Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred. METHODS AND FINDINGS: We performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches. CONCLUSIONS: A significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Adopting an intersectoral One Health approach in India: Time for One Health Committees.

Following the several episodes of zoonotic disease outbreaks and the more recent COVID-19 pandemic, the Indian policy initiatives are committed to institutionalize One Health (OH) approaches and promote intersectoral, transdisciplinary collaboration and cooperation. The OH principle needs to be visualized beyond the scope of zoonoses. While conservation, ecological and veterinary professions are getting increasingly engaged with OH, most of the medical/clinical and social sciences professions are only peripherally aware of its nuances. The OH initiatives, by their essentially multidisciplinary nature, entail working across ministries and navigating tacit institutional hierarchies and allocating leadership roles. The logical operational step will be the constitution of One Health Committees (OHC) at the State and district levels. Here, we outline the key foundational principles of OHC and hope that the framework for implementation shall be deliberated through wider consultations and piloted and adopted in a phased manner.

Potential pharmacological agents for COVID-19.

A novel coronavirus disease 2019 (COVID-19) infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) first emerged in December 2019 in Wuhan, China, has become a global pandemic. Currently, the management of COVID-19 infection is mainly supportive. Several clinical trials worldwide are evaluating several drugs approved for other indications, as well as multiple investigational agents for the treatment and prevention of COVID-19. Here, we give a brief overview of pharmacological agents and other therapies which are under investigation as treatment options or adjunctive agents for patients infected with COVID-19 and for chemoprophylaxis for the prevention of COVID-19 infection. At the time of writing this commentary, there is no peer-reviewed published evidence from randomized clinical trials of any pharmacological agents improving outcomes in COVID-19 patients. However, it was reported that remdesivir an investigational antiviral agent hastens clinical recovery, but a study is yet to be published in peer-reviewed medical journal.

Promoting quality use of medicines in South-East Asia: reports from country situational analyses.

BACKGROUND: Irrational use of medicines is widespread in the South-East Asia Region (SEAR), where policy implementation to encourage quality use of medicines (QUM) is often low. The aim was to determine whether public-sector QUM is better in SEAR countries implementing essential medicines (EM) policies than in those not implementing them. METHODS: Data on six QUM indicators and 25 EM policies were extracted from situational analysis reports of 20 country (2-week) visits made during 2010-2015. The average difference (as percent) for the QUM indicators between countries implementing versus not implementing specific policies was calculated. Policies associated with better (> 1%) QUM were included in regression of a composite QUM score versus total number of policies implemented. RESULTS: Twenty-two policies were associated with better (> 1%) QUM. Twelve policies were associated with 3.6-9.5% significantly better use (p < 0.05), namely: standard treatment guidelines; formulary; a government unit to promote QUM; continuing health worker education on prescribing by government; limiting over-the-counter (OTC) availability of systemic antibiotics; disallowing public-sector prescriber revenue from medicines sales; not charging fees at the point of care; monitoring advertisements of OTC medicines; public education on QUM; and a good drug supply system. There was significant correlation between the number of policies implemented out of 22 and the composite QUM score (r = 0.71, r2 = 0.50, p < 0.05). CONCLUSIONS: Country situational analyses allowed rapid data collection that showed EM policies are associated with better QUM. SEAR countries should implement all such policies.

Role of endocannabinoids in the progression of diabetic retinopathy.

In the past decades, the role of numerous factors in the pathophysiology of diabetic retinopathy has been explored, following which marked progress has been made in developing several novel therapeutic options, such as anti-vascular endothelial growth factor, anti-tumor necrosis factor-alpha and various other anti-inflammatory and anti-angiogenic agents, for the treatment of diabetic retinopathy. However, the involvement of endocannabinoid system in its pathogenesis has not been much explored. This review aims at unveiling every aspect of association of the endocannabinoid system and its interactions with various physiological and pathological pathways to induce disease progression. The various alterations induced by endocannabinoids, such as anandamide and 2-arachidonylglycerol, in retina during hyperglycaemia clearly demonstrate and verify their involvement in aggravating the pathological conditions, hence leading to the progression of diabetic retinopathy. Exploring this involvement furthermore, in greater depths, might be beneficial in acknowledging and understanding the hidden aspects of the pathogenesis of this complication even better and might provide a therapeutically beneficial alternative target to combat and restrict its progression amongst diabetic patients.

Role of leukotrienes in diabetic retinopathy.

