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Background The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate. Methods and findings We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%–53%), with a prediction interval of 44%–60%. Individual studies’ estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription. Conclusions Antibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines. Trial registration PROSPERO registration number: CRD42019123269., Giorgia Sulis and colleagues report the prevalence of antibiotic prescriptions in primary care in low-middle income countries in a systematic review and meta-analysis., Author summary Why was this study done? Inappropriate use of antibiotics, both in terms of incorrect regimens and prescription without clinical indication, is a major driver of antibiotic resistance. Global drug sales data indicate a substantial increase in antibiotic use in low- and middle-income countries (LMICs) over the past 2 decades. An accurate quantification of antibiotic prescribing in primary care across LMICs is not available. What did the researchers do and find? We conducted a systematic review and meta-analysis to estimate the proportion of antibiotic prescribing across primary care settings in LMICs. Our study showed that, on average, approximately half of patients attending primary care facilities in LMICs received at least 1 antibiotic. Very few included studies made an attempt to assess the extent of inappropriate prescriptions and indicate potential misuse. Among studies that provided information on the types of antibiotics used, we found that, in 12/16 studies, 60% of prescriptions were for antibiotics with low potential for resistance selection as defined by the World Health Organization (WHO). What do these findings mean? Our study highlights that antibiotics are highly prescribed in outpatient primary care settings. Better quality data are necessary to dig deeper into the patterns of inappropriate use according to local epidemiologic scenarios. Adapting WHO treatment recommendations and incorporating the WHO Access, Watch, and Reserve (AWaRe) classification of antibiotics into national guidelines will be a first key step to improve prescription practices.

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., Giorgia Sulis and co-workers analyze sales of antimicrobials and hydroxchloroquine in India during 2018-20 to assess possible changes across the COVID-19 epidemic., Author summary Why was this study done? There are concerns that the widespread and often inappropriate use of antibiotics has been aggravated by the COVID-19 pandemic, but little is known regarding the true impact of the pandemic on antibiotic use, particularly in low- and middle-income countries (LMICs). India is the largest antibiotic user in the world and is among the countries that are most severely affected by the pandemic. About 75% of healthcare in India is private, and this unregulated and fragmented private sector accounts for 90% of antibiotic consumption, raising major concerns about the potential effects of COVID-19 on prescribing and dispensing practices. What did the researchers do and find? Using an interrupted time series (ITS) design, we examined sales volumes of total antibiotics, azithromycin alone, and hydroxychloroquine (HCQ) in India’s private sector from January 2018 to December 2020. Focusing on non-pediatric formulations and adjusting for underlying seasonal and non-seasonal trends and accounting for the effect of lockdown, we estimated the impact of the first epidemic wave on monthly sales. Based on our models, COVID-19 likely contributed to about 216 million excess doses (95% CI: 68.0 to 364.8 million; P = 0.008) of total antibiotics and 38.0 million excess doses (95% CI: 26.4 to 49.2 million; P < 0.001) of azithromycin between June and September 2020 (i.e., after the lockdown and until the epidemic peak). HCQ sales peaked in March 2020, reflecting the widespread use of this drug for both prophylaxis and treatment of COVID-19 (+11.1 million doses [95% CI: 9.2 to 13.0 million]; P < 0.001), followed by a slow decline afterwards. What do these findings mean? Our findings indicate a significant increase in antibiotic sales, particularly of azithromycin, during the peak phase of the first COVID-19 epidemic wave in India. Similar trends are likely to have occurred in other LMICs, where antibiotics are often overused. The medium- and long-term consequences for bacterial resistance patterns are highly concerning, highlighting the need for urgent antibiotic stewardship measures.