An article published in the venerable British Medical Journal (BMJ) on Wednesday has been picked up by several news agencies.

CNA-AB-2017Guardian-AB-2017

I had described this culture of doctors recommending that “antibiotic courses should be completed” in an earlier post on URTI, and how the doctors I had encountered all felt that failure to finish antibiotics would “result in antibiotic resistance developing”. In the BMJ analysis article, the authors (a mix of doctors including infectious diseases specialists, an epidemiologist, a health psychologist, and a retired building surveyor) described how the concept of “a course of antibiotics” evolved historically, as well as the idea that inadequate treatment could result in a drug-resistant pathogen that could then be transmitted to others – ironically, the first person to conceive of this latter idea and to communicate it publicly was none other than Alexander Fleming himself.

The authors usefully distinguished between “target antibiotic resistance selection” and “collateral antibiotic resistance selection”, which are important concepts for considering this quandary of an “antibiotic course”.

In the former scenario, the pathogen mutates and becomes antibiotic resistant as a consequence of inadequate therapy (inadequate dose or duration), and these drug-resistant mutants may then spread to infect others. Classic examples are: Mycobacterium tuberculosis (which causes tuberculosis), Neisseria gonorrhoeae (which causes the sexually transmitted disease gonorrhoea), the HIV virus, and the collection of Plasmodium spp. that cause malaria.

In the latter scenario, antibiotic resistance is selected in commensal/environmental bacteria as a consequence of treatment of other infections, or from giving antibiotics to livestock as growth promoters. Antibiotics are not really “silver bullets” or “targeted therapy”, but function more like nuclear bombs – ingesting a single antibiotic pill, for example, results in that antibiotic affecting the entire community of bacteria in the human body (including gut, skin, and respiratory tract commensals), as well as the environment contaminated by that person (because the antibiotic can be excreted in sweat, urine and stool). In this scenario then, the more antibiotics are prescribed (regardless of whether or not the dose/duration is appropriate or not), the more antibiotic-resistant bacteria there will be.

This second scenario is far more prevalent and of far greater concern today when one considers the problem of antibiotic resistance and the potential harm that antibiotics can achieve – and it also “co-exists” with the first scenario. Commensal or environmental bacteria seldom cause human disease, but the antibiotic resistance genes can be passed along to other bacteria that have a greater propensity to cause human disease. We have strong reasons to believe, for instance, that the genes coding for methicillin resistance and extended-spectrum beta-lactamase  (ESBL) production did not arise de novo in Staphylococcus aureus or Escherichia coli, but were transferred to them from other harmless commensal/environmental bacteria, creating MRSA and ESBL-producing Enterobacteriaceae respectively.

The authors therefore argue – quite reasonably in my opinion – that in general, we should no longer link failure to complete a course of antibiotics with the development of antibiotic resistance, and that this idea of “completing a course of antibiotics” is a great barrier to preserving the useful “life-span” of antibiotics. Patients and the general public should therefore be educated correspondingly – at least until more appropriate messages have been developed through research and testing. These messages will need to be nuanced and balanced, so that they are not unnecessarily extrapolated to the antimicrobial treatment of specific diseases such as HIV, tuberculosis, osteomyelitis or endocarditis (for the latter two, especially, stopping antibiotics early will not result in drug resistance, but will also result in higher risks of treatment failures).

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