The knowledge, attitudes and practices of doctors, pharmacists and nurses on antimicrobials, antimicrobial resistance and antimicrobial stewardship in South Africa

Background Sustained injudicious and indiscriminate use of antimicrobials has exerted selection pressure for developing antimicrobial resistance (AMR), requiring behaviour change from healthcare professionals (HCPs) based on their knowledge, attitudes and practices (KAP) on antimicrobials, AMR and antimicrobial stewardship (AMS). Methods A cross-sectional online questionnaire-based survey was conducted nationally amongst doctors, pharmacists and nurses from November 2017 to January 2018. The questionnaire comprised demographic information and KAP questions. Results Respondents comprised of 1120 doctors, 744 pharmacists and 659 nurses. Antimicrobial resistance was considered a severe problem globally and nationally by majority of HCPs. Self-assessment of knowledge revealed gaps in understanding of antimicrobials, AMR and AMS. Confidence scores in prescribing by doctors, pharmacists and nurses were 57.82%, 32.88% and 45.28%, respectively. Doctors, 441 (45.2%) indicated no confidence in using combination therapy. Prescribing correctly showed a confidence level of 33.99% from 436 doctors, 41.88% from nine pharmacists and 35.23% from 107 nurses. Healthcare professionals (1600 [91.22%]) stated educational campaigns would combat AMR. Only 842 (40.13%) HCPs attended training on these topics and 1712 (81.60%) requesting more education and training. Conclusion This is the first comparative survey on KAP of practising doctors, pharmacists and nurses in South Africa. Doctors had the highest knowledge score followed by nurses and pharmacists. Practice scores did not corroborate knowledge and the higher attitude scores. Gaps in KAP were evident. Healthcare professionals indicated the need for more education and training, thus requiring a review of pre-service and in-service education and training in addition to continued professional development programmes for practising HCPs.


Introduction
The injudicious and irrational use of antimicrobials, vis-à-vis, incorrect clinical indication, dosing and administration, and, non-complaince of patients have been implicated in the development of antimicrobial resistance (AMR). 1 Antimicrobial resistance, an escalating threat globally, is of concern in human and animal health, the food industry and agriculture. 2 It adversely affects treatment, increases morbidity and mortality, results in extended hospital stays and necessitates more expensive, and often more toxic, treatment options. 3 According to best available data, an estimated 700 000 people worldwide die of resistant bacterial infections a year, and it is estimated that this may increase to 10 million people dying a year at a cost of 100 trillion USD by 2050. 4 Change lies in the hands of healthcare professionals (HCPs) responsible for the prescription, dispensing and administration of antimicrobial medicines to patients, namely doctors, pharmacists and nurses, respectively.
The Global Action Plan (GAP) on AMR addresses AMR through five strategic objectives. Of these, strategic objective 1 is increased awareness of AMR through effective communication, education and training. This would be achieved by each member state implementing interventions to: (1) increase national awareness of AMR via programmes that target the different audiences in human health, animal health and the environment, (2) incorporate AMR as a core component in professional education, training and certification, (3) incorporate antimicrobial use and resistance into the school syllabus to improve understanding and further awareness with all information being accurate and relevant, (4) prioritise AMR as an important health issue requiring urgent action from all governmental departments and (5) create a multisectoral committee to address AMR from a One Health perspective. 2 Education for all HCPs on antimicrobial prescribing needs to begin at undergraduate levels, and should continue in post-graduation with specific training in using treatment guidelines. 5 The range of antimicrobial prescribers has been changing, with legislation allowing nurses, pharmacists and emergency care personnel to prescribe antimicrobials under certain conditions in South Africa (SA). 6,7,8 Healthcare professionals are responsible for managing antimicrobials, namely prescribing, dispensing and administering antimicrobials to patients. They must be knowledgeable and up-to-date on issues related to antimicrobials, AMR and antimicrobial stewardship (AMS). This study therefore ascertained the knowledge, attitudes and practices (KAP) of doctors, pharmacists and nurses in order to identify gaps for educational intervention.

Study design and population
A descriptive cross-sectional online survey was conducted nationally. Study sample included 15 111 (40.77%) pharmacists, including community-service pharmacists registered with the South African Pharmacy Council (SAPC). There were also 16 260 (43.87%) doctors and 5695 (15.36%) nurses, comprising of 5630 registered nurses and 65 enrolled nurses, who subscribed to Medpages, an SA database with contact information of HCPs in SA. The SAPC provided contact information of pharmacists and community-service pharmacists to the principal investigator, which was used to email the survey questionnaires. Medpages distributed the survey questionnaire to all doctors and nurses on their database. The study was undertaken from November 2017 to January 2018.

