A survey of knowledge, attitudes and use of antibiotics among Bulgarian population

Abstract Antimicrobial resistance occurs naturally but is enhanced by human activities related to the use of antibiotics (for example, excessive use and misuse of antimicrobial agents). Our study aimed to gain insight into the knowledge, attitudes and practice of the use of antibiotics among the general Bulgarian population. A cross-sectional survey was conducted during a 4-week period in April-May 2022. Our sample included 516 participants of whom 398 (77.1%) were females, mainly Bulgarians by ethnic group, with a university degree (master degree 58.9%; bachelor degree 17.2%) and living in big regional cities (91.5%). The main health reasons that respondents from all age groups share for taking antibiotics in the last year were bronchitis, sore throat, infections, including urinary tract infections, and pneumonia. Interestingly, about 14% of the respondents have treated the SARS-2-coronavirus infection with antibiotics. Our results highlighted existing attitudes toward antibiotic use in the surveyed sample. Overall, respondents from all age groups showed similarities in their attitudes toward treatment with antibiotics. People’s behavior and actions toward antibiotics play an important role in the spread of antimicrobial resistance. Our study provided some important insights concerning the knowledge and practices related to antibiotic use and antimicrobial resistance in the Bulgarian population. In general, good knowledge of antibiotic use and antimicrobial resistance was evident among the surveyed sample.


Introduction
The development of antimicrobial resistance (AMR) by microorganisms is a natural phenomenon but can be accelerated by indiscriminate use of antimicrobial agents in humans. Antibiotic misuse is a serious problem on a global scale [1] and there is a growing consensus to develop new strategies for prevention of AMR [2] as AMR poses a silent but major threat to global health, with a projected annual mortality rate of 10 million deaths per year by 2050 [3][4][5].
Other contributing factors include self-medication, gaps in knowledge about antibiotics, and the lack of adequate policies for control of prescribed antibiotics [6][7][8][9]. Improper use of antibiotics contributes significantly to the progression of AMR, and it is often driven by the general population's poor knowledge of appropriate antibiotic use and factors leading to AMR [10][11][12][13][14][15][16]. Due to AMR, numerous antibacterial, anti-parasitic, antiviral and antifungal medicines have become ineffective, making treatment difficult, costly or even impossible, especially for vulnerable patients, which has resulted in prolonged treatment and increased mortality rates [9]. The level of knowledge and attitudes concerning antibiotic use are relevant to development of AMR and may vary across different countries and communities [17,18].
The problem of antibiotic misuse has prompted many surveys on the knowledge, attitude and practice toward antibiotics use among the public [1,[19][20][21][22]. In general, these studies warn that the public tends to demonstrate inadequate [insufficient/poor] understanding of the proper use of antibiotics. Poor knowledge of antibiotic use was associated with a higher probability of inappropriate practice, including self-medication, using leftover antibiotics, sharing antibiotics and stopping the treatment when symptoms disappear [23][24][25]. In addition, the use of antibiotics is often not supported by culture and sensitivity testing, nor is it always in line with the recommendations governing clinical practice [18,26] and Bulgaria is not an exception [27].
Identifying gaps in understanding the appropriate use of antibiotics is important in defining strategies to address antimicrobial resistance, and this needs to be tailored according to the findings for specific countries and communities. Several studies have evaluated the knowledge, attitudes, and perceptions among general population about the use of antibiotics and AMR [22,[28][29][30][31][32]; however, we found only one publication that focused on these issues among patients from Bulgaria [27]. Another survey focused on AMR of S. pneumoniae in four neighboring countries, including Bulgaria [32].
The aim of this study was to survey the knowledge, attitudes and practice of antibiotic usage among the Bulgarian population and to discuss the results in the light of other similar surveys.

Ethics statement
Informed consent was signed by all participants.

Background and respondents
The approach was similar to previous studies [19]. A cross-sectional survey among a sample of the general Bulgarian population was conducted during a 4-week period in April-May 2022, using an internet-based questionnaire. The target participants were adult citizens of Bulgaria aged 18 years and over who could read and understand Bulgarian. The survey was performed using an online Google Forms questionnaire because of limited options for face-to-face data collection during the active COVID outbreak. The online questionnaire was distributed using a snowball sampling strategy via social media (mainly Facebook, Twitter and Viber) and E-mails. Participants were asked to share the questionnaire link to individuals in their social circles (aged 18 years and over). These social media platforms were chosen because they are widely used among the Bulgarian population across sociodemographic characteristics. A total of 516 completed responses were collected. An informed consent was signed by all participants.

