title: Evidence for clonal expansion after antibiotic selection pressure: pneumococcal multilocus sequence types before and after mass azithromycin treatments.
abstract: BACKGROUND
  A clinical trial of mass azithromycin distributions for trachoma created a convenient experiment to test the hypothesis that antibiotic use selects for clonal expansion of preexisting resistant bacterial strains.
  
  
  METHODS
  Twelve communities in Ethiopia received mass azithromycin distributions every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored by means of nasopharyngeal swab sampling before mass azithromycin distribution and after 4 mass treatments. Swab specimens were tested for Streptococcus pneumoniae, and isolates underwent multilocus sequence typing.
  
  
  RESULTS
  Of 82 pneumococcal isolates identified before treatment, 4 (5%) exhibited azithromycin resistance, representing 3 different sequence types (STs): 177, 6449, and 6494. The proportion of isolates that were classified as one of these 3 STs and were resistant to azithromycin increased after 4 mass azithromycin treatments (14 of 96 isolates [15%]; P = .04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P < .0001). The diversity of STs-as calculated by the unbiased Simpson index-decreased significantly after mass azithromycin treatment (P = .045).
  
  
  CONCLUSIONS
  Resistant clones present before mass azithromycin treatments increased in frequency after treatment, consistent with the theory that antibiotic selection pressure results in clonal expansion of existing resistant strains.
authors.affiliation: Francis I Proctor Foundation Department of Ophthalmology, University of California, San Francisco.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Keenan
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Klugman
authors.affiliation: Respiratory Diseases Branch, Centers for Disease Control and Prevention.
authors.forename: Lesley
authors.initials: L
authors.lastname: McGee
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Vidal
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University Respiratory Diseases Branch, Centers for Disease Control and Prevention.
authors.forename: Sopio
authors.initials: S
authors.lastname: Chochua
authors.affiliation: Hubert Department of Global Health, Rollins School of Public Health, Emory University Respiratory Diseases Branch, Centers for Disease Control and Prevention.
authors.forename: Paulina
authors.initials: P
authors.lastname: Hawkins
authors.affiliation: Francis I Proctor Foundation.
authors.forename: Vicky
authors.initials: V
authors.lastname: Cevallos
authors.affiliation: The Carter Center, Addis Ababa, Ethiopia.
authors.forename: Teshome
authors.initials: T
authors.lastname: Gebre
authors.affiliation: The Carter Center, Addis Ababa, Ethiopia.
authors.forename: Zerihun
authors.initials: Z
authors.lastname: Tadesse
authors.affiliation: The Carter Center, Atlanta, Georgia.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Emerson
authors.affiliation: University of Texas Health Sciences Center, San Antonio.
authors.forename: James H
authors.initials: JH
authors.lastname: Jorgensen
authors.affiliation: Francis I Proctor Foundation Department of Ophthalmology, University of California, San Francisco.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gaynor
authors.affiliation: Francis I Proctor Foundation Department of Ophthalmology, University of California, San Francisco.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Lietman
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D005260:Female; D005798:Genes, Bacterial; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D058885:Multilocus Sequence Typing; D009296:Nasal Cavity / Q000382:microbiology; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin
keywords: Africa; MLST; Streptococcus pneumoniae; clonal expansion; multilocus sequence typing