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Abstract
BackgroundDoes the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the MIC distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible.MethodsWe conducted a historical analysis based on a literature review of changes of N. gonorrhoeae MIC distribution over the past 75 years for 3 antimicrobials (benzylpenicillin, ceftriaxone and azithromycin) in five countries (Denmark, Japan, South Africa, the United Kingdom and the United States).ResultsChanges in MIC distribution were most marked for benzylpenicillin and showed evidence of a right shifting of MIC distribution that was associated with a reduction/elimination of susceptible strains in all countries. In the case of ceftriaxone and azithromycin, where only more recent data was available, right shifting was also found in all countries but the extent of right shifting varied and the evidence for the elimination of susceptible strains was more mixed.ConclusionsThe finding of right shifting of MIC distribution combined with reduction/elimination of susceptible strains is of concern since it suggests that this shifting may not be reversible. Since excess antimicrobial consumption is likely to be responsible for this right shifting, this insight provides additional impetus to promote antimicrobial stewardship.
Highlights
Does the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the minimum inhibitory concentrations (MIC) distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible
Typically, investigations of antimicrobial resistance (AMR) in Neisseria gonorrhoeae have focused on the right-hand tail of the MIC distributions [1,2,3]
An under investigated topic is what happens to the left-hand tail of the MIC distribution and whether or not the emergence of AMR is associated with a right shifting of the entire MIC distribution including the left-hand tail [4,5,6,7]? One previous ecological analysis of 5 year data from 24 European countries found that the emergence of gonococcal AMR was associated with a right shift of the susceptible isolates [6]
Summary
Does the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the MIC distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible. Increase in gonococcal AMR leads to a wider MIC distribution This is followed, in the second stage, by a reduction in MIC distribution width as most of the highly susceptible isolates are lost through evolution. This process leads to the (close to) elimination of the highly susceptible isolates in type A (stage 2 and 3) but not B shifts. An elimination of highly susceptible strains would likely increase the risk that the loss of susceptibility is irreversible This may have important consequences for gonococcal AMR and that of commensal bacteria. If excess antimicrobial consumption results in a type A, stage 2 or 3 trajectory in N. gonorrhoeae and in these commensal species this may be a warning of more wide-ranging adverse effects of antimicrobials on our microbiomes and resistomes [10]
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