Antibiotic means a substance produced by living microbes that kills or inhibits the growth of other microbes (in the present context, this also includes compounds that are partly or fully synthetically produced). Antibiotics have been used since the 1930s to treat infectious diseases in humans and animals. Antibiotics and antimicrobials are often used as synonyms. In the broad sense of the word antimicrobials also cover antifungal, antiparasitic and antiviral preparations, but only agents with antibacterial effects (antibiotics) are discussed here.
Modes of action of antibiotics
Some antibiotics kill the target bacteria, while some only inhibit their growth. In the latter case in particular, the bacteria are ultimately killed by the body's own defence mechanisms. Antibiotics may, among other things, affect bacterial cell wall structures, protein synthesis or nucleic acid metabolism. Antibiotics have action spectra of varied width. Some are effective against many bacterial species (broad-spectrum antibiotics) while others have effect only against certain species (narrow-spectrum antibiotics).
The natural resistance of bacteria is a characteristic typical of a certain bacterial genus or species. Acquired resistance refers to a phenomenon whereby strains originally susceptible to a specific antibiotic substance become resistant to it, due to, for example, a genetic mutation. There are various kinds of resistance mechanisms. Bacteria may produce enzymes that break down antibiotics, or the antibiotic's binding site or site of action in the bacterial cell may change. Some bacteria are capable of hindering the entrance of an antibiotic through their cell wall or effectively pumping it out of the bacterial cell. Certain resistance mechanisms are based on alternative metabolic pathways. Multiresistant bacteria exhibit simultaneous resistance to several antibiotic groups.
Over the past few years, the prevalence of antibiotic resistant bacteria has rapidly increased and resistance mechanisms have become more varied. Increasing antibiotic resistance also increases human and animal morbidity and mortality and heath care costs, which is why antibiotic resistance has become one of the most severe threats to human and veterinary medicine.
FINRES-Vet resistance monitoring programme
In Finland, a programme for monitoring antibiotic resistance, FINRES-Vet, has been underway since 2002. The programme monitors the antibiotic susceptibility of zoonotic bacteria (pathogenic bacteria that can spread between animals and humans), animal pathogens and indicator bacteria.
In addition to the resistance situation, the programme also monitors the use of feed additives and the consumption of veterinary antibiotics. In addition to Finnish Food Authority, the Finnish Medicines Agency Fimea and the Faculty of Veterinary Medicine of the University of Helsinki are also involved in the implementation of the FINRES-Vet programme. From 2012 onwards, resistance data from pet animals have been gathered in the Clinical Microbiology Laboratory of the Faculty of Veterinary Medicine. Resistance monitoring in EU countries is based on the EU legislation (up to year 2020, Decision 2013/652/EU, and from 2021, Decision (EU) 2020/1729), which specifies the bacterial and animal species and food stuffs to be included. FINRES-Vet program is carried out based on the EU legislation as well as national decisions.
The mandatory resistance monitoring in EU and the voluntary national monitoring
Comission Implementing Decision on the monitoring of antimicrobial resistance in zoonotic and commensal bacteria changed the existing resistance monitoring programme gradually also in Finland from the beginning of 2014. From 2015, the screening of extended-spectrum betalactamase producing E. coli from food-producing animals and meat thereof was included in the mandatory monitoring programme in all member states.
From 2021, monitoring of resistant bacteria in imported bovine and porcine meat from third countries started with the new Comission Decision. Because the amount of imported meat is low in Finland only few samples are analysed yearly. The screening of extended-spectrum betalactamase producing E. coli will be further extended to include turkey meat at retail in the beginning of 2022. Resistance monitoring in veal calves and turkeys mentioned in the two Comission Decisions is not conducted in Finland as the production volumes are low.
Besides EU monitoring, the voluntary resistance monitoring in Finland includes certain animal pathogens. The prevalence of MRSA in pigs and pork, and resistance in bacteria isolated from bovines is followed from time to time. In addition, the prevalence of extended-spectrum betalactamase producing E. coli is screened from imported poultry flocks according to ETT instructions.
