Antibiotic Prescribing Patterns in Adult Patients According to the WHO AWaRe Classification: A Multi-Facility Cross-Sectional Study in Primary Healthcare Hospitals in Lusaka, Zambia

Steward Mudenda^1*, Mary Chomba¹, Billy Chabalenge², Christabel Nang’andu Hikaambo¹, Michelo Banda¹, Victor Daka³, Annie Zulu⁴, Abraham Mukesela⁵, Maxwell Kasonde⁵, Peter Lukonde⁵, Enock Chikatula⁶, Lloyd Matowe⁷, Ronald Kampamba Mutati¹, Tyson Lungwani Muungo¹, Tobela Mudenda⁸, Shafiq Mohamed⁹, Scott Matafwali¹⁰

¹Department of Pharmacy, School of Health Sciences, University of Zambia, Lusaka, Zambia.
²Department of Medicines Control, Zambia Medicines Regulatory Authority, Lusaka, Zambia.
³Department of Public Health, Michael Chilufya Sata School of Medicine, Copperbelt University, Ndola, Zambia.
⁴Bell Pharmacy, Kabulonga Centro Mall, Lusaka, Zambia.
⁵Ministry of Health Headquarters, Ndeke House, Lusaka, Zambia.
⁶Department of Pharmacy, Levy Mwanawasa University Teaching Hospital, Lusaka, Zambia.
⁷Faculty of Pharmacy, School of Pharmacy, Eden University, Lusaka, Zambia.
⁸Department of Pathology, Ndola Teaching Hospital, Ndola, Zambia.
⁹Remedium Pharmaceuticals Limited, Lusaka, Zambia.
¹⁰Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.

DOI: 10.4236/pp.2022.1310029                

Abstract

Introduction: Indiscriminate prescribing and using of antibiotics have led to the development of antimicrobial resistance (AMR). To reduce this problem, the World Health Organization (WHO) developed the “Access”, “Watch”, and “Reserve” (AWaRe) classification of antibiotics that promotes antimicrobial stewardship (AMS). In Zambia, there are gaps in practice regarding prescribing of antibiotics based on the AWaRe protocol. This study assessed antibiotic prescribing patterns in adult in-patients in selected primary healthcare hospitals in Lusaka, Zambia. Materials and Methods: This retrospective cross-sectional study was conducted using 388 patient medical files from September 2021 to November 2021, five primary healthcare hospitals namely; Chawama, Matero, Chilenje, Kanyama, and Chipata. Data analysis was performed using the Statistical Package for Social Sciences version 23. Results: Of the selected medical files, 52.3% (n = 203) were for male patients. Overall, the prevalence of antibiotic use was 82.5% (n = 320) which was higher than the WHO recommendation of a less than 30% threshold. The most prescribed antibiotic was ceftriaxone (20.3%), a Watch group antibiotic, followed by metronidazole (17.8%) and sulfamethoxazole/trimethoprim (16.3%), both belonging to the Access group. Furthermore, of the total antibiotics prescribed, 41.9% were prescribed without adhering to the standard treatment guidelines. Conclusion: This study found a high prescription of antibiotics (82.5%) that can be linked to non-adherence to the standard treatment guidelines in primary healthcare hospitals. The most prescribed antibiotic was ceftriaxone which belongs to the Watch group, raising a lot of concerns. There is a need for rational prescribing of antibiotics and implementation of AMS programs in healthcare facilities in Zambia, and this may promote surveillance of irrational prescribing and help reduce AMR in the future.

Keywords

Antibiotic Prescribing, Antimicrobial Resistance, Antimicrobial Stewardship, AWaRe Classification, Prescribing Patterns, Primary Healthcare, Surveillance, Zambia

1. Introduction

Antibiotics have been critical in managing infectious diseases [1] [2]. However, their inappropriate use has contributed to the development of antimicrobial resistance (AMR) [3] [4] [5]. AMR is a global public health issue that has been exacerbated by an increase in the consumption of antibiotics [3] [4] [6]. Prescribers of medicines may help reduce the problem of AMR by ensuring that they avoid overprescribing antibiotics [7] [8]. Besides, they should adhere to the guidelines when prescribing antibiotics [8] [9] [10]. Additionally, all healthcare workers (HCWs) should collaborate to address AMR and promote antimicrobial stewardship (AMS) programs [11] [12] [13] [14] [15]. This can improve the surveillance and reduction of AMR [16] [17] [18].

The World Health Organization (WHO) developed the “Access”, “Watch”, and “Reserve” (AWaRe) classification of antibiotics to tackle AMR [19] [20] [21] [22]. In the Access group, narrow-spectrum antibiotics are generally used as the first and second choice for most infections, while broad-spectrum antibiotics comprise the Watch group antibiotics [20] [23]. Access group antibiotics must be readily available, affordable, and of good quality in treating infections [23]. The Reserve group contains last resort antibiotics and is usually used to treat multi-drug resistant infections [20] [23]. Therefore, the reserve antibiotics must be left as a treatment of last resort, which may preserve the effectiveness of antibiotics [23]. Literature has shown that prescribers which adhere to the AWaRe protocol have reported a reduction in AMR cases in their healthcare facilities [24] [25]. However, most prescribers do not adhere to the AWaRe protocol, thereby worsening the number of microorganisms developing resistance to antibiotics [26] [27]. Conversely, in Ghana, prescribers adhered to the AWaRe classification protocol, indicating good AMS [28].

