Non-prescription acquisition of antibiotics: Prevalence, motives, pathways and explanatory factors in the Swedish population.

Prior studies indicate prevalence of unregulated non-prescription use of antibiotics also in the northern European countries. The aim of this study is to investigate the extent to which antibiotics are acquired without prescription in Sweden, and people's attitudes and motives linked to this practice. We use data from an online survey of a representative sample of the Swedish general population which included questions about respondents' antibiotic use, attitudes towards antibiotics, health care contacts, self-rated health and trust in health care. We also asked about their reason for obtaining/not obtaining antibiotics without a prescription. The results show that, in the last five years, 2,3% of the respondents had acquired antibiotics in other ways than from a Swedish physician having issued a prescription, and 4,3% reported that they are likely to do so in the future. We also show that the two most important reasons for non-prescription acquisition were physicians' refusal to prescribe antibiotics followed by travel abroad. The most important reason for not obtaining antibiotics without a prescription was to not contribute to antibiotic resistance. Using logistic regression, we show that non-prescription acquisition of antibiotics, and the intention to engage in this practice in the future, are strongly associated with low trust in health care.

1. Introduction

How people acquire pharmaceuticals is of a general interest from a drug safety perspective [1-3]. However, the specific case of antibiotics places this question in the acutely pressing context of antimicrobial (especially antibiotic) resistance (AMR). AMR is considered a major threat to global health and the progress of modern medicine, increasingly causing significant harm in terms of human mortality and morbidity, and global economic and social development [4, 5]. In the global action plan on AMR, launched by the World Health Organization in 2015, antibiotic stewardship (AS) is a main strategic avenue, besides AMR surveillance and boosting of antimicrobial innovation [6]. AS signifies a battery of measures aimed to manage AMR. A core component is to rationalize the use of antimicrobial drugs, with tighter control over prescription as the main tool for outpatient care and use among the general public [6]. There are well-known structural problems in effecting and implementing such prescription regimes even when a mandatory prescription system is in place. For instance, a study in Catalonia in 2008 indicated a very high willingness of pharmacists to supply antibiotics without prescription, despite a legally strict prescription mandate [7] and ensuring that doctors adhere to prescription standards when patients request antibiotics is known to be challenging [8-10], linking to a general connection between antibiotic consumption volumes and corruption levels [11].

However, even if no such implementation problems would be present, the strategy assumes that reduction of antibiotic prescription will significantly reduce access to and use of antibiotics. This link is usually assumed in research on AMR and AS, e.g., in large studies of antibiotics use [12, 13] and major studies supporting the design of AS regimens [14]. However, various avenues for the general public to acquire antibiotics without prescription exist, e.g., sharing between friends or relatives, private import from countries with lax or no prescription mandates for antibiotics, or purchase from offshore online pharmacies evading regulatory prescription mandates. Such behaviors potentially limit the effectiveness of prescription control as a tool for AS. They also complicate the assessment of this tool because surveying prescription data may underestimate antibiotics use and overestimate the effectiveness of AS prescription control. It is therefore a crucial task for research related to AS and the general assessment and design of AMR policy to clarify the extent of non-prescription acquisition of antibiotics.

Previous research has examined self-medication with (i.e., non-prescription use of) antibiotics, indicating that the prevalence of this phenomenon varies greatly across countries. A 2006 survey of populations in 19 European countries found that between 1 and 210 in 1000 had self-medicated using antibiotics in the last 12 months, with higher rates in eastern and southern Europe than in northern and western Europe [15, 16]. Similarly, in a 2018 Eurobarometer survey the proportion of respondents stating that their last antibiotics course was not obtained from a health care professional ranged from 1% (the Netherlands) to 15% (Romania and Austria) [17]. A recent review of the US literature found that the prevalence of self-medication ranged from 1% to as high as 66% in certain populations [18], and on a global level the variation is even more striking [19]. The intention to self-medicate in the future is subject to similar variation [15, 18].

Studies on self-medication (or non-prescription use) typically define this phenomenon as the use of antibiotics obtained without prescription from a health care professional, and thus indirectly shed light on non-prescription acquisition. However, non-prescription use and non-prescription acquisition of antibiotics must be distinguished. A drug may be obtained without prescription by one person (e.g., a parent) and then used by another (e.g., a child), a situation not captured in surveys on non-prescription use, potentially leading to underestimation of this phenomenon. Moreover, non-prescription antibiotic acquisition raises concern even if the drug is not imminently used, because it may be saved for future use or inappropriately disposed of, potentially contributing to resistance-driving pollution [20]. Therefore, non-prescription acquisition of antibiotics needs attention in its own right.