The pathophysiology of diabetic retinopathy is highly complex and encompasses the detrimental roles of numerous factors/mediators in inducing various molecular pathological alterations. Although the roles of many inflammatory mediators, involved in the progression of this complication, have been thoroughly researched and studied, the part played by leukotrienes remains widely neglected. This review focuses on leukotrienes-induced mediation and aggravation of the pathological pathways, such as inflammation, oxidative stress and retinal angiogenesis, responsible for exhibition of various characteristic events including leukostasis, macular edema, retinal neovascularization and vitreous hemorrhages, hence, marking the advent of diabetic retinopathy. Acknowledging these roles, it might be possible to potentially utilize leukotrienes antagonists for suppressing or reducing the intensity of the mentioned pathological alterations. Hence, leukotrienes antagonists may act as an effective adjuvant therapy either along with other developing novel therapies (such as anti-VEGF or anti-TNF-α therapy), or with the established conventional laser photocoagulation treatment, to provide additional symptomatic relief or, possibly prevent the progression of diabetic retinopathy.

Exploring the various aspects of the pathological role of vascular endothelial growth factor (VEGF) in diabetic retinopathy.

Diabetic retinopathy, a sight-threatening microvascular complication of diabetes mellitus, is initiated by retinal endothelial dysfunction and succeeded by various pathological events, eventually resulting in vision-loss. These events are regulated by numerous mediators, including vascular endothelial growth factor (VEGF), which induces the progression of various events characterizing diabetic retinopathy, such as neovascularization and macular edema. VEGF is physiologically required for regulating proliferation and assembling of endothelial cells, during vasculogenesis, as well as for their maintenance and survival throughout the lifetime of blood vessels. However, various pathological conditions are induced in the body during diabetes (such as ischemia, oxidative stress and overactivation of protein kinase C), which upregulate the expression of VEGF, thereby deviating it from its physiological role and leading to various pathological demonstrations such as angiogenesis, increased permeability of endothelium, decreased inhibition of pro-apoptotic proteins and activation of various other inflammatory mediators. Such events disrupt vascular homeostasis and play key roles in the pathophysiology of diabetic retinopathy. Hence, acknowledging various VEGF-mediated pathways helps in understanding the deeper aspects related to progression of this disorder. Targeting and inhibiting VEGF-mediated disease progression might provide an effective alternative therapy and hence prove beneficial in the treatment of diabetic retinopathy.

Antibiotic prescribing practice for acute, uncomplicated respiratory tract infections in primary care settings in New Delhi, India.

OBJECTIVE: To obtain information on prescribing rates and choice of antibiotics for acute, uncomplicated respiratory tract infections (RTIs) in the community. METHODS: Antibiotic use in acute, uncomplicated RTIs consisting of common cold/sore throat/cough for not more than five days was surveyed in the community (December 2007-November 2008) using patient exit interviews at public and private facilities from four localities in New Delhi. Data were collected from 10 public sector facilities and 20 private clinics over one year. The percentage of acute, uncomplicated RTIs patients receiving antibiotics in general and using the Anatomical Therapeutic Chemical classification and the Defined Daily Dose (ATS/DDD) were analysed. RESULTS: At public and private facilities, 45% (746/1646) and 57% (259/457) of acute, uncomplicated RTI patients were prescribed at least one antibiotic, respectively. The main antibiotic class calculated as percentage of total antibiotics DDDs/1000 prescribed to acute, uncomplicated RTI patients at private clinics was cephalosporins, J01DA (39%), followed by fluoroquinolones, J01MA (24%), penicillins, J01C (19%) and macrolides, J01FA (15%). Newer members from each class were prescribed; older antibiotics such as co-trimoxazole or tetracyclines were rarely prescribed. At public facilities, the main class of antibiotic prescribed was penicillins (31%), followed by macrolides (25%), fluoroquinolones (20%) and cephalosporins (10%). CONCLUSIONS: Study clearly shows overuse and inappropriate choice of antibiotics for the treatment of acute, uncomplicated RTIs which are mainly due to virus and do not require antibiotic treatment. Results of the study warrant interventional strategies to promote rational use of antibiotics to decrease the overgrowing threat of antibiotic resistance.

Where are we now: assessing the price, availability and affordability of essential medicines in Delhi as India plans free medicine for all.

