Abstract
Background
Mapping general practitioners’ antibiotic prescribing practices is essential to optimize antibiotic use in primary care and mitigate antibiotic resistance.
Objectives
The objective of this study was to examine the adherence of Dutch general practitioners to prescribing guidelines for ear and respiratory tract symptoms and conditions.
Methods
A cross-sectional study was conducted on Dutch electronic health records from 2018 to 2021. Antibiotic prescribing frequency and type were examined for ear and respiratory tract symptoms and conditions based on professional prescribing guidelines. Descriptive statistics and multilevel logistic regression analyses were applied.
Results
Patient records from up to 384 general practices were analysed for 15 ear and 27 respiratory tract conditions. For 11 of the 15 (73%) ear and 17 of the 27 (63%) respiratory tract conditions, more than 95% of patients were treated according to the prescribing guidelines. Most potential non-adherence to antibiotic prescribing guidelines occurred for acute otitis media (31%–34%), acute bronchitis/bronchiolitis (26%–39%), and acute sinusitis (25%–34%). Several other respiratory tract conditions showed non-indicated prescribing rates above 10%. For otitis externa, many broad-spectrum antibiotics were prescribed, which rarely happened for respiratory conditions. High variation in prescribing frequency and type between general practices occurred.
Conclusions
For most conditions, Dutch general practitioners adhere well to antibiotic prescribing guidelines. There are conditions for which there is a high potential for inappropriate prescribing. High variation between practices suggests room for improvement. Stricter implementation of prescribing guidelines may help improve prescribing practice. Alternatively, a practice-specific approach could be effective. The Dutch setting may be exemplary for international antibiotic prescribing practice.
Keywords: antibiotic prescribing, respiratory tract infections, ear infections, electronic health record data
Key Messages.
Optimizing antibiotic prescribing is essential to mitigate antibiotic resistance
Dutch general practitioners adhere well to antibiotic prescribing guidelines
For certain infections, there is a high potential for inappropriate prescribing
High variation between practices suggests room for improvement
Interventions tailored to infections and prescribers could improve prescribing
Introduction
An association between antibiotic use and antibiotic resistance has been reported extensively [1, 2], implying that reducing the total amount of antibiotics used and enhancing the rational prescribing of antibiotics are necessary [3, 4]. More than 90% of the total consumption of systemic antibiotics refers to consumption in primary care [5]. Therefore, enhancing the rational use of antibiotics in primary care is essential in mitigating the impact of antibiotic resistance.
Although the Netherlands had the lowest human consumption of antibiotics for systemic use in the EU in 2019 [5], earlier research still reported possibilities for improving rational antibiotic prescribing [6, 7]. Specifically, previous research has identified ear, nose, and throat infections as an important area to target for improvement of rational antibiotic prescribing due to high antibiotic prescribing rates [6–8]. The Dutch College of General Practitioners develops diagnostic and prescribing guidelines for many conditions that occur often in the general practice setting. These guidelines aim to provide specific advice regarding the prescription of medicines [9]. General practitioners are supposed to adhere to these guidelines concerning whether or not to prescribe antibiotics. When antibiotic prescribing is appropriate, the guidelines should be followed for the correct type of antibiotics.
Many studies reporting on prescribing practice report overall prescribing trends [7, 10–12] or use relatively small sample sizes of general practices [7] rather than providing a more extensive overview of adherence to prescribing guidelines. The most recent Dutch report on respiratory tract guideline adherence dates from 2014 and is limited to 1 year [6]. Therefore, this study aimed to update and demonstrate the adherence of Dutch general practitioners to prescribing guidelines for ear and respiratory tract symptoms and conditions from 2018 until 2021, including an analysis of variation between general practices.
Methods
Study design
This cross-sectional study included patients throughout the Netherlands diagnosed in general practice with ear or respiratory tract infections per year between 2018 and 2021.
Setting
In the Netherlands, people are registered with one fixed general practice. General practices keep an electronic health record of medical history and prescription data. General practitioners are the first point of contact for receiving healthcare in the Netherlands. Antibiotics are only available with a prescription.