Survey instrument
The data were collected using a self-administered, web-based questionnaire with voluntary informed consent.
Questionnaire (Appendix 1) was adapted and piloted from a combination of questionnaires already available in literature. 9,10,11,12 Responses were anonymous. Questionnaire was divided into four sections and consisted of open-ended, closed-ended (yes or no) and Likert style questions (one of the following options: strongly agree, agree, neutral, disagree, strongly disagree).
The first section collected demographic, academic and professional data of the participants.
Second section consisted of questions that assessed the participants' knowledge on antimicrobials, AMR and stewardship, contributing factors to AMR, sources of information and confidence in prescribing antimicrobials. Third section evaluated the participants' attitudes and beliefs on antimicrobials, AMR and their contribution to AMR. Final section was practice-related and involved antimicrobial sensitivity-testing, empiric-prescribing, use of standard treatment guidelines (STGs), advice imparted to patients and prescribing for diagnosed medical conditions.

Statistical analysis
Dataset was analysed using IBM Statistical Package for the Social Sciences (IBM SPSS) version 25 (IBM Corp. Released 2018. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp) using simple descriptive statistics to create frequencies and percentages. Continuous variables, such as ages, were described as mean ± standard deviation or median and compared using the Student's t-test or Wilcoxon test as appropriate. Categorical variables, such as groups, were described as proportions and compared using Chi-square test or Fisher's exact test as appropriate. The analysis of variance (ANOVA) statistical test was used to compare the KAP scores between the three professions, and the Bonferroni post-hoc test further described the pairwise statistically significant difference between the professions. For each factual question, a mark was allocated when the answer was correct. Other questions were assessed and given a mark for the most appropriate correct response. Responses for 'strongly agree' and 'agree' were combined as well as for 'disagree' and 'strongly disagree'. The study population had declined from Section 1-4 of the questionnaire, thus completed sections were analysed separately. Partially completed questionnaires were also considered, hence the different 'n' values per section. The South African STGs were used to assess doctors and nurses' choices of antimicrobial treatment for given medical conditions and the primary care drug treatment (PCDT) list was used to assess pharmacists' choice of antimicrobial treatment in Section 4 of the questionnaire.

Ethical considerations
Ethical approval was obtained from the Humanities and Social Sciences Research Ethics Committee of University of KwaZulu-Natal (HSS/0868/017M) prior to the study.

Awareness of antimicrobial resistance
The majority of HCPs (93.37%) perceived AMR to be a serious problem globally (Table 1). Using a one-way ANOVA, there were statistically significant differences in the appreciation of the problem of AMR between the different professions ( p = 0.002) with nurses being least aware. Similar numbers of HCPs agreed it was a national problem. However, much lower number of HCPs (73.77%) agreed AMR was a serious problem in their hospital or practice and there was a statistically significant difference between them ( p = 0.011).

Assessment of knowledge on antimicrobials, antimicrobial resistance and antimicrobial stewardship
The self-assessment of knowledge indicated that 791 (37.70%) HCPs were 75% confident of their knowledge on all three topics with 349 (16.6%) HCPs showing 100% confidence ( Figure 1). Notably, a greater percentage of nurses (52.40%; 261) had ≤ 50% confidence levels on knowledge of all three topics as compared to pharmacists (45.3%; 283) and doctors (39.3%; 383). Using the ANOVA test, there were statistically significant differences in confidence levels of knowledge on antimicrobials, AMR and AMS between doctors, pharmacists and nurses ( p = 0.0001, 0.00001 and 0.009, respectively). A Bonferroni post-hoc test indicated that doctors were different from nurses and pharmacists were different from nurses, however doctors and pharmacists were not statistically different.
Varying numbers of HCPs correctly stated antimicrobials were not effective in treating acute viral infections ( p = 0.000), and a majority of HCPs correctly stated common colds are caused by viruses (Table 1).

Contributory factors towards antimicrobial resistance
Healthcare professionals identified the overuse of antimicrobials by prescriptions (1922; 91.61%), patient pressure for antimicrobial prescriptions (1579; 75.26%) and non-adherence of patients to prescribed treatment (1537; 73.26%) as most contributory towards AMR, as depicted in Figure 2. The least contributory was the lack of immunisation campaigns (262; 12.49%). Statistically significant differences ( p < 0.05) were noted between the three groups of HCPs in seven of the nine contributing factors.

Confidence in prescribing antimicrobials
Self-assessment on confidence in 10 aspects of prescribing antimicrobials showed 587 (60.21%) doctors were confident in 7 (70%) aspects. No confidence was reported by 433 (44.40%) doctors about using combination therapy when necessary, about when to stop or streamline therapy according to clinical evaluations and investigations and about making decision not to prescribe antimicrobials when there's fever with no serious criteria (

Strategies to combat antimicrobial resistance
The most important strategies the HCPs believed would aid in combatting AMR were educational campaigns (1600; 91.22%), use of therapeutic guidelines (1486; 84.72%) and improved infection control (1163; 66.31%). Vaccination campaigns (543; 30.96%) were surprisingly reported to be least important. Statistically significant differences (p < 0.05) were observed for two strategies (Figure 3). Advice imparted to patients on antimicrobial use is reported in Figure 4. On the safe use of antimicrobials, 309 (83.29%) nurses gave the most correct advice, followed by 404 (81.29%) pharmacists and 630 (74.82%) doctors (p < 0.00).
Based on a range of practice scores, between 0 (poor) and 100 (best practice), average scores for doctors, pharmacists and nurses were 57.68% ± 16.42%, 43.14% ± 16.53% and 54% ± 14.34%, respectively. Using an ANOVA test, practice scores for the three groups of HCPs were statistically significantly different (p < 0.05).

