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Klein et al. (1) suggest that defined daily doses (DDDs) are not a perfect outcome measure of antibiotic prescribing, particularly for penicillins (39% of total DDDs in 2015 for broad-spectrum penicillins). We identified the same limitations as illustrated by the results of our study (2), which measured the bias of estimation for amoxicillin’s indicators (oral and i.v. administrations) and oral amoxicillin clavulanic acid’s indicator.
We identified that the DDDs for amoxicillin (oral and i.v.) and oral amoxicillin clavulanic acid are 1 g/d, whereas the average maintenance dose recommended by actual guidelines to treat common infections is 3 g/d (3⇓–5). No difference was observed with i.v. amoxicillin clavulanic acid (3 g/d) (6).
By modifying these DDDs to 3 g/d, we recalculated the French community consumption rate for the years 2004 and 2014. We also applied modified DDDs of amoxicillin (i.v. and oral) for community consumption rate in 2015 for the 10 largest European consumers (2). Concerning evolution of the French community consumption rate between 2004 and 2014, an initial increase of 6.7% became, by applying modified DDDs, a decrease of 9.9% (2).
Similarly, using modified amoxicillin DDDs on an antibiotic consumption rate of high-income countries, we observed a decrease of 10.5% (from 20 to 17.9 DDDs per 1,000 inhabitants per day) in contrast to the initial consumption reduction (−4.0%) described by Klein et al. (1). It is notable that the worldwide amoxicillin consumption (39% in 2015) is similar to the French consumption rate (37.8% in 2015) (1). Thus, using an extrapolation of French results, it could be expected that the worldwide consumption rate in 2015 decreased approximately by 25%.
The DDDs of amoxicillin and oral association with clavulanic acid must be redefined to provide robust indicators of antibiotic consumption. These indicators must also consider antibiotic selection pressure and, thus, penalize antibiotic prescriptions that favor the emergence of resistant pathogens versus those that follow actual recommendations. Thus, antimicrobial stewardship programs appropriated to each country must be maintained, the efficacy of which would be assessed by modified DDDs.
Footnotes
- ↵1To whom correspondence should be addressed. Email: florent.charra{at}gmail.com.
Author contributions: F.B. designed research; F.C. and F.B. performed research; F.C. and F.B. analyzed data; P.B. promoted results to the relevant authorities; and F.C., P.B., and F.B. wrote the paper.
The authors declare no conflict of interest.
Published under the PNAS license.
Penicillins’ defined daily doses must be changed
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