Descriptive cross-sectional study to evaluate antibiotic prescriptions in outpatients using prescribing indicators and access, watch, reserve framework of the World Health Organisation in a teaching hospital

INTRODUCTION

Antimicrobial drugs are used to treat bacterial infections in humans and are considered lifesaving drugs; however, excessive and inappropriate use of antimicrobials contributes to the development of drug resistance and ineffective treatment.^[1] The emergence and spread of drug resistance have a significant impact on treatment outcomes. According to a report, the prevalence of multidrug-resistant pathogens is increasing rapidly and has become one of the greatest public health crises worldwide. It has an impact on both developed and underdeveloped countries.^[2] According to a report on ‘antibiotic resistance threats in the United States’, issued by the Centre for Disease Control and Prevention, 2 million infections and 23,000 deaths are recorded each year due to antibiotic resistance in the USA.^[3] The prevalence of infectious diseases, easy availability of antibiotics and poor living conditions are some of the major factors that lead to antimicrobial resistance worldwide.^[4] To improve the quality of use of antimicrobials, mainly antibiotics, the World Health Organisation (WHO) started a global action plan. In 2017, the access, watch, reserve (AWaRe) tool for antibiotic use was developed by the WHO to promote the rational use of antibiotics. This classification mainly includes 257 antibiotics under three categories: access, watch and reserve and also provides a list of not recommended combinations of broad-spectrum antibiotics.^[5] The access group includes antibiotics that have a wide range of activity against some common pathogens and also have lower resistance potential. The watch group includes critically important antibiotics. These antibiotics are used in case of serious infections and have the highest resistance potential. The reserve group includes antibiotics for the treatment of multidrug-resistant organisms. These antibiotics are used in cases of critical priority.^[6] WHO, in its 13^th General Program of Work for 2019–2023, has set a target that 60% of the national level antibiotic consumption should be from the access category. This will help in reducing the usage of watch and reserve category antibiotics.^[7] The WHO has updated the status of countries meeting the target of ≥60% of total antibiotic use from access group antibiotics in September 2024.^[8] These data are collected under the WHO global antimicrobial resistance and use surveillance system (GLASS). These data are available for the countries enrolled under GLASS-antimicrobial use (AMU). India has not enrolled for GLASS-AMU up to 31^st December 2023.^[9]

A survey conducted in 76 countries concluded that the use of watch antibiotics increased by 90.9% as compared to access antibiotics (26.2%) in the period 2000–2015. India was found to be among the countries reporting the highest increase in the rate of watch category antibiotic use over 15 years.^[10] A study exploring global antibiotic usage showed that in India, the consumption of access-category antibiotics was <30%.^[11] A cross-sectional study estimating antibiotic consumption in India in 2019 showed that watch antibiotic usage was 54.9% of defined daily doses (DDDs), and access antibiotics accounted for 27.0% of DDDs. The consumption of antibiotic combinations not recommended by the WHO was 48.8% of the fixed-dose combinations (FDCs) prescribed.^[12] A study conducted in a tertiary care hospital in India showed that the consumption of watch antibiotics was 55.5% and access category antibiotics was 44.4%.^[5] The annual report of the National Antimicrobial Surveillance Network documented the antimicrobial resistance from 1 January to 31 December 2022. The report showed that the percentage of methicillin-resistant Staphylococcus aureus was 59%, vancomycin-resistant Enterococcus spp. were 13% and extended-spectrum beta-lactamase-producing Escherichia coli was 76%. Further, it was reported that 35% of E. coli and 47% of Klebsiella spp. were resistant to at least one of the carbapenems.^[13]

The evidence from previous studies shows that till 2020, the consumption of access antibiotics in India is way low far <60%. A study to evaluate the progress towards achieving this target is required. The current study was planned to evaluate the antibiotic prescription pattern and adherence to the WHO AWaRE framework of antibiotic usage in a teaching hospital in North India.

MATERIALS AND METHODS

RESULTS

A total of 720 prescriptions were screened, of which 500 prescriptions contained antimicrobial drugs. Out of 500 prescriptions, 214 prescriptions were of male patients and 286 prescriptions were of female patients. The mean (±standard deviation) age of the study participants was 39.1 ± 17.6 years. 50% of the participants were from the age group 19–40 years. Department-wise analysis of the prescriptions showed that the maximum number of prescriptions was from the obstetrics and gynaecology department and the least from the oncology department [Table 1].