BACKGROUND: Inequitable access to medicines is a major weakness in the Indian health care system. Baseline data needed to develop effective public health policy and provide equitable access to essential medicines. The present survey was conducted to investigate the price, availability, and affordability of fifty essential medicines in the public and private sector in Delhi, India using standardized WHO/HAI methodology. METHODS: Data on procurement price and availability was collected (July-October 2011) from three public healthcare providers: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Data on price and availability of medicines was collected from private retail and chain pharmacies of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). RESULTS: The procurement price of surveyed medicines was 0.53-0.82 times the international reference price-IRP. However, the overall mean availability of surveyed medicines in facilities under state government and MCD was 41.3% and 23.2%, respectively. The overall mean availability of medicines in three tertiary care facilities operated by the federal government was 49.3%. Availability of generic medicines was much higher in the private sector. Off-patented medicines, like diazepam, diclofenac, and doxycycline had the highest MPRs. The price ratio between procurement and retail was as high as 28 (range 11-28) for certain medicines. Seven-day treatment with a popular brand of amoxicillin+clavulanic acid or one inhaler each of budesonide and salbutamol cost 2.3 and 1.4 days' wages for the lowest paid government worker. A majority of India's population cannot afford these prices. CONCLUSIONS: This study revealed that procurement prices of surveyed medicines were reasonable in comparison to IRP. However, variation in procurement prices of certain medicines by different public procurement agencies was noted. Availability of medicines was very poor in public sector facilities, which are the primary source of free medicines for a majority of India's low-income population. Availability of medicines is better in private retail pharmacies but affordability remains a big challenge for a majority of the population. These data have significant policy implications that could help in amending policies to increase the access to essential medicines for India's population.

Strengthening antimicrobial stewardship activities in secondary and primary public healthcare facilities in India: Insights from a qualitative study with stakeholders.

PURPOSE: Examining the existing federal and state policies in place that could strengthen antimicrobial stewardship (AMS) activities in district and sub-district hospitals in India. METHODS: In-depth interviews were conducted with national and state level policy makers and various stakeholders at a district hospital. For national level, officials from the National Health Systems Resource Centre (NHSRC) were approached. The state of Haryana was selected and officials from Haryana State Health Systems Resource Centre (HSHRC), a state-level counterpart of the NHSRC, along with officials from the Health Department and relevant stakeholders from one of the district hospitals of the Haryana state were selected as participants. The recorded interviews were transcribed verbatim and thematic analysis was done. RESULTS: Several measurable elements within the existing policies such as National Quality Assurance Program (NQAP) and Kayakalp program, could be leveraged to strengthen AMS activities in district and sub-district hospitals, were identified. These cover aspects such as infection control, standard treatment guidelines (STGs), prescription auditing, essential medicine list (EML), availability of antimicrobials and incentives for meeting quality standards. Revising the EML based on WHO AWaRe classification, incorporating the STGs for common clinical infections from the WHO AWaRe antibiotic book and Indian Council of Medical Research (ICMR), program mandated requirements for dedicated staff/standards for AMS activities and antimicrobial-specific prescription audits as per WHO AMS tool-kit and ICMR AMS guidelines are identified as opportunities for strengthening AMS activities. Further, hindrances in executing existing policies were also identified such as shortage of human resources, reluctance to follow STGs, and limited availability of diagnostic microbiology laboratory services. CONCLUSION: Implementing NQAS and Kayakalp program in public healthcare facilities are identified as existing well working key programs that aid in improving AMS activities with incorporation of WHO and ICMR recommended practices.

Treatment and disposal practices of pharmaceutical effluent containing potential antibiotic residues in two states in India and perceptions of various stakeholders on contribution of pharmaceutical effluent to antimicrobial resistance: a qualitative study.