Questionnaire development and testing
Like in Cals et al. [19], the questionnaire was developed by experts initially deciding which domains they considered most important. Questions to tap these domains were derived from previous international qualitative and quantitative scientific publications and further expert opinion [1,3,4,[6][7][8][9][10][11][12][13][14]. Prior to the major survey, a pilot study was done addressing fundamental issues about antibiotics and their use. The pilot research served as a basis to update and enhance the questionnaire with input from statisticians. The sample size included 49 respondents. The pilot study checked face validity, and the wording of some items was modified considering this. The final edition of the questionnaire had 31 questions grouped into three categories and a socio-demographic sector. Response options, including yes/no, agree/disagree, and Likert-type scale response items, were used as appropriate for each question.

Socio-demographic characteristics
Data on age, gender, ethnicity, education; additionally, on medical education (without specifying its type), own/or of a member of the family, urban/rural status, health status perception and financial status were obtained from respondents. Age was categorized into 3 groups: 17-29 years, 30-49 years and 50 + years. Self-assigned ethnicity was reported in four categories, and education (highest qualification) in five categories. Self-reported financial status was used.

Antibiotic perception
The survey per se consisted of a questionnaire divided into three parts: the first, to get an overview of people's knowledge of antibiotics and antibiotic resistance (13 questions); the second, to acquire information about people's attitude to antibiotic application (7 questions); the third, to gather insight on antibiotic practices (11 questions).

•
The first section on the knowledge of antibiotic use covered, among other topics, perspective of antibiotic use in viral and bacterial infections, concept of side effects and resistance due to antibiotic application, relationship between antibiotics, infection and efficacy, antibiotic timing, knowledge about commonly used biomedical terms, such as antibiotic resistance. • The attitude section had questions on the severity of antibiotic misuse, the practice of self-under-or overtreatment with antibiotics, compliance to practitioners' advice on antibiotics use, and desire to get antibiotics.
• The section on the practices pertained to the use of telemedicine for prescription of antibiotics, sources of information, frequency of antibiotic usage, and type of infections experienced during the last year in the family, antibiotic withdrawal status, compliance with doctor's antibiotic prescription among others.
A 5-point Likert scale with answers ranging from 4 = strongly agree, 3 = agree, 2 = neither agree nor disagree, 1 = disagree, to 0 = I do not know, was used to analyze the knowledge and attitudes regarding antibiotics and microbial resistance. Self-reported antibiotic use patterns were also evaluated using a Likert scale with answers ranging from "always" to "never".

Collection of data and statistical analysis
All responders' answers were automatically entered into a data file, which was checked for accuracy by two independent researchers. Descriptive statistics were reported as percentages for categorical data, mean ± standard deviation (SD) for normally distributed continuous data. The paired comparisons between predefined groups were done with independent samples t test for normally distributed variables. Additionally, chi-square test and analysis of variance (ANOVA) were used to test for significant associations between groups regarding different categorical and ordinal variables. Statistical data were processed using the IBM SPSS v.23 statistical package and Jamovi v.22.5. Differences were considered statistically significant at the p ≤ 0.05 level.

