Amoxicillin trihydrate and clavulanate potassium

However, inequities in drug access persist, as many LMICs continue to be burdened with high rates of infectious disease-related mortality and low rates of antibiotic consumption. Our findings emphasize the need for global surveillance of antibiotic consumption to support policies to reduce antibiotic consumption and resistance while providing access to these lifesaving drugs.

Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or

aiding

In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1–34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3–15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth ( P = 0.004).

In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC.

Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015.

Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs.

Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.

antimicrobial resistance low-income countries defined daily doses antibiotic stewardship antibiotics. Antibiotic resistance—the ability of microbes to evolve and withstand the effects of antibiotics—is a significant cause of morbidity and mortality globally (1 ? –3). Antibiotic consumption is a primary driver of antibiotic resistance (4).

The association between antibiotic consumption and resistance is well documented across spatial and temporal scales at individual hospitals (5), nursing homes (6), primary care facilities (7), and communities (8), as well as across countries (9). Many countries have adopted national action plans on antimicrobial resistance (AMR) that aim to reduce per capita antibiotic consumption.

The Global Action Plan on Antimicrobial Resistance endorsed by the member states of the World Health Organization (WHO) and affirmed at the high-level meeting on antimicrobial resistance during the 71st General Assembly of the United Nations (10), recommends that all countries collect and report antibiotic consumption data (11).

Surveillance data on country-level antibiotic use are needed to ( i ) monitor national and global trends over time; ( ii ) compare antibiotic use among countries; ( iii ) provide a baseline for the evaluation of future efforts to reduce antibiotic use; ( iv ) enable epidemiological analysis of the association between antibiotic use and resistance over time (12, 13); and ( v ) support policies that aim to reduce antibiotic resistance. Given the urgency of the threat posed by rising AMR levels (2), and in the absence of global, publicly funded, harmonized surveillance data on antibiotic use, alternative sources of data on antibiotic use must be used to track antibiotic consumption patterns across countries. Here, we use pharmaceutical sales data to document global trends in antibiotic consumption.

There have been few attempts to assess antibiotic consumption globally or in multiple countries (14 ? ? –17), none of which has reported data later than 2010. The largest prior study reported that antibiotic consumption increased 36% between 2000 and 2010 in 71 countries (15).

However, the results from this study cannot be directly compared with other studies (14, 16) because the data were not reported as defined daily doses (DDDs), the most commonly used metric to measure antibiotic consumption.

In this study, we report on antibiotic consumption in DDDs for an expanded number of countries ( n = 76) and over a longer time period (2000–2015). In addition, we assess differences in consumption between high-income countries (HICs) and low- and middle-income countries (LMICs), identify drivers of antibiotic use in each income group from a set of socioeconomic and medical indicators, and project future growth in global antibiotic consumption. We estimated global antibiotic consumption using the IQVIA MIDAS database.

IQVIA uses national sample surveys of antibiotic sales to develop estimates of the total volume of sales of each antibiotic molecule (or combination of molecules).

For each country, antibiotic consumption was reported by month or quarter and broken down between the retail and hospital sectors.

We obtained data for 76 countries from 2000 through 2015.

Central America (Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua, and Panama) and French West Africa (Benin, Burkina Faso, Cameroon, Chad, Cote d’Ivoire, Republic of Congo, Guinea, Mali, Niger, Senegal, and Togo) were included as two individual groups of countries with aggregated sales for these regions. Sixty-six countries had data available for every year between 2000 and 2015, while data on the remaining countries covered partial time periods ( SI Appendix , Table S1). In countries where both hospital and retail data were reported for some but not all years (2000–2015),

consumption

For molecules not included in the ATC/DDD index, DDD values were estimated from other sources or as the average of DDD unit values by class ( SI Appendix , SI Methods ).

Data for SUs were available for all years, whereas kilogram data were available only for the period 2005–2015. The ratio of SUs to kilograms for 2005–2015 was used to estimate kilograms and DDDs for 2000–2004.

A country’s annual antibiotic consumption rate in DDDs per 1,000 inhabitants per day was calculated using population estimates from the World Bank DataBank.

