Most health care decision-making occurs at the level of the physician-patient encounter, where incentives at the patient level often take priority to society. When priorities at the individual vs. the societal levels conflict, or if the involved tradeoffs seem unfavorable, guidelines established to maximize societal outcomes are less likely to be followed; [1] this is often the case with antibiotic prescribing. Each patient level antibiotic treatment decision is based on how we value potential outcomes, including short-term benefits and risks and longer-term risks, including those related to bacterial resistance to antibiotics. Unfortunately, antibiotics are often prescribed for illnesses unlikely to have a bacterial etiology; even a very small likelihood of benefit seems to outweigh an increased risk of future antibiotic resistance. While short-term effects of antibiotics on colonization with resistan bacteria have been demonstrated, the overall implications of each treatment for future individual, family and societal-level resistance remain difficult to quantify, and are often steepl discounted or ignored. [1,2] Knowledge regarding the longer-term effects of personal and household antibiotic use could better quantify these future resistance-related risks, and help guide antibiotic decision-making for physicians and patients. Infants are born with sterile nasopharyngeal and gastrointestinal tracts and yet, during the 1st year of life, become important reservoirs of resistant organisms; [3, 4] this creates an opportunity to study colonization and resistance starting from a microbiological tabula rasa. The overall goal of the proposed research is to develop strategies to improve judicious pediatric outpatient antibiotic prescribing, specifically, to reduce unnecessary treatment, minimize resistance, and promote favorable long-term clinical outcomes, simultaneously at the individual, family, and societal levels. In this proposal, we will 1) assemble an observational cohort, following newborns' antibiotic exposure and longitudinal colonization with specific bacterial pathogens and related antibiotic resistance in the 1st year of life, and 2) use these data to consider antibiotic decision-making within a broader framework, incorporating principles of behavioral economics. These goals will be achieved in a multidisciplinary training environment that combines the strengths of epidemiology and microbiology within the context of health services research.
Aim 1 : Observational cohort of longitudinal bacterial colonization and resistance in the first year of life. Primary Objectives: Objective 1.1: Characterize colonization with Streptococcus pneumoniae and Staphylococcus aureus. Objective 1.2: Characterize colonization with antibiotic-resistant S pneumoniae and S aureus and 3rd generation cephalosporin resistant and extended-spectrum beta lactamase (ESBL) producing gram-negative enteric bacilli. Objective 1.3: Assess the relationship between colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacilli, and ESBL-producing gram negative bacteria and infants' antibiotic exposure. Secondary Objectives: Objective 1.4: Assess the relationship between infants' colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacilli, and ESBL-producing bacteria and household members' antibiotic use. Objective 1.5: Assess the relationship between infants' colonization with antibiotic-resistant S. pneumoniae, S. aureus, gram negative enteric bacteria, and ESBL-producing bacteria, and infant and households daycare use. Hypothesis 1: During the 1st year of life, infants with antibiotic exposure will have greater colonization with resistan organisms than infants without antibiotic exposure. Hypothesis 2: During their 1st year, infants with personal or household day care use or antibiotic-exposed household members will have greater colonization with resistant organisms than those without such exposures Aim 2: Economic framework for pediatric antibiotic use. Objective 2: Describe how different stakeholders (parents, primary care physicians, specialists) make choices regarding antibiotic use, and where interventions to promote judicious use may be implemented. By making the tradeoffs considered for these decisions more explicit, we may clarify how to improve them, maximizing desired outcomes while minimizing risks. Using data from Aim 1 and decision analysis tools, we will develop a framework for an approach to patient-level decision-making regarding antibiotic prescribing. The framework will consider costs including future resistance risks, benefits, externalities (external effects), imperfect information, under-valuing (over-discounting) outcomes, and behavioral economics concepts including Prospect Theory. These interrelated projects exploit the applicant's unique background in medicine, epidemiology, health services research, and economics to present an innovative interdisciplinary perspective for an urgent public health problem: improving decision-making for antibiotic prescribing. The plan includes training by recognized and successful mentors to cultivate unique skills that can be applied in future independent research.

Public Health Relevance

Escalating resistance to antibiotics among disease-causing community bacteria increasingly threatens our ability to treat patients' infections, and young children are a major reservoir of resistant organisms. Antibiotic use contributes to further resistance; while antibiotic use has implications at the societal level, each pediatric antibiotic use decision is made at the physician-patient level, where individual considerations and short-term outcomes often take precedence over societal interests. These two interrelated innovative projects will address an urgent public health issue: understanding the development of bacteria that are resistant to antibiotics within the community, and improving judicious decision-making regarding antibiotic prescribing.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Microbiology and Infectious Diseases B Subcommittee (MID)
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Huntley, Clayton C
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Case Western Reserve University
Schools of Medicine
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Lee, Sara; Riley-Behringer, Maureen; Rose, Jeanmarie C et al. (2017) Parental Vaccine Acceptance: A Logistic Regression Model Using Previsit Decisions. Clin Pediatr (Phila) 56:716-722
Meropol, Sharon B; Stange, Kurt C; Jacobs, Michael R et al. (2016) Bacterial Colonization and Antibiotic Resistance in a Prospective Cohort of Newborn Infants During the First Year of Life. Open Forum Infect Dis 3:ofw221
Meropol, Sharon B; Edwards, Amy (2015) Development of the infant intestinal microbiome: A bird's eye view of a complex process. Birth Defects Res C Embryo Today 105:228-39
Meropol, Sharon B; Votruba, Mark E (2015) Decision-Making and the Barriers to Judicious Antibiotic Use. Pediatrics 136:387-8
Meropol, Sharon B; Watanabe, Michiko; Tuan, Rocky S (2015) Introduction. Birth Defects Res C Embryo Today 105:227