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

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; 0.008) of total antibiotics and 38.0 million excess doses (95% CI: 26.4 to 49.2 million; 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]; 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. 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.