Consumption rates were subsequently compared between groups of countries based on their World Bank income classification in 2007.

Fixed-effects panel regression analysis was used to quantify the association between economic and health indicators and the antibiotic consumption rate. The explanatory variables included per capita gross domestic product (GDP; purchasing power parity); imports of goods and services as a percentage of GDP (as a measure of trade); measles vaccination coverage in children between the ages of 12 and 23 mo [lack of pneumococcal conjugate vaccination (PCV) coverage information limited our ability to include PCV coverage as a variable]; physician density per 1,000 population; and percentage of the population living in urban areas (as a measure of health system access). All explanatory variables were pooled by country/year.

Regression models analyzed data for HICs and LMICs separately.

Health and economic factors were obtained from the World Development Indicators in the World Bank DataBank (18). Serial correlation was assessed using the Wooldridge test (19). Errors were clustered by country to account for high serial correlation.

STATA version 14.1 was used for all statistical analyses. Global antibiotic consumption was calculated by extrapolating use for countries not included in the IQVIA database. Extrapolations were based on the average per capita antibiotic use for countries from the same income group. We then projected global antibiotic use until 2030, assuming constant per capita use rates for all countries at current levels, with total use increasing only through population growth.

In addition to this baseline projection, we modeled two other scenarios: ( i ) no policy changes, where countries’ antibiotic consumption rates for 2016 through 2030 were assumed to continue to change based on their compounded growth rate between 2010 and

2015

Population projections were retrieved from the World Bank DataBank (18) except for Taiwan, for which data were obtained from the Taiwan National Development Council. Global antibiotic consumption increased by 65% between 2000 and 2015, from 21.1 to 34.8 billion DDDs, while the antibiotic consumption rate increased 39% from 11.3 to 15.7 DDDs per 1,000 inhabitants per day over the study period. The mean antibiotic consumption rate across countries increased 28% from 16.4 (SD 9.9) DDDs per 1,000 inhabitants per day to 20.9 (SD 9.8), and the median antibiotic consumption rate increased 25% from 15.5 to 19.5 amoxicillin and the pill DDDs per 1,000 inhabitants per day.

The increase in global consumption was primarily driven by increased consumption in LMICs.

In 2000, HICs, led by France, New Zealand, over the counter amoxicillin for humans Spain, Hong Kong, and the United States, had the highest antibiotic consumption rates.

In 2015, four of the six countries with the highest consumption rates were LMICs (Turkey, Tunisia, Algeria, and Romania; Fig. In HICs, although the total amount of antibiotics consumed increased 6% between 2000 and 2015, from 9.7 to 10.3 billion DDDs, the antibiotic consumption rate

decreased

In LMICs, antibiotic consumption increased 114%, from 11.4 to 24.5 billion DDDs, and the antibiotic consumption rate increased 77%, from 7.6 to 13.5 DDDs per 1,000 inhabitants per day.

Low- and lower-middle-income countries (LMICs-LM) accounted for a greater share of this increase than upper-middle-income countries (LMICs-UM): total antibiotic consumption in LMICs-LM increased 117%, from 8.1 to 17.5 billion DDDs, while, in LMICs-UM, antibiotic consumption increased 110%, from 3.3 to 6.9 billion DDDs (Fig.

The antibiotic consumption rate in both LMICs-UM and LMICs-LM increased 78%, from 12.0 to 21.3 DDDs per 1,000 inhabitants per day, and from 6.7 to 11.9 DDDs per 1,000 inhabitants per day, respectively.

Download figure Open in new tab Download powerpoint. Global antibiotic consumption by country: 2000–2015.

( A ) Change in the national antibiotic consumption rate between 2000 and 2015 in DDDs per 1,000 inhabitants per day. For Vietnam, Bangladesh, The Netherlands, and Croatia, change was calculated from 2005, and for Algeria from 2002 as data before those years for those countries were not available.

( B ) Antibiotic consumption rate by country for 2015 in DDDs per 1,000 inhabitants per day. All rights reserved (https://www.iqvia.com/solutions/commercialization/geographies/midas).

