Antibiotic stewardship: following in the footsteps of Nordic countries?

KEYWORDS:

• Pharmacies
• guideline
• antibiotic stewardship
• antibiotic resistance
• antibiotic consumption

In 1998 the EU countries met in Copenhagen, Denmark, for the Microbial Threat conference, which launched a united European effort to curb antibiotic resistance in human pathogenic bacteria [1]. The conclusion from the conference, the Copenhagen recommendations [1], formed the basis for the recommendations for an antibiotic policy, which were sent to all EU members in 2001 [2]. An important point was the demand for monitoring antibiotic resistance and consumption, which since then has been organized via the EARS-NET [3] and ESAC-NET [4] hosted by the European Center for Disease Control in Stockholm, Sweden. The data from such monitoring programs are crucial for several obvious reasons, apart from knowledge of resistance levels to direct empiric treatment and basis for benchmarking, they have provided an invaluable basis for research in the relationship between antibiotic consumption and resistance and which factors are important for this relationship.

The data on antibiotic resistance and consumption in Europe can be visualized using the abovementioned websites as colored maps. Regions with low use or resistance are represented in light green, green, or yellow, while areas with higher consumption or resistance are indicated in darker colors such as orange, red, or purple. Consistently, and for both parameters, Northern Europe has remained in the green or yellow spectrum, indicating low resistance or consumption. In contrast, Southern Europe consistently shows shades of orange, red, or purple, suggesting higher resistance or consumption for both parameters. For almost any antibiotic and any type of resistance there is a significant correlation between increasing consumption and increasing resistance [5]. Therefore, the overall aim must be to keep antibiotic consumption as low as possible without denying treatment for those patients, who need it.

Numerous factors are involved in why Northern Europe – here illustrated by the Nordic countries – can retain a relatively low antibiotic consumption in primary care, where about 90% of the countries´ antibiotics are consumed. Space prohibits a detailed discussion of all factors, but to mention a few – not ranked according to importance: Organization of general health care, strict enforcement of prescription rules, organization of pharmacies, clinical microbiology as medical specialty, education, and following the EU recommendations for antibiotic policy.

In all Nordic countries represented by Denmark, Norway, Sweden, Finland and Iceland, health care is free, i.e. paid over the taxes. Only in Sweden is there a small fee for visiting the primary care physician. All Nordic countries have rostering of patients, i.e. each person is connected to a certain primary care physician within the local community (commune or municipality), who is the ‘gatekeeper’ for further access to health care e.g. remittance to any specialist. This means that a patient cannot easily ‘shop around’ for another practitioner or specialist if he or she are not satisfied with the first visit. General practitioners, at least in Denmark, use – free of charge for the patient – rapid tests to support infection diagnoses such as CRP, group A streptococcus antigen-tests and various rapid tests for diagnosis of urinary tract infection such as phase contrast microscopy and – perhaps less rapid but still faster than sending to a microbiology laboratory – urine culture (inoculation on agar plates for quantitative growth and antibiotic susceptibility test, dipslide (Uricult), or ID-Sensicult [6]).

In the Nordic countries pharmacies are organized through the medicines agencies, who decide the number and distribution of pharmacies and control wages for pharmacists. In Denmark, Sweden, and Norway there are 9, 14 and 17 pharmacies per 100.000 inhabitants, respectively, contrasting with 88 per 100.000 in Greece [7]. Using these data together with antibiotic consumption data (4) one can calculate significant correlation between antibiotic consumption and number of pharmacies per inhabitant, i.e. the more pharmacies the higher consumption. Also, enforcement of prescription-only medicines, to which antibiotics must always belong, may be hampered by competition between many small pharmacies.

Subsidy of medicines has, in Denmark, been used as a tool to advance or restrict the use of recommended (or not) antibiotics, e.g. use of oral cephalosporins has been kept at a minimum by refusing subsidy of these drugs. Pricing of antibiotics can, however, lead to unintended mishaps as shown by the example of fall in price of fluoroquinolones when discontinuation of the patent allowed inflow of cheap copies of ciprofloxacin [8].

