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ANTIMICROBIAL CHEMOTHERAPY IN THE 20TH CENTURYSome recollections
Professor Alasdair Geddes
Some recollections
Professor Alasdair GeddesSchool of Medicine
University of BirminghamUniversity of BirminghamBirmingham UK
a.m.geddes@bham.ac.uk
1929
Gerhard DomagkGerhard Domagk(1895‐1964)
PRONTOSIL RUBRUM [Sulphonilamide] ‐ 1935
EARLY YEARS OF ANTIMICROBIAL CHEMOTHERAPY
1930’s/1940’s
Sulphonamides; penicillin; streptomycin
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐[1951 ‐ AG entered Medical School]‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
1950’s1950’s
Chloramphenicol tetracyclines erythromycinChloramphenicol; tetracyclines; erythromycin; (vancomycin)
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ ‐‐ [1957 ‐ AG graduated] ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
Sir Alexander Fleming ‐ Rector of Edinburgh University ‐ 1951g y
1940
Fleming, Chain & Florey receiving the Nobel Prize in 1945[Team work]
Fleming’s Nobel Prize Oration (1945)Fleming s Nobel Prize Oration (1945)
“The time may come when penicillinThe time may come when penicillin may be bought by anyone in shops. There is a danger that the ignorantAl d Fl i There is a danger that the ignorant man may under‐dose himself and make the microbes resistant (‘Stewardship’!?) ”
Alexander Fleming(1881‐1955)
the microbes resistant ( Stewardship !?).
“We may not be at the end of the ypenicillin story. We are in a chemical age and penicillin may be changed by g p y g ychemists so that its disadvantages may be removed and better derivatives
Ernst Chain(1906‐1979)
produced.”
THE ‘GOLDEN‘ DECADES OF CHEMOTHERAPY *
1960’s (ISC founded in 1961)
[‘Golden years of Pills and Profits’ ‐ David Greenwood]
1960’s (ISC founded in 1961)Semi‐synthetic penicillins:‐ ampicillin, amoxycillin cloxacillin; flucloxacillinamoxycillin, cloxacillin; flucloxacillinEarly cephalosporins:‐ cephaloridinegentamicin; trimethoprimgentamicin; trimethoprim
1970’s (BSAC founded in 1971)1970 s (BSAC founded in 1971)Newer cephalosporins (++) & cephamycins; carbenicillin; ureidopenicillins (mezlo & azlo);carbenicillin; ureidopenicillins (mezlo & azlo); clindamycin; imipenem
*Investigated in Birmingham
AMPICILLIN‐LIKE PENICILLINS
(a) Ampicillin
(b) Amoxycillin(b) Amoxycillin
19641964
1972
ISOXAZOLYL PENICILLINS
1970
ICC LONDON July 1975ICC LONDON July 1975
Hosted by the BSAC at i l C llImperial College,
London, courtesy of E.B. Chain
July 1975
Discoverer of the original source of the cephalosporin antibiotics from a sewage outfall in the sea off Sardinia:‐
Cephalosporium acremonium(Acremonium chrysogenum)
Giuseppe BrotzuGiuseppe Brotzu(1895‐1976)
1982
1980’s
Clavulanic acidCLAVULANIC ACID
Clavulanic acid
N fl i l *New fluoroquinolones*
Ciprofloxacin (typhoid)Ofloxacin; norfloxacin
CIPROFLOXACIN
etc, etc.
* [Nalidixic acid 1964]
1980
INTERNATIONAL CHEMOTHERAPYINTERNATIONAL CHEMOTHERAPY CONGRESS ‐ BIRMINGHAM 1999
[Hosted by the BSAC]
George Hitchings & Gertrude ElionGeorge Hitchings & Gertrude Elion(Nobel Prize‐winners)
Invented ‘Designer drugs’ based on purine/pyrimidinesynthesis :synthesis :‐
Pyrimethamine (malaria)Pyrimethamine (malaria)
Acyclovir (Herpes virus infections) ‐Martin Wood
Trimethoprim co trimoxazole (TMP + Sulpha)Trimethoprim co‐trimoxazole (TMP + Sulpha) (Typhoid fever)
1990’s ONWARDS
1] Marked slow down in discovery of new1] Marked slow down in discovery of new antimicrobial agents.
2] No major breakthrough in non‐antimicrobial therapy of infections (e.g. immunotherapy).
3] Resurrection of ‘old’ agents (daptomycin(lipopeptide); colistin (polypeptide).(lipopeptide); colistin (polypeptide).
4] Growing Interest in ‘natural products’. Plants, flowers (IJAA).
ANTIBIOTIC POLICIES ‐ Late 20th Century
1] Example & admonition (!) education
2] British National Formulary (Chapter 5.)
3] Prophylaxis dilemmas:‐
Elective orthopaedic surgery (J Charnley)
Endocarditis (BSAC leadership)
INFECTIOUS DISEASES IN BIRMINGHAMINFECTIOUS DISEASES IN BIRMINGHAM(1967 ‐ 1991: 6 wards initially incl. ITU)
• Childhood infections (measles; rotavirus infection; pertussis; meningitis)
• Imported infections (malaria; typhoid; leprosy; leishmaniaisis onchocerciasis)leishmaniaisis, onchocerciasis)
• Exotica: rabies; botulism; tetanus; smallpoxp
• Infection in the immunosuoppressed
• HIV/AIDS ‐ 1982
Collaboration, Research & Training!• Physicians• Physicians
• Microbiologists• Microbiologists
• Epidemiologists• Epidemiologists
• Pharmacists• Pharmacists
• Nurses• Nurses
• Students (all sorts)• Students (all sorts)
DAVID WILLIAMS[1936‐2005]
Dudley Road Hospital,Dudley Road Hospital, Birmingham (until 1975) & The London Hospital
[JAC O b 2005][JAC, October 2005]
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