Antibiotic resistance is a web of several problems
How to monitor antibiotic-resistant genes? How to prevent it? What is the connection between antibiotic resistance and microbiota? All your questions answered here.
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To mark World Antimicrobial Awareness Week (18-24 November), the Microbiota Institute is handing the floor to two antibiotic resistance’s experts: (sidenote: Dr. Windi Muziasari has gained years of experience and the know-how to monitor antibiotic resistance in the environment using a high-throughput gene profiling during her PhD and PostDoc at the University of Helsinki, Finland. She wanted other researchers to gain easy access to this technology and that was why she moved from academia to entrepreneurship by founding Resistomap in 2018. Headquartered in Helsinki, Resistomap's mission is to mitigate the spread of antibiotic resistance by providing robust tools for monitoring. Resistomap combines molecular genetics methods and data science to provide a service to detect and quantify antibiotic resistance genes from environmental samples such as wastewater and soils. Since fully operating in January 2019, Resistomap has served over 250 projects and analysed over 7000 environmental samples across 40 countries. ) , PhD, CEO of Resistomap, and Pr. (sidenote: Christian G. Giske is the head physician of bacteriology, mycobacteriology and mycology at Karolinska University Hospital, Solna, Sweden. He is also the head of the Division of Clinical Microbiology and the Division of Clinical Immunology at the Department of Laboratory Medicine at Karolinska Institute, where he also leads a research group. The most important research activities in Giske’s research group pertain to deep-characterization of molecular mechanisms of resistance, virulence, and molecular epidemiology of extensively drug-resistant enteric bacilli. Giske’s research is strongly translational, involving extensive collaboration with infectious diseases (including mycobacteriology), hematology, and intensive care. Giske also has extensive international collaboration, serving in the advisory board of ECDC’s European resistance surveillance, and as the chair of the European Committee on Antimicrobial Susceptibility Testing. ) from Karolinska Institute in Sweden.
Why is antibiotic resistance a major public health problem?
Dr. Windi Muziasari
Antibiotic resistance is indeed a global health threat that causes more than 1,2M deaths annually1. Antibiotic resistance is the condition when antibiotics are no longer efficient to treat bacterial infections. This can lead us back to the era before antibiotics were first discovered by Alexander Flemming in 1928. Bacterial infection diseases such as tuberculosis, pneumonia, and simply urinary tract infection could kill us again and in a worst-case scenario, performing any surgery and delivering a baby could have high mortality rates. Antibiotics are heavily used in both human and animal medicines which accelerate the increase of antibiotic resistance levels in bacteria.
Pr. Christian G. Giske
Antibiotic resistance is in fact a web of several problems. It varies a lot between geographical settings whether the problem is confined to hospital-acquired infections or also widespread in the community. The results of antibiotic resistance are well documented – it leads to increased mortality, longer hospital stays, increased costs for healthcare, and more side effects related to the treatment. In many cases some hospital-acquired infections can be extremely difficult-to-treat. Antibiotic resistance will also lead to fear of complications to complicated surgery and/or immunosuppressive treatment – infections with highly drug resistant strains that will severely compromise results of other treatments. Hospital-acquired infections will usually not affect so many individuals, but still represent a public health problem due to the fear that resistant infections cannot be managed. On an individual patient level, the consequences can be dire, but also for patients in the same unit in the hospital to which resistant strains can be transmitted. Community acquired infections will affect more individuals and will also lead to increased hospitalization and thus affect the capacity in health care. There is not one single solution to the antibiotic resistance problem – rather a complex combination of several mitigation approaches is needed.
Cornerstone of the modern therapeutic arsenal, antibiotics saved millions of lives. On the other hand, their excessive and sometimes inappropriate use can lead to the emergence of multiple forms of resistance in microorganisms. Each year, the World Health Organization (WHO) organizes the World Antimicrobial Awareness Week (WAAW) to increase awareness of this public health issue. Read the dedicated page:
Microbiota at the forefront of antibiotic resistance
You’re monitoring antibiotic-resistant genes at hospitals by collecting wastewater samples. Can you explain why, and why are you not collecting samples directly from patients to quantify these genes?
