The impact of the COVID-19 pandemic on antibiotic prescription rates in out-of-hours primary care – a register-based study in Denmark

Abstract

Background

Antibiotic prescription rates can be affected by pandemic measures such as lockdowns, social distancing, and remote consultations in general practice. Therefore, such emergency states may negatively affect antimicrobial stewardship, specifically in out-of-hours (OOH) primary care. As contact patterns changed in the COVID-19 pandemic, it would be relevant to explore the impact on antimicrobial stewardship.

Aim

To study the impact of the pandemic on antibiotic prescription rates in OOH primary care, overall and per age group.

Methods

This cross-sectional register-based study used routine data from OOH primary care in the Central Denmark Region. We included all patient contacts in two equivalent time periods: pre-pandemic and pandemic period. The main outcome measure was defined as the number of antibiotic prescriptions per contact (antibiotic prescription rate).

Results

The overall antibiotic prescription rate decreased during the first year of the pandemic compared to the pre-pandemic period (RR = 0.97, 95%CI: 0.96–0.98). Likewise, the rate decreased for clinic consultations (RR = 0.63, 95%CI: 0.62–0.64). However, an increase was seen for telephone consultations (RR = 1.73, 95%CI: 1.70–1.76). The decline in clinic consultations was largest for consultations involving children aged 0–10 years (RR = 0.53, 95%CI: 0.51–0.56).

Conclusion

Antibiotic prescription rates in Danish OOH primary care decreased during the first year of the COVID-19 pandemic, especially for young children. Prescription rates decreased in clinic consultations, whereas the rates increased in telephone consultations. Further research should explore if antibiotic prescription rates have returned to pre-pandemic levels, and if the introduction of video consultations has affected antibiotic prescription patterns in OOH primary care.

Background

Antimicrobial resistance must be prevented, as inappropriate antibiotic use may lead to multi-resistant pathogens [1,2]. Surveillance programs and antibiotic stewardship are fundamental to preserving the effect of antibiotics, which is important for treating simple infections [3,4].

In the early stages of the COVID-19 pandemic, lockdowns were enforced around the globe. This included closing of schools and daycare institutions and working from home. People were encouraged to social distancing and improving hygiene habits to prevent spread of disease [5]. The healthcare sector responded by changing the provision of care [6–8]. In general practice, many traditional face-to-face consultations were changed into remote consultations [9], and the number of consultations decreased during the first year of the pandemic [10,11].

These changes may have affected the antibiotic prescription rates in general practice [12,13]. Several reports have stated that preventive measures introduced during the pandemic may have negatively affected antimicrobial stewardship [14–16], which highlights the importance of monitoring prescription trends [17]. Antimicrobial stewardship may be even more at risk in out-of-hours (OOH) primary care [18,19]. Here, clinicians are unfamiliar with the patients and have no access to their previous medical records, the work pressure is high, follow-up consultations are not possible, and many calls concern acute health conditions.

Studies are sparse on antibiotic prescription in OOH primary care during the COVID-19 pandemic. The few existing studies are difficult to compare, but they suggest a decrease in antibiotic prescription rates in the early phases of the pandemic [17,20,21]. One study found this decrease to be most pronounced in the young age group [17]. However, these studies did not investigate whether changes in antibiotic prescription rates were related to consultation types. This could be highly relevant to explore, as consultation patterns changed significantly during the pandemic. Therefore, we aimed to describe the impact of the COVID-19 pandemic on the antibiotic prescription rates in OOH primary care, overall and per age group, for different types of consultations.

Methods

Design and population

This population-based cross-sectional study was based on routine data from OOH primary care in the Central Denmark Region. To account for seasonal fluctuations, we included all patient consultations during two equivalent time periods: 11 March 2018 − 30 June 2019 (pre-pandemic period) and 11 March 2020 − 30 June 2021 (pandemic period). All consultations between these two time periods were excluded from the data analysis. We choose 11 March 2020 because the first Danish national lockdown was announced on this day, and 30 June 2021 was the last full day in our collected data set.

