Antibiotic consumption and antimicrobial resistance in Poland; findings and implications

General

Antibiotics have significantly improved the prognoses of patients with infectious diseases, reducing morbidity and mortality. However, the use of antibiotics is invariably associated with the risk of resistance development, with numerous studies confirming the association between increasing use of antibiotics and enhanced antimicrobial resistance (AMR) [1–6]. Increasing AMR rates are not helped by concerns regarding the choice of antibiotic or duration of therapy, which can be incorrect in up to 50% of cases [3, 7], as well as the extent of irrational prescribing of antibiotics for essentially viral infections [3], or the increasing use of antibiotics in agriculture [7]. Acute upper respiratory tract infections (URTIs), which are the most common infections in ambulatory care, are essentially viral in origin but with high rates of inappropriate antibiotic use across countries [3, 8–10].

As a result of growing concerns, we are seeing an increasing number of programmes and activities across countries, including European countries, to enhance appropriate antibiotic use to reduce AMR rates. These include the development of Antimicrobial Stewardship Program (ASP), as well as educational activities among physicians and pharmacists [8, 11–17]. ASPs include analysis of the consumption of antibiotics over time alongside instigation and monitoring of activities to improve appropriate use.

However, whilst the European Surveillance of Antimicrobial Consumption (ESAC) network, and more recently the European Centre for Disease Prevention and Control (ECDC) [18, 19] and WHO Europe [20], have researched antibiotic utilisation across Europe including Poland, as well as assessed quality indicators for antibiotic utilisation, there is currently limited patient-level data to improve antibiotic prescribing in Poland. Physicians are one of the key stakeholders to improve future antibiotic use in Poland, with limited if any purchasing of antibiotics without a prescription due to current restrictions.

We are aware of concerns with antibiotic prescribing in Poland. A study published in 2008 showed that between 2002 and 2005, at least 64.3% of the studied population were prescribed antibiotics [21]. Panasiuk et al. reported that 78.5% of adults with acute URTIs had antibiotics as empirical first-line treatment [22]. Overall anti-infectives (Anatomical Therapeutic Chemical class: ATC J01-J07X) constituted approximately 5% of pharmaceutical reimbursement in ambulatory care in Poland in 2010, with amoxicillin with clavulanic acid among the top 25 reimbursed medicines with the greatest sales [23]. However, between 2004 and 2008, Poland’s total antibiotic use was comparable to the median European level [24].

There have been initiatives in Poland to improve physician antibiotic prescribing through guidelines, with the most recent guidelines published in 2016 [25]. However, there have been concerns whether these have been properly disseminated and implemented, especially given current individualism within the Polish healthcare system, acceptance of authority (‘power distance’), and physicians wishing to avoid uncertainty [26]. In addition, current short medical consultations do not allow for establishing a close relationship between physicians and their patients, including educating patients regarding the appropriate use of antibiotics. There are also concerns with the lack of National Health Fund (NHF) activity to improve the prescribing of antibiotics among physicians in Poland unlike co-ordinated activities in, for instance, the Republic of Srpska [14], as well as former Soviet Union Republics, such as Azerbaijan [17].

There are also concerns with the rate of hospital acquired infections in Poland [27], which need addressing alongside generally improving antibiotic utilization in Poland to reduce AMR rates.

Antimicrobial resistance patterns across Europe and activities to reduce AMR

The gathering and analysis of information on drug resistance of bacterial strains among European countries is facilitated by the Healthcare-Associated Infections Surveillance Network (HAI-Net) [28] within the European Centre for Disease Prevention and Control (ECDC). Detailed data on drug resistance of selected bacterial strains and groups of antibiotics are gathered within the European Antimicrobial Resistance Surveillance Network (EARS-Net) [29].

As discussed, there are several ongoing activities across countries to reduce rising AMR rates given ongoing concerns. Identified objectives within the WHO Global Plan on Antimicrobial Resistance [30] included sharing knowledge and evidence, as well as instigating programmes to optimise antibiotic use through education and other activities. This is particularly important in Poland, where the incidence of various types of infections, including surgical site infections [31] and bloodstream infections associated with central venous catheters, appear higher than in neighbouring countries [27].

We are aware there needs to be greater documentation and discussions about current activities in Poland to improve antibiotic use. This includes assessing the quality of antibiotic use in ambulatory care against agreed indicators, including the use of combination penicillins, third- and fourth-generation cephalosporins, as well as fluoroquinolones, as these are considered by the WHO and others as critically important antibiotics to monitor [20, 32, 33].

Consequently, the objective of this paper was to compare and contrast antibiotic resistance and antibiotic utilisation in Poland in recent years versus other European countries, including agreed quality indicators, alongside current AMR patterns and ongoing policies and initiatives in Poland to influence antibiotic prescribing. The findings will help guide the development of future pertinent policies to improve antibiotic prescribing in Poland, given current concerns.

Specific actions to prevent AMR in Poland

The coordinated system of monitoring AMR rates among patients in Poland has been implemented since 1997 with the establishment of the National Reference Centre for Antimicrobial Susceptibility Testing (NRCAST). Since 2002, information on antimicrobial utilisation across sectors, including hospitals and ambulatory care, has also been gathered via NRCAST. This organisation is also in charge of identification and susceptibility testing of bacterial strains from serious and difficult to diagnose infections, with a special focus on certain pathogens such as Methicillin-resistant Staphylococcus aureus (MRSA), and monitoring of the spread of resistant strains in hospitals and ambulatory care across Poland. NRCAST also provides data to the European Antimicrobial Resistance Surveillance Network (EARSS-Net) as well as ECDC.

