Bacteria are masters of survival, but they are also very efficient.They generally will not expend energy on something unless they have to, and that includes energy required for antimicrobial resistance. Bacteria best avoid becoming resistant to a particular antimicrobial if they can avoid exposure ( i.e. hide) to that anti-microbial (or a similar one). Antimicrobial exposure selects out resistant mutants of the bacterium.

Those that know me will be aware that I do not foresee a doomsday scenario in which all bacteria will be resistant to all antibiotics. This is mainly due to the fact that most bacterial populations exist in open systems (more about this in a later article).

However I do have some concerns about Neisseria gonorrhoeae, and in particular its susceptibility to ceftriaxone. This is simply because it is not very good at “hiding”, for the reasons below:

• N. gonorrhoeae usually only found in human flora: Other bacteria may be found both in human and environmental niches. The environmental niche may be a hiding place for bacteria from antibacterials manufactured in high dose for human consumption. (In the “pre-human antibiotic era”, bacteria that were confined solely to human flora did not need to be resistant, as they were to a large degree protected from naturally occurring antibacterial substances in the environment.)
• When N. gonorrhoeae found in humans, it usually causes symptoms rather than just colonising. Apart from a portion of females, most people who harbour Neisseria gonorrhoeae have symptoms. This usually triggers a visit to the doctors and ensuing antibiotic exposure. (Bacteria that mainly colonise can hide to some extent from antimicrobial pressure.)
• When “found”, the bacteria are usually exposed to ceftriaxone. The recent introduction of molecular testing has meant that more and more Neisseria gonorrhoeae is being diagnosed without antimicrobial susceptibility testing being performed. This means the majority of people are being exposed to ceftriaxone the only real empiric antibiotic that is available (at the moment). The bacteria are unable to “hide” from ceftriaxone by being exposed to another antibiotic.

There are already reports of Neisseria gonorrhoeae isolates that are becoming resistant to ceftriaxone. Given the points above, I fear that this is going to become more likely. (Click here for a presentation on multi-drug resistant gonorrhoea)

and the answer…Difficult to see an answer here. I think we have a genuine problem. Higher dosing with ceftriaxone may reduce the chances of ceftriaxone resistant mutants being selected out. It may be that as resistance to ceftriaxone gradually increases, we will be forced back into universal susceptibility testing for Neisseria gonorrhoeae.

Michael

Note that Streptococcus pyogenes is another organism that might fall into that “No hiding place” category of bacteria, in that it is confined to the niche of human flora, it usually infects rather than colonises, and is predominantly treated with one antibiotic, ie penicillin. Fortunately, Strep pyogenes is still exquisitely susceptible to beta-lactams so it may be some time (decades) before the resistance appears.

Click here for a few MCQs on Neisseria gonorrhoeae.