Setting

During the time of the study, OOH primary care was delivered by a regional OOH service to all citizens in the Central Denmark Region on weekdays between 4 pm and 8 am, on weekends, and during holidays. The OOH service comprised 13 locations for clinic consultations; some were affiliated with a hospital-based emergency department. At the OOH service, telephone triage was conducted (with no clinical decision support tools) by GPs and GP trainees in their last year of training. Triage GPs could decide to use video as a tool, as video had rapidly been implemented at the start of the COVID-19 pandemic. Triage GPs could choose to give telephone advice (telephone consultation), refer to a face-to-face GP consultation (clinic consultation or home visit), or refer directly to the hospital. During the pandemic, GPs were recommended to give telephone advice to patients with symptoms of infectious disease or refer them directly to hospital. General practice remained available during the pandemic, though the type of consultations changed. In a previous study, Huibers et al. found that the number of face-to-face consultations decreased, whereas the number of telephone and video consultations increased, thereby keeping a relatively stable level of consultations [10]. Furthermore, governmental hotlines were established concurrently with the first lockdown. These hotlines primarily advised about COVID-19 tests, vaccinations, and recommendations on self-isolation. In case of illness, they would refer to the patients’ own GP.

In Denmark, GPs are remunerated partly through a fee-for-service model, which is based on billing codes. Primary care is tax-funded and freely available for residents. Patients pay a fee for prescribed medications (including antibiotics), but many of these medications are reimbursed (i.e. deducted from price when buying).

Outcome measures

The main outcome measure was the number of antibiotic prescriptions per consultation (antibiotic prescription rate).

Data

From the regional OOH primary care registration system, we retrieved data on all telephone consultations and clinic consultations ending in an antibiotic prescription. For each contact, we included date and time of the consultation, consultation type (telephone consultation, clinic consultation, home visit), patient’s age and sex, and antibiotic prescription (coded as group J01 ‘antibacterial agents for systemic use’ according to the Anatomical Therapeutic Chemical (ATC) classification system). Patient age was categorized into seven groups: 0–4, 5–10, 11–20, 21–40, 41–60, 61–80, and >80 years old.

Analysis

We divided all consultations provided by the OOH service into two time periods: pre-pandemic period and pandemic period. As the pandemic went through different phases in Denmark, we sub-divided the pandemic period into four groups: 11 March − 7 May 2020 (severe restrictions), 8 May 2020 − 15 December 2020 (limited restrictions), 16 December 2020 − 4 May 2021 (severe restrictions), and 5 May 2021 − 30 June 2021 (limited restrictions). The periods of severe restrictions included closing of restaurants, schools, and institutions, whereas the periods of limited restrictions involved reopening of most activities [22].

First, we described the distribution of consultations (type), patient characteristics (sex and age), and antibiotic prescription rates; these were stratified for the two study periods. Second, we calculated the risk ratio (RR) and 95% confidence interval (CI) for receiving an antibiotic prescription in the pandemic period compared with the pre-pandemic period (Table 1). We described the number of consultations and the antibiotic prescription rate over time, both overall (Figure 1) and stratified for age 0–10 years (Figure 2). Third, we calculated monthly RRs for receiving an antibiotic prescription in the pandemic period compared with the pre-pandemic period, both overall and by consultation type. Finally, we calculated antibiotic prescription rates in both the pre-pandemic and the pandemic period for all age groups, stratified by consultation type.

Table 1.

Distribution of consultation types (%), antibiotic prescription rates, and risk ratios for contact type and patient characteristics (sex and age), stratified by COVID-19 pandemic periods.