W. Muziasari: There are two important limitations to how antibiotic resistance is currently monitored in hospitals. First, current monitoring focuses mainly on a limited number of pathogenic bacteria. Second, it is often based on passive surveillance of bacteria isolated from patients. This leads to delayed detection of outbreaks, non-comparable data, and the inability to capture other pathogenic bacteria and antibiotic resistance profiles which are often carried by commensal bacteria.
Wastewater-based monitoring will be a potentially valuable addition to current options for antibiotic resistance monitoring in hospitals. Though not a substitute for existing monitoring methods, wastewater monitoring can provide data that is otherwise hard to obtain and become the easiest means for obtaining comprehensive information on the prevalence of resistance in hospitals. As waste from all patients are released into wastewater, wastewater monitoring can cover a wider range of antibiotic resistance profiles compared to the partial data from a few selected pathogenic bacteria. In addition, analyzing wastewater samples does not require informed consent, thus limiting ethical concerns. The practical and logistical barriers for sampling wastewater are also limited. Wastewater-based monitoring can therefore be used to better understand the development and spread of antibiotic resistant bacteria in hospitals and serve as an early warning system for future outbreaks.
How does your research & technology help physicians to prevent antibiotic resistance?
W. Muziasari: Through wastewater-based monitoring physicians will have in-depth information on the levels of antibiotic resistance from their hospitals over time.
Output 1. Hospitals gain awareness of trends towards possible outbreaks.
Hospitals will gain a more complete overview on the presence of antibiotic resistance genes and pathogenic bacteria, which will allow them to identify possible outbreaks at an earlier stage. Hospitals will thus be better prepared to take mitigation measures which will lead to decreased outbreaks of antibiotic resistant bacteria in hospitals.
Output 2. Hospitals gain awareness on the implications of current prescribing practices on the emergence of antibiotic resistance.
Hospitals will be able to compare the levels of antibiotic resistance with antibiotic use within a specific period. In this manner, hospitals will gain awareness on the implications of current prescribing practices on the emergence of antibiotic resistance. Hospitals will therefore be encouraged to improve regulations on antibiotic prescribing which will lead to optimized use of antibiotics in hospitals.
Output 3. Hospitals gain awareness of the quality of wastewater outflow released into the environment.
Hospital wastewater is usually treated in a municipal or own wastewater treatment facility before being released in water environments. Hospitals will have additional information on the quality of outflow released into the community. This information is expected to encourage hospitals to improve their wastewater management which will ensure that local communities have access to water that is safe from antibiotic resistance.
What is the connection between antibiotic resistance and microbiota?
C. G.Giske: Many resistant strains are first acquired as colonizers in the human microbiome – either intestinal or respiratory. Once the strains are acquired in the microbiome, they can establish there as long-term carriage and will sometimes cause infections in the host, or potentially spread to other individuals who may be more susceptible to bacterial infections. Thus, carriage of resistant strains remains a significant risk for resistant infections in either the host or in other people in the proximity of the original host. While in the microbiome, strains can also easily exchange genetic material and thus transmit resistance to other bacterial strains – sometimes strains that are more adapted to the gut of that individual and can therefore remain in the microbiome for very long. Monitoring carriage of resistant strains in the microbiome remains an important part of infection control, as it can inform decisions on patients who need to be hospitalized in single rooms by dedicated staff for instance – to avoid transmission events.
Meet Professor Sørensen, 2022 Biocodex Microbiota Foundation International Grant Winner.
His team pioneered an ambitious study on the resistome of 700 children that will facilitate a breakthrough in the understanding of the evolution and dissemination of antimicrobial resistance in the early life human gut.
Could microbiota help researchers to tackle antibiotic resistance?
C. G.Giske: The microbiome is complex and contains a variety of microorganisms – among them also viruses. Some of the viruses, the so called bacteriophages, can infect selectively bacterial strains and kill them. Such bacteriophages can be isolated from the microbiome and could be used therapeutically to treat infections in patients. Numerous studies highlight the in vitro and in vivo potential of their therapeutic uses and while a number of clinical trials have taken place over the last decade, the biggest challenge remain to produce additional data presenting a robust regulatory case for their clinical use2. Moreover, monitoring resistance in the microbiome can be highly informative for understanding the pool of resistance genes available in a population and can be very useful to design strategies for counteracting antibiotic resistance.
