Antibiotic prescribing for acute, non-complicated infections in primary care in Germany: baseline assessment in the cluster randomized trial ARena

The use of antibiotics in German primary care is lower than average in other countries [1, 2] but there is still potential for lowering prescribing rates for specific conditions. In light of growing antimicrobial resistance, the holistic German national antibiotic resistance strategy (DART 2020) follows the One Health approach to promote awareness, counteract microbial resistance and preserve antibiotic treatment options [3]. Monitoring the use of antibiotics is an important strategy to reduce the spread of antimicrobial resistance, particularly in primary care where about 85% of the used antibiotics in Germany are prescribed [4, 5]. Antibiotics are prescribed in 41% of GP consultations for acute respiratory tract infections (ARTI) [4]. Only 52% of these prescriptions are in accordance with prevailing clinical recommendations [6].

In recent years, several research projects tested strategies that aim to enhance the rational and appropriate use of antibiotics in healthcare. In this context, the three-armed, cluster randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance; conducted from 2017 to 2020) aimed to foster the rational use of antibiotics for acute non-complicated respiratory tract infections in primary care in Germany [7]. By applying a multifaceted strategy with multiple interacting intervention components, ARena addressed primary care physicians, care teams as well as patients [7]. An innovative aspect of ARena was its embedding in 14 primary care networks (PCNs) across two German federal states. PCNs can be described as formalized collaborations of economically independent physicians and other healthcare providers working in single or joint practices who interact regularly, share patients, standardize treatment and care according to evidence-based practice guidance, regularly attend continuing education, and discuss concerns if these arise. They give support regarding practice management and quality improvement [8] and therefore were expected to amplify the impact of the ARena implementation program. More detailed description of the study design and interventions can be found elsewhere [7].

Previous research investigated the development of antibiotic prescribing rates in primary care and found a relatively stable utilization in Germany from 2008 to 2014 [9]. However, strong variations of overall and age-group-specific distributions of antibiotic subgroups could be identified [10]. A strong awareness of antimicrobial resistance has been observed among German General Practitioners (GPs), while measures to improve rational prescribing were found to be not widely implemented [11]. In more recent research, a 5-year cohort study of antibiotic prescribing rates by family physicians in Ontario, Canada, aimed to describe predictors of antibiotic prescribing and inter-physician variability in antibiotic prescribing. It was concluded that observed substantial inter-physician variability in antibiotic prescribing could not be explained by sociodemographic and clinical patient characteristics [12]. Further recent research also found that the use of antibiotics in German primary care showed large variations between and within medical specialties and seasons, and that a considerable proportion of antibiotic prescribing lacked conformity with national guideline recommendations [13]. Though these study findings might not reflect the most current situation or guideline-conformity of prescribing, there is an indication that antibiotics are still not prescribed appropriately regarding indication and spectrum and thus are frequently used inappropriately. For targeted quality improvement, it is relevant to know which subgroups of patients and physicians are at highest risk of inappropriate utilization of antibiotics.

For the ARena study, the outcome evaluation is based on quarterly claims-data as provided by a large German statutory health insurer and references established indicators of the European Surveillance of Antimicrobial Consumption Network (ESAC-Net) [14] which were tailored to the specifics of the study. Primary and secondary outcomes are related to general prescribing of systemic antibiotics as well as indication-specific prescribing of antibiotics currently recommended [15, 16] by German clinical guidelines [15, 16]. To explore the actual antibiotic prescribing rates in the participating PCNs and their determinants, this present study aimed to define the baseline antibiotic prescribing rates as percentage of cases with acute non-complicated respiratory tract infections prior to the start of the ARena project and explore potential percentage variation across the intervention arms, medical specialties and subgroups of patients. Also, this baseline situation was to be compared to a non-PCN standard care reference group (RG), using the provided claims data and considering characteristics such as patient age, gender and insurance and health status.

This study explored baseline antibiotic prescribing rates in PCNs at the start of the ARena project regarding cases with acute non-complicated respiratory tract infections. In about a third of all observed cases, patients received an antibiotic. Younger patients were less likely to receive antibiotics. More antibiotics were prescribed to female than to male patients. GPs were the largest included group of prescribers and prescribed antibiotics more frequently than other medical specialists. Prescribing rates for quinolones were moderate, and patients with comorbidities had a higher likelihood of receiving an antibiotic and quinolone prescription and less likely to receive a guideline-recommended substance.

Rates of antibiotic prescribing in German primary care overall have been decreasing constantly between 2010 and 2018, particularly with regards to children and adolescents [22] who were underrepresented in this study sample. Room for improvement can be expected to be more visible in ‘high prescribers’, but since the potential for improvement noticeably decreased in recent years already, nevertheless, there remains substantial room for further reduction of antibiotic prescribing.