The AWaRe protocol of antibiotics is an important tool for AMS [29] [30]. The tool may help prescribers minimise prescribing antibiotics and adhere to the prescription of less than 30% as recommended by the WHO [31] [32]. The AWaRe protocol also guides prescribers to ensure that they prescribe more than 60% of Access group antibiotics compared to the other groups [33]. However, evidence has shown an overprescribing of Watch group antibiotics compared to Access antibiotics [27] [30] [33] [34].

Evidence has shown that antibiotics are overprescribed in healthcare facilities across countries [26] [35] [36] [37]. Approximately 20 to 50% of antibiotics are prescribed inappropriately without adhering to the standard treatment guidelines (STG) [33] [35] [38]. Therefore, educating prescribers about the rational prescribing of antibiotics is crucial to reducing AMR in the future [15] [39] [40] [41]. Alongside, educating healthcare students about AMR is critical as they are the future HCWs [42] [43].

In Zambia, AMR is of public health concern and has been reported in various studies [42] [44] - [53]. However, little is known about the antibiotic prescribing patterns based on the WHO AWaRe classification in primary healthcare hospitals that offer primary healthcare services. Therefore, this study assessed antibiotic prescribing patterns in in-patients according to the WHO AWaRe classification in selected primary healthcare hospitals in Lusaka, Zambia.

2. Materials and Methods

2.1. Study Design, Site and Population

This was a retrospective cross-sectional study that was conducted by reviewing medical records of in-patients in five first-level hospitals, namely Matero, Chawama, Chipata, Chilenje, and Kanyama in Lusaka, Zambia. In Zambia, first-level hospitals offer primary care services and usually act as the first point of contact with the healthcare system. The study was conducted from September 4^th to November 9^th, 2021, and we included all patient medical files from January 2021 to October 2021.

2.2. Sample size Determination and Sampling Technique

The sample size was determined using the Raosoft online sample calculator [54]. With no known previous study done in primary healthcare hospitals in Zambia, a 50% prevalence was used at a 95% confidence level and a margin of error of 5%. This resulted in a sample size of 385 patient medical files. All patient medical files were randomly selected to increase the chance of every file being part of the study.

2.3. Data Collection Tool

A data entry sheet was used to collect data on diseases diagnosed and antibiotics prescribed in primary healthcare hospitals in Lusaka, Zambia. Furthermore, a consent form was given to prescribers who agreed to participate in the study. The data collection tool was adapted from a similar study [55]. Before carrying out this study, a pilot survey was done using 30 patient medical files. Data collection was done by two data collectors who were trained on how to select patient medical files and data entry. The collected information included gender and age of the patient, name of the healthcare facility, antibiotic use, adherence to treatment guidelines, and type of antibiotics prescribed. Adherence to prescribing antibiotics was done based on the Zambia STG [56] and AWaRe classification was used to classify antibiotics into Access, Watch, and Reserve groups [22]. Overall, 388 patient medical files were selected and used in this study.

2.4. Data Analysis

The collected data were entered into Microsoft Excel 2016 for cleaning and coding. Subsequently, the data was exported to the Statistical Package for Social Sciences (SPSS) for Windows Version 23 for analysis. Descriptive statistics were then presented in the form of tables.

3. Results

Of the 388 patient files that were screened, 52.3% were male, 19.3% were 34-41 years old, 82.5% (n = 320) received antibiotics, and 41.9% (n = 134) prescribers did not adhere to the STG as shown in Table 1.

The most prescribed antibiotic was ceftriaxone (20.3%) which belongs to the Watch group of antibiotics. However, the overall proportion showed that antibiotics belonging to the Access group were the most prescribed (55%) in primary healtcare hospitals. A total of 10 Access and 6 Watch antibiotics were prescribed (Table 2).

4. Discussion

This study assessed antibiotic prescribing patterns in five primary healthcare hospitals in Lusaka, Zambia. The study reported a high rate (82.5%) of antibiotic prescribing, and ceftriaxone was the most prescribed for in-patients. Adherence to the national STG was found to be 58.1%, meaning that 41.9% of antibiotics were prescribed without adhering to the national STG.

The prevalence of antibiotic use in the present study was high. Our findings are in line with a study that was conducted in Iraq though a higher prevalence (93.7%) was reported [57], 88.2% in Eswatini [58], slightly lower prevalence (82.3%) in Pakistan [35], 74% in Uganda [59], and 60.6% in Ethiopia [60]. These findings are higher than the reference value of less than 30% recommended by the WHO [31] [32]. This high use of antibiotics in healthcare facilities may be due to various diseases that in-patients suffer from and puts pressure on the prescribers to prescribe these drugs for disease prevention and treatment [61] but may promote the emergence of antibiotic-resistance microbes [62]. The

Table 1. Sociodemographic characteristics.

Table 2. Prescribing patterns of antibiotics according to WHO AWaRe classification.

most prescribed antibiotic in our study was ceftriaxone (20.3%) which belongs to the Watch group. These findings are comparable with reports from other countries [33] [35] [59] [60] [63] [64] [65]. The high prescription rate of ceftriaxone has a high resistance potential and should not be prescribed routinely [65]. The over-prescription and use of ceftriaxone also highlight the need for antibiotic prescription guidelines at these facilities per national and international guidelines to reduce its irrational use. Contrary to our findings, the most prescribed antibiotic was amoxicillin in Eswatini [58], penicillins in China due to increased respiratory tract infections [62], and metronidazole in Ghana due to increased dental and gastrointestinal problems [28].

