No More Last Resort?
Antibiotic Resistance, Carbapenem Failure, and the Sewage Crisis in Our Rivers
Increasing antibiotic resistance is one of the most important public health threats of our time. In England alone, the number of antibiotic-resistant bloodstream infections rose by 9.3% in a single year, from 18,740 cases in 2023 to 20,484 in 2024, while estimated deaths from resistant infections increased from 2,041 to 2,379 over the same period.
Those affected are often elderly, often from the most deprived communities.
The UK Health Security Agency (UKHSA) now documents close to 400 new drug-resistant infections every week in England 1. Globally, more than one million people have died each year as a direct result of antimicrobial resistance (AMR) since 1990, and the situation is getting worse. Modelling published in The Lancet in 2024 predicts that, without intervention, AMR deaths could reach 1.91 million annually by 2050, a near 70% increase on current figures 2.
And there is worse news: resistance to carbapenems, a class of antibiotics that has long served as medicine’s final line of defence, is increasing.
The Carbapenem Problem
Carbapenems - a group that includes meropenem, imipenem and ertapenem - occupy a critical position in the antibiotic arsenal. They are broad-spectrum beta-lactam antibiotics, reserved for severe or multidrug-resistant infections where other agents have failed. When a bacterium becomes resistant to carbapenems, doctors are left with very limited, often more toxic alternatives. In many cases, there is no good option at all.
Among Gram-negative bacteria, pathogens including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, resistance to carbapenems has increased more than any other antibiotic class between 1990 and 2021, with attributable deaths rising by 89,200 over that period 2. Carbapenem-resistant A. baumannii and carbapenem-resistant Enterobacterales are classified by the World Health Organization (WHO) as critical priority 1 pathogens, the highest category of concern, reserved for organisms where new active antibiotics are most urgently needed 3.
Carbapenem resistance can arise through several mechanisms, but the most clinically and epidemiologically important involves the production of carbapenemase enzymes. These are proteins that chemically hydrolyse the carbapenem molecule, rendering it inactive. The most transferable and globally distributed carbapenemase genes include KPC (Klebsiella pneumoniae carbapenemase), NDM (New Delhi metallo-beta-lactamase), OXA-48 and VIM (Verona integron-encoding metallo-beta-lactamase). What makes these genes particularly problematic is their capacity to move between bacteria through a process known as horizontal gene transfer.
Horizontal Gene Transfer
Unlike vertical transmission, where a parent bacterium passes genes to its offspring, horizontal gene transfer (HGT) allows resistance genes to move laterally between entirely different bacterial species. The primary vehicle for carbapenemase gene transfer is the plasmid: a small, circular piece of DNA that sits in the bacterium’s cytoplasm separate from the main chromosome and can be readily copied and passed to neighbouring organisms through a process called conjugation. Plasmids are frequently mobile genetic elements; some can transfer themselves to bacteria of entirely different genera, or even different phyla.
Research published in The Lancet Microbe in 2023 demonstrated just how actively this process occurs in real-world bacterial communities within hospital sewage. Using CRISPR-tagged plasmids, the study tracked the transfer of NDM-5-positive plasmids across multiple bacterial phyla within a hospital wastewater treatment system, the first culture-independent evidence of interphylum gene transfer in such an environment 4.
Plasmids and transposons also carry integrons, genetic structures that can capture and accumulate multiple resistance genes, creating bacteria resistant to several antibiotic classes simultaneously.
Crucially, horizontal gene transfer does not require contact between clinical pathogens. It can occur among the broader microbial communities that inhabit wastewater, river sediments and agricultural soil. At this is point we have to consider the problem of sewage pollution.
The UK’s Sewage Problem
The United Kingdom’s waterways are in a dire state. Routine sewage overflows, inadequate wastewater treatment and agricultural runoff have created conditions in which antibiotic-resistant bacteria and resistance genes are accumulating in rivers, lakes and coastal waters. Every water body in England currently fails the Water Framework Directive standards for ecological quality - a systemic failure with direct implications for AMR.
A 2024 study led by the University of York, conducted in partnership with Surfers Against Sewage, tested 23 designated inland bathing sites across England, Wales and Scotland. Antimicrobial resistance genes were detected at all sites but one; the most heavily contaminated - the River Dart in Devon - harboured 53 of the 71 resistance genes tested for. Among those detected were genes conferring resistance to last-resort antibiotics 5.
