Antimicrobial resistance in Streptococcus pneumoniae, Streptococcus pyogenes and Escherichia coli from the Faroese population, correlation with antimicrobial use and comparison with Denmark and Iceland
Marita Debess Magnussen
Heilsufrøðiliga Starvsstovan og Landspitali
Karl G. Kristensson, Shahin Gaini
Stuðul úr Granskingargrunninum:
There is very limited knowledge about antimicrobial resistance in bacterial pathogens in the Faroese population. Antimicrobial resistance has become a global problem and new resistant pathogens are continuously emerging. It should be assumed that resistance is also increasing in the Faroe Islands a potential threat for future treatment of infectious diseases.
This research project is important for the Faroese community since it will give valuable information about antimicrobial resistance in three of the most significant human pathogens in addition, it could make antimicrobial treatment more focused by reducing the use of broad spectrum antimicrobials. Information will be collected about the consumption of antimicrobial agents in the Faroese community, which will subsequently be compared with the use in Iceland and Denmark.
Representative isolates of Streptococcus pneumoniae from healthy children. Streptococcus pyogenes from patients with sore throat and Escherichia coli from patients with urinary tract infections will be collected from the Faroese population. The cultures, identification and susceptibility testing will be performed at Landssjúkrahúsið but serotyping, molecular typing and investigation of multiresistant isolates at the Department of Clinical Microbiology, Landspitali University Hospital, Iceland. Correlation the antimicrobial susceptibility data and antimicrobial consumption data from the Faroese Islands, Iceland and Denmark will give important information about the relationship between usage and resistance thereby providing tools for interventions.
Although the remotely located Faroe Islands could be ideal for carriage, clonal and vaccine studies, a severe lack of data has, prior to our study, limited such investigations. Our novel data collection and analysis has provided valuable knowledge on the antibacterial resistances in the three human bacterial pathogens - group A streptococcus (GAS), Escherichia coli (E. coli) and pneumococci. By comparing this new knowledge with the neighboring countries, Iceland and Denmark, we have provided the first assessment of our community’s status with regards to the global multi-resistance threat. Compiling sales data, we found differences in total antibacterial use and in the use of individual antibacterials between the three countries. The difference was mainly caused by the higher tetracycline sale in Iceland and there was variation within the penicillin and macrolide groups in the three countries. The higher use of broad-spectrum penicillin and the combinations with beta-lactamase inhibitors in Iceland could reflect problems associated with the higher antibacterial resistance among pneumococci causing infection there.
The antibacterial use in the Faroe Islands is particularly stable, and a partial explanation for this is likely the fact that there is no antimicrobial policy and no information on antimicrobial resistance in this country. One suspicion derived from the sales study concerns a potentially improper use of erythromycin for children in the Faroes.
There was a variation in resistance prevalence between the investigated GAS bacterial isolates in the Faroe Islands. The resistance prevalence among GAS isolates was lower than expected after the insight of improper use of erythromycin among children. We observed a sudden decrease of tetracycline resistance among GAS isolates in patients from 2009 to 2010. In similar fashion, the erythromycin resistance decreased in Iceland from 2008 to 2009. Though antimicrobial use probably influences the prevalence of erythromycin and tetracycline resistance in the Faroe Islands and Iceland, this is unlikely to explain the observed sudden changes. We thus suggest that the resistance peaks are caused by intermittent introductions of novel resistant clones from abroad. A significant difference in tetracycline resistance between age groups was also observed in the Faroes, which cannot be ascribed to tetracycline consumption, as one of the highest resistance prevalence was in the youngest age group which hardly used any tetracycline. A more probable explanation is that tetracycline-resistant isolates are being spread between family members, and that one or very few clones can be circulating in this small community at any given time. The resistance prevalence among E. coli isolates was high with regard to ampicillin, trimethoprim, SXT and sulphonamides, and we found significant linear relationships between antibacterial mean sales and antibacterial resistances. In addition, we developed a novel logistic modelling approach, which can facilitate representative predictions of the future developments in resistance with increased antibiotic sales. This model enables us to categorize the resistance increases induced by the different types of antibiotic into two groups – ‘steep’ and ‘gradual’. This knowledge can potentially be used to predict and control the future increase in resistance with antibacterial sales – e.g. prescriptions of drugs within the ‘steep’ group should be given in moderation, since these can result in increased resistances.
The pneumococcal carriage prevalence in children attending day-care centres is relatively low and antibacterial resistance in pneumococci is presently very rare in the Faroe Island. The prevalence of penicillin non-susceptible pneumococci (PNSP) was low compared to Iceland and Denmark, likely because of conservative use of antibiotics in the Faroese community. The established vaccine program in the Faroese community in 2008 seems to have reduced incidence of PCV-7/13 serotypes among invasive pneumococcal disease (IPD), and there is, furthermore, an indication of serotype shift in pneumococcal carriage.
Further monitoring is important to detect new serotypes in invasive disease and changes in pneumococcal disease prevalence.
Our study has already provided important knowledge to general practitioners regarding medical treatment, and its potential as a basis for further studies on serotype shift, vaccine impact, carriage and surveillance studies in the Faroes is apparent. As an example, we see that the high level of resistance prevalence to sulphonamides among E. coli isolates is concerning, especially since they are still considered the first-choice treatment for uncomplicated urinary tract infections (UTIs) in the Faroe Islands. We suggest that the association between antibacterial resistance and antibacterial use in the Faroe Islands, Iceland and Denmark justifies a re-evaluation of antibacterial policies against UTIs treatment in the Faroe Islands. Our study on the clonality of GAS in the Faroe Islands has already prompted a follow-up study by Prof. James Musser's group, Houston Methodist Hospital, Houston, Texas. Isolates from our GAS strain collection were sent to Houston where whole genome sequencing is being performed to genetically characterize and compare these isolates with other countries in Europe and North America. From this new study, it will be of special interest to see if the GAS isolates are genetically distinct due to the small population and isolated location of Faroe Islands. Finally, as a direct result of the work completed in this thesis, a political action group has been established in the Faroe Islands to monitor and address antibacterial survelliance and stewardship.
Ph.d.verkætlanin varð vard á Háskúla Íslands 21. september 2018.
Paper I: Antibacterial use in the Faroe Islands, Iceland, and Denmark 1999 – 2011
MARITA DEBESS MAGNUSSEN , THOROLFUR GUDNASON, ULRICH STAB JENSEN, NIELS FRIMODT-M Ø LLER & KARL G. KRISTINSSON
Scandinavian Journal of Infectious Diseases, 2014
Paper II: Antibacterial resistance in Streptococcus pyogenes(GAS) from healthy carriers and tonsillitis patients and association with antibacterial sale in the Faroe Islands
MARITA D. MAGNUSSEN, SHAHIN GAINI, HANNES GISLASON and KARL G. KRISTINSSON
APMIS 124: 327–332
Paper III: Antibacterial Susceptibilities of Escherichia coli from Community-Acquired Urinary Tract Infections in the Faroe Islands, Associations with Antibacterial Sales, and Comparison with Iceland and Denmark
Marita Debess MNagnussen, Hannes Gislason, Shahin Gaini, and Karl G. Kristinsson
MICROBIAL DRUG RESISTANCE
Volume 24, umber 1, 2018
Paper IV: Streptococcus pneumoniae: Antimicrobial resistance and Serotypes of Strains Carried by Children and Causing Invasive Disease in the Faroe Islands.
Marita Debess Magnussen, helga Erlendsdóttir, Shahin Gaini, Thorolfur Gudnason and Karl G. Kristinsson
MICROBIAL DRUG RESISTANCE, 2018