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

Keenan JD1, Klugman KP2, McGee L3, Vidal JE2, Chochua S4, Hawkins P4, Cevallos V5, Gebre T6, Tadesse Z6, Emerson PM7, Jorgensen JH8, Gaynor BD1,Lietman TM1.

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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 pre-existing resistant bacterial strains.

METHODS:

Mass azithromycin was distributed to 12 communities in Ethiopia every 3 months for 1 year. A random sample of 10 children aged 0-9 years from each community was monitored with nasopharyngeal swabs before mass azithromycin distributions and after 4 mass treatments; S. pneumoniae was isolated and multilocus sequence typing performed.

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=0.04). Using a classification index, we found evidence for a relationship between ST and macrolide resistance after mass treatments (P<0.0001). The diversity of STs-as calculated by the unbiased Simpson's index-decreased significantly after mass azithromycin treatment (P=0.045).

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.