	All consultations		Prescription rates
	Pre-pandemic	Pandemic	Pre-pandemic	Pandemic	RRa (95% CI)b
N (%)	888,944 (50.9)	858,146 (49.1)	64,691 (7.3)	60,550 (7.1)	0.97 (0.96,0.98)
Consultation typec
Clinic	32.5	20.3	14.6	9.2	0.63 (0.62,0.64)
Telephone	67.5	79.7	3.8	6.5	1.73 (1.70,1.76)
Sex
Female	54.2	54.9	8.4	8.4	0.99 (0.98,1.01)
Male	45.8	45.1	5.9	5.5	0.92 (0.91,0.94)
Age (years)
0–4	16.3	12.4	4.2	2.2	0.53 (0.51,0.56)
5–10	6.6	5.7	5.3	3.7	0.69 (0.65,0.73)
11–20	12	12.2	6.3	6.4	1.02 (0.99,1.06)
21–40	27.3	28	7.5	7.5	1.00 (0.98,1.02)
41–60	19.1	19.7	8.6	8.3	0.98 (0.95,1.00)
61–80	13.3	15.2	9.8	9.0	0.91 (0.89,0.94)
>80	5.3	6.8	9.5	10.1	1.06 (1.02,1.10)

^aRR: risk ratio; ^b95% CI: 95% confidence interval; ^cClinic consultations and telephone consultations (with/without video use).

Figure 1.

Average number of consultations per day, average number of out-of-hours consultations, and antibiotic prescription rates per month over time in primary care. Blue boxes: periods with severe restrictions due to the COVID-19 pandemic; Grey box: period for which data was not included in the comparative analysis. *Clinic: clinic consultations; Telephone: telephone consultations.

Figure 2.

Average number of consultations per day, average number of out-of-hours consultations, and antibiotic prescription rates per month over time in primary care for children aged 0–10 years. Blue boxes: periods with severe restrictions due to the COVID-19 pandemic; Grey box: period for which data was not included in the comparative analysis. *Clinic: clinic consultations; Telephone: telephone consultations.

Statistical analysis was performed with Stata software, version 17 (StataCorp. 2021. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC.).

Results

Consultations and antibiotic prescription rates

The OOH primary care service in the Central Denmark Region conducted 888,944 consultations in the pre-pandemic period and 858,146 consultations in the pandemic period (Table 1). During the pandemic, clinic consultations dropped from 288,907 to 174,204, whereas the number of telephone consultations increased from 600,037 to 683,942. The overall antibiotic prescription rate remained relatively stable (RR = 0.97, 95%CI: 0.96–0.98). However, during the pandemic, the rate decreased by 37% (RR = 0.63, 95%CI: 0.62-0.64) for clinic consultations, whereas the rate increased by 73% (RR = 1.73, 95%CI: 1.70–1.76) for telephone consultations.

When stratifying antibiotic prescription rates by age group, we observed the most significant changes in the youngest age groups. For children aged 0–4 years, the risk of receiving an antibiotic prescription declined by 47% (RR = 0.53, 95%CI: 0.51–0.56) during the pandemic period. For children aged 5–10 years, this risk declined by 31% (RR = 0.69, 95%CI: 0.65–0.73). Likewise, the number of consultations for children aged 0–10 years declined from 203,568 to 155,324.

Antibiotic prescription rates over time

In March 2020 when the first lockdown was announced, the number of telephone consultations increased, whereas the number of clinic consultations decreased (Figure 1). Furthermore, antibiotic prescription rates in clinic consultations decreased from 0.15 to 0.10 per consultation. Conversely, the prescription rate for telephone consultations increased from 0.2 to 0.7 per consultation. This change was especially pronounced for children aged 0–10 years (Figure 2). The antibiotic prescription rates in clinic consultations decreased from 0.11 to 0.05 prescriptions per consultation when the first lockdown was announced. Antibiotic prescription rates increased in telephone consultations. A short spike was seen just after the announced lockdown, but it later levelled out and stabilized at a level similar to the pre-pandemic period.

Monthly risk ratios of receiving an antibiotic prescription

The overall risk of receiving an antibiotic prescription in the pandemic period compared with the pre-pandemic period was relatively similar, with RRs varying between 0.85 and 1.1 (Figure 3). The risk of receiving antibiotics in clinic consultations was lower during the pandemic period compared to the pre-pandemic period (range RRs: 0.5 − 0.7). However, the risk of receiving antibiotics was higher in telephone consultations (range RRs: 1.4 − 2.0).

