill J, Peacock SJ. Longitudinal genomic surveillance of MRSA in the UK reveals transmission patterns in hospitals and the community. Sci Transl Med. 2017 Oct 25;9(413).
5. Holmes AH, Moore LS, Sundsfjord A, Steinbakk M, Regmi S, Karkey A, Guerin PJ, Piddock LJ. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet. 2016 Jan 9;387(10014):176-87
6. Ludden C, Raven KE, Jamrozy D, Gouliouris T, Blane B, Coll F, de Goffau M, Naydenova P, Horner C, Hernandez-Garcia J, Wood P, Hadjirin N, Radakovic M, Brown NM, Holmes M, Parkhill J, Peacock SJ.One Health Genomic Surveillance of Escherichia coli Demonstrates Distinct Lineages and Mobile Genetic Elements in Isolates from Humans versus Livestock. mBio. 2019 Jan 22;10(1).