Journal Article

Pre-exposure to azithromycin enhances gonococcal resilience to subsequent ciprofloxacin exposure: an in vitro study version 2; peer review: 2 approved

González, Natalia, Abdellati, Saïd, de Block, Tessa, Van Dijck, Christophe, Elise Laumen, Jolein Gyonne, S. Manoharan-Basil, Sheeba, De Baetselier, Irith, Kenyon, Chris

2023

Overview

Background: The effect of sequential exposure to different antibiotics is an underexplored topic. Azithromycin can be detected in humans for up to 28 days post-ingestion and may prime bacterial responses to subsequently ingested antibiotics. Methods: In this in vitro study, we assessed if preexposure to azithromycin could accelerate the acquisition of resistance to ciprofloxacin in Neisseria gonorrhoeae reference strain, WHO-F. In a morbidostat, we set two conditions in 3 vials each: mono-exposure (preexposure to Gonococcal Broth followed by exposure to ciprofloxacin) and dual sequential exposure (preexposure to azithromycin followed by exposure to ciprofloxacin).The growth of the cultures was measured by a software (MATLAB). The program decided if gonococcal broth or antibiotics were added to the vials in order to keep the evolution of the cultures. Samples were taken twice a week until the end of the experiment i.e. until resistance was achieved or cellular death. Additionally, six replicates of WHO-F WT and WHO-F with rplV mutation, caused by azithromycin, were exposed to increasing concentrations of ciprofloxacin in plates to assess if there were differences in the rate of resistance emergence. Results: We found that after 12 hours of pre-exposure to azithromycin, N. gonorrhoeae's resilience to ciprofloxacin exposure increased. Pre-exposure to azithromycin did not, however, accelerate the speed to acquisition of ciprofloxacin resistance. Conclusions:  We found that azithromycin does not accelerate the emergence of ciprofloxacin resistance, but there were differences in the molecular pathways to the acquisition of ciprofloxacin resistance: the strains preexpossed to azithromycin followed a different route (GyrA: S91F pathway) than the ones without antibiotic preexposure (GyrA:D95N pathway). However, the number of isolates is too small to draw such strong conclusions.

• Publisher: Faculty of 1000 Ltd,F1000 Research Limited,F1000 Research Ltd
• Subject: AMR / Anti-Bacterial Agents - pharmacology / Anti-Bacterial Agents - therapeutic use / Antibiotics / Antimicrobial agents / antimicrobial consumption / Azithromycin / Azithromycin - pharmacology / Bacteria / Ciprofloxacin / Ciprofloxacin - pharmacology / Drug resistance / Drug Resistance, Bacterial / eng / Experiments / fluoroquinolone / Gonorrhea / Gonorrhea - drug therapy / Humans / Hypotheses / macrolide / Microbial Sensitivity Tests / Mutation / N. gonorrhoeae / Neisseria gonorrhoeae / Proteins / resistance / Software