The emergence of drug resistant pneumococcal disease is a significant public health problem. Risk factors include individual use of antibacterial drugs as well as social factors that promote human-to-human transmission of the pathogen. In addition, the introduction of a new vaccine for use in children has resulted in strong selective forces that are changing the epidemiology of this disease. Understanding the relationship between these forces is a critical component of efforts to design programs to preserve the efficacy of antimicrobial drugs for the future. Few studies have considered the geographic nature of this problem in analyzing the relationship between individual and community-level risk factors. The proposed study is a novel merger of geographical, epidemiological and microbiological analytic strategies to identify factors that promote the spread of drug resistant pneumococci. Our primary aim is to compare the serological, molecular, and geographic distributions of macrolide resistant and macrolide susceptible pneumococci over the Southeastern Pennsylvania region. Our hypothesis is that antibiotic susceptibility displays significant geographic heterogeneity over a small region and that heterogeneity reveals small-area characteristics, which increase the spread of drug resistant S. pneumoniae. The proposed study is a population-based case-control study to compare the individual and community level characteristics of patients with drug resistant and susceptible pneumococcal bacteremia with a focus on macrolide resistant infections. By identifying all bacteremic pneumococcal infections within a 5 county region, we will be able to examine small area heterogeneity in the levels of drug susceptibility. Serological and molecular typing of all isolates will permit separate analyses for geographic heterogeneity within subgroups of isolates that are clonally related as well as assess the impact of vaccine strategies on the spread of drug resistance. Statistical analyses incorporating multilevel and diffusion models will examine spatial and temporal relationships over a six-year period in order to determine the relative impact of individual and community-level factors on the spread of drug resistant pneumococcal infections. This proposal is a competitive renewal of an ongoing population-based case-control study to develop a prediction rule for penicillin drug resistance among patients with bacteremic pneumococcal pneumonia. The proposed study will maintain our enrollment over an additional three years in order to complete six-years of active enrollment and achieve the necessary sample size for the proposed molecular and geographic analyses. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI046645-05A1
Application #
6872501
Study Section
Special Emphasis Panel (ZRG1-HOP-N (90))
Program Officer
Lambert, Linda C
Project Start
2000-04-01
Project End
2010-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$621,971
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Feemster, K A; Li, Y; Localio, A R et al. (2013) Risk of invasive pneumococcal disease varies by neighbourhood characteristics: implications for prevention policies. Epidemiol Infect 141:1679-89
Liu, Zhenying; Nachamkin, Irving; Edelstein, Paul H et al. (2012) Serotype emergence and genotype distribution among macrolide-resistant invasive Streptococcus pneumoniae isolates in the postconjugate vaccine (PCV-7) era. Antimicrob Agents Chemother 56:743-50
Metlay, Joshua P; Lautenbach, Ebbing; Li, Yimei et al. (2010) Exposure to children as a risk factor for bacteremic pneumococcal disease: changes in the post-conjugate vaccine era. Arch Intern Med 170:725-31
Flory, J H; Joffe, M; Fishman, N O et al. (2009) Socioeconomic risk factors for bacteraemic pneumococcal pneumonia in adults. Epidemiol Infect 137:717-26
Berjohn, Catherine M; Fishman, Neil O; Joffe, Marshall M et al. (2008) Treatment and outcomes for patients with bacteremic pneumococcal pneumonia. Medicine (Baltimore) 87:160-6
Gould, Carolyn V; Sniegowski, Paul D; Shchepetov, Mikhail et al. (2007) Identifying mutator phenotypes among fluoroquinolone-resistant strains of Streptococcus pneumoniae using fluctuation analysis. Antimicrob Agents Chemother 51:3225-9
Metlay, Joshua P; Fishman, Neil O; Joffe, Marshall M et al. (2006) Macrolide resistance in adults with bacteremic pneumococcal pneumonia. Emerg Infect Dis 12:1223-30
Metlay, Joshua P; Fishman, Neil O; Joffe, Marshall et al. (2006) Impact of pediatric vaccination with pneumococcal conjugate vaccine on the risk of bacteremic pneumococcal pneumonia in adults. Vaccine 24:468-75
Czaja, Chris; Crossette, Linda; Metlay, Joshua P (2005) Accuracy of adult reported pneumococcal vaccination status of children. Ann Epidemiol 15:253-6
Metlay, Joshua P; Branas, Charles C; Fishman, Neil O (2004) Hospital-reported pneumococcal susceptibility to penicillin. Emerg Infect Dis 10:54-9