Estimating the proportion of bystander selection for antibiotic resistance in the US

AbstractBystander selection -- the selective pressures exerted by antibiotics on microbial flora that are not the target pathogen of treatment -- is critical to understanding the total impact of broad-spectrum antibiotic use; however, to our knowledge, this effect has never been quantified. Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS), the Human Microbiome Project, and additional carriage and etiological data from existing literature, we estimate the magnitude of bystander selection for a range of clinically relevant antibiotic-species pairs as the proportion of all exposures of an antibiotic experienced by a species for conditions in which that species was not the causative pathogen (“proportion of bystander exposures”). For outpatient prescribing in the United States, we find that this proportion over all included antibiotics is over 80% for 8 out of 9 organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or a high proportion of antibiotic prescribing focused on conditions caused by the species of interest. Using the proportion of bystander exposures, we roughly estimate that S. aureus and E. coli may benefit from 90.7% and 99.7%, respectively, of the estimated reduction in antibiotic use due to pneumococcal conjugate vaccination, despite not being the pathogen targeted by the vaccine. These results underscore the importance of considering antibiotic exposures to bystanders, in addition to the targeted pathogen, in measuring the impact of antibiotic resistance interventions.Significance StatementThe forces that contribute to changing population prevalence of antibiotic resistance are not well understood. Bystander selection -- the inadvertent pressures imposed by antibiotics on the microbial flora other than the pathogen targeted by treatment -- is hypothesized to be a major factor in the propagation of antibiotic resistance, but its extent has not been characterized. We estimate the proportion of bystander exposures across a range of antibiotics and organisms and describe factors driving variability of these proportions. Impact estimates for antibiotic resistance interventions, including vaccination, are often limited to effects on a target pathogen. However, the reduction of antibiotic treatment for illnesses caused by the target pathogen may have the broader potential to decrease bystander selection pressures for resistance on many other organisms.

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Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810840115 ◽

2018 ◽

Vol 115 (51) ◽

pp. E11988-E11995 ◽

Cited By ~ 50

Author(s):

Christine Tedijanto ◽

Scott W. Olesen ◽

Yonatan H. Grad ◽

Marc Lipsitch

Keyword(s):

Antibiotic Resistance ◽

Medical Care ◽

Bacterial Species ◽

Bacterial Flora ◽

The United States ◽

Vaccination Programs ◽

Care Survey ◽

Selection For ◽

Ambulatory Medical Care ◽

The Impact

Bystander selection—the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment—is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic–species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen (“proportion of bystander exposures”). Data sources include the 2010–2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.

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1099. Antibiotic Prescriptions for Acute Gastroenteritis during Office and Emergency Department Visits–United States, 2006–2015

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.934 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S330-S330

Author(s):

Jennifer P Collins ◽

Louise Francois Watkins ◽

Laura M King ◽

Monina Bartoces ◽

Katherine Fleming-Dutra ◽

...

Keyword(s):

United States ◽

Emergency Department ◽

Medical Care ◽

Acute Gastroenteritis ◽

Antibiotic Use ◽

The United States ◽

Emergency Department Visits ◽

Antibiotic Prescribing ◽

Care Survey ◽

Ambulatory Medical Care

Abstract Background Acute gastroenteritis (AGE) is a major cause of office and emergency department (ED) visits in the United States. Most patients can be managed with supportive care alone, although some require antibiotics. Limiting unnecessary antibiotic use can minimize side effects and the development of resistance. We used national data to assess antibiotic prescribing for AGE to target areas for stewardship efforts. Methods We used the 2006–2015 National Hospital Ambulatory Medical Care Survey of EDs and National Ambulatory Medical Care Survey to describe antibiotic prescribing for AGE. An AGE visit was defined as one with a new problem (<3 months) as the main visit indication and an ICD-9 code for bacterial or viral gastrointestinal infection or AGE symptoms (nausea, vomiting, and/or diarrhea). We excluded visits with ICD-9 codes for Clostridium difficile or an infection usually requiring antibiotics (e.g., pneumonia). We calculated national annual percentage estimates based on weights of sampled visits and used an α level of 0.01, recommended for these data. Results Of the 12,191 sampled AGE visits, 13% (99% CI: 11–15%) resulted in antibiotic prescriptions, equating to an estimated 1.3 million AGE visits with antibiotic prescriptions annually. Antibiotics were more likely to be prescribed in office AGE visits (16%, 99% CI: 12–20%) compared with ED AGE visits (11%, 99% CI: 9–12%; P < 0.01). Among AGE visits with antibiotic prescriptions, the most frequently prescribed were fluoroquinolones (29%, 99% CI: 21–36%), metronidazole (18%, 99% CI: 13–24%), and penicillins (18%, 99% CI: 11–24%). Antibiotics were prescribed for 25% (99% CI: 8–42%) of visits for bacterial AGE, 16% (99% CI: 12–21%) for diarrhea without nausea or vomiting, and 11% (99% CI: 8–15%) for nausea, vomiting, or both without diarrhea. Among AGE visits with fever (T ≥ 100.9oF) at the visit, 21% (99% CI: 11–31%) resulted in antibiotic prescriptions. Conclusion Patients treated for AGE in office settings were significantly more likely to receive prescriptions for antibiotics compared with those seen in an ED, despite likely lower acuity. Antibiotic prescribing was also high for visits for nausea or vomiting, conditions that usually do not require antibiotics. Antimicrobial stewardship for AGE is needed, especially in office settings. Disclosures All authors: No reported disclosures.