In 2004, the Ministry of Health (MoH) established the National Programme for the Protection of Antibiotics (NPPA) coordinated by the National Institute of Medicines. with the main goal: to monitor AMR in Poland. The MoH is also the main stakeholder in charge of policy development to help prevent or reduce AMR in Poland as well as providing the legal framework for hospital infection control. The Chief Sanitary Inspectorate is responsible for suggesting potential initiatives where concerns exist. In practice, activity of the MoH in the area of AMR monitoring and prevention has been limited, principally left to the State Consultant for Microbiology and the Chief Sanitary Inspectorate to formulate policies on AMR. As far as the NHF’s involvement is concerned, usually only limited activities have been undertaken to date to help improve antibiotic use with appreciable autonomy among physicians. Having said this, pneumococcal vaccination became compulsory in Poland in January 2017. The roles of other Polish health care system stakeholders in policy formulation to prevent or reduce AMR are principally advisory ones.

Current resistance patterns in Poland

Infections in Polish patients illustrate the relationship between high utilisation and high levels of resistance, i.e. the high consumption of trimethoprim and sulfamethoxazole [35] has been accompanied by high levels of antibiotic resistance [5]. Having said this, the prevalence of MRSA in Poland in 2013 was 16%, with prevalence rates exceeding 25% in many EU Member States [35].

Concerns with current AMR rates in Poland are confirmed by data on Acinetobacter baumannii infection (ACI), which are some of the most important opportunistic pathogens responsible for the most severe infections characterised by the high level of resistance to commonly used antibiotics. More than 75% of ACI strains of A. baumannii isolated from pneumonia cases among hospitalised patients in southern Poland were resistant to 14 out of 16 antimicrobials tested [36], with approximately 60% of A. baumannii strains from patients with invasive infections, pneumonia, bloodstream infections and meningitis, resistant to all antimicrobials tested with the exception of colistin. The extensively-drug resistant strains accounted for 80.8% of isolates tested [37]. The largest AMR outbreak in Poland in recent years was observed between 2012 and 2014 in two major cities (Warsaw and Poznan). It concerned New Delhi metallo-β-lactamase (NDM)-producing Enterobacteriaceae. Out of 374 cases of infection/colonisation with NDM-positive Enterobacteriaceae identified in that period, 370 cases were associated with a Klebsiella pneumoniae outbreak [38].

Concerns with AMR are exacerbated by the fact that the current surveillance systems in Poland do not currently function optimally. Examples include concerns with data on MRSA epidemiology both in the general population of hospitalised patients, as well as new-borns with very low birth weight [39]. Interestingly, along with a high level of MRSA prevalence at 15% among adult patients in general hospitals, considerable heterogeneity of strains has been detected.

Empiric use of antibiotics vs. routine testing as well as prevention

Efforts in Poland to contain AMR should ideally rely on microbiological tests to guide current treatment as well as provide guidance on optimal empiric treatment when the need arises. A good example is the Polish Neonatological Network where data is gathered from Neonatal Intensive Care Units (NICU) on infection surveillance among newborns with very low birth weights [39]. The analysis of antibiotic utilisation in MRSA infections compared with methicillin-sensitive Staphylococcus aureus (MSSA) infections revealed that average therapy durations were 11.2 and 12.3 days respectively [39]. Concurrently, the level of glycopeptides’ use was high in both MRSA and MSSA infections, providing a rationale for the introduction of quick molecular tests into routine clinical practice, especially in NICUs [40].

Despite situations such as this, the role of microbiological diagnostics to reduce empiric use of antibiotics as well as efforts to prevent infection is currently underestimated by physicians in Poland [38, 41, 42]. Nowadays, there is a greater focus on treatment rather than prevention, since in Poland, unlike some Western European countries, diagnostic laboratories are organised separately from hospital structures, with most microbiologists not directly involved in treatment decisions. This is particularly problematic for nosocomial infections.

In addition, usually health care providers (hospitals, family physicians) must pay for microbiologic diagnostic tests from their budgets and ambulatory care patients must pay for tests out of pocket. Both of these can be a concern. Consequently, most community acquired infections are currently treated empirically.

Quantitative analysis of antibiotic prescribing quality indicators in ambulatory care

The total consumption of antibiotics in the surveyed European countries ranged in 2016 from 10 DIDs in the Netherlands to 36 DIDs in Greece (median 12 DIDs), while Poland had one of the highest consumption rates, exceeding the European median (expressed in DIDs) more than twice (Fig. 1). Only some countries of Southern Europe had higher consumption rates, while in the remaining 78.3% countries the consumption rates were lower than in Poland.

However, interpretation of the other assessed indices does not bring unequivocally negative conclusions. There has been a sizeable increase in consumption of beta-lactamase sensitive penicillins (J01 CE) from a very low share of total antibiotic consumption in previous years (Table 2). The current share of these antibiotics in treatment is on a notably low level when compared with other European countries (Fig. 2). Encouragingly, the consumption of combination penicillins (J01CR), third- and fourth-generation cephalosporins (J01(DD + DE)) and fluoroquinolones (J01MA) is on a relatively low level (Figs. 3, 4, 5). Poland is among the European countries with the lowest share of these antibiotics within overall antibiotic consumption, especially with regard to third- and fourth-generation cephalosporins. On the other hand, in ambulatory care wide-spectrum antibiotics are used relatively more often (ratio J01(CR + DC + DD+(F-FA01) to J01(CE + DB + FA01)) – Fig. 6 (explanation of acronyms is provided in Table 1, see also Abbreviations). However, the situation has improved in comparison to the past years. In 2007 the share of wide-spectrum antibiotics was 30.3%, while in 2016 it was 25.8% (Table 2).