Scientific scope

Drug resistance is a naturally occurring phenomenon; microorganisms protect themselves against naturally occurring antimicrobials. The widespread use of antibiotics in the health care sector as well as animal production has changed the scale of drug resistance development processes, and new highly virulent ‘superbugs’ have emerged¹.

Denmark has lower rates of antimicrobial drug resistance than most European countries due to restrictive use, but recently the incidence of Methicillin-resistant Staphylococcus aureus (MRSA) in humans² has increased significantly, primarily due to spread from animal production. Furthermore, extremely drug-resistant superbugs, carbapenemases, have spread rapidly around the world3 and Denmark has experienced several hospital outbreaks. Carbapenemase-producing bacteria resistant to all known antibiotics are increasingly being reported, also from European countries^3,4, marking the beginning of an era of untreatable infections.

Recently, these superbugs have been linked to food sources⁵, indicating a possible transfer of drug-resistant bacteria from food. In countries with high levels of inequity and poorly functioning healthcare systems, attempts to enhance access to medical treatment for infections such as TB and HIV have saved millions of lives while creating conducive conditions for the development and spread of drug-resistant strains of the pathogens⁶.

The former Soviet Union has seen a dramatic increase in multidrug-resistant tuberculosis (MDR-TB) due to partial breakdown of healthcare services and widespread transmission in prisons⁷. A particularly challenging dimension of epidemics of difficult to treat infections is the public response. Secondary epidemics of stigmatization, fear and panic⁸ may amplify the impact of disease itself in terms of mortality, morbidity, economic loss and social costs.

Cultural epidemics⁹ may directly impact the ability of patients to adhere to treatment and thereby increase risks of further drug resistance. In fact, the secondary cultural/societal effects of an epidemic episode may directly affect the population behaviour and thereby the infectious dynamics itself. Feedback between the cultural and biological levels may make it particularly difficult to predict (and model) the fate of the infection.

While microbiological and genetic research has increased our understanding of intracellular mechanisms leading to drug resistance¹⁰ and has pursued knowledge contributions to diagnostics,¹¹ vaccines^12,13 and medical alternatives to known therapeutic drugs¹⁴, epidemiological and social science research has primarily focused on the prevalence of drug resistance¹⁵ and/or non-adherence to treatment as a risk factor; few attempts have been made to bring together different levels of analysis across key disciplines.

Future applications and activities

Drug resistance will increase in the future. Despite efforts to limit antibiotic use in the health care sector, widespread agricultural usage has lead to transmission of drug-resistant bacteria from animal production to humans. The case of MRSA shows that drug resistance is not limited to the medical domain and emphasizes the need for interdisciplinary research. Furthermore, increased global trade, travel and migration lead to international spread of extremely drug-resistant pathogens^16,17. More patients with complex diseases are expected to require more complex antibiotic regimes. As a consequence, this area will be one of the strategic areas for clinical development at Department of Infectious Diseases, AUH. The applicants behind this network application have been actively involved in forming the Danish input to the Horizon 2020 process, and it is expected that a specific call will appear in the area of infectious diseases and resistance. The present network application is an important step to assess and strengthen AU’s chances of playing a leading role in this regard, and to attract other external funding.

References

1. Fuursted, K. et al. Virulence of a Klebsiella pneumoniae strain carrying the New Delhi metallo-betalactamase-1 (NDM-1). Microbes and Infection 14, 155-158 (2012).
2. Agersø, Y. et al. DANMAP 2011: DANMAP 2011-Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark. (DANMAP, 2012).
3. Cantón, R. et al. Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe. Clinical Microbiology and Infection 18, 413-431 (2012).
4. Elemam, A., Rahimian, J. & Mandell, W. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clinical infectious diseases 49, 271-274 (2009).
5. Rubin, J. E., Ekanayake, S. & Fernando, C. Carbapenemase-producing Organism in Food, 2014. Emerging infectious diseases 20, 1264 (2014).
6. Seeberg, J. The event of DOTS and the transformation of the tuberculosis syndemic in India. Cambridge Anthropology 32, 95-113 (2014).
7. Farmer, P. Pathologies of power: health, human rights, and the new war on the poor (with a new preface by the author). (University of California Press, 2005).
8. Frankenberg, R. & Aggleton, P. One epidemic or three? Cultural, social and historical aspects of the AIDS pandemic. AIDS social representations social practices. London: Falmer (1989).
9. Seeberg, J. & Meinert, L. Can epidemics be non-communicable? Towards a research agenda on the spread of non-communicable diseases. Medicine Anthropology Theory (forthcoming).
10. Søndergaard, A. et al. Molecular organization of small plasmids bearing blaTEM-1 and conferring resistance to β-lactams in Haemophilus influenzae. Antimicrobial agents and chemotherapy 56, 4958-4960 (2012).
11. Søndergaard, A., Petersen, M. T., Fuursted, K. & Nørskov-Lauritsen, N. Detection of N526K-substituted penicillin-binding protein 3 conferring low-level mutational resistance to β-lactam antibiotics in Haemophilus influenzae by disc diffusion testing on Mueller-Hinton agar according to EUCAST guidelines. Journal of antimicrobial chemotherapy 67, 1401-1404 (2012).
12. ECDC. Strategies for disease-specific programmes 2010–2013. (European Centre for Disease Prevention and Control, Stockholm, 2010).
13. Jalilian, B. et al. Properties and prospects of adjuvants in influenza vaccination-messy precipitates or blessed opportunities? Molecular and Cellular Therapies 1, 2 (2013).
14. Wang, M. et al. Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis. Journal of Cystic Fibrosis 12, 638-643 (2013).
15. Hansen, F. et al. Characterization of Carbapenem Nonsusceptible Pseudomonas aeruginosa in Denmark: A Nationwide, Prospective Study. Microbial Drug Resistance 20, 22-29 (2014).
16. Lausch, K. R., Fuursted, K., Larsen, C. S. & Storgaard, M. Colonisation with multi-resistant Enterobacteriaceae in hospitalised Danish patients with a history of recent travel: A cross-sectional study. Travel medicine and infectious disease 11, 320-323 (2013).
17. Hammerum, A. M. et al. Patients transferred from Libya to Denmark carried OXA-48-producing Klebsiella pneumoniae, NDM-1-producing Acinetobacter baumannii and meticillin-resistant Staphylococcus aureus. International journal of antimicrobial agents 40, 191-192 (2012).