In February 2026, research from Index Microbiology found that 97% of water samples taken from Oxford’s rivers tested positive for bacteria producing extended-spectrum beta-lactamases (ESBLs), a key step on the pathway towards carbapenem resistance 6. A 2019 analysis of the River Thames catchment found that large portions of the river system are chronically exposed to antibiotic concentrations sufficient to promote resistance gene selection, even after wastewater treatment, with 64% of the catchment at risk of selection for macrolide resistance and 74% for fluoroquinolones resistance 7.
Hospital effluent is a particularly concentrated source. Studies of hospital wastewater in Wales, conducted under the PATH-SAFE programme, found the ‘big five’ carbapenemase gene variants distributed across NHS sites, along with concentrations of antibiotics exceeding thresholds associated with resistance emergence 8. When this effluent passes through wastewater treatment plants (WWTPs), treatment reduces but does not eliminate resistance genes. The treated water, along with sewage sludge subsequently applied to agricultural land, then disperses resistant organisms and genetic material into the wider environment.
Animal Agriculture and One Health
Human sewage is not the only source of risk; animal agriculture contributes substantially to antibiotic resistance. Antibiotics used in livestock, including those related to classes used in human medicine, are excreted in manure which can then enter watercourses through runoff. A nationwide wastewater study published in Nature Communications in January 2026 found aminoglycoside resistance genes present at concentrations 50% higher in sewage than in clinical samples, a discrepancy attributed to inputs from poultry, aquaculture and other agricultural sources 9.
Studies of rural English rivers, including the Eden in Cumbria and the Coquet in Northumberland, have confirmed that diffuse agricultural pollution, mediated by soil saturation and surface runoff, measurably increases the abundance of resistance genes in river microbiomes10. In Northern Ireland, veterinary antibiotics have been found downstream of farm sites, consistent with farm runoff as a direct source. This runoff, along with the disposal of treated and untreated human sewage, is implicated in the heavy pollution of Lough Neagh, a water source which supplies approximately 40% of Northern Ireland’s drinking water.
This interplay between human medicine, veterinary practice and environmental contamination is why AMR is increasingly approached from a One Health perspective, recognising that human, animal and environmental health are inseparably linked. The carbapenemase genes accumulating in the rivers of the United Kingdom do not distinguish between clinical and non-clinical bacteria. Through horizontal gene transfer, antibiotic resistance can transfer from environmental organisms to pathogens that subsequently cause human infection.
The Politics of Antimicrobial Resistance
Antibiotic resistance is not a politically neutral crisis. UKHSA data consistently demonstrate that people in the most deprived communities bear a disproportionate burden. In 2022, individuals from the most deprived 10% of the population were more than twice as likely to carry carbapenemase-producing Gram-negative bacteria than those from the least deprived 10% - rates of 6.8 compared to 2.8 per 100,000 11. Resistant infections are substantially more common in areas of poverty, where overcrowding, poorer housing conditions, reduced access to timely healthcare and higher baseline rates of comorbidity combine to increase both vulnerability and exposure.
The communities most likely to swim in polluted rivers, to live near water company sewage overflow points or to work in agricultural settings with high antibiotic use are rarely those with the most political or economic power to demand regulatory action. This is an environmental justice failure as much as a scientific one.
The UK Response
The UK published a new five-year National Action Plan (NAP) for antimicrobial resistance in 2024, setting targets including a 5% reduction in total antimicrobial use in humans by 2029 relative to 2019 levels, and strengthened One Health surveillance 12. There has been progress: overall NHS antibiotic use in 2024 was 2% below the pre-pandemic 2019 baseline. But the trend remains concerning, with resistant bloodstream infections continuing to rise and the surveillance gap between human and animal sectors still inadequately closed. The National Audit Office and Public Accounts Committee both highlighted in early 2025 that further action is urgently required.
On the environmental front, antibiotics discharged into rivers and waterways remain largely unregulated. No environmental quality standards currently exist in England for antibiotic concentrations in surface water, a gap that researchers in the field have called untenable given the evidence of resistance selection at concentrations which are routinely exceeded 7. Wastewater surveillance for AMR, pioneered during the COVID-19 pandemic, is now being extended; Wales is among the early adopters of national hospital wastewater screening for carbapenemase genes. But upgrading wastewater treatment infrastructure to reliably remove resistance genes remains a longer-term, expensive ambition. It is an upgrade that the water companies have not convincingly prioritised in the past.
Conclusion
The spread of carbapenem resistance represents a significant risk to medicine and to health. Procedures that depend on reliable antimicrobials, such as major surgery, cancer chemotherapy, organ transplantation, the care of premature infants, become more dangerous when bacterial infections that were once treatable can no longer be controlled.