Data source
The database used for this research was the Nivel Primary Care Database (Nivel-PCD). This database comprises data routinely registered in over 400 general practices with around 1.8 million enrolled patients (approximately 10% of the Dutch population). Data were only included from general practices that recorded prescriptions for at least 46 weeks, if at least 85% of the prescriptions were coded with a valid ATC code, and disease episodes could be constructed [13]. Patient registrations include office visits, home visits, phone consultations, and telehealth. The database does not provide information on the type of consultation. The general practices are spread all over the Netherlands, and age and sex of listed patients are representative for the Dutch population.
Inclusion and exclusion criteria
Patient registrations were included based on diagnoses using the International Classification of Primary Care (ICPC) codes. In the Netherlands, ICPC-I is used [14]. Patients with registered ICPC codes from chapters H (ear conditions) and R (respiratory tract conditions) were included if presented in at least one of the years of interest. Excluded were patients with (i) non-specific conditions (e.g. ‘ear injury, other’, and ‘respiratory disease, other’), (ii) conditions not mentioned in one of the guidelines from the Dutch College of General Practitioners and with an incidence of less than 1 per 1000 patients, or (iii) cancer-related conditions. In the Netherlands, specific ICPC codes are divided into subcodes. These subcodes were not used, except for ICPC code R83 ‘other respiratory tract infections’ for which subcode R83.03 ‘SARS-COV-2 (COVID-19)’ was analysed separately.
Antibiotic indication
All guidelines from the Dutch College of General Practitioners that give advice regarding antibiotic (ATC-code J01) prescribing and that are relevant to ICPC code chapters H (ear) and R (respiratory tract) were used to assess guideline adherence from general practitioners. This includes advice on whether an antibiotic should be prescribed and, if yes, which antibiotic should be prescribed. All ICPC codes were assigned to one of three categories based on the advice on antibiotic prescribing as described in the guidelines: (i) conditions for which there is no indication to prescribe an antibiotic, (ii) conditions for which the indication to prescribe an antibiotic is certain, and (iii) conditions for which the indication to prescribe an antibiotic is uncertain. Conditions were placed in the uncertain category if the guideline mentioned that prescribing an antibiotic could be considered or if the advice to prescribe an antibiotic was dependent on the clinical appearance of a patient which could not be extracted from the database (e.g. ‘prescribe an antibiotic in case of fever’). As the indication to prescribe antibiotics can differ for one ICPC code based on patient characteristics, one ICPC code could be assigned to three different categories. For example, the indication to prescribe an antibiotic could differ for adults versus children or people with versus without specific comorbidities. In total, 42 ICPC codes have been included in the study, 15 for ear and 27 for respiratory tract conditions (Supplementary Appendix 1). The prescribing guidelines were then used to determine whether antibiotics should be prescribed and which antibiotics should be prescribed if appropriate (Supplementary Appendix 2).
Data collection
For all consultations regarding the included ICPC codes, the following data were used from 2018 until 2021:
Prescription data
Diagnoses data
Patient information (i.e. age, sex, comorbidities, and comedication)
Data analysis
Frequency of antibiotic prescribing
All analyses were performed per year. The percentage of antibiotic prescriptions was calculated as the total number of conditions with an antibiotic prescription divided by the total number of registrations for that condition. These were uncorrected percentages. Each patient could be included more than once if there were multiple contact moments with the general practice.
Next, we aimed to account for case mix differences between practices and clustering within practices and estimate the variation between practices. Therefore, we conducted multilevel logistic regression analyses. These have been executed at the general practice level for unique patients to calculate the percentage of patients prescribed an antibiotic and the 90% variation between individual general practices. The multilevel logistic regression was corrected for practice case mix (age and sex of patients) and clustering within practices. For the multilevel logistic regression, if one patient had multiple registrations, only the first was included. As we aimed to identify deviations from the guidelines, this was only performed for conditions with an uncertain or no indication to prescribe antibiotics. Only ICPC codes for which, on average, at least five patients per general practice per year were registered were included. Results for the frequency of antibiotic prescribing with uncertain or no indication to prescribe are presented for conditions with at least 500 registrations in one of the years of interest. Results are presented for conditions for which more than 5% of the patients received an antibiotic in at least one of the four years.
