Lack of Association between Antimicrobial Consumption and Antimicrobial Resistance in a HIV Preexposure Prophylaxis Population: A Cross-Sectional Study

Abstract

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV preexposure prophylaxis (PrEP) have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6 months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population.

Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals.

Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals.

Conclusions: We conclude that in high-antimicrobial-consumption populations, the association between antimicrobial consumption and resistance may be attenuated. This conclusion would not apply to lower-consumption populations.

Keywords: Neisseria gonorrhoeae; Neisseria subflava; PrEP; antimicrobial resistance; gonorrhoea; saturation; stewardship.

Figure 1

A schematic of how high antimicrobial consumption in a population could obscure the association between azithromycin (AZM) consumption and azithromycin resistance in oral streptococci in three individuals: Andy, Bill and Chris. In the low-azithromycin-consumption population (A), all the streptococci are susceptible (green) to azithromycin at baseline. Bill takes azithromycin at time point 1, which has the twin effect of selecting for resistant streptococci (red) and reducing the abundance of susceptible streptococci [27]. This niche can be refilled by the growth of endogenous streptococci but also via transmission from Andy and Chris [27]. If the resistant streptococci have a fitness cost, then the susceptible streptococci should replace the resistant isolates. Azithromycin administered at the third time point to any individual would still have a detectable effect on resistance. In the high-consumption population (B), Andy, Bill and Chris take azithromycin at time point 1, which has the same effect, with a notable difference in that due to Bill’s preceding azithromycin exposure, the main effect of the azithromycin is to increase the absolute number of resistant streptococci in his oropharynx [27]. This in turn, increases the probability that the transmission of his resistant streptococci to Andy and Bill will take place to fill their oral niches that have been depopulated through azithromycin (red arrows). Continuing exposure to azithromycin leads to all three individuals being colonised predominantly by azithromycin resistant streptococci. In this setting, from time point 3 onward, there would be a high probability of finding no association between azithromycin consumption and resistance. (For a review of all the five population-level pathways that link antimicrobial exposure to AMR, please see [27]; Created with BioRender.com).