BACKGROUND: Antimicrobial resistance (AMR) is a looming pandemic, demanding prompt actions to avert catastrophic consequences. Effluents from pharmaceutical industries containing antimicrobial residues could serve as one of the entry points of these drugs to the environment. This qualitative study explores the treatment and disposal practices of pharmaceutical effluent (PE) containing potential antibiotic residues (ARs) by interviewing major stakeholders. In addition, we assessed their knowledge and perception on contribution of PE to AMR. METHODS: The study was conducted in the two Indian states, Haryana and Telangana and at the federal level. Data was collected by semi-structured in-depth interviews of 29 participants from 17 stakeholders/organizations viz. Central Pollution Control Board (CPCB), State Pollution Control Boards (SPCBs) of Telangana and Haryana, civic body, pharmaceutical manufacturers, pharmaceutical associations and civil society. Data was analyzed using thematic analysis. RESULTS: The effluent treatment and disposal practices varied with the multinational companies (MNCs) having advanced technologies whereas the small and medium-scale pharmaceutical companies (SMPCs) having effluent treatment plants as per the regulations but often under-utilized. The presence of ARs in the PE was considered inconsequential by SPCBs and SMPCs and majority of stakeholders imputed other causes as major contributors to AMR. However, the MNCs were well aware of the contribution of PE to AMR and CPCB also considered ARs as direct source of AMR. The central regulators as well as MNCs expressed concerns regarding the current regulations lacking maximum ARs in the PE. CONCLUSION: Setting up regulatory standards for maximum ARs in PE, their implementation and monitoring is an urgent need to curb environmental contribution of ARs to AMR. The findings of our study will help in systematic approach in policy making, awareness programs and capacity-building in dealing with the ARs in PE to combat AMR.

Antibiotic-prescribing practices of primary care prescribers for acute diarrhea in New Delhi, India.

OBJECTIVE: To obtain information on the current prescribing rates of antibiotics in acute diarrhea in the community. METHODS: Antibiotic use in acute diarrhea in the community (December 2007-November 2008) was surveyed by using patients' exit interviews at public and private facilities from four residential localities. Data were collected from 10 public sector facilities and 20 private clinics over 1 year. The percentage of patients receiving antibiotics and the prescribing pattern of antibiotics were analyzed by using the anatomical therapeutic chemical classification and the defined daily dose. RESULTS: At public facilities 43% (171 of 398) and at private facilities 69% (76 of 110) of the patients with acute diarrhea were prescribed at least one antibiotic. Diarrhea increased during peak humid summer months, but doctors were fairly consistent in their antibiotic prescribing throughout the year. The main antibiotic class that was prescribed in both public and private sector facilities was fluoroquinolones, J01MA (91.5% and 96%, respectively). Pediatricians working in the private sector prescribed antibiotics to 51.5% (17 of 33) of children with diarrhea, whereas pediatricians working in the public sector prescribed antibiotics to 23% of children with acute diarrhea. At public facilities, the most commonly prescribed fluoroquinolone was norfloxacin, followed by ofloxacin and ciprofloxacin. At private clinics, it was ofloxacin followed by ciprofloxacin. CONCLUSIONS: This study clearly showed the irrational use of antibiotics for the treatment of acute diarrhea in children and adults that warrants interventional strategies.

Quality of asthma management in an urban community in Delhi, India.

BACKGROUND & OBJECTIVES: High prevalence and poor control of asthma make its management a major public health issue worldwide, especially in developing countries. Optimum review of asthma management in the community is essential to improve asthma control. This study was conducted to investigate the quality of asthma management, knowledge about asthma and quality of life of asthma patients referred to a public tertiary care chest hospital in Delhi. METHODS: Diagnosis of asthma was confirmed by symptoms and reversible spirometry in 50 referred patients on their first visit. Patients were interviewed using three questionnaires on quality of asthma management before visiting referral hospital, asthma knowledge and asthma quality of life (AQLQ). Correlation amongst quality of treatment, asthma quality of life, and asthma knowledge was also determined. RESULTS: Findings revealed that only 60 per cent of patients were informed about their disease, and 10 per cent had undergone lung function tests previously. Only 44 per cent of patients were prescribed inhalers. None were provided with any educational material. Patients had poor knowledge of aetiology, pathophysiology, medication and how to assess the severity of their asthma. The mean scores in AQLQ indicated a moderate degree of impairment in quality of life. INTERPRETATIONS & CONCLUSIONS: This study provides evidence of unsatisfactory asthma management and patient-doctor interaction as patients had limited knowledge of asthma disease, its management and had poor quality of life as measured by a standardized questionnaire. Thus, there is need to implement suitable interventions to improve asthma management according to standard treatment guidelines in the community.

Marketing and Distribution System Foster Misuse of Antibiotics in the Community: Insights from Drugs Wholesalers in India.

