Strong Correlation Between Wastewater and Clinical Antimicrobial Resistance Data

Antimicrobial resistance (AMR) is one of the most pressing public health challenges of our time. Traditional methods of tracking AMR typically involve clinical surveillance, which can be slow, expensive, and limited in scope. However, recent advancements in wastewater surveillance offer a promising, non-invasive alternative that can provide valuable predictive data and enhance our ability to monitor and combat AMR.

Understanding AMR Through Wastewater Surveillance

Wastewater surveillance involves analyzing sewage samples for the presence of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs). Antimicrobial-resistant bacteria (ARBs) are bacterial strains that have acquired the ability to survive and proliferate in the presence of antibiotics that would typically inhibit their growth or kill them. Antibiotic resistance genes (ARGs) are specific genetic sequences in bacteria that encode the proteins or mechanisms that confer resistance to antibiotics. These genes can also be transferred between bacteria, leading to the emergence of multidrug-resistant strains

Wastewater samples are collected from various points within the sewage system, such as wastewater treatment plants (WWTPs), hospitals, and specific community locations. Unlike clinical surveillance, which relies on individuals seeking medical care, wastewater surveillance collects data from everyone in the community, including asymptomatic carriers and those who do not visit healthcare facilities. As a result, wastewater surveillance captures a broad snapshot of the health status of entire communities by detecting and quantifying ARB and ARGs shed in human waste. Studies have shown that the resistome (the collection of all ARGs) in wastewater mirrors the antibiotic-resistant profiles found in clinical settings, making it a valuable tool for public health monitoring.

Strong Correlation Between Wastewater and Clinical Data

A comprehensive systematic review conducted by Chau et al. (2022) analyzed wastewater-human AMR prevalence estimates in 33 studies. The review found a high concordance between AMR in wastewater and human populations, with a concordance correlation coefficient (CCC) of 0.85 for phenotypic data and 0.88 for genotypic data. This high concordance was particularly evident for specific bacteria and antibiotics, such as E. coli and aminoglycosides, and CTX-M β-lactamases. Despite diverse study designs, bacterial species investigated and phenotypic/genotypic targets, the overall wastewater-human AMR concordance was high, suggesting that wastewater can accurately reflect the resistance patterns observed in clinical settings.

The review highlighted that genotypic data showed slightly higher concordance with clinical data compared to phenotypic data. Genotypic data involves identifying and characterizing specific antibiotic resistance genes (ARGs) present in bacteria, while phenotypic data refers to the actual resistance behavior of bacteria when exposed to antibiotics. Genotypic methods, such as PCR, identify specific ARGs and can provide a more detailed understanding of the resistome within a community. High concordance was found in 73% of genotypic comparisons, indicating that wastewater analysis can reliably mirror clinical resistance patterns, especially for well-characterized ARGs.

Overall, wastewater surveillance is emerging as a robust tool for monitoring antimicrobial resistance in human populations. The high concordance observed between AMR profiles in wastewater and clinical settings indicates that wastewater surveillance could accurately predict future clinical cases. Furthermore, the higher concordance of genotypic data compared to phenotypic data emphasizes the importance of molecular techniques in identifying specific antibiotic-resistance genes (ARGs).

Case Studies

A study by Flach et al. (2021) investigated the presence of carbapenemase-producing Enterobacterales (CPE) in hospital wastewater. They detected a marked peak in CPE-producing OXA-48-like enzymes in sewage before any known clinical cases. Soon after, a few cases were detected in patient samples at the hospital, demonstrating the potential of wastewater surveillance as an early warning system for emerging resistance threats.

Another study by Hutinel et al. (2019) investigated the relationship between Escherichia coli resistance rates in sewage and clinical samples representing the same human populations. The results showed that E. coli resistance rates derived from hospital sewage and hospital patients strongly correlated, as did resistance rates in E. coli from municipal sewage and primary care urine samples.