Type of antibiotics
For conditions with an uncertain or certain indication to prescribe an antibiotic, the type of the prescribed antibiotic was compared to the recommended antibiotic in the prescribing guideline. Appropriateness of antibiotic type was calculated as the percentage of the prescribed antibiotics that belonged to the guideline’s first-, second- or third-choice options. Furthermore, the percentage of prescriptions of broad-spectrum or reserve antibiotics not mentioned in the guideline for a specific condition was calculated. This included the use of amoxicillin + clavulanic acid (J01CR02), cephalosporins of second (J01DC) or third (J01DD) generation, fluoroquinolones (J01MA), macrolides (J01FA), and other quinolones (J01MB) unless these were explicitly recommended in the guideline. Results for antibiotic type are presented for conditions with at least 500 antibiotic prescriptions in at least one of the years of interest. Practice variation was calculated as a 90% interval.
Ethics
The relevant governance bodies of Nivel-PCD approved the study under number NZR-00320.079. According to Dutch legislation, neither obtaining informed consent nor approval by a medical ethics committee is obligatory for this observational study containing no directly identifiable data [15–17].
Results
The number of general practices included differed per year and per ICPC code, as rare conditions are not diagnosed in all practices yearly; in 2018, up to 301 practices were included, 384 in 2019, 287 in 2020, and 301 in 2021.
Ear symptoms and conditions
The 15 conditions included from chapter H had 17 different indications for antibiotic prescribing, 15 indications not to prescribe an antibiotic, and 2 for which the indication was uncertain. For 8 of those 17 indications, there were more than five registrations per practice in at least one of the 4 years. For four conditions, patients received an antibiotic in more than 5% of the cases, despite no indication to do this (Fig. 1). When the indication to prescribe an antibiotic is uncertain, for otitis externa, antibiotics were prescribed in more than 5% of these cases in 2019 and 2020 but not in 2018 and 2021 (practice variation range is 2%–10%). About half the patients with acute otitis media received an antibiotic when the indication for this was uncertain (practice variation range is 37%–74%; Supplementary Appendix 3).
Figure 1.
Percentage and 90% practice variation of patients receiving an antibiotic from 2018 to 2021 for conditions without an indication to prescribe an antibiotic: ear discharge, otitis externa, acute otitis media, and chronic otitis media. Ninety per cent practice variation was calculated if average number of episodes per practice was ≥5 in at least 1 year and was corrected for age and sex.
Type of antibiotic prescribed for ear symptoms and conditions
Otitis externa is treated in just over 30% of cases with a macrolide or broad-spectrum antibiotic, regardless of whether there is an uncertain or no indication for an antibiotic. For patients with otitis externa for whom an antibiotic was uncertain and who did receive an antibiotic, this antibiotic was a first-, second-, or third-choice antibiotic in fewer than half of the cases. Acute otitis media was treated with macrolides or broad-spectrum antibiotics in fewer than 10% of the cases. When an antibiotic was prescribed for patients with acute otitis media with an uncertain or certain indication for an antibiotic, prescribers chose a first-, second-, or third-choice antibiotic in over 90% of the cases (Fig. 2, Supplementary Appendix 4).
Figure 2.
Type of antibiotics for ear symptoms and conditions as a percentage of all prescriptions for a specific indication. Macro = macrolides that are not mentioned in the appropriate guidelines, broad = broad-spectrum antibiotics that are not mentioned in the guidelines, top3 = total of first-, second- and third-choice of antibiotic according to the guideline, O.E. = otitis externa, O.M.A. = otitis media acute. Insufficient data were available to calculate practice variation. No = no indication to prescribe an antibiotic, Uncertain = uncertain indication to prescribe an antibiotic, Certain = certain indication to prescribe an antibiotic. For otitis externa, there is no group for which there is a certain indication to prescribe an antibiotic.