Our study revealed that most prescribed antibiotics belonged to the Access group. These findings corroborate reports from a point prevalence survey across six hospitals in Tanzania that revealed that most patients received antibiotics from the Access group [66], similar to what was reported in Eswatini [58], Ghana [28], and Uganda [59]. On the contrary, In China, a study revealed that most antibiotics consumed in healthcare facilities belonged to the Watch group [67]. According to a point prevalence survey carried out in 69 countries, the research found that the overall use of Watch group antibiotics was high, and stratification by World Bank classification showed that hospitals in lower-middle- and upper-middle-income countries contributed substantially to the proportion of Watch antibiotics [30]. Worldwide, a large proportion of Reserve group antibiotics were prescribed empirically [30]. In lower-middle-income countries, up to 53.0% of all Reserve prescriptions were empirical, which indicates a lack of diagnostic capacity [30]. This indicated poor prescribing patterns in these facilities and calls for strict implementation of AMS programs.

Interestingly, our study found that 55% of Access, 45% of Watch and no Reserve group antibiotics were prescribed. Unfortunately, this is not in line with the WHO recommendations in which Access group antibiotics must be prescribed more than 60% of all antibiotic prescriptions [33]. In Uganda, similarly, despite the Access group antibiotics reported to be prescribed more than Watch group antibiotics, the proportion was 47.2%, which did not meet the WHO recommendations [59]. In India, a study reported that 42.3% of Access group antibiotics were prescribed with no Reserve antibiotics recorded in their findings [63]. Since these findings did not meet the WHO recommendations of AWaRe prescribing of antibiotics, this may mean non-adherence to the protocols and a contributing factor to AMR in most healthcare facilities. In many health settings, non-adherence to protocols has been attributed to prescriber preferences [59], which may be the case in the current study. This result highlights the need for urgent AMS in these facilities, as prescribing watch antibiotics may scale up AMR and lead to the prescription of Reserve antibiotics. In contrast to our findings, other surveys reported the use of Access group antibiotics as more than 60% as recommended by the WHO [58] [64]. Similar to our study finding regarding Reserve group antibiotics, other studies also found that no Reserve group antibiotics were prescribed in their surveys [58] [63] [68]. This is a positive finding because Reserve group antibiotics must be preserved as the last resort of treatment after other options have failed. To maintain the status quo, AMS programs must be implemented or enhanced.

Of note is that some prescribers in our study did not adhere to the treatment guidelines. This practice is inappropriate and may contribute to the development of AMR. Similar findings were reported in other surveys where the overall compliance with the outlined prescribing guidelines was suboptimal [57] [69] [70]. Lower adherence to treatment guidelines was reported in Uganda [59]. Non-adherence to the standard treatment guidelines of infectious diseases may be due to the absence of these guidelines in healthcare facilities [35] [59], out of stock of key antibiotics [60], prescriber preferences, lack of efficient laboratory services and lack of proper diagnostic stewardship [59]. Additionally, shortages of medicines, increased burden of disease, and lack of healthcare workers put pressure on the prescribers leading to non-adherence to STGs when prescribing [71].

The current study findings may help identify key areas that require interventions through the promotion of AMS programs across healthcare facilities in Zambia. The study also highlights the need for rational prescribing and adherence to the National STG. Additionally, this calls for sensitisation and educational activities on the rational use of antibiotics across healthcare workers. Ministries responsible for health must ensure that all antibiotics listed under the Essential Medicines List (EML) are available to avoid inflicting pressure on prescribers and overuse of Watch group antibiotics.

This study was conducted in one province of Zambia, hence, the findings may not be generalized to the other provinces across the country.

5. Conclusion

Our study found high prescribing of antibiotics without adhering to the National Treatment Guidelines by the prescribers. Ceftriaxone, a Watch group antibiotic, was the most prescribed medicine, and this requires prescriber educational and training activities on the AWaRe protocol and adherence to the treatment guidelines. Therefore, AMS programs should be implemented and enhanced across healthcare facilities in Zambia.

Ethical Approval

This study was approved by the University of Zambia Health Sciences Research Ethics Committee (UNZAHSREC) with protocol ID 202112030048.

Acknowledgements

We are grateful to the management of the primary healthcare facilities that allowed us to collect the data we used in this study.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