DISCUSSION

The study results showed a high prescription of antibiotics. Our results were in line with the study conducted at rural community pharmacies in the southern region of India. In the study, authors reported that the highest number of prescriptions contained antibiotic drugs, and most of the prescriptions were incomplete in terms of the dose of prescribed antibiotics and frequency of administration.^[16] The antibiotic use pattern showed that the use of access category antibiotics was way lower than the WHO goal of 60% antibiotic usage to be achieved by 2023. Similar findings were reported by Mugada et al.^[5] In their study, 46.0% of the antibiotics were from the access category, and 53.0% of the antibiotics prescribed were from the watch category. In our study, 29.5% of prescriptions contained not recommended antibiotics. A study exploring antibiotic consumption between 2000 and 2015 reported an increase in the use of watch-category antibiotics in lower-middle-income countries. It was further reported that India and China were the main consumers of watch antibiotics. Out of a total of 15.2 billion DDDs of watch antibiotics consumed globally, India and China consumed 6.6 billion DDDs in the year 2015. According to the report, the consumption of non-recommended antibiotics in India was 7.5% of the total antibiotic consumption.^[10]

The antibiotic co-prescription/FDC prescription rate was high in our study. This observation is in contradiction to the national guidelines, which recommend the use of antimicrobial combinations in specific conditions in critically ill patients.^[17] The combination of a broad-spectrum and narrow-spectrum antibiotic is used in critically ill patients, usually when they require empiric therapy before any culture testing. Once bacteriological examination results are available, drug adjustments are desirable.^[18] In such cases, β-lactam antibiotics can be combined with broad-spectrum fluoroquinolones.^[19] Normally, combinational therapies are preferred in chronic diseases such as human immunodeficiency virus and tuberculosis to prevent antimicrobial resistance.^[20]

Among the antibiotic FDCs, 3 combinations had the potential for serious drug-drug interactions requiring close monitoring of the patient. The combination of azithromycin/ornidazole has the potential to increase the QTc interval, and similarly, the combination of fluconazole/azithromycin has the potential to increase the QTc interval.^[21,22] The combination of ciprofloxacin/tinidazole also shows interaction as ciprofloxacin inhibits the CYP3A4-mediated metabolism of tinidazole.^[23]

According to the WHO prescribing indicators, 100% of the prescribed drugs should be from NLEM. In our study, the prescription of drugs from NLEM was <50%. Studies have shown that non-adherence to NLEM indicates non-compliance with national prescribing guidelines and a lack of knowledge of practitioners regarding the role of NLEM in the management of a patient in a cost-effective manner.^[24] In our study, 147 prescriptions contained 5 or more drugs. Usually, 5 drugs per prescription are considered polypharmacy. Unless the presence of comorbidities, polypharmacy, in turn, indicates the non-clarity of diagnosis and disease symptom control approach of the practitioners. Previous prescription pattern analysis studies conducted in India have reported similar findings.^[25] Polypharmacy is also an indicator of a symptom-targeted treatment approach rather than treating the underlying pathology.^[23] The national guidelines issued by the Central Drug Standard Control Organisation and Ministry of Health and Family Welfare recommend the use of generic drugs over branded formulations, keeping the spirit of the NLEM issued from time to time.^[26] The probable reason for the low prescription rate of injection formulations could be that the majority of the prescriptions included in our study were of OPD patients, and their disease condition did not require injectables; moreover, self-administration of injectables is not feasible. This result was quite similar to the cross-sectional study done at six community pharmacies in Amaha et al.^[27]

There were some limitations to this study. First, our study was conducted in only a single hospital. The results may vary according to different population characteristics in different hospitals and hospital specialities. Second, the prescriptions were collected from the hospital pharmacy, and there are chances that some of the antibiotic prescriptions were missed.

CONCLUSION

The current usage of the access antibiotics in our study stands at 24.3% against the WHO goal of 60% to be achieved by the year 2023. Among the FDCs prescribed, 3 combinations had established drug–drug interactions. Prescriptions contained broad-spectrum antibiotic combinations not recommended by the WHO or DCGI. The average number of drugs prescribed was much higher than the optimal value set by WHO. Training programs to sensitise clinicians about the significance of prescribing drugs from NLEM and generic drugs are required. Stewardship programs to control irrational/inappropriate antibiotic prescribing and prevention of antibacterial resistance are also suggested.