Respiratory tract symptoms and conditions
The 27 conditions from chapter R comprised 33 different indications for antibiotic prescriptions. For 15 of those indications, there were 20 or fewer registrations per practice per year for the 4 years (Supplementary Appendix 5). For 11 respiratory tract conditions without an indication to prescribe an antibiotic, antibiotics were prescribed in more than 5% of the cases (Fig. 3). The highest practice variation is seen for acute/chronic sinusitis.
Figure 3.
Percentage of patients receiving an antibiotic for respiratory tract symptoms and conditions without indication for an antibiotic from 2018 to 2021. Ninety per cent practice variation was calculated if the average number of episodes per practice was ≥5 in at least 1 year and was corrected for age and sex.
There are six respiratory tract conditions, with an uncertain indication to prescribe an antibiotic, for which patients received an antibiotic in more than 5% of the cases. Fewer than 20% of patients received an antibiotic for upper acute respiratory tract infections. For the other five conditions, this is higher than 20%, up to around 50% for acute tonsillitis. There is a large variation between practices; patients with strep throat in 2021 received an antibiotic in 3% of cases in the least prescribing practice but in up to 96% of cases in the most prescribing practice (Fig. 4).
Figure 4.
Percentage of patients receiving an antibiotic for respiratory tract symptoms and conditions with uncertain indication for an antibiotic from 2018 to 2021. Ninety per cent practice variation was calculated if the average number of episodes per practice was ≥5 in at least 1 year and was corrected for age and sex. Tonsillitis acute includes peritonsillar abscess.
Type of antibiotic prescribed for respiratory tract symptoms and conditions
Upper respiratory tract infections are treated with macrolides or broad-spectrum antibiotics in fewer than 10% of the cases where an antibiotic is prescribed, although there is high practice variation. For patients where an indication for an antibiotic is uncertain, there is practically no use of macrolides and broad-spectrum antibiotics. Macrolides and broad-spectrum antibiotics are prescribed for sinusitis for just under 10% of cases when there is no indication for an antibiotic. Similarly, patients with tonsillitis, bronchitis/bronchiolitis, and pneumonia are treated with first-, second- or third-choice antibiotics in around 80% of cases (Fig. 5, Supplementary Appendix 6).
Figure 5.
Type of antibiotics for respiratory tract symptoms and conditions as a percentage of all prescriptions for a specific indication. Macro = macrolides that are not mentioned in the appropriate guidelines, broad = broad-spectrum antibiotics that are not mentioned in the guidelines, top3 = total of first-, second- and third-choice of antibiotic according to the guidelines, all = total of all antibiotics mentioned in the guidelines, U.RTI = upper respiratory tract infection, A/C Sin. = acute/chronic sinusitis, Tons. = acute tonsillitis/peritonsillar abscess, Bron = acute bronchitis/bronchiolitis, Pneu = pneumonia, Asth. = Asthma. Ninety per cent practice variation was calculated if the average number of episodes per practice was ≥5 in at least 1 year and was corrected for age and sex.
Discussion
Overall, Dutch general practitioners adhere well to prescribing guidelines, and prescription rates of antibiotics are low for conditions without an indication to prescribe antibiotics. General practitioners usually choose the appropriate antibiotic whenever antibiotics are or may be indicated. Nevertheless, several specific ear and especially respiratory ICPC codes are registered by general practitioners for which antibiotics are prescribed contrary to prescribing guidelines. It is important to note that there is a high variation between practices in guideline adherence.
Similar research from Nivel in Dutch general practice in 2014 [6] reported higher inappropriate prescribing rates for acute bronchitis (51%), acute sinusitis (48%), and most other conditions than this study. In other European countries, inappropriate prescribing is generally more common. Smieszek et al. [18] reported general inappropriate antibiotic prescription rates in England between 8.8% and 23.1%, with sore throat, cough, sinusitis, and acute otitis media as the greatest contributors. Bagger et al. [19] report inappropriate prescribing for upper respiratory tract infections in Lithuania (54.5%), Spain (48.6%), Denmark (24.1%), and Sweden (19.1%).
