Acute bacterial sinusitis in children is one of the most common clinical problems presenting to the primary care practitioner. A diagnosis of sinusitis results in over $1.8 billion spent on children < 12 years of age and is responsible for over 20 million antibiotic prescriptions per year in the US. Equally important, overtreatment contributes in large part to the development of antimicrobial resistance which has become one of the most serious obstacles to effective therapy since the pre-antibiotic era. Despite the frequency and importance of acute bacterial sinusitis, its incidence and the identity of the antecedent predisposing viral infections has never been reported. The goals of this study are to determine the burden of acute bacterial sinusitis in children and use state-of- the-art molecular techniques to determine the role of the nasopharyngeal microbiome and antecedent acute viral infections on the development of acute bacterial sinusitis in children. To accomplish these goals, we propose to conduct a systematic longitudinal study of the nasopharyngeal environment of otherwise healthy children who acquire viral upper respiratory infections (URIs). The specific viral agents that cause URIs in children 49 to 84 months of age will be identified and the nasopharyngeal microbiome will be characterized (regarding sinopathogens and commensal microbiota) using high-resolution, culture-independent methods as well as conventional microbiologic techniques at baseline and again within 2 to 3 days of onset of the viral URI. Children will be followed prospectively to determine which subjects develop acute bacterial sinusitis and which resolve their URI spontaneously. It is our overall hypothesis that the nasopharyngeal microbiome is a major factor in the maintenance of normal upper respiratory tract physiology and strongly influences the risk of developing sinusitis and other bacterial infections of the respiratory tract. By identifying certain demographic features (e.g., age, gender, siblings, attendance at daycare, etc), the characteristics of the nasopharyngeal microbiome (diversity, evenness and relative abundance of specific sinopathogens and commensal microbiota) and the antecedent viral infection, we will determine risk factors for the development of acute bacterial sinusitis. Ultimately, this information will help us to focus treatment on those at highest risk to develop acute bacterial sinusitis thereby limiting exposure to antimicrobials. Examining the bacterial diversity of the nasopharyngeal microbiome in health and after viral infection will provide critical insights with regard to several secondary bacterial infections of the respiratory tract in which there is an antecedent viral infection (acute otitis media, acute bacterial pneumonia and acute bacterial sinusitis). Finally, defining the mechanisms by which respiratory viruses cause changes in the nasopharyngeal microbiome will lead to new preventative and therapeutic measures which may be instituted long before the bacterial infection evolves. PUBLIC HEALTH RELEVANCE: Acute bacterial sinusitis in children is a common and important clinical problem. This study will define the burden of acute sinusitis and identify children at greatest risk of developing sinusitis enabling the limitation of antimicrobial therapy. Ultimately, we will propose alternatives to antimicrobial agents in both prevention and treatment thereby decreasing antimicrobial resistance. These strategies will also impact on management of acute otitis media and acute bacterial pneumonia. Decreased antimicrobial use will provide a huge benefit to the public health.