James D.
and Mathias W.
On returning from holiday to St Mary’s Hospital in London in 1928, Alexander Fleming
discovered something unexpected on a Petri dish containing Staphylococcus. Contamination
of the plate with a rare Penicillium fungus led to a zone of bacterial killing, demonstrating
that the fungus was secreting a factor that killed staphylococci.
Fleming observed that an extract from this fungus could kill a wide range of bacteria,
particularly Gram-positive bacteria. Subsequent work confirmed that some organisms were
susceptible to the Penicillium extract, while many, particularly Gram-negative organisms,
were not. Indeed the initial application of penicillin published in the British Journal of
Experimental Pathology in June 1929 appeared to be as a method to differentiate between
different bacteria in the laboratory [1]. However, in his Nobel Lecture on December 11,
1945, Fleming had already foreseen the “antibiotic resistance crisis” caused by overuse and
underdosing [2]:
But I would like to sound one note of warning. 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 by exposing his microbes to non-lethal
quantities of the drug make them resistant.
Thus, through a remarkable accident, one of the greatest medical advances in history was
made, i.e. the ability to cure disease through antibiotic treatment, and simultaneously the
threat of antibiotic resistance was also discovered.
These competing opportunities and threats continue in parallel to this day.
The lung is the key interface between the human body and the microbial world, with an
average person with a normal breathing rate inhaling nearly 1 000000 bacteria per day. It is
therefore not surprising that respiratory tract infections are the most common reason for
antibiotic prescribing in both primary and secondary care, and a leading cause of mortality
worldwide. Despite advances in hygiene and the availability of antimicrobials, TB and
pneumonia remain devastating on a global level, while bronchiectasis, cystic fibrosis, pleural
Copyright ©ERS 2017. Print ISBN: 978-1-84984-083-5. Online ISBN: 978-1-84984-084-2. Print ISSN: 2312-508X. Online ISSN: 2312-5098.
Correspondence: James D. Chalmers, Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital, Dundee, DD1 9SY,
UK. E-mail:
of Pathophysiology and Transplantation, University of Milan, and Cardio-thoracic Unit and Adult Cystic Fibrosis Centre,
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.
Centre for Respiratory Research, University of
Dundee, Dundee, UK.
for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany.
Research Campus, Jena, Germany.
for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
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