Our finding of high practice variation aligns with earlier research in the Netherlands that reported high variation between general practices for antibiotic prescribing for children with otitis media [20]. Various factors have been identified that influence antibiotic prescribing in primary care, including factors that influence inter-physician and intra-physician variability [21, 22]. The number of factors influencing antibiotic prescribing is extensive, examples include clinical guidelines, patient and prescriber experience, time pressure, financial considerations, lack of knowledge, colleagues’ prescribing practice, practice volume, comorbidities, the relationship between general practitioner and patient, and general practitioners’ perception of patient desire for antibiotics [21–23]. Another factor seems to be the type of visit, i.e. telehealth consultations versus office consultations, as telehealth has been associated with increased antibiotic prescribing rates [24]. This may be especially relevant as the COVID-19 pandemic resulted in an increase in telehealth consultations. Focus groups of Dutch general practitioners revealed disagreement with guidelines due to unclear evidence to support them, inapplicability of guidelines in heterogeneous patient populations, organizational constraints, and unawareness of specific guidelines content as reasons for non-adherence to guidelines [25]. This study shows relatively high adherence of Dutch general practitioners to their prescribing guidelines. This could imply that the abovementioned factors may be different in the Netherlands compared to other countries. Additional future research could focus on identifying factors that contribute to lower guideline adherence for ICPC codes where this study shows such low adherence.
It is important to consider the effect of the COVID-19 pandemic, as this has had major influences on the primary care sector and the daily practice of general practitioners. Van de Pol et al. [11] report a decrease in antibiotic prescribing in the Netherlands for respiratory tract and ear conditions during the COVID-19 pandemic. Similar findings were reported by Zhu et al. [26] in London. Our study shows guideline adherence improved for some respiratory tract conditions during the pandemic but not for ear conditions. This indicates that COVID-19, a viral respiratory condition, had more influence on antibiotic prescriptions for respiratory tract conditions than other conditions. This aligns with general practitioners’ perspectives in England [27], where two other studies [28, 29] have shown increased antibiotic prescribing rates during the COVID-19 pandemic for certain antibiotics, although guideline adherence was not assessed.
Implications for practice
There can be reasons why not adhering to guidelines is the better choice. A static body of data does not reflect the fluidity of daily general practice in which general practitioners can and sometimes must be flexible in their interpretation of guidelines based on the clinical presentation of patients. This means that for certain diagnoses, contrary to guidelines, prescribing antibiotics might be justified in specific cases. Moreover, guidelines can be ambiguous in their recommendations, especially for patients with more complex clinical characteristics. Therefore, prescription rates are not expected to be 0% for all conditions without antibiotic indication.
Nevertheless, improved antibiotic prescribing guideline adherence has generally improved antibiotic prescription rates and reduced inappropriate antibiotic prescribing [30]. Further implementation of guidelines may improve future antibiotic prescribing. Dutch general practitioners should carefully study their individual prescribing practice and look for indications where they prescribe suboptimal compared to their colleagues. Considering the high practice variability for many conditions, effective measures to improve antibiotic prescribing should target general practitioners individually. Further studies could also focus specifically on the indications for which too many patients receive antibiotics contrary to guidelines. Identifying specific patient groups that receive too many antibiotics could help develop more specific and possible effective interventions. Interventions that have been reported as effective are usually multifaceted and may include audit and feedback, educational meetings and outreach visits, and patient-based interventions [31, 32]. Dutch primary care practice may be exemplary for international practice. It would be valuable to assess which aspects of Dutch primary care positively affect antibiotic prescribing to see if these are transferrable to other settings.
Strengths and limitations
A strength of this study is that it is based on a data source from many general practices spread over the Netherlands that contains detailed diagnostic and prescription data from multiple years. The study focuses on antibiotic prescription rates and assesses the appropriateness of prescribing using nationally accepted prescribing guidelines.