Download figure Open in new tab Download powerpoint.

Global antibiotic consumption by country income classification: 2000–2015.

( A ) Graph showing how the antibiotic consumption rate in DDDs per 1,000 inhabitants

per

HICs

However, as shown in B , the larger population sizes in many LMICs result in greater total antibiotic consumption (DDDs) in LMICs even though their consumption rate (and thus per capita use) is lower.

In B , each bar reflects total consumption in the specified year for that country or group of countries.

All rights reserved (https://www.iqvia.com/solutions/commercialization/geographies/midas). In 2015, the leading HIC consumers of antibiotics were the United States, France, and Italy, while the leading LMIC consumers were India, China, and Pakistan. Whereas antibiotic consumption in the three leading HICs marginally increased, the highest-consuming LMICs saw large increases.

Between 2000 and 2015, antibiotic consumption increased from 3.2 to 6.5 billion DDDs (103%) in India, from 2.3 to 4.2 billion DDDs (79%) in China, and from 0.8 to 1.3 billion DDDs (65%) in Pakistan. The antibiotic consumption rate increased from 8.2 to 13.6 DDDs per 1,000 inhabitants per day (63%) in India, from 5.1 to 8.4 DDDs per 1,000 inhabitants per day (65%) in China, and from 16.2 to 19.6 DDDs per 1,000 inhabitants per day (21%) in Pakistan.

The antibiotic consumption rate of broad-spectrum penicillins, the most commonly consumed class of antibiotics (39% of total DDDs in 2015), increased 36% between 2000 and 2015 globally. The greatest increase was in LMICs (56%), although the antibiotic consumption rate in HICs increased 15% (Fig. While the antibiotic consumption rate of the next three most consumed classes—cephalosporins (20% of total DDDs), quinolones (12% of total DDDs), and macrolides (12% of total DDDs)—all increased overall, the antibiotic consumption rate decreased in HICs.

In LMICs, the antibiotic consumption rate increased 399, 125, and 119% for cephalosporins, quinolones, and macrolides, respectively, while the antibiotic consumption rate of these three drugs in HICs decreased by 18, 1, and teva amoxicillin 25%, respectively (Fig. Download figure Open in new tab Download powerpoint.

Antibiotic consumption rate for HICs, LMICs-UM, and LMICs-LM of the four most-consumed therapeutic classes of antibiotics in DDDs per 1,000 inhabitants per day.

( A ) Broad-spectrum penicillins, which correspond to the Anatomical Therapeutic Chemical (ATC) classification of penicillins with extended spectrum (J01CA) excluding carbenicillins. ( B ) Cephalosporins, which correspond to the ATC classification

codes

The United States was the largest consumer of glycylcyclines (tigecycline) and oxazolidinones (primarily linezolid as tedizolid was not introduced until 2014) through the late 2000s. However, the antibiotic consumption rate of these drugs in the United States began declining in 2009 (Fig.

4 A and B ), and in 2015, Taiwan, Italy, Turkey, and Austria all had higher consumption rates for glycylcyclines than the United States, while India surpassed the United States antibiotic consumption rate for oxazolidinones in 2012 to become the highest consumer.

The antibiotic consumption rate of carbapenems increased greatly in LMICs between 2000 and 2015 but remained far below consumption rates in HICs (Fig.

Similarly, the antibiotic consumption rate of polymyxins (largely colistin) also increased in LMICs, particularly in LMICs-UM countries, but remained much lower than in HICs (Fig.

The highest polymyxin consumption rates were in Spain, the United Kingdom, and Ireland, all of which had rates greater than 0.05 DDDs per 1,000 inhabitants per day in 2015. Download figure Open in new tab Download powerpoint.

Antibiotic consumption rate for HICs, LMICs-UM, and LMICs-LM of new and last-resort antibiotics in DDDs per 1,000 inhabitants per day.

( A ) Glycylcyclines, which correspond to the ATC classification for tigecycline (J01AA12). ( B ) Oxazolidinones, which correspond to the ATC classifications for linezolid (J01XX08) and tedizolid (J01XX11).