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J Infect Dis. 2015 Mar 15;211(6):988-94. doi: 10.1093/infdis/jiu552. Epub 2014 Oct 6.

Evidence for clonal expansion after antibiotic selection pressure: pneumococcal multilocus sequence types before and after mass azithromycin treatments.

Author information

1
Francis I Proctor Foundation Department of Ophthalmology, University of California, San Francisco.
2
Hubert Department of Global Health, Rollins School of Public Health, Emory University.
3
Respiratory Diseases Branch, Centers for Disease Control and Prevention.
4
Hubert Department of Global Health, Rollins School of Public Health, Emory University Respiratory Diseases Branch, Centers for Disease Control and Prevention.
5
Francis I Proctor Foundation.
6
The Carter Center, Addis Ababa, Ethiopia.
7
The Carter Center, Atlanta, Georgia.
8
University of Texas Health Sciences Center, San Antonio.

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.

KEYWORDS:

Africa; MLST; Streptococcus pneumoniae; clonal expansion; multilocus sequence typing

PMID:
25293366
PMCID:
PMC4416126
DOI:
10.1093/infdis/jiu552
[Indexed for MEDLINE]
Free PMC Article

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