Evaluation of Healthcare Students’ Knowledge on Antibiotic Use, Antimicrobial Resistance and Antimicrobial Stewardship Programs and Associated Factors in a Tertiary University in Ghana: Findings and Implications

Antimicrobial resistance (AMR) is a major public health problem globally, and Ghana is no exception. Good knowledge regarding antibiotic use, AMR, and the concept of antimicrobial stewardship (AMS) is critical among healthcare students to curb rising AMR rates in the future. Consequently, a need to ascertain this. A cross-sectional survey was undertaken among fifth-year pharmacy, medical students and fourth (final)-year nursing and physician assistantship students at the University of Health and Allied Sciences in Ghana to assess their knowledge on antibiotic use, AMR and AMS using a web-based self-administered structured questionnaire. Descriptive statistics, Fishers’ exact test, and multiple logistic regression analyses were performed. A total of 160 healthcare students were interviewed, of which 56.3% (n = 90) were male and 58.8% (n = 94) were in their fourth year of study. Good knowledge of antibiotic use, AMR, and AMS was associated with the study course (p = 0.001) and the number of years of study (p < 0.001). Overall, there were differences in the level of knowledge of antibiotics among the different healthcare students and their years of study. Efforts must now be made to enhance the curricula to ensure an improved and uniform transfer of knowledge of antibiotics, AMR, and AMS among the different healthcare students to sustain the fight against AMR in Ghana given growing concerns.


Introduction
In 2019, there were an estimated 4.95 million deaths globally associated with antimicrobial resistance (AMR), with estimates that up to 10 million lives will be lost annually to AMR by 2050 if no appropriate activities are instigated by governments and other key stakeholders to slow its progression [1,2]. There are also appreciable costs associated with AMR, with the World Bank believing that costs globally could rise to over $1 trillion per year by 2050, equivalent to 3.8% or more of gross domestic product, if the current situation continues unabated [3,4]. This combination is a concern especially among countries in sub-Saharan Africa, which currently have the highest rates of AMR worldwide, and they university in Ghana. The objective is to evaluate healthcare students' knowledge regarding antibiotic use, AMR, and ASPs, with the findings subsequently to be used to update educational activities to address ongoing concerns in Ghana.
We are aware that there have been studies seeking to increase the prescribing of topical antibiotics for acute respiratory infections. However, the principal focus among healthcare professionals (HCPs) should be to reduce antimicrobial use for potentially self-limiting viral infections [8,78].Consequently, such studies were considered outside the scope of this paper. Similarly, we have not considered studies demonstrating inappropriate antibiotic prescribing among dentists and dental surgeons, combined with potential ways to address this including local administration of antibiotics [79,80], as we did not included dental students in our study. Finally, we have not commented on ways to increase the uptake of COVID-19 vaccines across Africa by healthcare professionals (HCPs), including Ghana, given current appreciable hesitancy to reduce future serious illness and hospitalization [81], thereby reducing inappropriate antibiotic prescribing, as this is again outside the scope of this paper.

Results
We will first document the characteristics of the respondents before assessing any association between their characteristics and knowledge of antibiotics, AMR and ASPs.

Characteristics of the Respondents
A total of 160 students from the University of Health and Allied Sciences comprising of 33.1% (n = 53), 25.6% (n = 41), 29.4% (n = 47), and 11.9% (n = 19) nursing, medicine, physician assistantship, and pharmacy students, respectively, were surveyed, giving a response rate of 100% among those approached. This high rate was achieved with the help of constant reminders to recruited students, including emails and WhatsApp contact.
From the interviews conducted, 56.3% (n = 90) were male, 91.9% (n = 147) were within the age group of 20-25 years, 58.8% (n = 94) were in their final fourth year, 79.4% (n = 127) had no training in antibiotics prior to entering the university, and 77.0% (n = 120) had no close friends or relatives working in health-related fields (Table 1). The Fisher's exact test of independence showed a statistically significant association between the knowledge of AMR and gender (p = 0.004), and knowledge of antibiotics and training on antibiotics prior to entering the university (p < 0.000). There were associations between students' knowledge on antibiotics use, AMR, ASP, and the course of study and the year of study. Overall knowledge of antibiotics was also associated with students' course of study (p = 0.001) and year of study (p < 0.001) ( Table 2).