Results
Our sample included 516 participants of whom 398 (77.1%) were females, mainly Bulgarians by ethnic group, with a university degree (master degree 58.9%; bachelor degree 17.2%) and living in big regional cities (91.5%). More than 63% defined themselves as employees with income above the country average (Table 1). More than 53% were aged between 30 and 49 years. The size of the sample is comparable with similar studies performed by WhO in other regions (507 participants in Barbados, 510 in Serbia, 511 in Egypt, 518 in Sudan) [16].
The main health reasons that respondents from all age groups (χ 2 = 19.4, p = 0.365) shared for taking antibiotics in the last year were bronchitis, sore throat, infections, including urinary tract infections, and pneumonia. Interestingly, about 14% of the respondents had treated the SARS-2-CoV infection with antibiotics ( Figure 1). Some of the respondents (N = 64, 12.4%) indicated that they had taken antibiotics prescribed for another patient.
We tested the knowledge of the respondents in our sample regarding antibiotics and antimicrobial resistance. Overall, the participants shared satisfactory answers pointing out true knowledge about most of the statements listed in Table 2. Around 93.6% of the respondents declared that antibiotics are used to treat bacterial infections. At the same time 17% answered that antibiotics are used to treat viral infections as well; 14.5% believed that antimicrobial products could shorten the convalescent stage of flu infection. About 16.2% expected that the therapy with antibiotics should start immediately after first signs of the disease are noted. There were some doubts in the correct answers among the participants from the group of 50+ year-olds as to whether antibiotic use should start from the first day of the illness (F = 2.497, p = 0.306) and the certainty that the use of the same antibiotics helps respondents for different diseases (F = 4.575, p = 0.011). This trend of unclear knowledge was obvious in the opinion of the 50+ year old participants, as they were less aware compared to the younger   respondent groups if skipping one or two doses of an antibiotic could lead to antimicrobial resistance. The post-hoc analysis of Tukey showed that the difference between the 50+ year old group and the 17-29-yearold group (mean difference = −0.543, p = 0.003) and 30-49-year-old group (mean difference = −0.333, p = 0.039) were statistically significant. Most of the respondents (92.3%) were aware that the frequent use of antibiotics can cause adverse drug reactions and 94.2% believed that frequent use of antibiotics could decrease the efficiency of treatment of future infections. Significant differences in the reported results were observed between the 17-29-year-old group and the 30-49-year-old group, supporting firmer knowledge about the risk of frequent use of antibiotics among the younger respondents (mean difference = −0.285, p = 0.011). Of the respondents, 87.2% (N = 450) gave the correct definition of "antimicrobial resistance" and 86.4% (446) considered it a real threat to public health. Part of the respondents, 20.5% (N = 106), could not judge whether skipping a dose of antibiotics could result in antimicrobial resistance, while 55.5% (N = 286) believed that this could lead to development of resistance. A considerable number of respondents (46.9%, N = 242) believed that they usually know when they need antibiotics.
Additionally, a small percent of respondents had incorrect knowledge about antimicrobical resistance. Significant differences between the age groups were not observed (χ 2 = 21.0, p = 0.051), and common wrong beliefs about the term "antimicrobial resistance "were reported among all participants (Table 3) Our results highlighted the existing attitudes toward antibiotic use in the surveyed sample. Overall, the respondents from all age groups showed similarities in their attitudes toward treatment with antibiotics. Notably, their answers showed that the responders were not convinced, as their choices to the listed attitudes were mostly "rather not true". Interesting differences in the opinions in the three age groups was observed regarding their likelihood to buy antibiotics in pharmacies without having the prescription for that (F = 3.472, p = 0.032). Greater second thought was observed among the older age groups (30-49 years with M = 1.78 ± 1.049 and 50+ years with M = 2.02 ± 1.104) where Tukey's post hoc analysis showed a significant difference (mean difference = −350, p = 0.032). Likewise, the respondents in the oldest age group (M = 1.97 ± 1.188) showed greater readiness to possibly buy a new antibiotic because they consider them more effective (F = 4.744, p = 0.009). The post hoc analysis by Tukey showed similar mean difference between respondents' opinions in the 50+ year old group and 17-29 years (mean difference = −0.423, p = 0.018) and the 50+ year old group and 30-49 years (mean difference = −0.356, p = 0.017).
The present study adds on the practices of antibiotic use in Bulgaria. Some respondents, 26.9% (N = 149), reported readiness to try to buy antibiotics without prescription in the pharmacy. On the other hand, 31.4% (N = 162) tended not to take an antibiotic, even if prescribed by a physician. Only 26.5% (N = 137) perceived the new antibiotics as more effective than the products that are well established on the market although we could not locate any age-specific trend in the worrisome practice of antibiotic use prescribed for other people (χ 2 = 1.74, p = 0.420), our results showed that about 12% of the sample had done so. Likewise, no age differences in the self-treatment practices were found (χ 2 = 5.58, p = 0.062), with an overall misuse of antibiotics in the sample reaching more than 28%. Additionally, about 29.2% of the respondents did not take the antibiotics as prescribed, but rather stopped taking the medications. Overall, most participants in the survey, including their family members, had taken an antibiotic on average about once in the past year ( Table 4). The results show that differences favoring antibiotic use among adult family members were observed in the age groups of 17-29 years and 30-49 years (F = 3.2289, p = 0.041) ( Table 5).