A recent national cross-sectional study in USA identified that 57% of 130.5 million prescriptions for antibiotics written during ambulatory care visits in 2015 were for appropriate indications, 25% were inappropriate and 18% had no documented indication. It was noted that being an adult male, spending more time with the provider and seeing a non-primary care specialist were significantly positively associated with non-indicated antibiotic [23]. In contrast to these findings, our data indicate that antibiotics were most frequently prescribed by general practitioners. In addition, the prescribing of broad-spectrum antibiotics showed slightly higher rates in PCNs compared to RG. These discrepancies in antibiotic prescribing rates between PCNs and RG might be explained by the differing specialist group distribution between PCNs and RG and a small percentage of specialists and a higher percentage of GPs in PCNs than RG. A contributing factor towards the slight difference in prescribing rates between PCNs and RG can also be seen in higher patient age and morbidity in PCNs which is in line with findings of Shaver et al. [24] who recently examined antibiotic prescribing in the outpatient setting in USA. Exception here in our study is prescribing for Otitis media where cases were included from the age of two and above and therefore morbidity considerations cannot deliver explanations for higher prescribing rates in PCNs. Prescribing rates for quinolones were generally moderate to low in PCNs (9.9%) and RG (8.1%) and thus also match findings of the study from USA where in 9.4% of investigated visits for acute respiratory infections a broad-spectrum antibiotic was received [24]. Prescribing quinolones seemed to be associated with a higher number of comorbidities and higher patient age as well which complements findings of the process evaluation conducted alongside ARena where uncertainty about diagnoses, prognosis, continuity of care and perceptions about patient preferences were found to be among the reasons for non-indicated prescribing [25, 26]. To some extend this confirms findings from a 2010 study that investigated fluoroquinolone prescribing for acute cough in German primary care to find predictors for unjustified prescribing. The researchers then concluded that unjustified quinolone prescribing was determined by patient characteristics such as severity and duration of illness and patient age. However, they also found that physicians with higher individual antibiotic prescribing rates and physicians with hospital-based specialty training—versus combined hospital and ambulatory training—were more likely to prescribe fluoroquinolones than physicians who specifically trained as GPs [27]. Interestingly, our data showed that in PCN practices in locations with increasing urbanization, quinolone prescribing rates were lower than in rural locations. This complements results from a previous study where German GPs working in urban areas were found to be more likely to use the strategy of delayed prescribing of antibiotics than GPs working in rural areas [11]. Such discrepancies between urban and rural prescribing habits potentially could root in more ample opportunities for self-reflection about prescribing motivated by regular peer exchange and a broader and more frequent offer of continued training and upskilling in urban locations. Efforts to educate physicians, care teams and patients continuously about current and appropriate diagnosis and therapy options as well as communication about them may remedy this to some extent.

The perceived, but not actually communicated patient request for antibiotics is often overrated by physicians [28] and may initiate unfounded assumptions of losing patients to another physician when therapy followed guideline recommendations and antibiotics are not prescribed. In this study, the rate for prescribing of guideline-recommended antibiotics was remarkably low and in line with the high rate for broad-spectrum antibiotics on practice level which is another potential indicator for physicians’ uncertainty. Though quinolone prescribing was moderate overall, patients with higher comorbidity and patients participating in DMPs were more likely to receive a quinolone prescription, and less likely to receive one of the guideline-recommended substances. This might be related to higher age and poorer health status of these patients as supported by previous research [24], but also to the physicians’ striving for the elimination of both their own and patients’ insecurities and potential complications. One effective way to eliminate insecurities and reduce prescribing of antibiotics was found to be the promotion of communication skills by means of a short communication training for primary care physicians [29, 30]. In a recent study in Germany, results showed a prescribing probability decrease of 6.5 percentage points for the treatment of URTI and an even stronger impact for female patients aged below 35 [31]. As the ARena project also used an intervention component to strengthen communication skills, similar effects can be expected.

The rate of prescribed broad-spectrum antibiotics in PCNs in this study seemed slightly higher compared to the study by Shaver et al. conducted in USA [24]. However, for this present study the outcome was assessed by DDD% on practice level whereas Shaver et al. evaluated on patient level. Factors associated with the prescribing of guideline-recommended antibiotics for the considered infections could not be clearly identified. Information about patient nationality was not available for all cases, yet the percentage of nationalities other than German was low. However, our data showed that the percentage of observed cases of Eastern European patients was higher than the one of Southern Europeans in PCNs as well as in RG. This is contrasted by findings of the process evaluation in ARena where physicians indicated their subjective perception of many Southern Europeans asking for antibiotics [25].

Primary care antibiotic prescribing rates for acute non-complicated respiratory tract infections were moderate prior to the intervention start of the ARena project, but indicate room for improvement. Lower rates for guideline-recommended substances indicate a need for creating stronger awareness of guideline-conform use of antibiotics as intended by the implementation program used in ARena. This baseline assessment of prescribing will serve as comparator in the post-interventional outcome evaluation and support describing of potentially observed effects of the program.