Practical and Ethical Benefits of Wastewater Surveillance

Wastewater surveillance presents practical and ethical advantages over traditional clinical surveillance methods, making it a valuable tool against AMR. By detecting changes in resistance patterns before they become clinically evident, wastewater surveillance serves as an early warning system to prevent the spread of resistant bacteria and mitigate the emergence of AMR hotspots.

Moreover, wastewater surveillance offers cost-effectiveness and comprehensive coverage. Compared to individual medical testing, wastewater surveillance involves lower per capita costs and provides broader spatial coverage, making it feasible for monitoring AMR in entire communities, regardless of whether individuals display symptoms or seek medical help. This cost-effectiveness is particularly beneficial in low-income regions where resources for individual diagnostic facilities are limited, as wastewater surveillance can provide critical public health data at a fraction of the cost of traditional testing methods.

Furthermore, wastewater surveillance is non-invasive and does not require informed consent from individuals. This ethical advantage bypasses the ethical and logistical challenges associated with medical privacy and consent, allowing for large-scale monitoring without compromising individual privacy rights. This facilitates easier implementation across diverse populations and ensures that ethical considerations are upheld throughout the surveillance process.

By leveraging these benefits, wastewater surveillance supports effective public health interventions aimed at mitigating the spread of antimicrobial resistance and preserving the efficacy of antimicrobial agents for future generations.

The Future of Public Health: Alignment with the CDC’s Investments

Wastewater monitoring for AMR aligns with the CDC's strategic investments aimed at enhancing public health infrastructure. By providing comprehensive and cost-effective surveillance, wastewater monitoring supports the Emerging Infections Program (EIP) by offering population-level insights that inform policy and public health practices. The EIP is dedicated to improving public health through population-based surveillance and research activities, and wastewater monitoring plays a crucial role in achieving these goals by detecting resistance patterns across entire communities. By understanding the spread of specific AMR genes and pathogens, health departments will be equipped with the data needed to better fight infections in healthcare facilities and contain infectious disease threats.

References

Chau, K. K., Barker, L., Budgell, E. P., Vihta, K. D., Sims, N., Kasprzyk-Hordern, B., Harriss, E., Crook, D. W., Read, D. S., Walker, A. S., & Stoesser, N. (2022). Systematic review of wastewater surveillance of antimicrobial resistance in human populations.?Environment international,?162, 107171. https://doi.org/10.1016/j.envint.2022.107171

Flach, C. F., Hutinel, M., Razavi, M., ?hrén, C., & Larsson, D. G. J. (2021). Monitoring of hospital sewage shows both promise and limitations as an early-warning system for carbapenemase-producing Enterobacterales in a low-prevalence setting.?Water research,?200, 117261. https://doi.org/10.1016/j.watres.2021.117261

Gholipour, S., Shamsizadeh, Z., Halabowski, D., Gwenzi, W., & Nikaeen, M. (2024). Combating antibiotic resistance using wastewater surveillance: Significance, applications, challenges, and future directions.?The Science of the total environment,?908, 168056. https://doi.org/10.1016/j.scitotenv.2023.168056

Hutinel, M., Huijbers, P. M. C., Fick, J., ?hrén, C., Larsson, D. G. J., & Flach, C. F. (2019). Population-level surveillance of antibiotic resistance in?Escherichia coli?through sewage analysis.?Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin,?24(37), 1800497. https://doi.org/10.2807/1560-7917.ES.2019.24.37.1800497

Tiwari, A., Kurittu, P., Al-Mustapha, A. I., Heljanko, V., Johansson, V., Thakali, O., Mishra, S. K., Lehto, K. M., Lipponen, A., Oikarinen, S., Pitk?nen, T., WastPan Study Group, & Heikinheimo, A. (2022). Wastewater surveillance of antibiotic-resistant bacterial pathogens: A systematic review.?Frontiers in microbiology,?13, 977106. https://doi.org/10.3389/fmicb.2022.977106