Few studies of non-prescription acquisition of prescription drugs focus specifically on antibiotics [1]. A recent study of a representative sample of the Norwegian population found that 1.5% had purchased antibiotics without a prescription during travel abroad. Non-prescription purchase was associated with younger age, female gender, number of travels, occurrences of diarrhoea, and domestic antibiotic use [21]. By contrast, a Swedish pilot study of a non-representative sample of 500 people found that 20% had acquired antibiotics in other ways than from a Swedish physician issuing a prescription. Motives and pathways varied, but foreign travel or visits and online pharmacies were commonly stated sources, while dissatisfaction with or distrust in the health care system was the most common motive disclosed [22]. These findings, together with the dearth of research in this area and documented pathways for non-prescription access to medicines in general [3, 23], give cause for concern and provide strong reason to study the matter more closely.

A limitation of previous studies on non-prescription antibiotic acquisition concerns the explanatory factors used in the analysis–mainly socioeconomic/demographic factors and health-related behaviors [21]. This limited focus makes it difficult to draw broader conclusions regarding different societies’ ability to counter non-prescription antibiotics acquisition or connect findings to a general discussion about the prospect for legitimacy and compliance in relation to public health policy regulations. A potentially relevant explanatory factor in this regard is trust, which is believed to increase compliance with governmental rules and regulations and sustain confidence in information provided by authorities [24-28]. Moreover, trust in health care is important to sustain the legitimacy of the health care system in general, as well as to maintain adherence to regulations and motivate patients to accept health care interventions [29]. Moreover, the results from the aforementioned pilot study [22] indicate trust in health care as a possible motivational driver worth more extensive inquiry.

Several studies bring up trust as potentially significant for antibiotic use [30-32], and some assess this assumption empirically. Touboul-Lundgren and colleagues include trust in medical doctors as an integrated part of their indicator of culture [32]. Other studies suggest that practitioners are concerned about losing patients’ trust if they do not prescribe antibiotics [33, 34]. In terms of explanations for between-country variation in antibiotic consumption, Blommaert and colleagues [34] found social trust–trust in other people–to be linked to country-levels of antibiotic consumption. A few studies pay attention to the individual-level relationship between trust and attitudes towards antibiotics and antibiotic use. In survey data research for Sweden, both social trust and trust in health care have been found to be positively linked to willingness to limit antibiotic use [35, 36]. Carlson and colleagues [37] found that trust in physicians was associated with acceptance of doctors’ decision not to prescribe antibiotics. In view of these findings and given that trust in institutions is linked to confidence in information and decision acceptance, the potential role of trust in health care as constraining people’s willingness to acquire antibiotics without a prescription warrants scrutiny.

We therefore conducted a survey of a sample of the Swedish population (representative in terms of age, gender and education), with previous non-prescription acquisition of antibiotics and willingness to engage in this practice in the future as primary outcomes. Non-prescription acquisition was defined as acquiring antibiotics in other ways than from a Swedish physician issuing a prescription. The outcome variables were analytically linked to each other and to background variables considered potentially interesting, including trust in health care. Motives and sources of non-prescription acquisition were also examined.

2. Materials and methods

Pilot study

The aim and design of the present study comes out of the aforementioned pilot study [22]. This study indicated two particularly important results. First, that acquisition of antibiotics without prescription may undermine the effectiveness of Swedish AS strategies. Second, that motives relating to people’s trust in health care may be a driver of their antibiotics acquisition behavior. The pilot study included a mix of preset response alternatives and open qualitative questions, and the responses to the latter grounded the design of the preset response alternatives in the survey of the present study. They also grounded our aim to test the specific hypothesis that trust in health care may explain antibiotics acquisition behavior. This since responses to the open questions in the pilot study strongly indicated distrust in health care as a main motivation among the respondents reporting that they had or were prepared to acquire antibiotics without a prescription. While the pilot study was exploratory and therefore did not control for bias in collected data and employed a mix of quantitative and qualitative method, the present study was designed to assess the magnitude of antibiotics acquisition behaviors and attitudes related to prescription in the Swedish population, focusing on trust in health care as a main potential explanatory factor of these behaviors. Since one’s personal view of one’s own health and one’s general health care seeking behavior are a priori confounder-candidates for any specific health service seeking attitude and behavior, and also weakly signaled among the motives described in the pilot, we added these as further explanatory factors to be tested alongside the trust hypothesis. Likewise, we added education level as a possible explanatory factor (besides a background variable used to stratify the sample together with age and gender, see below), since this factor is often considered a potential explanation of differences in health service seeking attitudes and behaviors in general.

Data collection

Data were collected through an online survey via the Citizens Panel, administered by the SOM Institute, University of Gothenburg, Sweden. The Citizens panel consists of a pool of self-recruited respondents who answer questions about four times a year without remuneration. The respondents are invited to participate in each survey wave via email, and a maximum of three reminders are sent out during the field period. The respondents had to provide informed consent before they could take the survey. The number of respondents who did not consent and thus declined participation was 23 respondents (0,54 percent).

The survey was open between 15 September and 26 October 2020. The sample was pre-stratified to mirror the Swedish population in terms of gender, age and education. Alongside questions regarding antibiotics and antibiotic use, the survey also contained questions about respondents’ health care contacts, self-rated health and trust in health care (see S1 Appendix).

