Clostridium epidemics and the overprescription and use of antibiotics - some history notes

Lancelot Hogben in his entertaining "unauthorised autobiography" explained how when he was Head of Medical Statistics at the War Office his team unearthed the localised resistance of Neisseria gonorrhoeae in the region of Naples at the end of the war.

This resistance of up to 40% of the strains tested, was a direct result of the German military medical authorities in providing free supplies of sulphonamides as a prophylactic measure to prostitutes who might entertain the bored German soldiery.

This is the first recorded instance of micro-organisms developing resistance to chemical treatments. A remarkable and little known success of medical science.

Hgben was to remark in his autobiography ( page 186) that even 15 years later "surgeons were dismayed by the incidence of post-operative sepsis due to resistant strains of microorganisms which had developed following indiscriminate prescribing of sulphonamides and antiobiotics."

The continuing widespread use of vancomycin and other "wide spectrum" antibiotics in UK medicine which has contributed (with many other factors) to the epidemics of Staphylococcal and Clostridium is a lesson still to be learnt over 60 years later.

History of Sulfonamides

Bayer AG (who had synthesised apirin) first synthesised the drug as part of their work on dye chemicals, they eventually marketed as Prontasil in 1932. This was undertaken by Josef Klarer and was tested in animals by Gerhard Domagk.

For this Klarer was awarded the 1939 Nobel prize, but in 1937, Hitler had issued a decree that forbade Germans from accepting Nobel Prizes. He considered pacifist journalist Carl von Ossiettzky's 1935 peace prize a slap in the face. ( He was a German pacifist, editor of the antimilitarist weekly Weltbühne from 1927, imprisoned in 1932 for articles exposing secret rearmament in Germany. After election in 1933 Hitler had him put in a concentration camp. Suffering from tuberculosis, he was removed to a prison hospital shortly before the announcement that he had been awarded the 1935 Nobel Peace Prize. Brandt a Swedish MP nominated Hitler for the Peace prize in 1938 !)

Publication of the results of the antiobiotic effects of the sulphonamides was delayed until 1935 and it was patented at the same time by Klarer and his research partner Fritz Mietzsch.

Later the Pasteur Insitute discovered that the action of the drug was a result of being metabolized into 2 parts - one of which interrupted the folate synthesis system which was critical to the production of nucleic acids... an important step in unravelling the structure and function of DNA. (See pic of Linus Pauling with model of sulfanilimide structure)

This wasn't helpful to Bayer because sulfanilimide's dye patent had expired and its manufacture readily undertaken , the drug was therefore widely available.

The drug was widely used throughout WWII on the surface of open battle wounds, shaken on by a sort of pepper pot, by all the forces in the conflict.

In war time and post war Britain the drug M&B 693 , (boxed in 25's) synthesised by May & Baker in Dagenham from Sulphapyridine provided the cure for the hitherto killer-disease, bacterial pneumonia. Their prescription by the doctor signified to the family the measure of concern for the patient - no doubt they were a huge expemnse in pre NHS Britain.

A variant was branded and sold as "Gonazole".

The pale pink tablets stamped with the initials M&B were probably one of the first widely counterfeited pharmacuetical products.

M&B 760 was Sulphathiazole and introduced later ,then came Sulphanilamide then Sulphadiazine, etc each a little better and less dangerous than the previous one. Sulphacetamide is still in use - one of the best eye drops for conjunctivitis.