The accidental discovery of penicillin and the threats of antibiotic resistant infections - Part 1

Sir Alexander Fleming

Close to a century ago, an accidental discovery by Sir Alexander Fleming changed the trajectory of medicine. At the time, Alexander Fleming, a Scottish assistant bacteriologist and researcher, was experimenting with microbes in the laboratory of the Inoculation Department at St. Mary's Hospital in London. Fleming was often described as a careless laboratory technician among his peers but at one time he had returned from his usual two-week holiday, he saw an unusual growth on a bacteria culture plate in the laboratory which his trained eye did not neglect. He noticed an accidental growth of a mould that had contaminated the bacteria culture plate and upon further examination, he found that the mould had stifled the growth of the bacteria (called staphylococci).

The mould prevented the growth of the bacteria, the mould was a killer of bacteria, it was a naturally occurring antibiotic drug; it was penicillin he had discovered-the first therapeutically used antibiotic. Since then, the discovery of penicillin changed the course of medicine and has enabled doctors to treat formally severe and life-threatening diseases such as bacterial endocarditis, bacterial meningitis, pneumococcal pneumonia, gonorrhoea and syphilis . Because the mould was identified as belonging to the fungus plant of the genus penicillium, Fleming named the antibacterial substance penicillin. After curiously studying the characteristics of the accidental growth for sometime, Fleming published an article in the British journal of Experimental Pathology in 1929 that reads: “The staphylococcus colonies became transparent and were obviously undergoing lysis … the broth in which the mould had been grown at room temperature for one to two weeks had acquired marked inhibitory, bactericidal and bacteriolytic properties to many of the more common pathogenic bacteria.” In his published journal, Fleming was basically describing the amazing potency and antibacterial properties of penicillin that he had observed in his lab.

In its early days, penicillin was used by many and made tremendous impact therapeutically though its therapeutic potential was unexplored. A Clinical Pathologist named Cecil George Paine successfully used penicillin to treat neonates suffering from gonorrhoea infection of the eye (gonococcal conjunctivitis) in 1930. Fleming had challenges obtaining purified penicillin in his lab so he stopped studying penicillin a year later, but his research was continued and finished by his colleagues Howard Flory and Ernst Chain at University of Oxford. Howard and Chain are the researchers who are credited with the development of penicillin for use as a medicine in mice. Their results were found to be promising and that paved the way for penicllin to be used in humans in 1941.

After the work of Howard and Chain, one of the first patients to receive a treatment with penicillin was a British policeman called Albert Alexander who had developed a deadly infection after scratching himself on a rosebush. The infection was spreading fast and poisoning his blood. After five days of penicillin injections, the infection began to heal but unfortunately, there was not enough pure penicillin available to continue the treatment so Albert eventually suffered a relapse and died a month later.

In the USA, the first patient with an infection of blood poisoning (streptococcal septicaemia) was successfully treated with penicillin in 1942. Penicillin was also used to curtail the number of deaths and amputations of soldiers during World War II. Similarly, not quite long, the impact of penicillin was evident among wounded soldiers during the Gulf War involving Iraq and the USA and her Allied Forces. Today, penicillin is considered one of the most widely used antibiotics in the world.The emergence of penicillin in the field of medicine also led the way for the development of other antibiotics such as tetracycline, aminoglycosides, streptomycin and the like by pharmaceutical companies.

It is interesting to note that despite its use in the treatment of severe and life-threatening infections, penicillin was never subjected to the rigorous scrutiny of randomised, controlled trials because the impact it had on treatment was so significant that no one thought of setting up randomised controlled trials. Randomised controlled trials are a very significant stage in new drug or vaccine development to ensure its efficacy, effectiveness and safety before it can be administered in humans. But we seem to have built up complex resistance mechanisms in germs due to misuse since the discovery of penicillin.

The misuse of antibiotics has led to the emergence of antibiotic resistance, which is considered one of the greatest threats to global public health today. Not even the warning signalled by Fleming in his Nobel lecture in 1945 about the dangers of misusing penicillin was heeded: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.

The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself, and exposing his microbes to non-lethal quantities of the drug make them resistant. " Today his words proved prophetic regarding the misuse of antibiotics and the emergence of bacterial resistance to antibiotics. Today, the misuse of antibiotics by health practitioners, unskilled practitioners and the general public is a serious challenge to the fight against antibiotic resistance globally.

Today in Ghana, non-prescriptive sale of antibiotics is widespread in the common markets, lorry stations, in buses, chemical stores and community pharmacies amid poorly enforced regulations. Today, we also see an alarming increase in new bacterial strains resistant to several antibiotics at the same time often known as multidrug-resistant bacteria or superbugs. Such bacteria may eventually become resistant to all existing antibiotics, and we will then be going back to pre-penicillin era or be entering the post-antibiotic era where physicians will run out of infection treatment options and watch their patients suffer and die helplessly. The phenomenon is already happening, and the rate is alarming. This is a wake-up call to policymakers.

Authored by: Ismael Niadawe Issaka (MLS, MPH, RSTMH Fellow)

References:

1. Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. British Journal of Experimental Pathology. 1929; 10:226-236.
2. https://ghanamedicals.com/list-of-common-stds-in-africa-with-numbers-in-2019/
3. Journal of Pharmaceutical and Biological Sciences. https://jpabs.org/misc/the-first-antibiotic-was.html