Antibiotics excreted by patients promote antibiotic-resistant bacteria in hospital sewers, according to a new study by researchers at the University of Gothenburg, Sweden. Ultimately, this may contribute to the development and spread of hard-to-treat infections. Pinpointing the responsible antibiotics paves the way for targeted measures.
"To my best knowledge, this is the first direct field evidence in over 25 years conclusively linking observed environmental effects to pharmaceuticals excreted from humans", says Joakim Larsson, Professor of Environmental Pharmacology at the University of Gothenburg in Sweden.
The study, published in Nature Communications, examined sewer systems and wastewater from hospitals and municipal treatment plants in eight Swedish cities. Sewage from all ten hospitals promoted antibiotic-resistant bacteria, while no such effects were found after exposure to sewage from the corresponding municipal treatment plants.
Paves the way for tailored measures
International guidelines emphasize the need to limit selection for antibiotic-resistance in the environment, as antibiotic pollution could ultimately render antibiotics ineffective. The observation of strong resistance selection in hospital sewer systems, but not in municipal ones, is significant for where measures should be prioritized. While advanced treatment at municipal sites can reduce the further spread of antibiotics and other pharmaceuticals, it cannot prevent the resistance evolution that has already taken place in hospital sewage. The results therefore point to hospital sewage systems as a critical site for future targeted interventions.
"Knowing where resistant bacteria are promoted—and where they are less likely to be—is crucial when deciding how resources and efforts should be allocated to limit risks for antibiotic resistance development," says Joakim Larsson.
Similar selection likely occurs in hospital sewers worldwide
When the researchers made a sensitive E. coli strain resistant to fluoroquinolones and penicillin-like antibiotics it was able to grow well in hospital sewage where it otherwise could not. This showed that it was primarily these antibiotic classes that were responsible for giving resistant bacteria an advantage. Ciprofloxacin was identified as a key driver, a commonly used antibiotic in the fluoroquinolone group often prescribed for urinary tract infections. Cefotaxime, a penicillin-like antibiotic only used at hospitals, also contributed. Several independent lines of evidence, including chemical analyses and studies of bacterial cell responses, pointed in the same direction.
"The findings suggest that similar resistance selection occurs in the sewers of most hospitals worldwide. In Sweden, total antibiotic use is relatively low, but hospital use is comparable to that in many other European countries," explains Joakim Larsson.
"Antibiotic use must always be guided by patients' medical needs," he continues. "But now that we know which types of drugs drive resistance selection in sewage, we can also develop more targeted solutions to mitigate risks."
The research team is currently working intensively to develop a simple, targeted treatment method to reduce the selection pressure in the sewers.
Rare direct evidence in the environment
Most conclusions about environmental effects of pharmaceuticals are based on experiments where researchers intentionally add drugs at concentrations matching those measured in the environment. Such studies show what effects drugs can cause, but not whether those effects actually occur under real-world environmental conditions. The current study goes one step further by documenting effects directly within hospital sewer pipes. Resistant E. coli were enriched in biofilms in hospital sewers compared with the wastewater, whereas no corresponding enrichment was observed at municipal treatment plants.
The last clear field evidence of a similar nature dates back to the late 1990s, when feminization of fish downstream of treatment plants was linked to pharmaceuticals from human use. Then, as now, Joakim Larsson contributed to identifying the substance responsible, in that case the contraceptive hormone ethinylestradiol.
The study was conducted at 10 Swedish Hospitals:
• Sahlgrenska Hospital (Sahlgrenska University Hospital, Gothenburg)
• Östra Hospital (Sahlgrenska University Hospital, Gothenburg)
• Mölndal Hospital (Sahlgrenska University Hospital, Gothenburg)
• Södra Älvsborg Hospital (Borås)
• Norra Älvsborgs Länssjukhus, NÄL (Trollhättan)
• Skaraborg Hospital (Skövde)
• Kungälv Hospital (Kungälv)
• Uppsala University Hospital (Uppsala)
• Södersjukhuset (Stockholm)
• Karolinska University Hospital Huddinge (Stockholm)