Outcome variables

The two outcome variables were 1) previous acquisition of antibiotics other than from a physician in Sweden having issued a prescription and 2) likelihood of future acquisition of antibiotics other than from a physician in Sweden issuing a prescription. The survey question used to capture the first outcome variable was: “In the last five years, have you obtained antibiotics without a prescription from a physician in Sweden?”. The response alternatives were “Yes”, “No” and “Don’t remember”. The second outcome variable survey question was: “If you or a close relative were to become ill at some point during the next five years, how likely is it that you would obtain antibiotics without a prescription from a physician in Sweden (regardless of the cause)?”. The response alternatives were: “Very likely”, “Fairly likely”, “Fairly unlikely” and “Very unlikely”.

Explanatory variables

Trust in health care was measured by the question “How much trust do you have in Swedish health care?”. Five response alternatives were given: “Very much trust”, “Fairly much trust”, “Neither much nor little trust”, “Fairly little trust”, and “Very little trust”.

Self-rated health was measured using the following question: “How would you rate your general health status?”. The response alternatives ranged on a scale from 0 (very poor health) to 10 (very good health).

The education variable was built upon in total nine survey response categories. “Low education” = completed or incomplete 9-year elementary school, “Medium–low” = gymnasium/similar < 3 years or ≥ 3, “Medium–high” = post gymnasium studies other than university education < 3 years or ≥ 3, and “High education” = university education < 3 years, ≥ 3 years or graduation from third-cycle university education.

Ethics

The study processed potentially sensitive personal information about the respondents and therefore required legally mandatory ethics review, secure storage of raw data and standard collection of informed consent. All members of the Citizen Panel had given generic informed consent to be approached for studies, and those invited to participate in the present one were given specific information about the study before consenting (or declining) to participate. All results below are presented on a generic group level. The study received authorization by the Swedish Ethical Review Authority (no. 2020–03019) before initiation.

Statistics

Two multiple logistic regression models were used to investigate the association between the explanatory variables and the two dependent variables: 1) previous non-prescription acquisition of antibiotics (Tables 2 and 3) likelihood of future non-prescription acquisition of antibiotics (Table 4). Tables 3 and 4 reports Odds ratios (ORs) and 95% confidence intervals (CIs). All data were analysed with the STATA 17 statistical software package.

Table 2

Reasons against engaging in non-prescription acquisition of antibiotics (mean, 95% confidence interval, median, and number of respondents).

	Mean (1–5) and Confidence interval (95%)	Median	n
To avoid getting worse health	3.95 (3.91–4.00)	5	3880
In order not to contribute to antibiotic resistance	4.64 (4.61–4.66)	5	3910
The quality of over-the-counter antibiotics feels unsafe	4.48 (4.45–4.51)	4	3911
I trust that physicians can decide if I need antibiotics	4.53 (4.50–4.56)	4	3911
There is a risk of incorrect dosing (taking too much or too little of the antibiotic)	4.19 (4.15–4.23)	4	3913
Prescriptions are safer due to pharmacists’ control	4.33 (4.30–4.37)	4	3917

Comment: Question wording: “How important or unimportant are the following reasons why you would probably not buy antibiotics without a prescription from a doctor in Sweden?” The scale in the survey was from 1 (Very important) to 5 (Very unimportant), but it is reversed in the presentation of data (1 = Very unimportant, 5 = Very important) Source: The Citizens Panel wave 39.

Table 3

Previous non-prescription acquisition of antibiotics, according to demographic variables, self-rated health, trust in health care, antibiotic use and health care contacts.

Odds ratios (OR), 95 confidence intervals (95% CI) and p-values (n = 4 169).

	Odds Ratio (OR)	C.I. (95%)	P-value
Woman (Ref. Cat.)	1.00
Man	1.21	0.80–1.85	0.367
16–29 years (Ref. Cat.)	1.00
30–39 years	0.91	0.39–2.10	0.825
40–49 years	0.71	0.30–1.67	0.430
50–59 years	1.24	0.57–2.72	0.592
60–69 years	1.40	0.64–3.07	0.396
70 years or older	0.63	0.24–1.61	0.332
Low education (Ref. Cat.)	1.00
Medium low education	0.79	0.26–2.35	0.666
Medium high education	1.22	0.41–3.67	0.719
High education	1.14	0.40–3.28	0.805
Self-rated health (0–10)	1.01	0.91–1.14	0.801
Very much trust (Ref. cat.)	1.00
Fairly much trust	2.35	1.14–4.83	0.020
Neither much nor little trust	2.78	1.21–6.42	0.016
Fairly little trust	6.46	2.84–14.72	0.000
Very little trust	9.19	3.10–27.27	0.000
No antibiotics last year (Ref. Cat.)	1.00
Antibiotics 1 time last year	0.91	0.43–1.92	0.804
Antibiotics 2 time or more last year	1.36	0.48–3.85	0.564
Care contact last year (Ref. Cat.)	1.00
No care contact last year	1.61	1.00–2.60	0.049

Comment: The antibiotic use question was: “Have you used antibiotics (e.g., penicillin) prescribed by a doctor in Sweden in the last 12 months?”. Health care contact was captured with the question “When was your last contact with health care regarding yourself?” Source: The Citizens Panel wave 39.