References

[1]	Adedeji, W.A. (2016) The Treasure Called Antibiotics. Annals of Ibadan Postgraduate Medicine, 14, 56-57.
[2]	Nigam, A., Gupta, D. and Sharma, A. (2014) Treatment of Infectious Disease: Beyond Antibiotics. Microbiological Research, 169, 643-651. https://doi.org/10.1016/j.micres.2014.02.009
[3]	Ramachandran, P., Rachuri, N., Martha, S., Shakthivel, R., Gundala, A. and Battu, T. (2019) Implications of Overprescription of Antibiotics: A Cross-Sectional Study. Journal of Pharmacy & Bioallied Sciences, 11, 434-437. https://www.jpbsonline.org/article.asp?issn=0975-7406;year=2019;volume=11;issue=6;spage=434;epage=437;aulast=Ramachandran https://doi.org/10.4103/JPBS.JPBS_62_19
[4]	Llor, C. and Bjerrum, L. (2014) Antimicrobial Resistance: Risk Associated with Antibiotic Overuse and Initiatives to Reduce the Problem. Therapeutic Advances in Drug Safety, 5, 229-241. https://journals.sagepub.com/doi/10.1177/2042098614554919 https://doi.org/10.1177/2042098614554919
[5]	Belachew, S.A., Hall, L. and Selvey, L.A. (2022) Community Drug Retail Outlet Staff’s Knowledge, Attitudes and Practices towards Non-Prescription Antibiotics Use and Antibiotic Resistance in the Amhara Region, Ethiopia with a Focus on Non-Urban Towns. Antimicrobial Resistance & Infection Control, 11, Article No. 64. https://aricjournal.biomedcentral.com/articles/10.1186/s13756-022-01102-1 https://doi.org/10.1186/s13756-022-01102-1
[6]	Saliba-Gustafsson, E.A., Nyberg, A., Borg, M.A., Rosales-Klintz, S. and Lundborg, C.S. (2021) Barriers and Facilitators to Prudent Antibiotic Prescribing for Acute Respiratory Tract Infections: A Qualitative Study with General Practitioners in Malta. PLOS ONE, 16, e0246782. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246782 https://doi.org/10.1371/journal.pone.0246782
[7]	Wilkinson, A., Ebata, A. and Macgregor, H. (2019) Interventions to Reduce Antibiotic Prescribing in LMICs: A Scoping Review of Evidence from Human and Animal Health Systems. Antibiotics, 8, Article 2. https://www.mdpi.com/2079-6382/8/1/2/htm https://doi.org/10.3390/antibiotics8010002
[8]	McDonagh, M.S., Peterson, K., Winthrop, K., Cantor, A., Lazur, B.H. and Buckley, D.I. (2018) Interventions to Reduce Inappropriate Prescribing of Antibiotics for Acute Respiratory Tract Infections: Summary and Update of a Systematic Review. Journal of International Medical Research, 46, S3337-S3357. https://doi.org/10.1177/0300060518782519
[9]	Oliveira, I., Rego, C., Semedo, G., Gomes, D., Figueiras, A., Roque, F., et al. (2020) Systematic Review on the Impact of Guidelines Adherence on Antibiotic Prescription in Respiratory Infections. Antibiotics, 9, Article 546. https://doi.org/10.3390/antibiotics9090546
[10]	Tell, D., Engstrom, S. and Molstad, S. (2015) Adherence to Guidelines on Antibiotic Treatment for Respiratory Tract Infections in Various Categories of Physicians: A Retrospective Cross-Sectional Study of Data from Electronic Patient Records. BMJ Open, 5, e008096. https://bmjopen.bmj.com/content/5/7/e008096 https://doi.org/10.1136/bmjopen-2015-008096
[11]	McKenzie, D., Rawlins, M. and Del Mar, C. (2013) Antimicrobial Stewardship: What’s It All about? Australian Prescriber, 36, 116-120. https://www.nps.org.au/australian-prescriber/articles/antimicrobial-stewardship-whats-it-all-about
[12]	Kimbowa, I.M., Eriksen, J., Nakafeero, M., Obua, C., Lundborg, C.S., Kalyango, J., et al. (2022) Antimicrobial Stewardship: Attitudes and Practices of Healthcare Providers in Selected Health Facilities in Uganda. PLOS ONE, 17, e0262993. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262993 https://doi.org/10.1371/journal.pone.0262993
[13]	Doornebosch, A.J., Smaling, H.J.A. and Achterberg, W.P. (2022) Interprofessional Collaboration in Long-Term Care and Rehabilitation: A Systematic Review. Journal of the American Medical Directors Association, 23, 764-777.e2. https://doi.org/10.1016/j.jamda.2021.12.028
[14]	Rogers Van Katwyk, S., Jones, S.L. and Hoffman, S.J. (2018) Mapping Educational Opportunities for Healthcare Workers on Antimicrobial Resistance and Stewardship around the World. Human Resources for Health, 16, Article No. 9. https://human-resources-health.biomedcentral.com/articles/10.1186/s12960-018-0270-3 https://doi.org/10.1186/s12960-018-0270-3
[15]	Godman, B., Egwuenu, A., Haque, M., Malande, O.O., Schellack, N., Kumar, S., et al. (2021) Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries. Life, 11, Article 528. https://pubmed.ncbi.nlm.nih.gov/34200116/ https://doi.org/10.3390/life11060528
