Reflections on speeches by Nobel Prize winners - Bob Dylan to Alexander Fleming to BLING-3
The Nobel Prize website is full of absolute gems. In addition to a searchable list of "who won" and "what for", it also has bios of the winners, a listing of who nominated them and PDFs of both their Nobel lecture and their banquet speech.
Bob Dylan's fabulous speech is found here:
https://www.nobelprize.org/nobel_prizes/literature/laureates/2016/dylan-lecture.html
Moving back to ID, Sir Alexander Fleming's Nobel lecture can be found here:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf
For those of you who are microbiologists, it is interesting to learn that Fleming used his newly discovered penicillin as a selective agent in culture medium to isolate Bordetella pertussis and "Pfeiffer's influenza bacillus" (presumably H. influenzae) from respiratory samples.
Famously Fleming delivered an important message to those of us who are antibiotic stewards or interested in antibiotic dosing:
"I would like to sound one note of warning. Penicillin is to all intents
and purposes non-poisonous so there is no need to worry about giving an
overdose and poisoning the patient. There may be a danger, though, in
underdosage. 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.
Here is a hypothetical illustration. Mr. X. has a sore
throat. He buys some penicillin and gives himself, not enough to kill the
streptococci but enough to educate them to resist penicillin. He then infects
his wife. Mrs. X gets pneumonia and is treated with penicillin. As the streptococci
are now resistant to penicillin the treatment fails. Mrs. X dies. Who
is primarily responsible for Mrs. X’s death? Why Mr. X whose negligent
use of penicillin changed the nature of the microbe. Moral: If you use penicillin,
use enough."
Important lessons indeed!
In Fleming's era, "enough" of an antibiotic was not well defined. We now know that it is not just the dosage of an antibiotic, but also the frequency and the duration of administration which are important determinants of "what is enough".
Continuous infusion or extended-infusion of beta-lactam antibiotics remains a hot topic.
We had been hoping that "BLING-2" would have given the answer. (read it here:)
Unfortunately, it didn't answer the question so BLING-3 has now been funded.
http://www.anzics.com.au/CTGmembers/Noosa_2017_Thursday/ANZICS_CTG_19th_Annual_Meet_BLING_III_Lipman.pdf
Let's hope it delivers answers to the question as to whether continuous infusion truly improves patient outcomes!
Bob Dylan's fabulous speech is found here:
https://www.nobelprize.org/nobel_prizes/literature/laureates/2016/dylan-lecture.html
Moving back to ID, Sir Alexander Fleming's Nobel lecture can be found here:
https://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf
For those of you who are microbiologists, it is interesting to learn that Fleming used his newly discovered penicillin as a selective agent in culture medium to isolate Bordetella pertussis and "Pfeiffer's influenza bacillus" (presumably H. influenzae) from respiratory samples.
Famously Fleming delivered an important message to those of us who are antibiotic stewards or interested in antibiotic dosing:
"I would like to sound one note of warning. Penicillin is to all intents
and purposes non-poisonous so there is no need to worry about giving an
overdose and poisoning the patient. There may be a danger, though, in
underdosage. 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.
Here is a hypothetical illustration. Mr. X. has a sore
throat. He buys some penicillin and gives himself, not enough to kill the
streptococci but enough to educate them to resist penicillin. He then infects
his wife. Mrs. X gets pneumonia and is treated with penicillin. As the streptococci
are now resistant to penicillin the treatment fails. Mrs. X dies. Who
is primarily responsible for Mrs. X’s death? Why Mr. X whose negligent
use of penicillin changed the nature of the microbe. Moral: If you use penicillin,
use enough."
Important lessons indeed!
In Fleming's era, "enough" of an antibiotic was not well defined. We now know that it is not just the dosage of an antibiotic, but also the frequency and the duration of administration which are important determinants of "what is enough".
Continuous infusion or extended-infusion of beta-lactam antibiotics remains a hot topic.
We had been hoping that "BLING-2" would have given the answer. (read it here:)
A Multicenter Randomized Trial of Continuous versus
Intermittent β-Lactam Infusion in Severe Sepsis.
Dulhunty JM, Roberts JA, Davis JS, Webb SA, Bellomo R, Gomersall C,
Shirwadkar C, Eastwood GM, Myburgh J, Paterson DL, Starr T, Paul SK, Lipman J;
BLING II Investigators for the ANZICS Clinical Trials Group *.
Am J Respir Crit Care
Med. 2015 Dec 1;192(11):1298-305.
PMID:26200166
Unfortunately, it didn't answer the question so BLING-3 has now been funded.
http://www.anzics.com.au/CTGmembers/Noosa_2017_Thursday/ANZICS_CTG_19th_Annual_Meet_BLING_III_Lipman.pdf
Let's hope it delivers answers to the question as to whether continuous infusion truly improves patient outcomes!
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