Table 4

Likelihood of future non-prescription acquisition of antibiotics, according to demographic variables, self-rated health, trust in health care, antibiotic use and health care contacts.

Odds ratios (OR), 95 confidence intervals (95% CI) and p-values (n = 4 195).

	Odds Ratio (OR)	C.I. (95%)	P-value
Woman (Ref. Cat.)	1.00
Man	2.19	1.58–3.04	0.000
16–29 years (Ref. Cat.)
30–39 years	1.36	0.72–2.60	0.347
40–49 years	1.33	0.71–2.51	0.372
50–59 years	1.25	0.66–2.36	0.501
60–69 years	1.06	0.55–2.04	0.862
70 years or older	1.31	0.68–2.53	0.424
Low education (Ref. Cat.)	1.00
Medium low education	0.78	0.38–1.58	0.484
Medium high education	0.89	0.431.86	0.762
High education	0.75	0.37–1.51	0.425
Self-rated health (0–10)	1.05	0.97–1.15	0.242
Very much trust (Ref. cat.)	1.00
Fairly much trust	2.00	1.23–3.25	0.005
Neither much nor little trust	2.92	1.67–5.13	0.000
Fairly little trust	5.16	2.87–9.26	0.000
Very little trust	5.18	2.16–12.39	0.000
No antibiotics last year (Ref. Cat.)	1.00
Antibiotics 1 time last year	1.29	0.80–2.09	0.293
Antibiotics 2 time or more last year	1.49	0.70–3.16	0.302
Care contact last year (Ref. Cat.)	1.00
No care contact last year	1.14	0.79–1.65	0.489

Comment: The antibiotic use question was: “Have you used antibiotics (e.g., penicillin) prescribed by a doctor in Sweden in the last 12 months?”. Health care contact was captured with the question “When was your last contact with health care regarding yourself?” Source: The Citizens Panel wave 39.

3. Results

The survey yielded 4243 responses and the participation rate was 57%. We calculated the participation rate by the quotient of the number of respondents who completed more than 50 percent of all questions in the survey and the number of respondents in the initial sample. Among the respondents who completed the survey, the gender balance was very equal– 51 percent were women and 49 percent men. The share of respondents who were 70 years or older when completing the survey was 17 percent and the share of respondents with three years of university education or more was 27 percent. This is reasonably similar to the Swedish population over 18 years (2020), where the 70+ group was 13 percent of the population and the share of people with university education (three years or more) was 24 percent.

Descriptive and bivariate

In total, 2,3% (n = 97) answered that they had obtained antibiotics in other ways than from a doctor in Sweden having issued a prescription over the last five years. 43% of these answered that they had received antibiotics via a prescription by a physician abroad, 28% had bought antibiotics abroad without a prescription, 15% had received antibiotics from a relative or friend, and 9% had bought it via an online pharmacy without prescription.

About one in four answered that the most common reason for non-prescription acquisition was that they knew what kind of antibiotics they needed (26%). About one in five wanted to stockpile antibiotics in case they were to be denied antibiotics by a physician (18%) and 14% because it is easier to obtain antibiotics without than with a prescription. Less than 10% stated that the reason for non-prescription acquisition was that a physician had denied them antibiotics (5%), or that they expected to be denied a prescription (8%). The largest group selected the open-ended response alternative which gave the respondents the possibility to write their own words (53%). Almost all of these answers concerned the use of antibiotics while being abroad.

The survey also contained a question about whether respondents believed that they would obtain antibiotics in other ways than from a physician in Sweden issuing a prescription in the future should they or a relative become ill. Out of the four response alternatives provided, the two most common responses were “Very unlikely” (75.8%, n = 3 176) and “Rather unlikely” (19.9%, n = 833). About 2.5% of the respondents answered “Somewhat likely” (n = 103) and 1.9% “Very likely” (n = 80).

The likelihood of future non-prescription acquisition of antibiotics differed depending upon previous non-prescription acquisition. Among the respondents who had previously obtained antibiotics in other ways than from a physician in Sweden issuing a prescription, about 30 percent reported that they were likely to do so in the future (30 out of 97 respondents). This share is less than 4 percent among respondents who responded not having obtained antibiotics in such ways before (153 out of 4081).

Table 1 reports responses to the question of reasons for possible future non-prescription acquisition of antibiotics. The question was: “How important or unimportant are the following reasons why you would probably buy antibiotics without a prescription from a doctor in Sweden?”. This question was only asked to respondents who in the previous question stated that it is “Somewhat likely” or “Very likely” that they will obtain antibiotics in such a way in the future (n = 183). The number of respondents who responded to the questions about reasons for future non-prescription acquisition of antibiotics varied between 161–167.

Table 1

Reasons for non-prescription acquisition of antibiotics in the future (mean, 95% confidence interval, median, and number of respondents).