Up to 2018 several countries in mid- and southern Europe did not – in contrast to most countries in northern Europe – have clinical or medical microbiology as a medical specialty. The general belief is that a clinical physician will rather take the advice from a physician colleague than from a non-medical microbiologist. The clinical microbiological specialty has been integrated into the healthcare system with a focus on accurate and relevant diagnosis of infectious diseases, aiming for rational antibiotic treatment. All clinical microbiologists are trained medical doctors with clinical expertise, specializing specifically in the diagnosis and treatment of infectious diseases. Having these key stakeholder individuals, serving as ambassadors for antimicrobial treatment without interfering with the clinical specialties’ patient management, is an important element. It promotes a shared sense of respect and comprehension during discussions regarding antibiotic treatment and while performing audits. All antibiotic treatment guidelines either in primary care or in hospitals have in the Nordic countries since the 1980´ies been supervised by clinical microbiologists in association with other relevant specialists. An annually updated national antibiotic treatment guideline is in Denmark available in the national medicines list (pharmacopoeia; ProMedicin.dk, also available as an App [9]); this is edited and written by specialists from relevant specialties, and the specialty societies designate these specialists, i.e. the guideline is independent of the pharmaceutical industry. The national guideline forms the basis for regional and subsequent local guidelines for specialized departments who experience different/diverse and complicated infections During routine audits on antibiotic use in hospitals we found that hospital physicians in most cases follow the local antibiotic treatment guideline; this has the advantage that it is easy to change prescription practices by revising the treatment guideline.

Finally, an important factor in regulating antibiotic use is education in – and knowledge about the role about antibiotics, both among physicians in general and the common public: Do they work on viruses e.g. for common cold? Do all bacterial infections need antibiotics? What are the consequences of their use i.e. adverse effects and resistance development? The better knowledge of the patient, the easier for the doctor to persuade the patient not to use antibiotics where not indicated. Surveys conducted by the European Commission have shown that awareness about infections and antibiotic´s roles is high in northern Europe although also improving in the rest of the region [10].

Maintaining the activity of common antibiotics, i.e. keeping resistance at minimal level, appears to be associated with well-structured healthcare systems, often observed in societies resembling those in Northern Europe. This ‘medical model’ is a consequence and part of the welfare societies to which all Nordic countries belong. The structure of the societies has enforced a range of social determinants, e.g. level of income, job security, education, general information etc. which all play into preserving the medical model and therefore have a major role in controlling antimicrobial resistance (AMR).

If this observation holds true, addressing the concerning issues related to resistance in nations across Asia, Africa, and South America seems to necessitate fundamental logistical and regulatory changes regarding social determinants and health policies with antibiotic policy as one end point. An excuse for not implementing such advice could be that it is not possible for low-income countries. However, the Baltic countries are good examples of communities who albeit relatively low-income status at least at the time when joining the EU have been able to restrict antibiotic use with concomitant low resistance levels.

Enforcing prescription-only rules for antibiotics is key to reducing misuse of antibiotics. Pharmacies both in- and outside hospitals are the hubs for these transactions, and if over-the-counter sale of antibiotics is legal the flow of these drugs into the community is endless. If it is too difficult or expensive to obtain a prescription from a medical doctor the patient is prone to ask the pharmacist for help and without restrictions, they are only happy to help. How this vicious cycle is broken is one of the important issues for low- and middle-income countries to focus on to reduce antibiotic consumption. Importantly, there are efforts in some of these countries to ascertain the problems around antibiotic misuse [11–14]; such work should be heavily supported both by international organizations and by local governments; it is crucial that the latter understand that human lives are at stake, first their own populations but also for humans in general, for antibiotic resistance knows no boundaries.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.