The emergence of antibiotic resistance

There is increasing evidence that antibiotics are ancient, originating anywhere between two billion and 40 million years ago. Resistance is also ancient and certainly predates the medical use of antibiotics. A paper published in 2011 reported on an analysis of bacteria isolated from deep in the permafrost of the Yukon Canada. This permanently frozen ground had preserved 30,000-year-old bacteria so well that it was possible to detect bacterial genes and coding for resistance to a range of antibiotics, including members of the penicillin family, tetracyclines, and glycopeptides. Amazingly, glycopeptide resistance genes could be synthesised from their DNA sequence and used to generate enzymes that were functionally very similar to modern day vancomycin resistance enzymes.

Even much of the structure of the ancient vancomycin resistance proteins were similar to contemporary vancomycin resistance enzymes. The authors concluded that resistance is an ancient, naturally occurring phenomenon, and that new antibiotics introduced into clinical practise will rapidly select for preexisting resistance determinants that have been circulating within the microbial community for thousands of years.

The rapid emergence of resistance following the introduction of a new antibiotic class into medical practise is certainly something that has been seen several times. Mary Barber, a British bacteriologist, was among the first to draw attention to this concern. In 1947, she wrote a letter to the British Medical Journal that described how more and more strains of Staphylococcus bacteria isolated from clinical specimens in her laboratory were proving to be resistant to penicillin. Up to 38% of the Staphylococcal islets tested were found to be resistant within around five years, after the introduction of penicillin into clinical practise. Dr.

Barber clearly identified the problem when she wrote, “It is obvious that the main cause for this increase in resistance is the widespread use of penicillin, although a patient yielding such an organism may not himself have ever had any.” She went on to write that in her opinion, this was not an example of bacteria becoming resistant to penicillin, but a process of natural selection of resistant strains driven by the use of penicillin and subsequent person-to-person spread.

This slide juxtaposes the date of introduction of antibiotics with the date of identification of clinically important resistant bacteria. A regular feature, which is obvious from this slide, is the short interval between the date of first regular clinical use of a new antibiotic and the date when resistance was first identified. This is such a regular and predictable phenomenon that it really deserves to be considered as a law of nature. It is certainly something that presents an important challenge to everyone responsible for antibiotic prescribing.