	Mean (1–5) and Confidence interval (95%)	Median	n
Physicians don’t want to prescribe antibiotics	3.1 (2.9–3.4)	3	167
Avoid getting in contact with a physician	2.1 (1.9–2.3)	1	161
I can decide for myself if I or a close relative/child need antibiotics	2.4 (2.2–2.7)	2	163
I am abroad and can get antibiotics without a prescription	2.6 (2.4–2.9)	3	165
I am abroad and can get antibiotics via prescription from a doctor there	3.0 (2.8–3.2)	3	166
To keep antibiotics at home as a reserve in case I do not get it prescribed by physician	2.5 (2.3–2.8)	2	166
Because it’s easy	2.6 (2.3–2.8)	3	164

Comment: Question wording: “How important or unimportant are the following reasons why you would probably buy antibiotics without a prescription from a doctor in Sweden?” The scale in the survey was from 1 (Very important) to 5 (Very unimportant), but it is reversed in the presentation of data (1 = Very unimportant, 5 = Very important) Source: The Citizens Panel wave 39.

The table shows that the most important reason was that respondents expected physicians not to prescribe antibiotics. On the scale from 1 (Very unimportant) to 5 (Very important), the means score for this reason was 3.1 (median 3). The second most important reason was obtaining antibiotics via prescription from a physician abroad (mean 3.0, median 3). Reasons such as ease of acquisition (mean 2.6, median 2), availability abroad (mean 2.6, median 3) and stockpiling to keep antibiotics as reserve (mean 2.5, median 2) are in the middle in terms of importance. Less important reasons are avoiding getting in contact with a physician (mean 2.1, median 1) and ability to decide about antibiotics oneself (2.4, median 2).

Respondents rather or very unlikely to obtain antibiotics in other ways than from a physician in Sweden issuing a prescription were asked about the importance of different reasons for not doing so. The results are presented in Table 2 and show that the most important reason was to not contribute to antibiotic resistance (mean 4.64, median 5). Other important reasons were trust in physicians’ judgment about whether antibiotics are needed (mean 4.53, median 4), that over-the-counter antibiotics are unsafe (mean 4.48, median 4) and the safety of pharmacists’ control (mean 4.33, median 4). Reasons less important were risk of incorrect dosing (mean 4.19, median 4) and health risks (mean 3.95, median 4).

The role of trust in health care

Fig 1 demonstrates non-prescription acquisition of antibiotics according to respondents’ level of trust in Swedish health care. It shows that trust is strongly negatively linked to both having engaged in this practice in the previous five years and intention to do so in the coming five years. Non-prescription acquisition is three-fold higher in the distrust group, as compared to the trust group.

Fig 1

Non-prescription acquisition of antibiotics according to trust in health care (percent 95% confidence interval).

Comment: Antibiotics acquisition question wordings: see Tables 1 and 2. Trust question wording: “How much trust do you have in Swedish health care?” The three trust categories are based on five response alternatives: “Trust” (fairly much and very much trust), “Neither trust nor distrust” (Neither much nor little trust) and “Distrust” (very little and fairly little trust). Source: The Citizens Panel wave 39.

Regressions

Using logistic regression, Table 3 illustrates the association between the outcome variable previous five-year non-prescription acquisition of antibiotics and the explanatory variables sex, age, education, self-rated health, trust in health care, use of antibiotics last year and health care contacts last year.

The table shows no significant associations between previous non-prescription acquisition of antibiotics and the explanatory factors sex, education, age, self-rated health and usage of prescribed antibiotic. There is a weak but significant association between contact with health care and non-prescription antibiotic acquisition; the likelihood for this is higher in the group of people that had not been in contact with health care the past year. Furthermore, there is a significant and strong association between trust in health care and previous non-prescription acquisition of antibiotics. The likelihood of this is significantly higher in the four groups “Fairly much trust”, “Neither much nor little trust”, “Fairly little trust” and “Very little trust”, as compared to the “Very much trust” reference category. The odds of previous acquisition of antibiotics not prescribed by a physician in Sweden is 9 times higher in the group with very little trust in health care compared to the very much trust category.

Table 4 shows the association between the dependent variable likelihood of future non-prescription acquisition of antibiotics and the explanatory variables sex, age, education, self-rated health, trust in health care, antibiotic use and health care contacts. The table shows that men are more likely to have the intention to obtain antibiotics in such a way in the future. There are no significant differences in the likelihood depending on age, education, self-rated health, antibiotic use and health care contacts. However, similar to previous non-prescription antibiotics acquisition, there is a significant and strong association between trust in health care and the intention to engage in non-prescription antibiotic acquisition in the future. The likelihood for such acquisition is higher for each “step down” on the trust five-point scale. The likelihood is about five times as high in the “Very low trust” category, as compared to the “Very high trust” reference category.

4. Discussion

Our study indicates that few people in Sweden acquire antibiotics in other ways than via a physician in Sweden issuing a prescription. This share is 2,3%. The share of survey respondents who say they are likely to obtain antibiotics in such ways in the future is also quite small–slightly over 4% say that this is somewhat or very likely.