The sewage crisis contaminating Britain’s rivers isa significant factor. Environmental reservoirs of resistance genes, amplified by HGT in microbial communities and dispersed by failing water infrastructure and agricultural runoff, represent a source of developing resistance that clinical antibiotic stewardship alone cannot address. Reducing medical use of antibiotics, though desirable, will have little effect unless all the other factors are addressed.
Tackling this will require enforced reductions in agricultural antibiotic use, no more antibiotic prescriptions for viral chest infections, the development and dissemination of vaccines for bacterial infections, enforceable regulation of antibiotic discharges into waterways, investment in wastewater treatment capable of removing resistance genes, and a recognition that the communities most harmed by environmental AMR are those already least supported by the systems meant to protect them. The science is clear. The politics is hazy. The effects of profiteering are disastrous.
References
1. UK Health Security Agency. Nearly 400 antibiotic-resistant infections each week in 2024 [Internet]. London: UKHSA; 2025 [cited 2026 Mar 14].
3. World Health Organization. WHO Bacterial Priority Pathogens List, 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: WHO; 2024.
4. Prof Qiu E Yang, Xiaodan Ma, Lingshuang Zeng, Qinqin Wang, Minchun Li, Lin Teng, Mingzhen He, Chen Liu, Mengshi Zhao, Mengzhu Wang, Deng Hui, Jonas Stenløkke Madsen, Hanpeng Liao , Prof Timothy R Walsh, Prof Shungui Zhou. Interphylum dissemination of NDM-5-positive plasmids in hospital wastewater from Fuzhou, China: a single-centre, culture-independent, plasmid transmission study. Lancet Microbe. 2024;5(1):e13–e23.
5. University of York. UK inland bathing sites polluted by chemicals and antibiotic-resistant genes [Internet]. York: University of York; 2024 [cited 2026 Mar 14].
6. Morley R. Antibiotic-resistant bacteria in Oxford rivers [Internet]. Oxford: Index Microbiology/Oxford Daily News; 2026 Feb [cited 2026 Mar 14].
7. Singer A, Quiying Xu, Keller VDJ. Translating antibiotic prescribing into antibiotic resistance in the environment: a hazard characterisation case study. PLoS One. 2019;14(9):e0221568.
8. Reshma Silvester, William B. Perry, Gordon Webster, Laura Rushton, Amy Baldwin, Daniel A. Pass, Neil Andrew Byrnes, Kata Farkas, Margaret Heginbothom, Noel Craine, Gareth Cross, Peter Kille, Barbara Kasprzyk-Hordern, Andrew J. Weightman, Davey L. Jones. Metagenomic profiling of hospital wastewater: a comprehensive national scale analysis of antimicrobial resistance genes and opportunistic pathogens. J Infect. June 2025.
Integrons are bacterial genetic mechanisms that enable the rapid adaptation and evolution of bacteria by capturing, storing, rearranging, and expressing gene cassettes.
Integrons are primarily found in bacteria, where they serve as genetic platforms for capturing and expressing mobile genes. Approximately 15–17% of all sequenced bacterial genomes contain these elements.
National Institutes of Health (NIH) | (.gov) +4
They are typically found in two distinct genetic contexts:
Bacterial Chromosomes: Many integrons are sedentary components of the host chromosome. These “chromosomal integrons” (sometimes called super-integrons) can be very large, carrying hundreds of gene cassettes that contribute to general bacterial adaptation and evolution.
Mobile Genetic Elements (MGEs): Integrons are frequently found on plasmids and transposons. These “mobile integrons” (MIs) are much smaller, typically carrying fewer than ten cassettes, and are the primary drivers for spreading antibiotic resistance in clinical settings.
Wikipedia +4
Environmental Distribution
Beyond clinical isolates, integrons are ubiquitously distributed in diverse natural habitats, including:
Aquatic Environments: Freshwater (rivers, lakes, and hot springs) and marine environments (deep-sea sediments and aquatic biofilms).
Terrestrial Environments: Forest, desert, and Antarctic soils.
Human-Impacted Sites: Wastewater treatment plants, hospital effluents, and agricultural areas treated with manure.
Biological Surfaces: On the surfaces of plants and in the symbionts of eukaryotes
Gene Cassettes: These are small, mobile, circular DNA elements, often carrying a single, promoterless antibiotic resistance gene.
Transposons, or "jumping genes," are DNA sequences that move (transpose) from one location to another within a genome.