Could the effect of antimicrobials on antimicrobial resistance be saturated at high-antimicrobial consumption? A comparison of the MORDOR and ResistAZM studies

Sheeba Santhini Manoharan-Basil; Zina Gestels; Saïd Abdelatti; Irith De Baetselier; Thibaut Vanbaelen; Armin Hinterwirth; Thuy Doan; Thomas Lietman; Chris Kenyon

doi:10.1016/j.ijid.2024.107082

Could the effect of antimicrobials on antimicrobial resistance be saturated at high-antimicrobial consumption? A comparison of the MORDOR and ResistAZM studies

Int J Infect Dis. 2024 May 3:145:107082. doi: 10.1016/j.ijid.2024.107082. Online ahead of print.

Authors

Sheeba Santhini Manoharan-Basil¹, Zina Gestels², Saïd Abdelatti³, Irith De Baetselier³, Thibaut Vanbaelen², Armin Hinterwirth⁴, Thuy Doan⁴, Thomas Lietman⁴, Chris Kenyon⁵

Affiliations

¹ STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium. Electronic address: sbasil@itg.be.
² STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
³ Clinical Reference Laboratory, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
⁴ Department of Ophthalmology, University of California, San Francisco, CA, USA.
⁵ STI Unit, Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Division of Infectious Diseases and HIV Medicine, University of Cape Town, Cape Town, South Africa.

PMID: 38703812
DOI: 10.1016/j.ijid.2024.107082

Abstract

Objectives: Antimicrobial resistance poses a considerable threat in high-antimicrobial-consumption populations, such as men who have sex with men (MSM) taking HIV pre-exposure prophylaxis. While the ResistAZM trial found no increase in macrolide resistance genes in MSM with gonorrhea after azithromycin treatment, the MORDOR trial observed an increase in these genes after mass azithromycin distribution. We hypothesized that this could be due to saturation of the resistome. To test this hypothesis, we compared the abundance of macrolide resistance determinants in anorectal samples between the baselines of the two trials.

Methods: Shotgun metagenome reads from the anorectal baseline samples from the ResistAZM (n = 42) and MORDOR (n = 30) trials were analyzed using AMRPlusPlus. Nonhost reads were mapped to the MEGARes database to detect antibiotic resistance genes (ARG). Antimicrobial resistance (AMR) was normalized using cumulative sum scaling, and ARG abundance was estimated.

Results: Macrolide, lincosamides, and streptogramins determinants were approximately 10-fold more abundant in the ResistAZM than the MORDOR samples (P ≤ 0.001).

Conclusion: The findings are compatible with our hypothesis. Thus, in populations with high-antimicrobial use, the relationship between antimicrobial consumption and AMR may be diminished due to saturation. These findings are vital for future studies investigating the resistogencity of novel interventions, such as doxycycline post-exposure prophylaxis, in populations with high preceding consumption of antimicrobials.

Keywords: Neisseria gonorrhoeae; Proportion resistant; Saturation of AMR.