The distribution of antibiotic use and its association with antibiotic resistance

  1. Scott W Olesen
  2. Michael L Barnett
  3. Derek R MacFadden
  4. John S Brownstein
  5. Sonia Hernández-Díaz
  6. Marc Lipsitch
  7. Yonatan H Grad  Is a corresponding author
  1. Harvard T.H. Chan School of Public Health, United States
  2. Brigham and Women’s Hospital, Harvard Medical School, United States
  3. University of Toronto, Canada
  4. Boston Children’s Hospital, United States
  5. Harvard Medical School, United States
5 figures and 2 additional files

Figures

Figure 1 with 1 supplement
The distribution of antibiotic use within individuals.

Bars indicate the proportion of members in the MarketScan data with different numbers of prescription fills in 2011 for each of the drug groups. TMP/SMX: trimethoprim/sulfamethoxazole.

https://doi.org/10.7554/eLife.39435.002
Figure 1—figure supplement 1
Cumulative distribution of antibiotic use.

Each point represents a group of people with a certain number of associated claims for any antibiotic, starting at the left with the members with the greatest number of claims. The upper-right line segment shows members with one claim, the next segment shows members with two claims, etc. Colors indicate data years. Panels indicate study population. MarketScan: main data set. Children: MarketScan data including only members 15 and younger.

https://doi.org/10.7554/eLife.39435.003
Figure 2 with 3 supplements
The distribution of antibiotic use across US states.

Each point indicates first use and repeat use of a single drug group in a single US state (averaged over the data years). Points falling on the black line have three times as much first use as repeat use (i.e. repeat use is one-quarter of total use). The curves show the relationships between first use and repeat use expected from the Poisson and geometric distributions. TMP/SMX: trimethoprim/sulfamethoxazole.

https://doi.org/10.7554/eLife.39435.004
Figure 2—figure supplement 1
Distribution of tetracycline use by age.

Colors indicate data years.

https://doi.org/10.7554/eLife.39435.005
Figure 2—figure supplement 2
Distribution of antibiotic use by population.

Each point represents average use of a drug group in a state across data years. Children: MarketScan data including only members 15 and younger.

https://doi.org/10.7554/eLife.39435.006
Figure 2—figure supplement 3
Distribution of antibiotic use by region.

Each point shows use for a drug group in a state, averaged over data years. Colors indicate US Census region (red, South; light red, Midwest; gray, Northeast; black, West). Line shows unweighted linear best fit.

https://doi.org/10.7554/eLife.39435.007
Figure 3 with 1 supplement
Correlations between total antibiotic use and resistance are biased toward positive values.

Error bars show 95% confidence intervals. The color strip visually displays the drug groups. Statistical significance is indicated by color of the points (black, significant at FDR = 0.05, two-tailed; dark gray, significant at α = 0.05, two-tailed; light gray, not significant). TMP/SMX: trimethoprim/sulfamethoxazole. CoNS: coagulase-negative Staphylococcus.

https://doi.org/10.7554/eLife.39435.008
Figure 3—source data 1

Antibiotic use data.

For each data source (MarketScan or Medicare), data subset or population among MarketScan records, state (with masked ID), and drug group, annual first and repeat claims per 1000 members. Main: main data set. Children: members at most 15 years old. Days supply: first and repeat use are reported as days supply, not claims. Multiyear: among members in the data for all four data years.

https://doi.org/10.7554/eLife.39435.010
Figure 3—source data 2

Antibiotic resistance data.

For each adequately-represented pathogen and drug group (see Materials and methods) and state (with masked ID matching the antibiotic use data), the proportion of isolates collected in that state susceptible to that drug.

https://doi.org/10.7554/eLife.39435.011
Figure 3—figure supplement 1
Correlations between total antibiotic use and resistance using subsets of the resistance data.

Error bars show 95% confidence intervals. Statistical significance is indicated by color of the points (black, significant at FDR = 0.05, two-tailed; dark gray, significant at α = 0.05, two-tailed; light gray, not significant). IP: inpatient. OP/ER: outpatient/emergency room. TMP/SMX: trimethoprim/sulfamethoxazole. CoNS: coagulase-negative Staphylococcus.

https://doi.org/10.7554/eLife.39435.009
Total macrolide use and macrolide resistance among Streptococcus pneumoniae correlate across US states.

Labels indicate selected states. Colors indicate US Census region (red, South; light red, Midwest; gray, Northeast; black, West). Line shows unweighted linear best fit. Southern states have highest macrolide use and resistance.

https://doi.org/10.7554/eLife.39435.012
Repeat use tends to be negatively associated with resistance when controlling for first use.

Each point represents a pathogen-antibiotic combination. The position of the point shows the two coefficients from the multiple regression. The units of the coefficients are proportion resistant per annual claim per 1000 people. Color indicates drug group. Error bars show 95% CIs. (a) All data. (b) Same data, showing only the center cluster of points.

https://doi.org/10.7554/eLife.39435.013

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  1. Scott W Olesen
  2. Michael L Barnett
  3. Derek R MacFadden
  4. John S Brownstein
  5. Sonia Hernández-Díaz
  6. Marc Lipsitch
  7. Yonatan H Grad
(2018)
The distribution of antibiotic use and its association with antibiotic resistance
eLife 7:e39435.
https://doi.org/10.7554/eLife.39435