Multiple Logistic Regression between Students' Characteristics and Their Overall Knowledge on Antibiotics
Healthcare students' overall knowledge on antibiotics was approximately six times (OR = 5.84, CI 2.09-16.26) more likely to be good knowledge if they were in their fifth year in the SOP and SOM, than if they were in their fourth year in the SONAM and SAHS (Table 3).

Discussion
We believe this is the first study of its kind in Ghana involving both health and allied science students in a single university. Encouragingly, there was a good overall level of knowledge regarding antibiotics among most of the healthcare students at the University of Health and Allied Sciences in Ghana, which is similar to some studies conducted among students in LMICs [53,54,58,59]. However, this is different from other studies conducted among students in LMICs where there have been concerns with their knowledge [46,55,56,64,82,83].
As seen, good knowledge of antibiotic use, AMR, and ASPs was associated with the study course (p = 0.001) and the number of years of study (p < 0.0001). A greater proportion of healthcare students from the School of Pharmacy (94.7%) and the School of Medicine (87.2%) in their fifth year had good knowledge of these matters versus their counterparts from the School of Nursing and Midwifery (62.3%) and the School of Allied and Health Sciences (63.4%), who were in their final year, i.e., their fourth year. This could be due to differences in the structure and depth of the curriculum among these different healthcare students regarding these key subject areas. As a result, leading to a greater exposure to the principles of antimicrobial stewardship (AMS) among the former group compared to the latter, similar to other studies conducted among LMICs [54,65,82,84]. The healthcare students from the School of Pharmacy were also observed as having a slightly better overall knowledge with respect to these subject areas. The exact cause of the differences among them is an important area for future research going forward.
The poor knowledge regarding antibiotic use, AMR, and AMS among nursing and physician assistantship students compared to other members of the healthcare team is a concern. This needs to be actively addressed going forward as good knowledge of these subjects among the entire multidisciplinary HCP team is an essential step towards optimizing the future use of antimicrobials. Consequently, immediate steps need to be taken to address these knowledge gaps among HCP students. Essential steps include an urgent review and refinement of current curricula especially among nursing and physician students to include greater input on AMR and AMS principles. This is because they are key stakeholders in the prescription, administration, and counselling on antibiotic use across all sectors in Ghana. Furthermore, there must be efforts to instigate mandatory, continuous professional development programs surrounding AMR and ASPs among all HCP groups post-qualification as Ghana strives to achieve the goals of the NAP [31,32]. This should help with combating rising rates of AMR across Ghana [31,85]. This will increasingly include hybrid approaches to learning [86], which is even more important post COVID-19 with the high inappropriate use of antimicrobials in Ghana and across countries to prevent and treat patients with COVID-19 [15,17,87,88].
We are aware of a number of limitations with this study. Firstly, this study is limited by the small sample size, as well as the non-inclusion of other core members of the AMS teams including laboratory personnel trained in microbiology. Secondly, we conducted this study in only one university in Ghana, which may affect the internal and external validity of our findings. Lastly, we used a questionnaire derived from published studies combined with the considerable knowledge of the co-authors. However, this was not validated among our study population. This though is similar to numerous other studies undertaken by the co-authors across countries utilizing their considerable knowledge and experience in this area. Notwithstanding these concerns, we believe our findings are robust, providing guidance for future activities in the developing and refining of curricula in this University and across Ghana.

Study Site and Population
The This study was conducted amongst four of the schools, namely the SOP, SOM, SONAM, and the SAHS. The target study population included fifth-year pharmacy and medicine students and fourth and final-year nursing and physician assistantship students. Fifth-year medical and pharmacy students were chosen as this is the final year for all classroom lectures and assessments. The sixth year is devoted mainly for clinical practice in hospitals outside the university campus, aimed at the acquisition of practical knowledge and skills, unlike their nursing and physician assistantship student counterparts who undertake similar practical training after completion of their four-year degree program.