[16]	Tacconelli, E., Sifakis, F., Harbarth, S., Schrijver, R., van Mourik, M., Voss, A., et al. (2018) Surveillance for Control of Antimicrobial Resistance. The Lancet Infectious Diseases, 18, e99-e106. https://doi.org/10.1016/S1473-3099(17)30485-1
[17]	Johnson, A.P., Muller-Pebody, B., Budd, E., Ashiru-Oredope, D., Ladenheim, D., Hain, D., et al. (2017) Improving Feedback of Surveillance Data on Antimicrobial Consumption, Resistance and Stewardship in England: Putting the Data at Your Fingertips. Journal of Antimicrobial Chemotherapy, 72, 953-956. https://doi.org/10.1093/jac/dkw536
[18]	Fadare, J.O., Ogunleye, O., Iliyasu, G., Adeoti, A., Schellack, N., Engler, D., et al. (2019) Status of Antimicrobial Stewardship Programmes in Nigerian Tertiary Healthcare Facilities: Findings and Implications. Journal of Global Antimicrobial Resistance, 17, 132-136. https://doi.org/10.1016/j.jgar.2018.11.025
[19]	Budd, E., Cramp, E., Sharland, M., Hand, K., Howard, P., Wilson, P., et al. (2019) Adaptation of the WHO Essential Medicines List for National Antibiotic Stewardship Policy in England: Being AWaRe. Journal of Antimicrobial Chemotherapy, 74, 3384-3389. https://doi.org/10.1093/jac/dkz321
[20]	Hsia, Y., Lee, B.R., Versporten, A., Yang, Y., Bielicki, J., Jackson, C., et al. (2019) Use of the WHO Access, Watch, and Reserve Classification to Define Patterns of Hospital Antibiotic Use (AWaRe): An Analysis of Paediatric Survey Data from 56 Countries. The Lancet Global Health, 7, e861-e871. https://www.global-pps.com
[21]	Sharland, M., Pulcini, C., Harbarth, S., Zeng, M., Gandra, S., Mathur, S., et al. (2018) Classifying Antibiotics in the WHO Essential Medicines List for Optimal Use—Be AWaRe. The Lancet Infectious Diseases, 18, 18-20. https://doi.org/10.1016/S1473-3099(17)30724-7
[22]	World Health Organization (2021) 2021 AWaRe Classification. WHO. https://www.who.int/publications/i/item/2021-aware-classification
[23]	McGettigan, P., Roderick, P., Kadam, A. and Pollock, A.M. (2017) Access, Watch, and Reserve Antibiotics in India: Challenges for WHO Stewardship. The Lancet Global Health, 5, e1075-e1076. https://doi.org/10.1016/S2214-109X(17)30365-0
[24]	Majumder, M.A.A., Rahman, S., Cohall, D., Bharatha, A., Singh, K., Haque, M., et al. (2020) Antimicrobial Stewardship: Fighting Antimicrobial Resistance and Protecting Global Public Health. Infection and Drug Resistance, 13, 4713-4738. https://doi.org/10.2147/IDR.S290835
[25]	Sulis, G., Sayood, S., Katukoori, S., Bollam, N., George, I., Yaeger, L.H., et al. (2022) Exposure to World Health Organization’s AWaRe Antibiotics and Isolation of Multi-Drug Resistant Bacteria: A Systematic Review and Meta-Analysis. Clinical Microbiology and Infection, 28, 1193-1202. https://doi.org/10.1016/j.cmi.2022.03.014
[26]	Amaha, N.D., Weldemariam, D.G., Abdu, N. and Tesfamariam, E.H. (2019) Prescribing Practices Using WHO Prescribing Indicators and Factors Associated with Antibiotic Prescribing in Six Community Pharmacies in Asmara, Eritrea: A Cross-Sectional Study. Antimicrobial Resistance & Infection Control, 8, Article No. 163. https://aricjournal.biomedcentral.com/articles/10.1186/s13756-019-0620-5 https://doi.org/10.1186/s13756-019-0620-5
[27]	Thomas, A.P., Kumar, M., Johnson, R., More, S.P. and Panda, B.K. (2022) Evaluation of Antibiotic Consumption and Compliance to Hospital Antibiotic Policy in the Surgery, Orthopedics and Gynecology Wards of a Tertiary Care Hospital. Clinical Epidemiology and Global Health, 13, Article ID: 100944. https://doi.org/10.1016/j.cegh.2021.100944
[28]	Darkwah, T.O., Afriyie, D.K., Sneddon, J., Cockburn, A., Opare-Addo, M.N.A., Tagoe, B., et al. (2021) Assessment of Prescribing Patterns of Antibiotics Using National Treatment Guidelines and World Health Organization Prescribing Indicators at the Ghana Police Hospital: A Pilot Study. The Pan African Medical Journal, 39, Article 222. https://www.panafrican-med-journal.com/content/article/39/222/full https://doi.org/10.11604/pamj.2021.39.222.29569
[29]	Hillock, N.T., Connor, E., Wilson, C. and Kennedy, B. (2021) Comparative Analysis of Australian Hospital Antimicrobial Utilization, Using the WHO AWaRe Classification System and the Adapted Australian Priority Antimicrobial List (PAL). JAC-Antimicrobial Resistance, 3, dlab017. https://doi.org/10.1093/jacamr/dlab017
[30]	Pauwels, I., Versporten, A., Drapier, N., Vlieghe, E. and Goossens, H. (2021) Hospital Antibiotic Prescribing Patterns in Adult Patients According to the WHO Access, Watch and Reserve Classification (AWaRe): Results from a Worldwide Point Prevalence Survey in 69 Countries. Journal of Antimicrobial Chemotherapy, 76, 1614-1624. https://academic.oup.com/jac/article/76/6/1614/6210595 https://doi.org/10.1093/jac/dkab050