Antibiotic misuse is one of the major drivers of antimicrobial resistance (AMR). In India, evidence of antibiotic misuse comes largely from retailers as well as formal and informal healthcare providers (IHCPs). This paper presents the practices and perspectives of drug wholesalers, a critical link between manufacturers and last-mile dispensers. Four experienced wholesalers and an ex-State Drug Controller (ex-SDC) were interviewed in depth, using semi-structured guides in the National Capital Region of Delhi, India, between November 2020 and January 2021. Four main findings were that wholesalers (i) have limited knowledge about wholesale licensing and practice regulations, as well as a limited understanding of AMR; (ii) directly supply and sell antibiotics to IHCPs; (iii) facilitate medical representatives (MRs) of pharmaceutical companies and manufacturers in their strategies to promote antibiotics use in the community; and (iv) blame other stakeholders for unlawful sale and overuse of antibiotics. Some of the potential solutions aimed at wholesalers include having a minimum education qualification for licensing and mandatory Good Distribution Practices certification programs. Decoupling incentives by pharmaceutical companies from sales targets to improve ethical sales practices for MRs and optimize antibiotic use by IHCPs could alleviate wholesalers' indirect actions in promoting antibiotic misuse.

India's ban on antimicrobial fixed-dose combinations: winning the battle, losing the war?

BACKGROUND AND OBJECTIVES: India, the country with the largest market availability of antimicrobial fixed-dose combinations (FDCs), banned certain antimicrobial FDCs in September 2018. Our objective was to examine the impact of Government ban on the sales of antimicrobial FDCs. METHODS: The sales patterns of 14 of the 26 banned antimicrobial FDCs were analyzed using monthly private sector drug sales data from IQVIA (a comprehensive and nationally representative drug sales database) between January 2018 and December 2019. We carried out descriptive analyses to evaluate the trend in sales over time for banned and non-banned antimicrobial FDCs using cumulative sales volumes. RESULTS: Overall, the cumulative sales volume of banned antimicrobial FDCs declined by 75% between January and September 2018 and the same months of 2019, although some banned FDCs continued to be available in significant volumes. The effectiveness of the ban was offset by several pathways. First, the sales of combinations containing moieties belonging to the same drug-classes as the antimicrobials in the banned FDCs increased after the ban. Second, while certain formulations of particular combinations were banned, the sales of other non-banned formulation of these combinations increased. Third, in some cases, products containing new non-antimicrobial components added to the banned combinations remained available. INTERPRETATION AND CONCLUSIONS: While sales of the banned antimicrobial FDCs decreased in 2019, we identified several mechanisms that counterbalanced the ban, including implementation failure, rising sales of congeners, and products with additional non-antimicrobial components.

Trends in antibiotic use among outpatients in New Delhi, India.

BACKGROUND: The overall volume of antibiotic consumption in the community is one of the foremost causes of antimicrobial resistance. There is much ad-hoc information about the inappropriate consumption of antibiotics, over-the-counter availability, and inadequate dosage but there is very little actual evidence of community practices. METHODS: This study surveyed antibiotic use in the community (December 2007-November 2008) using the established methodology of patient exit interviews at three types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private clinics to obtain a complete picture of community antibiotic use over a year. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) measurement units were assigned to the data. Antibiotic use was measured as DDD/1000 patients visiting the facility and also as percent of patients receiving an antibiotic. RESULTS: During the data collection period, 17995, 9205, and 5922 patients visiting private retail pharmacies, public facilities and private clinics, respectively, were included in our study. 39% of the patients attending private retail pharmacies and public facilities and 43% of patients visiting private clinics were prescribed at least one antibiotic. Consumption patterns of antibiotics were similar at private retail pharmacies and private clinics where fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three most commonly prescribed groups of antibiotics. At public facilities, there was a more even use of all the major antibiotic groups including penicillins, fluoroquinolones, macrolides, cephalosporins, tetracyclines, and cotrimoxazole. Newer members from each class of antibiotics were prescribed. Not much seasonal variation was seen although slightly higher consumption of some antibiotics in winter and slightly higher consumption of fluoroquinolones during the rainy season were observed. CONCLUSIONS: A very high consumption of antibiotics was observed in both public and private sector outpatients. There was a high use of broad spectrum and newer antibiotics in the community. Suitable and sustainable interventions should be implemented to promote rational use of antibiotics that will help in decreasing the menace of antibiotic resistance.

Rationalizing antibiotic use to limit antibiotic resistance in India.

Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics.

Over-the-counter sale of antibiotics - Using Net-Map to identify and segment stakeholders as the first step towards the development of smart regulation.

