Less Antibiotic Use Lowers Prevalence of Genetic Antibiotic Resistance Determinants

Communities randomly assigned to less frequent use of antibiotics may have a significantly lower prevalence of genetic antibiotic resistance determinants, according to a study recently published in Clinical Infectious Diseases.¹ 

Antibiotic selective pressure contributes to the spread of resistant bacteria² and although it has been difficult to study, mass drug administrations for trachoma provide an opportunity to do so. After the World Health Organization called for the global elimination of trachoma by 2020, mass distributions of azithromycin to entire communities resulted, making trials of mass drug administrations an attractive way to study community spread of antibiotic resistance. This cluster-randomized trial determined the causal relationship between antibiotic consumption and antibiotic resistance by comparing 2 different frequencies of mass azithromycin distribution for trachoma.

This study describes a secondary outcome of the Niger site of the Partnership for the Rapid Elimination of Trachoma study (PRET; ClinicalTrails.gov identifier: NCT00792922). A total of 24 communities were randomly assigned (via stratification on health catchment area and trachoma prevalence) for either annual or biannual mass azithromycin distribution for trachoma. Communities were eligible if they had a population of 250 to 600 people and had >10% prevalence of clinically active trachoma among children 0 to 5 years of age. Active trachoma was defined as the presence of trachomatous inflammation-follicular and/or trachomatous inflammation-intense.

For resistance testing, 5 swabs from the baseline visit and 5 from the 24-month visit were randomly selected from each of the 24 communities, resulting in 240 total swabs. Swabs were processed for the genetic macrolide resistance determinants ermB and mefA/E in a masked fashion by means of polymerase chain reaction. This analysis characterized the resistome of the entire nasopharyngeal niche as opposed to the resistance of a single bacterial isolate.

The prevalence of genetic macrolide resistance determinants was identical in both the annual and biannual group before treatment, with a median of 20% for each community’s 5 randomly selected swabs positive for ermB and/or mefA/E. After 2 years of mass treatments, there was an increase in the proportion of swabs positive for ermB and/or mefA/E, with a median of 40% in the annual group (P =.08) and 60% in the biannual group (P =.002). Furthermore, the biannually treated communities were more likely to test positive for ermB or mefA/E at month 24 than were the annually treated communities (P <.001). The 24-month prevalence of macrolide resistance determinants remained higher than the annual group by 29.4% after adjusting for baseline. Overall, results suggest that more frequent mass azithromycin treatments for trachoma were causally associated with an increased prevalence of genetic macrolide resistance.

Study authors concluded that “reducing levels of antibiotic consumption in a population is an effective method for reducing the community prevalence of antibiotic resistance.

References

1. Keenan JD, Chin SA, Amza A, et al; PRET Study Group. The effect of antibiotic selection pressure on the nasopharyngeal macrolide resistome: a cluster-randomized trial [published online April 20, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy339
2. Lipsitch M, Samore MH. Antimicrobial use and antimicrobial resistance: a population perspective. Emerg Infect Dis. 2002;8(4):347-354.