Minimal impact on the resistome of children in Botswana after azithromycin treatment for acute severe diarrhoeal disease

Allison K Guitor; Anna Katyukhina; Margaret Mokomane; Kwana Lechiile; David M Goldfarb; Gerard D Wright; Andrew G McArthur; Jeffrey M Pernica

doi:10.1093/infdis/jiae049

Minimal impact on the resistome of children in Botswana after azithromycin treatment for acute severe diarrhoeal disease

J Infect Dis. 2024 Jan 31:jiae049. doi: 10.1093/infdis/jiae049. Online ahead of print.

Authors

Allison K Guitor^{1

2

3}, Anna Katyukhina^{1

2

3}, Margaret Mokomane^{4

5}, Kwana Lechiile⁶, David M Goldfarb^{6

7}, Gerard D Wright^{1

2

3}, Andrew G McArthur^{1

2

3}, Jeffrey M Pernica^{2

8

9}

Affiliations

¹ Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
² Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.
³ David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada.
⁴ School of Allied Health Professions, Faculty of Health Sciences University of Botswana, Gaborone, Botswana.
⁵ Botswana National Health Laboratory, Gaborone, Botswana.
⁶ Botswana-UPenn Partnership, Gaborone, Botswana.
⁷ Department of Pathology and Laboratory Medicine, BC Children's Hospital, Vancouver, British Columbia, Canada.
⁸ Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
⁹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

PMID: 38298144
DOI: 10.1093/infdis/jiae049

Abstract

Background: Macrolide antibiotics, including azithromycin, can reduce under-five mortality rates and treat various infections in children in sub-Saharan Africa. These exposures, however, can select for antibiotic-resistant bacteria in the gut microbiota.

Methods: Our previous randomized controlled trial (RCT) of a rapid-test-and-treat strategy for severe acute diarrhoeal disease in children in Botswana included an intervention (three-day azithromycin dose) group and a control group that received supportive treatment. In this prospective matched cohort study using stools collected at baseline and 60 days after treatment from RCT participants, the collection of antibiotic resistance genes or resistome was compared between groups.

Results: Certain macrolide resistance genes increased in prevalence by 13% to 55% at 60 days, without differences in gene presence between the intervention and control groups. These genes were linked to tetracycline resistance genes and mobile genetic elements.

Conclusions: Azithromycin treatment for bacterial diarrhoea for young children in Botswana resulted in similar effects on the gut resistome as the supportive treatment and did not provide additional selective pressure for macrolide resistance gene maintenance. The gut microbiota of these children contains diverse macrolide resistance genes that may be transferred within the gut upon repeated exposures to azithromycin or co-selected by other antibiotics.

Keywords: antibiotic resistance; azithromycin; bacterial diarrhoea.