Most respondents who had acquired antibiotics without such prescription had received a prescription from a physician abroad (43%). Thus, the share of the Swedish population that has obtained antibiotics without a physician in Sweden or elsewhere having issued a prescription is about 1,4%. Those who indicate that they have bought antibiotics without a prescription abroad was 28%, indicating a share of the Swedish population of less than 1%. These results are in line with a recent study from Norway, indicating that purchase of antibiotics during travel abroad is rare in the Norwegian general population [21]. The same low prevalence of purchase of antibiotics during travel abroad was found in a survey study in Denmark in 2003 [38].

The analysis shows that trust in health care is an important factor when it comes to non-prescription acquisition of antibiotics. This is in line with previous research indicating that trust in physicians is linked to higher willingness to accept doctors’ decisions not to prescribe antibiotics [37] and higher willingness to postpone antibiotic use [35]. One possible interpretation of the results is that when people are being denied antibiotics from a physician, people with low trust look for alternative sources of antibiotics.

While the current study follows much of the previous literature in making use of a uni-dimensional indicator of trust in the health care system [39, 40], theoretical arguments speak in favor of institutional trust being a multi-dimensional concept. Institutions can be trusted if they are competent, have the motivation and the opportunity to fulfill their tasks in a good way [41]. Given the results of the current study, an interesting avenue for future research could be to measure the dimensionality of trust in the health care system and analyze what specific components of trust that may be important in curbing the demand for the use of non-prescription antibiotics. One such factor could be the degree of trust in the competence characterizing the health care system or health care personnel. The perceived competence is likely to influence the degree to which patients think doctors’ decisions not to prescribe antibiotics is reasonable and medically motivated, and this trust dimension may thus lower the demand for antibiotics without a prescription. Another trust component is the perception that an actor or institution has good intentions. This dimension of trust could potentially trigger a reciprocal and prosocial feeling of collective responsibility for the problem of antibiotic resistance. This way, people might want to contribute to the fight against antibiotic resistance.

The strong link between trust and non-prescription antibiotic acquisition is interesting in the light of the variation in trust between countries world-wide. The level of trust in health care is rather high in Sweden in a country comparative perspective [42]. It is therefore likely that non-prescription acquisition of antibiotics is higher in countries where the level of trust is lower. Furthermore, the results indicate that implementing prescription control policies against overuse may be difficult in a low trust context, since many more people will look for antibiotics elsewhere, for example via online pharmacies. What complicates this further is that low trust societies often are characterized by corruption and low quality of government, features that may complicate the implementation of AS programs in general [43].

Regarding AS programs, our results suggest, first, that maintaining high levels of trust in health care institutions is a critical factor for the effectiveness of prescription control. Where general trust levels are known to be low, there are reasons for AS programs to include trust enhancing measures to accompany prescription control measures. Merely denying patients antibiotics is not enough; rather these people need to be made sufficiently motivated not to acquire antibiotics from other sources. Second, the wide variations of trust patterns worldwide is a reason to assess the level of non-prescription acquisition of antibiotics, and further test the hypothesis of the role of trust for such acquisition, in other countries that apply AS. High levels of non-prescription acquisition indicate that AS may be ineffective, and that additional measures to enhance trust in health care and/or to block pathways to such acquisition should be contemplated.

Limitations

Our focus on acquisition rather than use, albeit motivated (see Introduction), means that we have not measured self-medication with leftover antibiotics previously obtained with a prescription. Similarly, there remains a possibility that antibiotics obtained without prescription are not used in some cases. Nevertheless, the phenomenon still highlights a challenge for AS through prescription control. The survey questions’ simplified formulations in terms of physician prescription ignore the fact that some especially qualified specialist nurses may in some instances prescribe antibiotics in Sweden. However, almost all prescriptions of antibiotics in Sweden are made by physicians. Moreover, the motivations listed by respondents who stated that they had obtained antibiotics without prescription did not indicate any instance of nurse prescription. Given the generally high level of awareness about antibiotic resistance in Swedish society [44, 45]—including knowledge about the link between antibiotics overuse and resistance—there may be some underreporting due to preferences to avoid social stigma also in an anonymous online survey.

The results reported in this paper come from an online survey pre-stratified to mirror the Swedish population in terms of age, gender and education, and the sample is reasonably similar to the Swedish population with regard to these factors. However, one limitation in the data is that there might be other variables that would improve the estimates of behaviors and attitudes towards antibiotics, which were not included in the pre-stratification process.

5. Conclusion

The prevalence of non-prescription acquisition of antibiotics in the Swedish population is low, and the share of respondents intending to engage in this practice in the future is small. However, both past and intended non-prescription acquisition are strongly associated with low trust in health care. This highlights the importance of future studies of non-prescription antibiotics acquisition in low trust contexts and the need to consider trust preserving and enhancing measures when designing and implementing AS programs.

Questionnaire translated into English.

(PDF)

Click here for additional data file.