Study Design
A cross-sectional study design was employed to evaluate the knowledge of antibiotic use, AMR, and ASP among pharmacy, medical, physician assistantship and nursing students in the University of Health and Allied Sciences.

Sample Size and Sampling Procedure
Based on a student population of 252, comprising of 30 pharmacy students, 73 medical students, 84 nursing students and 65 physician assistantship students, a minimum sample size of 153 students was calculated, using the Raosoft Inc. online sample size calculator (http://www.raosoft.com/samplesize.html (accessed on 10 May 2021)), assuming an expected frequency of 50% to yield the largest sample size, at 80% power and 95% confidence level. The sample size was increased to 160 to account for any incomplete data. Probability proportional sampling, based on the size of each school's student population, was used to estimate the number of students from each school to be included in the final sample of 160 students. Simple random sampling, using a random number generator (https://www.random.org (accessed on 10 May 2021)) was used within each school to recruit the required number of students with the help of a class list obtained from the administration for the survey, which included 19 pharmacy students, 47 medical students, 53 nursing students, and 41 physician assistants.

Data Collection
A structured self-administered 35-item questionnaire was developed using online google forms for the survey, based on published literature of similar student studies including validated questionnaires, combined with the considerable knowledge and experience of the co-authors [54,58,60,66,89]. We have used this approach previously to investigate key issues and their implications across LMICs [8,31,81,86,[90][91][92][93]. The questionnaire included firstly the socio-demographic characteristics of participating students, followed by questions aimed at assessing their knowledge about antibiotic use, antibiotic resistance, and ASPs, using three response options, namely 'Agree', 'Disagree', and 'Do not know' (Supplementary Table S1). This included 7 questions assessing students' knowledge regarding antibiotics, 12 questions on AMR, and 8 questions on ASPs.
The link for access to the questionnaire and the consent form was sent to the recruited students via both their collected e-mail addresses and WhatsApp contact numbers since these media are widely used by the students. The same questionnaire was answered by all the different categories of students who participated in the study since we wanted to assess and compare their basic knowledge on these important subject areas.
Data were collected between June 2021 and October 2021. All students who were sampled and consented to participate in the study were emailed the web-based designed questionnaire.

Data Analysis
Data generated from the completed online google forms in a Microsoft Excel format were imported into STATA version 14 (StrataCorp, College Station, TX, USA) for analysis. A total score was calculated for knowledge regarding antibiotic use, AMR, and ASPs, and dichotomized as a "good" versus "poor" score. A correct response was assigned a score of one while an incorrect response was assigned a zero score.
A total score ≥ 60% for knowledge on antibiotic use, AMR, and ASP was considered as good based on similar studies [46,60,62]. We are aware other studies have used lower and higher cut-off scores up to 80% for good knowledge [53,94,95]. However, we chose ≥ 60% based on previous published studies [46,60,62]. An overall knowledge score was subsequently determined using the same cut off score. Descriptive statistics were used to summaries variables using percentages for all categorical variables. Inferential statistics, using the Fisher's exact test of independence, and multiple logistic regression using explanatory variables that were statistically significant after the former analysis were subsequently conducted to determine associated variables and predictors of overall knowledge of antibiotics respectively.

Conclusions
There are disparities in the overall level of knowledge of antibiotics, AMR, and ASPs among the different healthcare students at this University in Ghana. Efforts must be made to address these concerns in updated curricula as well as the continual development postqualification. The objective is to ensure an improved and uniform transfer of knowledge on these subjects among the different student populations. This is imperative to sustain the fight against AMR in Ghana in line with the objectives of the NAP. We will be following this up in future studies.
Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/antibiotics11121679/s1, Table S1: Questionnaire.  Furthermore, administrative approvals were sought from the Deans of the SOP, SOM, SONAM and SAHS. Confidentiality and anonymity of the information provided by participants was ensured by substituting codes for participant identifiers and keeping all data collected secured with the principal investigator using password protection.
Informed Consent Statement: Informed consent was obtained from each student who participated in the study by ensuring that a student must consent before being allowed to proceed to respond to the questionnaire. Data Availability Statement: Additional data are available from the corresponding authors on reasonable request.

Conflicts of Interest:
The authors declare no conflict of interest.