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: Jeremy D Keenan, Keith P Klugman, Lesley McGee, Jorge E Vidal, Sopio Chochua, Paulina Hawkins, Vicky Cevallos, Teshome Gebre, Zerihun Tadesse, Paul M Emerson, James H Jorgensen, Bruce D Gaynor, Thomas M Lietman
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 211 Issue 6 Pg. 988-94 (Mar 15 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 25293366 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Anti-Bacterial Agents
• Azithromycin

Topics

• Anti-Bacterial Agents (therapeutic use)
• Azithromycin (therapeutic use)
• Child
• Child, Preschool
• Drug Resistance, Bacterial
• Female
• Genes, Bacterial
• Humans
• Infant
• Infant, Newborn
• Male
• Multilocus Sequence Typing
• Nasal Cavity (microbiology)
• Pneumococcal Infections (drug therapy, microbiology)
• Streptococcus pneumoniae (drug effects, genetics, isolation & purification)