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Outpatient Macrolide Antibiotic Prescribing in the United States, 2008–2011

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx220 ◽

2017 ◽

Vol 4 (4) ◽

Cited By ~ 2

Author(s):

Guillermo V Sanchez ◽

Daniel J Shapiro ◽

Adam L Hersh ◽

Lauri A Hicks ◽

Katherine E Fleming-Dutra

Keyword(s):

United States ◽

Medical Care ◽

Survey Data ◽

Antibiotic Stewardship ◽

Macrolide Antibiotic ◽

The United States ◽

Antibiotic Prescribing ◽

Family Practitioners ◽

Care Survey ◽

Ambulatory Medical Care

Abstract National Ambulatory Medical Care Survey data were used to assess outpatient macrolide prescribing and selection. Conditions for which macrolides are firstline therapy represented 5% of macrolide prescribing. Family practitioners selected macrolides for children more frequently than pediatricians. Macrolides are an important antibiotic stewardship target.

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2742. The Impact of Influenza Vaccination on Antibiotic Use in the United States, 2010–2017

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2419 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S965-S966

Author(s):

Eili Klein ◽

Emily Schueller ◽

Katie K Tseng ◽

Arindam Nandi

Keyword(s):

United States ◽

Antibiotic Resistance ◽

Influenza Vaccination ◽

Vaccination Coverage ◽

Seasonal Influenza ◽

Antibiotic Use ◽

The United States ◽

Antibiotic Prescribing ◽

Coverage Rates ◽

The Impact

Abstract Background Antibiotic resistance is a cause of morbidity and mortality driven by inappropriate prescribing. In the United States, a third of all outpatient antibiotic prescriptions may be inappropriate. Seasonal influenza rates are significantly associated with antibiotic prescribing rates. The impact of influenza vaccination coverage on antibiotic prescribing is unknown. Methods We conducted a retrospective analysis of state-level vaccination coverage and antibiotic prescribing rates from 2010 to 2017. We used fixed effects regression to analyze the relationship between cumulative vaccine coverage rates for a season and the per capita number of prescriptions for systemic antibiotics for the corresponding season (January–March) controlling for temperature, poverty, healthcare infrastructure, population structure, and vaccine effectiveness. Results Rates of vaccination coverage ranged from 33% in Nevada to 52% in Rhode Island for the 2016–2017 season, while antibiotic use rates ranged from 25 prescriptions per 1,000 inhabitants in Alaska to 377 prescriptions per 1,000 inhabitants in West Virginia (Figure 1). Vaccination coverage rates were highly correlated with reduced prescribing rates, and controlling for other factors, we found that a one percent increase in the influenza vaccination rate was associated with 1.40 (95% CI: 2.22–0.57, P < 0.01) fewer antibiotic prescriptions per 1,000 inhabitants (Table 1). Increases in the vaccination coverage rate in the pediatric population (aged 0–18) had the strongest effect, followed by the elderly (aged 65+). Conclusion Vaccination can reduce morbidity and mortality from seasonal influenza. Though coverage rates are far below levels necessary to generate herd immunity, we found that higher coverage rates in a state were associated with lower antibiotic prescribing rates. While the effectiveness of the vaccine varies from year to year and the factors that drive antibiotic prescribing rates are multi-factorial, these results suggest that increased vaccination coverage for influenza would have significant benefit in terms of reducing antibiotic overuse and correspondingly antibiotic resistance. Disclosures All authors: No reported disclosures.

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