The study also has several limitations. Even this extensive data source does not contain all the details about patients. For example, information on fever or severity of illness or allergies could not be derived, even though the guidelines urge doctors to use that information to make treatment decisions. Moreover, free text fields of the database have not been analysed due to privacy reasons, although these could contain information about reasons for deviating from guidelines. Therefore, for some conditions, antibiotics should not be prescribed to most patients, but for exceptions, it is justified. Nevertheless, in this study, the antibiotic indication for such conditions was uncertain as it was impossible to distinguish the exceptions from the other patients. In some instances, general practitioners may continue antibiotic treatment started in the hospital setting. Whether the prescribed antibiotics were justified for those conditions could not be determined. Additionally, general practitioners may register different ICPC codes for similar patients differently. Especially for ICPC codes with few registrations per year, such differences in registration may have relatively large effects on the data. Moreover, differences in triage by physician assistants may lead to fewer but relatively sicker patients visiting general practices or vice versa. Additionally, some general practitioners may change the registration of an ICPC code based on the treatment they have based on ‘gut feeling’. Such differences between individual general practitioners may explain some practice variation, although it is uncertain to what extent.
Conclusion
Dutch general practitioners commonly adhere well to antibiotic prescribing guidelines for ear and respiratory tract infections. Nevertheless, for certain ICPC-coded conditions, especially for the respiratory tract, antibiotics are more often prescribed than would be expected based solely on the guidelines. This does not necessarily mean that patients received suboptimal treatment, as valid reasons exist for deviating from guidelines. However, given the considerable variation between general practices, it seems that optimization of antibiotic prescribing is possible for at least the practices with the highest prescribing rates. Given the relatively good antibiotic prescribing practice from an international perspective, Dutch practice could be exemplary in other settings.
Supplementary Material
Acknowledgements
We thank the operational staff of Nivel Primary Care Database (Nivel-PCD) for their preparation of the research data.
Contributor Information
Maarten Lambert, Unit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands.
Renee Veldkamp, Nivel, Netherlands Institute for Health Services Research, Otterstraat 118, Utrecht 3515 CR, The Netherlands.
Yvette Weesie, Nivel, Netherlands Institute for Health Services Research, Otterstraat 118, Utrecht 3515 CR, The Netherlands.
Anke Lambooij, IVM, The Dutch Institute for Rational Use of Medicine, Churchilllaan 11, Utrecht 3527 GV, The Netherlands.
Jochen W L Cals, Department of Family Medicine, Maastricht University Care and Public Health Research Institute, Maastricht University, Universiteitssingel 40, Maastricht 6229 ER, The Netherlands.
Katja Taxis, Unit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands.
Liset van Dijk, Unit of PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen 9713 AV, The Netherlands; Nivel, Netherlands Institute for Health Services Research, Otterstraat 118, Utrecht 3515 CR, The Netherlands.
Karin Hek, Nivel, Netherlands Institute for Health Services Research, Otterstraat 118, Utrecht 3515 CR, The Netherlands.
Author contributions
Conceptualization: M.L., Y.W., A.L., J.W.L.C., L.v.D., and K.H.; Methodology: M.L., R.V., Y.W., and K.H.; Validation: M.L., R.V., and K.H.; Formal analysis: M.L., R.V., and K.H.; Writing—original draft preparation: M.L.; Writing—review & editing: R.V., Y.W., A.L., J.W.L.C., K.T., L.v.D., and K.H.; Supervision: K.H. All authors have read and agreed to the published version of the manuscript.
Conflict of interest
L.v.D. reports funding from Biogen and Teva not related to this study. All other authors declare no conflicts of interest.
Funding
This project was funded by ZonMw, the Netherlands Organisation for Health Research and Development (grant number: 541003003).
Data availability
Access to data is subject to the Nivel-PCD governance code. Requests for access to the data can be directed to gegevensaanvragen@nivel.nl. Restrictions involve establishing a data-sharing agreement and approval by the appropriate Nivel Primary Care Database governance bodies.
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Data Availability Statement
Access to data is subject to the Nivel-PCD governance code. Requests for access to the data can be directed to gegevensaanvragen@nivel.nl. Restrictions involve establishing a data-sharing agreement and approval by the appropriate Nivel Primary Care Database governance bodies.