[31]	Ofori-Asenso, R., Brhlikova, P. and Pollock, A.M. (2016) Prescribing Indicators at Primary Health Care Centers within the WHO African Region: A Systematic Analysis (1995-2015). BMC Public Health, 16, Article No. 724. https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-016-3428-8 https://doi.org/10.1186/s12889-016-3428-8
[32]	Ofori-Asenso, R. (2016) A Closer Look at the World Health Organization’s Prescribing Indicators. Journal of Pharmacology and Pharmacotherapeutics, 7, 51-54. http://www.ncbi.nlm.nih.gov/pubmed/27127400 https://doi.org/10.4103/0976-500X.179352
[33]	Mugada, V., Mahato, V., Andhavaram, D. and Vajhala, S.M. (2021) Evaluation of Prescribing Patterns of Antibiotics Using Selected Indicators for Antimicrobial Use in Hospitals and the Access, Watch, Reserve (AWaRe) Classification by the World Health Organization. Turkish Journal of Pharmaceutical Sciences 18, 282-288. https://pubmed.ncbi.nlm.nih.gov/34157817/ https://doi.org/10.4274/tjps.galenos.2020.11456
[34]	Zhussupova, G., Utepova, D., Orazova, G., Zhaldybayeva, S., Skvirskaya, G. and Tossekbayev, K. (2021) Evaluation of Antibiotic Use in Kazakhstan for the Period 2017-2019 Based on Who Access, Watch and Reserve Classification (AWaRe 2019). Antibiotics, 10, Article 58. https://www.mdpi.com/2079-6382/10/1/58/htm https://doi.org/10.3390/antibiotics10010058
[35]	Atif, M., Azeem, M., Saqib, A. and Scahill, S. (2017) Investigation of Antimicrobial Use at a Tertiary Care Hospital in Southern Punjab, Pakistan Using WHO Methodology. Antimicrobial Resistance & Infection Control, 6, Article No. 41. https://aricjournal.biomedcentral.com/articles/10.1186/s13756-017-0199-7 https://doi.org/10.1186/s13756-017-0199-7
[36]	Sulis, G., Daniels, B., Kwan, A., Gandra, S., Daftary, A., Das, J., et al. (2020) Antibiotic Overuse in the Primary Health Care Setting: A Secondary Data Analysis of Standardised Patient Studies from India, China and Kenya. BMJ Global Health, 5, e003393. https://gh.bmj.com/content/5/9/e003393 https://doi.org/10.1136/bmjgh-2020-003393
[37]	O’Doherty, J., Leader, L.F.W., O’Regan, A., Dunne, C., Puthoopparambil, S.J. and O’Connor, R. (2019) Over Prescribing of Antibiotics for Acute Respiratory Tract Infections; A Qualitative Study to Explore Irish General Practitioners’ Perspectives. BMC Family Practice, 20, Article No. 27. https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-019-0917-8 https://doi.org/10.1186/s12875-019-0917-8
[38]	Andrajati, R., Tilaqza, A. and Supardi, S. (2017) Factors Related to Rational Antibiotic Prescriptions in Community Health Centers in Depok City, Indonesia. Journal of Infection and Public Health, 10, 41-48. https://doi.org/10.1016/j.jiph.2016.01.012
[39]	Jiang, T.T., Yang, Y.Q., Cao, N.X., Yin, Y.P. and Chen, X.S. (2020) Novel Education-Based Intervention to Reduce Inappropriate Antibiotic Prescribing for Treatment of Gonorrhoea in China: Protocol for a Cluster Randomised Controlled Trial. BMJ Open, 10, e037549. https://bmjopen.bmj.com/content/10/7/e037549 https://doi.org/10.1136/bmjopen-2020-037549
[40]	Ozcebe, H., üner, S., Karadag, O., Daryani, A., Gershuni, O., Czabanowska, K., et al. (2022) Perspectives of Physicians and Pharmacists on Rational Use of Antibiotics in Turkey and among Turkish Migrants in Germany, Sweden and the Netherlands: A Qualitative Study. BMC Primary Care, 23, Article No. 29. https://bmcprimcare.biomedcentral.com/articles/10.1186/s12875-022-01636-8 https://doi.org/10.1186/s12875-022-01636-8
[41]	de With, K., Allerberger, F., Amann, S., Apfalter, P., Brodt, H.R., Eckmanns, T., et al. (2016) Strategies to Enhance Rational Use of Antibiotics in Hospital: A Guideline by the German Society for Infectious Diseases. Infection, 44, 395-439. https://link.springer.com/article/10.1007/s15010-016-0885-z https://doi.org/10.1007/s15010-016-0885-z
[42]	Mudenda, S., Mukela, M., Matafwali, S., Banda, M., Mutati, R.K., Muungo, L.T., et al. (2022) Knowledge, Attitudes, and Practices towards Antibiotic Use and Antimicrobial Resistance among Pharmacy Students at the University of Zambia: Implications for Antimicrobial Stewardship Programmes. Scholars Academic Journal of Pharmacy, 11, 117-124. https://doi.org/10.36347/sajp.2022.v11i08.002
[43]	Efthymiou, P., Gkentzi, D. and Dimitriou, G. (2020) Knowledge, Attitudes and Perceptions of Medical Students on Antimicrobial Stewardship. Antibiotics, 9, Article 821. https://doi.org/10.3390/antibiotics9110821