The indicator bacteria included in the programme are present in the normal intestinal bacterial flora of healthy animals. Resistance occurring in these bacteria is regarded to reflect the spectrum and frequency of the antibiotic treatments used in the animal populations concerned. Indicator bacteria are also considered of being capable of functioning as a pool of resistance factors from which these factors can transmit to animal or human pathogens. Indicator bacteria are isolated from bovines, pigs and broilers and the animal species is changed on an annual basis.
In the FINRES-Vet programme, the broth microdilution method is mainly used for susceptibility testing, and the bacteria are classified as susceptible or resistant based on their epidemiological cut-off values. This means that bacterial populations can be divided into susceptible or 'wild type' and resistant or 'non-wild type' populations. Significant changes and trends in the occurrence of resistance can be observed by applying these epidemiological cut-off values to the analysis of the populations conducted at regular intervals.
The programme also provides information about the occurrence of novel resistance mechanisms in Finland, and the correlation between the occurrence of resistance and the consumption of antimicrobials. Acquired information can be utilized when varied measures are taken to prevent the spread of antibiotic resistance, when recommendations for the use of antibiotics are given, and as the impacts of these recommendations are assessed. The information obtained from the programme can also be used for assessing the risks associated with human and animal health as well as providing personal protection guidance for people working with production animals.
Results of the FINRES-Vet monitoring programme
Results of the FINRES-Vet programme have been collected into summaries published at regular intervals. All reports are available online at the the Finnish Food Authority website.
The overall sales of veterinary antibiotics is very low in Finland. The sales decreased by 22% in the 2010s although a slight increase was observed between 2018 and 2019. As the data on consumption volumes are based on product-specific statistics provided by pharmaceutical wholesalers, they cannot be used for reliably calculating the amounts of antibiotics administered to different animal species. The product most widely used for animals is injectable penicillin. The use of antibiotic feed additives are no longer allowed for animal growth promotion in the EU countries. More information on the sales of veterinary medicines in Finland can be found at the Fimea website.
Of the zoonotic bacteria, salmonella is only rarely found in the Finnish food-producing animals or foods of animal origin, for which reason the number of strains subjected to susceptibility testing is also small. The tested strains have in most cases been susceptible to the tested antibiotics although especially in 2018 and 2019, multiresistant salmonella strains were found on a few pig and bovine farms.
The proportion of resistant campylobacter isolates in Finalnd is also low on international comparison. Noteworthy, though, is the increase of fluoroquinolone resistant isolates from broilers, pigs and cattle in the 2010s.
Resistance is unusual in indicator bacteria isolates from bovines and broilers. Regarding broilers, this might be at least partially be explained by the fact that broilers are not treated with antibiotics during the growth period. In indicator E. coli from pigs, resistance was most commonly detected against ampicillin, tetracycline, sulfamethoxazole and trimethoprim.
The occurrence of ESBL-producers is monitored from food-producing animals and their meat according to the EU monitoring program. In Finland, ESBL-producers have been only rarely found in pigs, bovines or their meat while ESBL has been more common in poultry.
The prevalance of methicillin resistant Staphylococcus aureus (MRSA) strains has mostly been studied in pigs in Finland. Based on the surveys conducted in pig slaughterhouses, the prevalence of MRSA increased significantly between 2009 and 2017. On the other hand, MRSA prevalence in fresh pork at retail has been relatively low. MRSA bacteria have occasionally been found also in horses, dogs, cats and raw, frozen pet food.
More information on resistance in indicator and zoonotic bacteria as well as on ESBL and MRSA prevalence in production animals and meat can be found from FINRES-Vet reports.
The resistance situation of certain animal pathogenic bacteria is worrying. For example, E. coli isolated from pig enteritis is commonly multiresistant. Also, canine Staphylococcus pseudintermedius bacteria have been resistant to several antibiotics for more than a decade. For example, the proportion of methicillin resistant S. pseudintermedius strains, so called MRSP bacteria, isolated from dogs varied around 10% in the 2010s but was on a downward trend in the second half of the decade. Extended-Spectrum Beta-Lactamase (ESBL)-producing bacteria have also been found in companion animals and horses. More information on resistance in bacteria isolated from production animals, pets and companion animals can be found from FINRES-Vet reports.