25 Feb 2022

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Francesca Baratta, PharmD, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following in the Acknowledgments Section of your manuscript:

“This study was funded by the UGOT-Challenges Initiative of the University of Gothenburg.”

We note that you have provided additional information within the Acknowledgements Section that is not currently declared in your Funding Statement. Please note that funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“Christian Munthe, no award no., UGOT Challenges Initiative, URL: https://www.gu.se/en/research/ugot-challenges

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

Additional Editor Comments:

Dear Author,

The study can be very interesting, the introduction is well written but the results and conclusions must be substantially implemented.

The reviewers gave key directions for implementing the manuscript.

Best regards

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript addresses the non-prescription use of antimicrobials in Sweden from the perspective of the issue of trust or lack of it in the healthcare system.

Overall, a well conceptualized and written manuscript

Main concern is the use of mean as measure of central tendency with Likert-like responses such as Very much trust”, “Fairly much trust”, “Neither much nor little trust”, “Fairly little trust”, and “Very little trust. Using the median will be more appropriate in these cases. This will apply to Tables 1 and 2.

Table 3 and are too bulky. The authors should kindly format according to the journal's specifications.

Limitations: I am not sure if "limitations should come under "Results". The authors to kindly check the journal's template/ submission guidelines

Reviewer #2: I think this paper has some interesting perspectives measuring the extent of acquiring antibiotics (AB) without prescription in a Northern European country. Even so, one would think there is no problem to explore, I think the authors do a good job in the introduction arguing for why such a study is still needed.

I think, however, there are several major problems with the study. This include: 1) lack of conclusion of the relevance of the study, 2) lack of methodological rigor, and 3) mis-/over-interpretation of the concept ‘trust in health care’, why I don’t think the study is ready to be published. Perhaps it can be considered a pilot study, showing an overall association between low trust in health care (whatever that is) and acquisition of AB that can be further explored in more studies (if one can justify such a study); or go amore in a more methodological direction and discuss in detail how the survey might be transformed to be used in other health care settings. See the comments below.

1: I think the authors fail really to discuss if the extend of acquiring AB as they measure it, proves if there really is a problem, that justifies spending time on the subject. In the introduction, the authors state p.5 that:

‘If a significant portion of people acquire antibiotics without prescription, the effectiveness of prescription control as a tool for AS would be undermined. Moreover, surveying prescription data to track the effect of AS on antibiotics use would provide a false picture that underestimates antibiotics use and overestimates the effectiveness of AS prescription control.’

However, I only see the authors making an indirect conclusion of whether they found a ‘significant portion’ of use of AB without prescription. Further, in the conclusion they don’t provide explicitly guidance to how the developed survey-tool could be used by authorities/ researchers from other countries:

‘The prevalence of non-prescription acquisition of antibiotics in the Swedish population is low, and the share of respondents intending to engage in this practice in the future is small. However, both past and intended non-prescription acquisition are strongly associated with low trust in health care. This highlights the importance of future studies of non-prescription antibiotics acquisition in low trust contexts and the need to consider trust preserving and enhancing measures when designing and implementing AS programs.’

2: I think the paper lacks rigorous theoretical and methodological underpinning. The authors develop if, I understand correctly, a completely new survey, however, there is no description of relevance of hardly any of the specific content of the survey. This includes a lack of explanation of most of the included questions and pre-determined nominal answers. This is in particular a problem since some answers such as the one: ‘How important or unimportant are the following reasons why you would probably buy antibiotics without a prescription from a doctor in Sweden?, only contains answers, predetermined by the authors. Further, there is no explanation of any validation process of this new developed survey. And lastly, there is no precise explanation of the sampling procedure.

Further, the key explanatory variable is ‘trust in health care’ or ‘institutional trust’. The authors explain that institutional trust can be measured with regard to trust in: government, agencies, or public institutions, and in relation to: if they are competent, have the motivation and the opportunity to fulfill their tasks in a good way. However, even so the authors describe the variable being multidimensional, only one question is asked in they survey: ‘How much trust do you have in Swedish health care?’ How do the authors know how respondents have interpreted this question, i.e. what their answers actually cover of all the possible dimensions.

3: In addition, despite the multidimensional construct of ‘trust in health care’, there seems to be an understanding among the authors in the discussion that this question in the survey covers respondents’ trust in physicians, which I find is a huge possible misinterpretation.

Further, the authors suggest that the developed survey could be used as a tool in other countries to show how low trust in health care are associated with high non-prescription AB acquisition. Here, I completely miss a discussion and literature of all the possible factors that might influence a difference in perception in ‘trust in health care’ between different cultural health care contexts, and therefore how you cannot repeat just this sole question on trust in the survey.

Lastly, there is no description of how the end responders represent or do not represent the Swedish population (including a more precise description of the sampling procedure), which however, doesn’t prevent the authors from making extrapolations of the results.

Reviewer #3: Summary

In their manuscript, “Non-prescription acquisition of antibiotics: prevalence, motives, pathways and explanatory factors in the Swedish population,” Munthe and colleagues describe a cross-sectional survey that asked about obtaining non-prescription antibiotics, sociodemographic factors, attitudes, and trust in healthcare.