Selection of appropriate antimicrobial treatment
There was a higher percentage of appropriate treatment (41.88%) provided by nine pharmacists compared to 33.99% from 436 doctors and 35.23% from 107 nurses. However, there were fewer pharmacists who were eligible to provide treatment for the given conditions. It must be noted only 1.87% of nurses provided the correct strength, interval and duration for treatment.

Discussion
To our knowledge, this is the largest national study ascertaining KAP on antimicrobials, AMR and AMS amongst prescribers, dispensers and administrators of antimicrobial medicines to patients. This is the first KAP study amongst doctors, pharmacists and nurses in SA using the same tool and it provides valuable insights and information on strengths and weaknesses of KAP amongst HCPs and indicates areas where interventions are required.
Antimicrobial resistance is an increasingly serious public health threat. 13 Awareness of AMR is the first step in addressing and reducing this global problem. 2 We found that majority of HCPs in SA have been sensitised to AMR as a national and global concern, with doctors having most awareness followed by pharmacists and then nurses who had the least conceptual awareness. However, as a group, HCPs' awareness of AMR was comparable to a study by Burger et al. (2016)   Based on their self-assessment, only 16.6% of HCPs were 100% confident in their knowledge of antimicrobials, AMR and AMS. The percentage of HCPs that had 75% confidence in their knowledge of antimicrobials and AMR, respectively, was 43% and 37%. This is in contrast to the report by Dall (2019) whereby 80% of HCPs from 30 European countries stated they possessed sufficient knowledge on correct antimicrobial use and 96% stated having knowledge of AMR. 20 Several aspects must be comprehensively considered when prescribing antimicrobials and complete confidence in each aspect is essential in achieving positive patient outcomes. In this study, diminished levels of confidence in the 10 aspects of prescribing antimicrobials were observed, with 587 (60.21%) doctors confident in only seven aspects. A third of pharmacists stated confidence in all aspects whilst almost a quarter of the nurses were not confident in prescribing. Wasserman et al. (2017) reported that only a third of the students were confident in prescribing. 17 Our results are also similar to findings by Pulcini et al. (2010), where it was found junior doctors in France and Scotland shared similar overall confidence (57.61%) in prescribing antimicrobials to that of our doctors (57.82%). 9 Forty per cent of HCPs had attended or received training on antimicrobials and AMS with majority (81.61%) indicating a need for more education and training. According to our research, the most appropriate resources for antimicrobial selections were STGs, SAMF and international guidelines, respectively. This is in contrast to Wasserman et al. (2017) who reported that medical textbooks (87%), registrars (85%) and consultants (83%) were most common learning resources. 17  Attitude scores amongst all professions were slightly higher than knowledge scores and practice scores were the lowest. The doctors and pharmacists indicated higher attitude scores than nurses. Doctors obtained the highest knowledge scores. Practice scores did not corroborate the self-proclaimed knowledge and attitude scores.

Limitations
Gatekeeper permission to contact the HCPs proved problematic.

Conclusion
This is the first comparative survey on KAP of practising doctors, pharmacists and nurses in SA. Doctors had the highest knowledge score followed by nurses and pharmacists, respectively. Practice scores did not corroborate knowledge and the higher attitude scores.
Self-assessment of knowledge showed that marginally more than half (< 55%) of HCPs were ≥ 75% confident in their knowledge on these topics. Confidence on prescribing antimicrobials showed that < 60% of doctors were confident in prescribing antimicrobials, with the confidence level even further reduced for pharmacists and nurses. Confidence in prescribing the correct treatment for given conditions ranged between 34% and 42% for the HCPs. Gaps in KAP were thus evident. Healthcare professionals indicated the need for more education and training, thus requiring a review of pre-service and in-service education and training in addition to CPD programmes for practising HCPs. It is recommended that both higher education institutions offering medical, pharmacy and nursing degrees as well as professional bodies regulating this education should map and update their existing curricula and scopes of practice, respectively, against the World Health Organization's competency framework and associated curriculum for healthcare workers' education and training on AMR. 22 Which of the following sources do you refer to for information on appropriate usage of antimicrobials? Please select your appropriate choice and rate on a scale of 1 to 5 (1 = lowest preference and 5 = highest preference):   The patient should never share antimicrobial treatment with anyone.
° The patient must not stop treatment even if they are feeling better after a few doses.° The patient must save the remaining antimicrobials for the next time they are unwell.° The patient must dispose of remaining antimicrobials appropriately.