A paper published in Lancet Infectious Diseases (behind a paywall) by researchers from the Institut Pasteur and the French National Reference Centre for Escherichia coliShigella and Salmonella generated much buzz online among those interested in antimicrobial resistance.

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They had studied 288 historical (1911-1969) isolates of Salmonella enterica serotype Typhimurium – a zoonotic bacterium that is one of the most common causes of non-typhoidal Salmonella invasive disease in immunocompromised humans – and had found 11 with ampicillin resistance genes (mostly TEM-1B and OXA) on a variety of plasmids. In particular, 3 isolates were obtained from human clinical samples in 1959 and 1960.

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Screen capture from the paper published in Lancet Infectious Diseases last week, showing the distribution of S. enterica serovar Typhimurium isolates from the study.
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Screen capture from the paper published in Lancet Infectious Diseases last week, showing the 3 pre-1961 S. enterica serovar Typhimurium isolates with ampicillin resistance.

Why would this be of any interest? It turns out that ampicillin was only commercialised by Beecham Research Laboratories in 1961, where it was marketed under two trade names Penbritin and Polycillin (behind a paywall). How could ampicillin resistance – moreover transmissible ampicillin resistance – arise before the drug was widely consumed?

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Screen capture from Anderson and Datta’s 1965 article from the Lancet.

The authors postulated that their findings supported the hypothesis of others in the past – such as Dr E.S. Anderson and Dr Naomi Datta from U.K. – who had implicated the use of penicillins as growth promoters in livestock. Penicillin has very poor activity against Enterobacteriaceae (such as Salmonella spp. and E. coli), and the penicillin concentration required for treating infections in humans – even for ampicillin-susceptible Enterobactericeae isolates – is extremely high. However, such high concentrations may not be necessary in the environment in order to exert a selection pressure that led to the appearance of ampicillin resistance plasmids in S. enterica serotype Typhimurium.

Similar “archaeological” studies that help us understand the complicated relationship between antibiotic use and resistance should hopefully be performed and published in the near future, and these studies also help us understand the value of archiving bacterial isolates (and by extension, clinical samples), which permit a future generation to better understand the phenomena that we poorly comprehend today.

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