The authors found that 2.3% of respondents reported obtaining non-prescription antibiotics, 4.3% are likely to do so in the future, and that prior receipt and intent to obtain non-prescription antibiotics in the future were associated with low trust in health care. People obtained antibiotics via prescription from a physician abroad (43%), bough antibiotics abroad without a prescription (28%), received antibiotics from a relative or friend (15%), or bought it through an online pharmacy without a prescription (9%).

General Comments

The manuscript is interesting, especially given the very low overall history and intent of receiving non-prescription antibiotics. The authors usefully frame their results as an example of what is possible in a high-trust environment. I especially appreciated the sentence “Merely denying patients antibiotics is not enough; rather these people need to be made sufficiently motivated not to acquire antibiotics from other sources.”

The study and manuscript have several weaknesses.

First, hopefully something is not getting translated accurately, but the wording of the main question in English is unclear. When I read the phrase “acquired antibiotics without a prescription from a Swedish physician” I took it to mean that Swedes were getting antibiotics directly from Swedish physicians, but without a prescription. Perhaps Swedish physicians were giving out sample antibiotics or had some other mechanism to give out antibiotics without issuing a prescription. (In a totally unscientific test, I asked my spouse how they interpreted the question, and they interpreted it the same way.)

It was not until page 11, at the beginning of the Results that includes the ways in which Swedes obtained non-physician-issued antibiotics that I understood the authors meant “acquired antibiotics, but not from a Swedish physician having issued a prescription.” Another way to word this in the Abstract and early in the manuscript is “acquired antibiotics, other than from a Swedish physician issuing a prescription.” With that, the authors’ meaning should be clear.

Second, the authors repeatedly state that the sample is representative, but the respondents are non-representative for at least two reasons. First, to even be included in the survey, potentially participants had to give informed consent. Second, the sample was “pre-stratified to mirror the Swedish population,” but there was a 57% response rate. Those willing to give informed consent and respondents are likely to be systematically different from Swedes who did or would not give informed consent and non-respondents (e.g., in their interest in the topic, willingness to report non-socially acceptable or illegal behavior, and other factors). I would guess consenting respondents would be less likely to acquire non-prescription antibiotics than the average person. Do the authors have any data about how respondents were demographically similar or different from the Swedish population?

Third, I would want the authors to report on the overlap of respondents who said they had obtained non-prescription antibiotics in the past and intend to do so in the future. Are these the same people? If so, this problem could be very limited. If not, the disconnect between past behavior and future intended behavior could be interesting for the authors to discuss.

Fourth, the authors never state what kind of statistical analysis they are using. Also, it is not clear how the authors are evaluating each variable in a model. I would think they should be using a Type 3 test or a test-of-trend for some of the variables, but there appear to be p-values for all levels of all variables.

Fifth, the data presented in the tables is difficult to interpret. The authors do not describe how importance was asked in the Methods section. Also, the Ns are hard to follow. For Table 1, each variable has an N of about 160 to 170, but 183 respondents said they were somewhat or very likely to obtain antibiotics in the future. Are these the same subsets? The tabular results need to more clearly state who is responding to each question.

Specific Comments

Page 4, 1st paragraph: The Introduction seems like a repeat of information that should be in an Abstract rather than an introduction.

Page 4-9: The Background and Introduction are very long. I am accustomed to a Background section that is 1-2 pages and gets right to the point of the study.

Page 9, paragraph 3: The authors need to explain the parenthetical “AAPOR RR5” and why they chose that method of calculating the response rate. Also, the reporting of responses and response rate seems like it belongs in the Results section.

Page 12, Table 1: The authors should clarify in the table title whether this refers to past behavior or future intent (I believe it is future intent).

Page 15, Table 3: There are some formatting problems with some of the confidence intervals. Perhaps the hyphen is missing?

Page 17, paragraph 2: The authors are incorrect in saying the odds ratio represents something is “9 times higher.” It is actually “9 times the odds,” which is different.

Page 20, paragraph 1: The authors should include data to their statement that Swedes have a “high level of awareness about antibiotic resistance.”

Figure: There is no key for the y-axis. I presume this is %.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Prof. Joseph O. Fadare

Reviewer #2: No

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

7 Jul 2022

See the Cover letter and the response to reviewers files for details.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

3 Aug 2022

Non-prescription acquisition of antibiotics: prevalence, motives, pathways and explanatory factors in the Swedish population

PONE-D-22-02565R1

Dear Dr. Munthe,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Francesca Baratta, PharmD, PhD

Academic Editor

PLOS ONE

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: (No Response)

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Prof. Joseph O. Fadare

**********

29 Aug 2022

PONE-D-22-02565R1

Non-prescription acquisition of antibiotics: prevalence, motives, pathways and explanatory factors in the Swedish population

Dear Dr. Munthe:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Francesca Baratta

Academic Editor

PLOS ONE