INTRODUCTION: Antimicrobial resistance (AMR) is a complex public health problem requiring coordinated efforts by a multitude of public and private sector stakeholders. Over-the-counter (OTC) antibiotics sale is contributing to rising AMR. We applied NetMap, a research tool to identify, prioritize and assess relationships among stakeholders, also to identify the stakeholders that must be engaged for regulating antibiotic OTC sale for humans in India. METHODS: Through a one-day workshop, a team of expert facilitators engaged with a mixed group of stakeholders-regulators, drug manufacturers, retailers and consumers of antibiotics to identify and rank stakeholders based on their role, power/interest and influence. Stakeholders were listed and grouped as per the type of agency represented. Carrom discs were stacked against each stakeholder with the height of stack reflecting perceived power. RESULTS: A total of 25 stakeholders were identified from government, non-government, private/corporate, academic and research agencies and the general public. Based on the stacking exercise, a power/interest matrix was developed with six stakeholders having high power and high interest, five having high power but low interest, six having low power but high interest and eight having low power. A visual NetMap was developed to position the stakeholders as proximal, middle and distal based on their perceived influence. CONCLUSIONS: NetMap can be used with stakeholders with varying skill sets. It is a useful project initiation tool that was successfully used to prioritize stakeholders for reaching out, for targeted outreach and development of customized tools for developing innovative regulation for tackling OTC sale of antibiotics. It also pre-empted any conflict of interests.

Pharmaceutical effluent: a critical link in the interconnected ecosystem promoting antimicrobial resistance.

Antimicrobial resistance (AMR) is a complex global health issue and will push twenty-four million people into extreme poverty by 2030, risking the sustainable development goals (SDGs) 2, 3, 6, 9, 12, and 17 if not addressed immediately. Humans, animals, and the environment are the reservoirs that contribute and allow AMR to propagate in interconnected ecosystems. The emergence of antibiotic-resistant bacteria and antibiotic-resistant genes in the water environment has become an important environmental health issue. One of the major influencers from environment sector is the pharmaceutical industry which is growing globally to meet the ever-increasing demand of antibiotics, especially in low- and middle-income countries. The pharmaceutical effluent has a mix of large concentrations of antibiotics and antibiotic resistance genes, and these sites act as hotspots for environmental contamination and the spread of AMR. Inadequate treatment of the effluent and its irresponsible disposal leads to unprecedented antibiotic contamination in the environment and their persistent presence in the environment significantly modulates the bacterial genomes' expression that is responsible for increase and spread of AMR. However, not much interventions are suggested in the National Action Plan developed on AMR by many countries. There are no regulations across the globe till date for the level of antibiotic residues in pharmaceutical effluent for the growing pharmaceutical industry. This review put together the work done showing several detrimental effects of the antimicrobial residues in the pharmaceutical effluent which leads to rise in development of AMR. The environment risk approach and need to have indicators to measure environment risk is a way forward for all countries engage in antibiotic manufacturing. Overall, efforts to address the problem are isolated and fragmented. Policymakers, regulators, manufacturers, researchers, civil society, and the community need to collaborate so that antibiotics are produced sustainably and continue to stay effective in treating bacterial infections.

Over-the-Counter Sale of Antibiotics in India: A Qualitative Study of Providers' Perspectives across Two States.

India has one of the highest rates of antimicrobial resistance (AMR) worldwide. Despite being prescription drugs, antibiotics are commonly available over-the-counter (OTC) at retail pharmacies. We aimed to gain insight into the OTC sale of antibiotics at retail pharmacies and to elucidate its underlying drivers. We conducted face-to-face, in-depth interviews using convenience sampling with 22 pharmacists and 14 informal dispensers from 36 retail pharmacies across two Indian states (Haryana and Telangana). Thematic analysis revealed that antibiotics were often dispensed OTC for conditions e.g., fever, cough and cold, and acute diarrhea, which are typically viral and self-limiting. Both Access and Watch groups of antibiotics were dispensed for 1-2 days. Respondents had poor knowledge regarding AMR and shifted the blame for OTC practices for antibiotics onto the government, prescribers, informal providers, cross practice by alternative medicine practitioners, and consumer demand. Pharmacists suggested the main drivers for underlying OTC dispensing were commercial interests, poor access to public healthcare, economic and time constraints among consumers, lack of stringent regulations, and scanty inspections. Therefore, a comprehensive strategy which is well aligned with activities under the National Action Plan-AMR, including stewardship efforts targeting pharmacists and evidence-based targeted awareness campaigns for all stakeholders, is required to curb the inappropriate use of antibiotics.