Discussion
Population plays an important role in the irrational use of antibiotics, as well as in the spread of perceptions on bacterial resistance [9]. Our study provided some important insights concerning the knowledge and practices related to antibiotic use and antimocrobial resitance in the Bulgarian population. In general, good knowledge of antibiotic use and AMR was evident, similar to studies performed in other European union member-states [9]. This could be also due to the fact that the sample has weak generalizability: 86.4% of the respondents have higher education. Most of the respondents (93.6%) answered correctly that antibiotics are used to treat bacterial infections. Only a small percent of respondents had incorrect knowledge about what antimicrobial resistance is, and significant differences between the age groups were not observed.
Some doubts in the correct answers regarding the factors leading to AMR were observed among the 50+ year-old participants. Most of the respondents (92.3%) were aware that the frequent use of antibiotics can cause adverse drug reactions and 94.2% believed that frequent use of antibiotics could decrease the efficiency of treatment of future infections. A large fraction, 86.4% considered AMR a real threat to public health.
Despite the satisfactory level of knowledge on antibiotics and AMR found in the sample, we detected some practices of improper use of antibiotics. Some (28.3%) reported self-medication with antibiotics, which is considerably higher than the findings for Spain (15.2%), Malta (19%) and Romania (19.8%). Comparable data are reported for Lithuania (22%), the Czech Republic (31.1%) [34][35][36]38] and Nigeria (31.3%) [37]. As discussed by Voidăzan et al. [9], two main routes of access to antibiotics used for self-medication have been suggested in the literature: the first is direct distribution to the patient with no prescription and the use of antibiotics left over from previous treatment [33].
In our study, 12.4% of the respondents had used antibiotics prescribed for another person vs. 25% of surveyed people across 12 countries [16], who thought it is acceptable to use antibiotics prescribed for another person they know if they were used to treat the same illness. No age differences in the self-treatment practices were found in our sample, but the overall misuse of antibiotics was more than 28%. Almost one third of the respondents (29.2%) did not take the antibiotics as prescribed. having in mind the educational status in the sample, this percentage is alarming and further studies are needed to be performed in a representative sample with a focus on possible reasons for non-compliance. The respondents in the oldest age group showed greater readiness to possibly buy a new antibiotic because they consider new products more effective.
The awareness regarding medical conditions warranting antibiotics was adequate. Most respondents in our study identified conditions such as bronchitis, infections, including urinary tract infections and pneumonia as treatable with antibiotics. In our sample, 44.30% of the respondents had not used any antibiotics during the last year.
At the same time 17% answered that antibiotics are used to treat viral infections as well vs. 65% in Singapore for example and 80% in Malasia [40,41].
The first study in Bulgaria that performed a survey of self-medication of antibiotics was pubished in 2014 by Dimova et al. [27]. They reported an observed self-medication rate of 43% amongst the general Bulgarian population (vs. 26.9% according to our survey). A progress was also made regarding the level of knowledge about AMR: our study showed that only a small percent of respondents had incorrect knowledge about what antimicrobical resistance is and that 86.4% considered AMR a real threat to public health, whereas the earilier study [27] reported that 40.0% had never considered the importance of AMR. The statistical analysis performed by Dimova et al. [27] revealed that a higher level of education might have positively influenced the awareness of antimicrobial resistance, which was also confirmed in the present study. The percentage of people who believe that antibiotics are used to treat viral infections is similar: 16.4% [27] (vs. 17% reported in our study).
Public misconceptions on the effectiveness, indications and proper use of antibiotics exist and the relation between improper use of antibiotics and antimicrobial resiantce is clear and often studied and discussed in the specialized literature as well as presented to broader audidence to combat the consequences on public health [1, 3, 6, 8-10, 12-14, 16-22, 24,25, 27-29, 31-34, 36,37, 39-41]. understanding the national-specific factors that influence the inappropriate antibiotic use can help develop appropriate measures to improve antibiotic practices and reduce AMR. The results of surveys of public knowledge about antibiotics will ensure more succesfull campaigns targeting the key gaps in knowledge and correct common misunderstandings.

Limitations
This study has some limitations, including an online sample with no random selection and weak generalizability.

Conclusions
This study adds an additional perspective on the practices of antibiotic use in Bulgaria. The obtained results can be used to develop certain guidelines for public education on the use of antibiotics based on the findings. In general, there is realtively good knowledge about the use of antibiotics among the respondents; however the survey findings point to the need to increase public education so that people better understand the importance of taking the full prescription as prescribed and why antibiotics should be taken only by a particular person for a particular episode of illness by prescription (12.4% of the respondents had used an antibiotic which had been prescribed to another person). Another knowledge gap is the need of antibiotics in the treatment of viral infections. Special focus when designing educational programs should be put on the population aged 50 years and older.