European cross-border study highlights how microbes ignore boundaries

The history of antibiotic resistance documents the natural response of bacteria to the presence of antibiotics, now widespread in the environment.

For example, a 2020 report on antibiotics in wastewater treatment plants noted that of seven European countries studied, those “exhibiting the highest effluent average concentrations of antibiotics were Ireland and the southern countries, Portugal and Spain”. And an Irish environmental survey in 2018/2019 found a “significant number of multidrug-resistant bacteria circulating in wastewater and aquatic environments throughout Ireland”, highlighting “the need for routine monitoring of water bodies used for recreational and drinking purposes for the presence of multidrug-resistant organisms”.

Given this context, a growing awareness of antibiotic-resistant bacteria and their related antimicrobial resistance genes (ARGs) in the hospital environment and its associated wastewater raises potential cross-infection threats in hospital and community settings. Such concerns have been sharpened by the findings of a recent collaboration between the University of Limerick School of Medicine (ULSM) in partnership with University Hospital Limerick (UHL) and Queen’s University Belfast (QUB). In the first large-scale study of its kind — published in the Journal of Hospital Infection — researchers both identified multidrug-resistant bacteria in UHL’s wastewater system and correlated their presence with clinical isolates from patients who became infected while in hospital.

A UHL medical ward had been the focus of persistent harmful bacterial infections since 2009 and, during its refurbishment, samples for microbial analysis were taken from the wastewater drains of 10 sinks and four showers — and the U-bends of six toilets. The report’s corresponding author Prof Colum Dunne — head of school, foundation chairman and director of research at ULSM — explained to The Irish Times that all the bacterial DNA present in the samples was analysed, “the entire metagenome, or complete collection, underwent sequencing and the sequences were subjected to bioinformatic analysis. These analyses not only provided a picture of all bacteria there but also included profiles of ARGs (antimicrobial resistance genes) that were present.”

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This same process was also applied to bacteria isolated from patients who had become infected at least 48 hours post-admission to the ward … and there were matches between bacteria detected in wastewater and bacteria isolated from patients. Thus, the genomes of five antibiotic-resistant bacterial isolates from patients, when analysed, showed that they harboured several ARGs, with the respective profiles of the clinical and wastewater isolates revealing a high degree of similarity with many shared ARGs. These findings invite the inference that the patients became infected in hospital, and the researchers note that “the highest numbers of ARGs observed were those encoding resistance to significant clinically and commonly used antibiotic classes”.

Interestingly, there were no significant differences between the genomic analyses of patient and staff wastewater outlets, “which may indicate that the microbiological wastewater highway may be multi-directional and that there is substantial scope for contamination exposure throughout this system”.

Given these findings, what are the implications for the management of hospital wastewater systems, and what mitigation measures might be appropriate? “Studies such as ours add insight,” says Prof Dunne, “and we now understand the complexity of the microbial communities present in the wastewater systems, and what ARGs and traits they possess. It follows, therefore, that stewardship of antibiotic use is essential. Similarly, effective, and targeted cleaning and hygiene systems, along with innovative cleaning solutions and infection prevention products, such as antimicrobial coatings, will prove important.”

In relation to engineering aspects, Dunne suggests there are opportunities to assess whether current numbers and placing of sinks and showers are appropriate: “Both retrofitting of existing facilities and a focus on this aspect for future new builds should consider this. However,” he adds, “a further implication of our work is that wastewater effluent should be monitored as it exits hospital or clinical sites, checking for both problematic microbes and antibiotic residues.”

Dunne also addresses concerns that might be harboured among those who could be preparing for a stay in hospital. “It is recognised internationally that hospital-acquired infections can sometimes occur, but infection prevention and control teams in hospitals work hard to protect patients and staff alike. While patients should be aware they can also be confident that safety measures are in place. “These risks,” Dunne emphasises, “are not being ignored; indeed, we are continuing to build on this work, and through collaborations like this we have increased the scale and accuracy of our analyses.”

It is apparent that the rise of such molecular-based epidemiology will occupy an important place in the infection control landscape, from influencing hospital architecture to determining the design of wastewater systems adjacent to patient-occupied areas. The researchers further cite evidence suggesting that wastewater-based epidemiology could also play a role in the detection of novel antibiotic-resistant pathogens and assist public health surveillance …”

However, they acknowledge that while it is difficult to “conclude definitively whether these isolates were transmitted from wastewater pipes to patients or vice versa, these data emphasise very clearly the potential for hospital wastewater systems to act as reservoirs of clinically relevant bacteria and ARGs.”

The cross-border nature of this study highlights the benefits of collaboration while underlining the fact that microbes ignore boundaries.