Figure 3.

The risk of receiving an antibiotic prescription during the pandemic period compared with the pre-pandemic period (monthly risk ratios), overall and stratified by consultation type. Blue boxes: Periods with severe restrictions due to the COVID-19 pandemic; Light blue boxes: Months only partially affected by severe restrictions; RR (95% CI): Risk ratio, 95% confidence interval; Consultation types: clinic consultations and telephone consultations (and overall).

Prescription rates for consultation types and age groups

Overall, the antibiotic prescription rates increased in telephone consultations and decreased in clinic consultations (Figure 4). This effect was most pronounced in the younger age groups. In clinic consultations, the prescription rate dropped from 0.1 to 0.05 for children aged 0–4 years and from 0.12 to 0.05 for children aged 5–10 years, whereas the smallest decrease from 0.17 to 0.13 was seen in the oldest age group (age >80 years). In telephone consultations, the increase in antibiotic prescription rates during the pandemic was most pronounced for patients aged 0–60 years, with a doubling of rates in most groups from 0.1 to 0.4 antibiotic prescriptions per consultation, whereas the smallest change in prescription rates was seen in the two oldest age groups; from 0.06 to 0.08 for patients aged 61–80 years, and from 0.09 to 0.1 in patients aged >80 years.

Figure 4.

Pre-pandemic and pandemic antibiotic prescription rates per age group, stratified by consultation type. *AB prescription rate: antibiotic prescription rate; 95% confidence intervals are not presented as all intervals are extremely narrow due to the large dataset.

Discussion

Main findings

The overall antibiotic prescription rate in OOH primary care in the Central Denmark Region was relatively unchanged during the first year of the COVID-19 pandemic compared to the pre-pandemic period. However, antibiotic prescription rates decreased for clinic consultations and increased for telephone consultations. Consultation numbers and prescription rates were largely unchanged for adults, whereas both of these decreased for children aged 0–10 years.

Strengths and limitations

We utilized routine data from the electronic registration system of the regional OOH primary care service, which ensured a high degree of data completeness. The fee-for-service payment of Danish GPs provides a strong incentive for careful registration of consultations, thereby ensuring high data validity.

Our study also had some limitations. First, video consultations were implemented at the OOH primary care service on 13 March 2020 to prevent spreading of COVID-19 during the pandemic [10]. Our data lacked specific information on the use of video, which made us unable to compare antibiotic prescription rates in telephone consultations with and without video. A recent Danish study described that almost 10% of all consultations in OOH primary care involved video use during the first two years of the pandemic [23]. If video consultations typically result in fewer prescriptions, we might have underestimated the impact of the pandemic on the antibiotic prescription rate in telephone consultations. Second, we had no data on OOH home visits. During the pandemic, GPs were recommended to give telephone advice or to refer directly to the hospital rather than performing home visits in case of infection-related symptoms. Therefore, we hypothesize that the antibiotic prescription rate has declined in home visits during the pandemic. The lack of data on home visits might have had a small effect on the overall antibiotic prescription rates in OOH primary care. Third, we had no information on the reasons for encounter or the actual diagnoses. It would have been valuable to sub-divide the different infectious diseases, as we believe that the treatment of especially respiratory tract infections (RTIs) may have changed more than other infectious diseases during the pandemic. Still, the incidence of urinary tract infections and related antibiotic prescriptions did not appear to be affected compared to the corresponding figures for RTIs in primary care during the pandemic [24,25]. Consequently, we were unable to evaluate the appropriateness of prescriptions in relation to antibiotic stewardship. Fourth, we had information only on the patient’s age and sex. Several other patient characteristics could have affected the risk of receiving antibiotics, such as comorbidities and socioeconomic status, and the pandemic is likely to have changed the composition of OOH patients considerably [10]. Patients with symptoms of RTIs who were in need of a face-to-face consultation with a doctor were referred to the hospital rather than seen in OOH primary care. In addition, patients may have changed help-seeking behavior, which could have affected the associations found.