[44]	Mudenda, S., Malama, S., Munyeme, M., Hang’ombe, B.M., Mainda, G., Kapona, O., et al. (2022) Awareness of Antimicrobial Resistance and Associated Factors among Layer Poultry Farmers in Zambia: Implications for Surveillance and Antimicrobial Stewardship Programs. Antibiotics, 11, Article 383. https://pubmed.ncbi.nlm.nih.gov/35326846/ https://doi.org/10.3390/antibiotics11030383
[45]	Mudenda, S., Mukosha, M., Godman, B., Fadare, J., Malama, S., Munyeme, M., et al. (2022) Knowledge, Attitudes and Practices of Community Pharmacy Professionals on Poultry Antimicrobial Dispensing, Use and Resistance in Zambia: Implications on Antibiotic Stewardship and WHO AWaRe Classification of Antibiotics. Antibiotics, 11, Article 1210. https://www.mdpi.com/2079-6382/11/9/1210/htm https://doi.org/10.3390/antibiotics11091210
[46]	Mpundu, P., Muma, J.B., Mukubesa, A.N., Kainga, H., Mudenda, S., Bumbangi, F.N., et al. (2022) Antibiotic Resistance Patterns of Listeria Species Isolated from Broiler Abattoirs in Lusaka, Zambia. Antibiotics, 11, Article 591. https://www.mdpi.com/2079-6382/11/5/591/htm https://doi.org/10.3390/antibiotics11050591
[47]	Samutela, M.T., Kalonda, A., Mwansa, J., Lukwesa-Musyani, C., Mwaba, J., Mumbula, E.M., et al. (2017) Molecular Characterisation of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolated at a Large Referral Hospital in Zambia. The Pan African Medical Journal, 26, 108.
[48]	Chishimba, K., Hang’ombe, B.M., Muzandu, K., Mshana, S.E., Matee, M.I., Nakajima, C., et al. (2016) Detection of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Market-Ready Chickens in Zambia. International Journal of Microbiology, 2016, Article ID: 5275724. https://doi.org/10.1155/2016/5275724
[49]	Mainda, G., Bessell, P.B., Muma, J.B., McAteer, S.P., Chase-Topping, M.E., Gib-bons, J., et al. (2015) Prevalence and Patterns of Antimicrobial Resistance among Escherichia coli Isolated from Zambian Dairy Cattle across Different Production Systems. Scientific Reports, 5, Article No. 26589. https://doi.org/10.1038/srep12439
[50]	Chiyangi, H., Muma, B., Malama, S., Manyahi, J., Abade, A., Kwenda, G., et al. (2017) Identification and Antimicrobial Resistance Patterns of Bacterial Enteropathogens from Children Aged 0 - 59 Months at the University Teaching Hospital, Lusaka, Zambia: A Prospective Cross-Sectional Study. BMC Infectious Diseases, 17, Article No. 117. https://doi.org/10.1186/s12879-017-2232-0
[51]	Kalungia, A.C., Burger, J., Godman, B., de Oliveira Costa, J. and Simuwelu, C. (2016) Non-Prescription Sale and Dispensing of Antibiotics in Community Pharmacies in Zambia. Expert Review of Anti-infective Therapy, 14, 1215-1223. https://doi.org/10.1080/14787210.2016.1227702
[52]	Mudenda, S., Hankombo, M., Saleem, Z., Sadiq, M.J., Banda, M., Munkombwe, D., et al. (2021) Knowledge, Attitude, and Practices of Community Pharmacists on Antibiotic Resistance and Antimicrobial Stewardship in Lusaka, Zambia. Journal of Biomedical Research & Environmental Sciences, 2, 1005-1014. https://doi.org/10.37871/jbres1343
[53]	Zulu, A., Matafwali, S.K., Banda, M. and Mudenda, S. (2020) Assessment of Knowledge, Attitude and Practices on Antibiotic Resistance among Undergraduate Medical Students in the School of Medicine at the University of Zambia. International Journal of Basic & Clinical Pharmacology, 9, 263-270. https://doi.org/10.18203/2319-2003.ijbcp20200174
[54]	Raosoft.com (2012) Sample Size Calculator. Raosoft, Inc., Page 1 of 1 Sample Size Calculator. http://www.raosoft.com/samplesize.html
[55]	Kalonga, J., Hangoma, J., Banda, M., Munkombwe, D. and Mudenda, S. (2020) Antibiotic Prescribing Patterns in Paediatric Patients at Levy Mwanawasa University Teaching Hospital in Lusaka, Zambia. International Journal of Pharmacy and Pharmacology, 4, 1-9. https://1library.net/document/yn44611z-antibiotic-prescribing-patterns-paediatric-patients-mwanawasa-university-teaching.html https://doi.org/10.31531/2581-3080.1000138
[56]	Republic of Zambia Ministry of Health (2020) Zambia Standard Treatment Guideline 2020. https://www.moh.gov.zm
[57]	Kurdi, A., Hasan, A.J., Baker, K.I., Seaton, R.A., Ramzi, Z.S., Sneddon, J., et al. (2021) A Multicentre Point Prevalence Survey of Hospital Antibiotic Prescribing and Quality Indices in the Kurdistan Regional Government of Northern Iraq: The Need for Urgent Action. Expert Review of Anti-infective Therapy, 19, 805-814. https://www.tandfonline.com/doi/abs/10.1080/14787210.2021.1834852 https://doi.org/10.1080/14787210.2021.1834852
