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Global antibiotic consumption by country income classification: 2000–2015. ( A ) Graph showing how the antibiotic consumption rate in DDDs per 1,

000

inhabitants per day has rapidly increased for LMICs, while remaining nearly constant for 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 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 J01DB, J01DC, J01DD, and J01DE for the four generations of cephalosporins. ( C ) Macrolides, which correspond to the ATC classification for macrolides, lincosamides, and streptogramins (J01F).

( D ) Quinolones, which correspond to the ATC classification for quinolone antibacterials (J01M).

All rights reserved (https://www.iqvia.com/solutions/commercialization/geographies/midas). Consumption of newer and last-resort antibiotic classes increased across all country income groups between 2000 and 2015.

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).

( C ) Carbapenems, metronidazole and amoxicillin together for tooth infection which correspond to the ATC classification for carbapenems (J01DH).

( D ) Polymyxins, which correspond to ATC classification for polymyxins (J01XB). All rights reserved (https://www.iqvia.com/solutions/commercialization/geographies/midas).

We found a significant positive association between GDP per capita and changes in the antibiotic consumption rate in LMICs ( P = 0.004), although no statistically significant association was found between these factors in HICs ( P = 0.52). Other indicators, including the measles vaccination rate (which is a proxy for

public

health intervention capability), imports as a percentage of GDP, and physician density, were not correlated with changes in per capita antibiotic use across countries, irrespective of income group (Table 1).

Fixed-effects regression analysis of factors associated with global antibiotic consumption (DDD per capita): 2000–2015.

Between 2000 and 2015, the estimated total global antibiotic consumption rate (including countries not reported in the IQVIA database) decreased slightly in HICs from 27.0 to 25.7 DDDs per 1,000 inhabitants per day in HICs and increased from 8.6 to 13.9 DDDs per 1,000 inhabitants per day in LMICs ( SI Appendix , Fig. Total global antibiotic consumption in 2015 was estimated to be 42.3 billion DDDs (15.8 DDDs per 1,000 inhabitants per day)—10.7 billion DDDs in HICs and 31.6

billion

DDDs in LMICs.

In our baseline condition, where we assumed no policy changes and constant antibiotic consumption rates set at current levels of use, global antibiotic use is projected to increase 15% between 2015 and 2030.

If all countries continue to increase their antibiotic consumption rates at their compounded annual growth rates, we estimate that total consumption would increase 202% to 128 billion DDDs, while the antibiotic consumption rate would increase 161% to 41.1 DDDs per 1,000 inhabitants per day.

Finally, if all countries converge on the global median antibiotic consumption rate in 2015 of 17.9 DDDs per 1,000 inhabitants per day by 2020, we estimate global antibiotic consumption would increase 32% to 55.6 billion DDDs (Fig. Download figure Open in new tab Download powerpoint.

Projected total global antibiotic consumption (billions of DDDs):

2000–2030

. Estimated global antibiotic consumption in all countries in billions of DDDs for three scenarios: ( i ) all countries continue to consume at current per capita rates; ( ii ) consumption of all countries continues to change at current compound annual growth rates; and ( iii ) all countries converge to the global median antibiotic consumption rate. Estimates were produced using antibiotic use data for 2000–2015 from the IQVIA MIDAS database and World Bank DataBank population estimates and projections for 2000–2030.

All rights reserved (https://www.iqvia.com/solutions/commercialization/geographies/midas). Using a global database of antibiotic sales, we found that antibiotic consumption rates increased dramatically in LMICs between 2000 and 2015, and in some LMICs have reached levels previously reported only in HICs. Overall consumption has also greatly increased, and the total amount of antibiotics consumed in LMICs, which was similar to HICs in 2000, was nearly 2.5 times that in HICs in 2015. Rising incomes are a major driver of increased antibiotic consumption in LMICs. Thus, although rates of antibiotic consumption in most LMICs remain below the general rate in HICs, barring major policy changes, they are expected to increase over time and converge, and possibly surpass, antibiotic consumption rates in HICs, in part due to the higher burden of infectious diseases in LMICs. Tracking rates of antibiotic use is vitally important because of the well-quantified relationship between antibiotic use and resistance. However, although data on the burden of resistant bacterial infections is limited, both in HICs and especially in LMICs (2), the magnitude of the challenge posed by rising antibiotic resistance levels has become increasingly visible.

Despite the emergence and spread of nearly untreatable infections, the global response to this public health crisis remains slow and inadequate.



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