Finally, we included only a single regional OOH primary care service, which could limit the generalizability of the findings. However, this region comprised 23% of the Danish population, and the organization of OOH primary care was similar in four out of five Danish regions at the time of the study. Due to the gatekeeping role of general practice in Denmark and the telephone triage being conducted by GPs in OOH primary care, the results may only be generalizable to other countries with similar organization of OOH primary care.

Interpretation of results

This study found a small overall decrease of 3% in the antibiotic prescription rate during the COVID-19 pandemic, which contrasts the findings in other countries in Western Europe, such as England, the Netherlands, and Belgium [17,20,21]. Zhu et al. found a decrease of around 10% in England during the first three months of the pandemic [20], and Colliers et al. found a 43% decrease of antibiotic prescriptions in the OOH primary care services in Belgium during the first lockdown [21]. Hek et al. found an overall decrease in antibiotic prescriptions in the Netherlands; the highest decrease of 34% was seen for consultations involving children aged 0–11 years [17]. The authors argued that this decrease could be explained by lockdown measures, such as social distancing and improved hygiene, which reduced the number of RTIs, for which antibiotics are often prescribed. This is in line with our findings of a decrease in antibiotic prescription rate, as we found a decrease of 47% in children aged 0–4 years and of 31% in children aged 5–10 years. In general, children have a higher RTI incidence than the rest of the population [26]. In our study, children also experienced the largest decrease in consultation number overall in OOH primary care during the pandemic. We believe that the decrease in antibiotic prescription rate and in number of OOH consultations can be explained by social restrictions leading to less spreading of infectious diseases, which was also reported in a previous study [17].

We found an increase in antibiotic prescription rates in telephone consultations and a decrease in clinic consultations. During the pandemic, the Danish clinical guidelines recommended GPs to avoid clinic consultations with patients experiencing respiratory symptoms and instead perform remote consultations by telephone or video [27]. It is unclear whether the use of remote consultations might have compromised the clinical decision-making concerning antibiotic prescription, which could have elevated prescription rates. A systematic review based on 12 studies could not conclude if remote consultations impacted antibiotic prescription rates and thereby antimicrobial resistance [28]. Evidence suggests that the number of acute infectious diseases decreased due to the restrictions (social distancing, disinfection) [29,30]. Consequently, lower prescription levels could be expected. Yet, the patients’ help-seeking patterns could vary for several reasons. On the one hand, patients could be more inclined to seek consultations with health care providers during a pandemic. On the other hand, governments advised patients to refrain from contacting the health care system, unless strictly necessary. Hence, patients contacting OOH primary care during the pandemic may have been more severely ill, making the pre-pandemic and pandemic study populations less comparable.

Implications for clinical practice and further research

We found that the antibiotic prescription rate increased in telephone consultations during the pandemic. However, we were unable to consider the potential impact of video, as we had no information on such use. Future studies should investigate whether antibiotic prescription rates remained higher in remote consultations post-pandemic compared to the pre-pandemic period. Future projects should investigate the appropriateness of antibiotic prescription by including clinical data. Studying appropriate antibiotic prescription in remote consultations is highly relevant in view of the extensive focus on digitalization of care.

Conclusion

Antibiotic prescription rates remained relatively unchanged in Danish OOH primary care during the first 15 months of the COVID-19 pandemic. Lower prescription rates were seen for clinic consultations, and higher rates were seen for telephone consultations, specifically for children aged 0-10 years, whereas the rates remained largely unchanged for adults.

Further studies should explore if antibiotic prescription rates were appropriate during the pandemic, and whether the introduction of video consultations affected antibiotic prescription patterns in OOH primary care.

Ethical approval

The study was listed in the record of processing activities at the Research Unit for General Practice in Aarhus in accordance with the provisions of the GDPR.

Funding Statement

This work was supported by the Foundation for Primary Health Care Research in the Central Denmark Region [grant no. 1-30-72-112-16]. The grant provider was not involved in any part of the study.

Disclosure statement

No potential conflict of interest was reported by the author(s).