[58]	Gwebu, P.C., Meyer, J.C., Schellack, N., Matsebula-Myeni, Z.C. and Godman, B. (2022) A Web-Based Point Prevalence Survey of Antimicrobial Use and Quality Indicators at Raleigh Fitkin Memorial Hospital in the Kingdom of Eswatini and the Implications. Hospital Practice, 50, 214-221. https://pubmed.ncbi.nlm.nih.gov/35450508/ https://doi.org/10.1080/21548331.2022.2069247
[59]	Kiggundu, R., Wittenauer, R., Waswa, J.P., Nakambale, H.N., Kitutu, F.E., Murungi, M., et al. (2022) Point Prevalence Survey of Antibiotic Use across 13 Hospitals in Uganda. Antibiotics, 11, Article 199. https://pubmed.ncbi.nlm.nih.gov/35203802/ https://doi.org/10.3390/antibiotics11020199
[60]	Tadesse, T.Y., Molla, M., Yimer, Y.S., Tarekegn, B.S. and Kefale, B. (2022) Evaluation of Antibiotic Prescribing Patterns among Inpatients Using World Health Organization Indicators: A Cross-Sectional Study. SAGE Open Medicine, 10. https://journals.sagepub.com/doi/full/10.1177/20503121221096608 https://doi.org/10.1177/20503121221096608
[61]	Vaughn, V.M., Hersh, A.L. and Spivak, E.S. (2022) Antibiotic Overuse and Stewardship at Hospital Discharge: The Reducing Overuse of Antibiotics at Discharge Home Framework. Clinical Infectious Diseases, 74, 1696-1702. https://academic.oup.com/cid/article/74/9/1696/6374407 https://doi.org/10.1093/cid/ciab842
[62]	Chang, Y., Chusri, S., Sangthong, R., McNeil, E., Hu, J., Du, W., et al. (2018) Clinical Pattern of Antibiotic Overuse and Misuse in Primary Healthcare Hospitals in the Southwest of China. PLOS ONE, 14, e0214779. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214779 https://doi.org/10.1371/journal.pone.0214779
[63]	Peddireddy, M., Mahin, J., Uppu, A. and Padi, S.S.V. (2021) Hospital Antibiotic Prescribing Pattern in General Surgery Specialty: Analysis Based on the WHO Access, Watch and Reserve (AWaRe) Classification. Journal of Pharmaceutical Research International, 33, 7-19. https://doi.org/10.9734/jpri/2021/v33i41B32339
[64]	Valia, D., Ingelbeen, B., Kaboré, B., Karama, I., Peeters, M., Lompo, P., et al. (2022) Use of WATCH Antibiotics Prior to Presentation to the Hospital in Rural Burkina Faso. Antimicrobial Resistance & Infection Control, 11, Article No. 59. https://doi.org/10.1186/s13756-022-01098-8
[65]	Kizito, M., Lalitha, R., Kajumbula, H., Ssenyonga, R., Muyanja, D. and Byakika-Kibwika, P. (2021) Antibiotic Prevalence Study and Factors Influencing Prescription of Who Watch Category Antibiotic Ceftriaxone in a Tertiary Care Private Not for Profit Hospital in Uganda. Antibiotics, 10, Article 1167. https://doi.org/10.3390/antibiotics10101167
[66]	Seni, J., Mapunjo, S.G., Wittenauer, R., Valimba, R., Stergachis, A., Werth, B.J., et al. (2020) Antimicrobial Use across Six Referral Hospitals in Tanzania: A Point Prevalence Survey. BMJ Open, 10, e042819. https://bmjopen.bmj.com/content/10/12/e042819 https://doi.org/10.1136/bmjopen-2020-042819
[67]	Yin, J., Li, H. and Sun, Q. (2021) Analysis of Antibiotic Consumption by AWaRe Classification in Shandong Province, China, 2012-2019: A Panel Data Analysis. Frontiers in Pharmacology, 12, Article ID: 790817. https://doi.org/10.3389/fphar.2021.790817
[68]	Nguyen, N.V., Do, N.T.T., Nguyen, C.T.K., Tran, T.K., Ho, P.D., Nguyen, H.H., et al. (2020) Community-Level Consumption of Antibiotics According to the AWaRe (Access, Watch, Reserve) Classification in Rural Vietnam. JAC-Antimicrobial Resistance, 2, dlaa048. https://academic.oup.com/jacamr/article/2/3/dlaa048/5905230 https://doi.org/10.1093/jacamr/dlaa048
[69]	Al-Maliky, G.R., Al-Ward, M.M., Taqi, A., Balkhair, A. and Al-Zakwani, I. (2018) Evaluation of Antibiotic Prescribing for Adult Inpatients at Sultan Qaboos University Hospital, Sultanate of Oman. European Journal of Hospital Pharmacy, 25, 195-199. https://ejhp.bmj.com/content/25/4/195 https://doi.org/10.1136/ejhpharm-2016-001146
[70]	Sánchez Choez, X., Armijos Acurio, M.L. and Jimbo Sotomayor, R.E. (2018) Appropriateness and Adequacy of Antibiotic Prescription for Upper Respiratory Tract Infections in Ambulatory Health Care Centers in Ecuador. BMC Pharmacology and Toxicology, 19, Article No. 46. https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-018-0237-y https://doi.org/10.1186/s40360-018-0237-y
[71]	Wiedenmayer, K., Ombaka, E., Kabudi, B., Canavan, R., Rajkumar, S., Chilunda, F., et al. (2021) Adherence to Standard Treatment Guidelines among Prescribers in Primary Healthcare Facilities in the Dodoma Region of Tanzania. BMC Health Services Research, 21, Article No. 272. https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-021-06257-y https://doi.org/10.1186/s12913-021-06257-y