Microbiology C21 Lecture notes p530-557 Pharmacology
Antibiotic: small mol. wt. compound produced by microbe that kills or inhibits others
5 major antibio. Genera: Bacillus, Micromonospora Streptomyces, Penicillium, Cephalosporium. Exhaustive screening in 1950s. often named for isolation. Bacitracin: from a wound in Tracy.
Fates, distribution. Varied for different people, ages. Repurify from urine? Routine early on. Compound 606; salvarsan (Ehrlich, contemporary of Felix Horowitz) Hiatus in antibiotic search: 1916-1930. Ehrlich died, WWI. (catastrophe). 85% of 1915 class
3-pronged search: 1.Toxic compounds (dyes), 2.medicinal plants, 3.microbial products. Prontosil = active in vivo, not in vitro. Reason, cleaved to sulfa. Penicillin: stroke of luck! 1st saved pt. alive today.
Fermentation technologies: massive increases in yields. TONS of penicillin produced per year. Most of antibiotic excreted unaltered.
Immediately noticed: selection for resistance. Varied levels of resistance occur naturally. Sulfa resistance started high (5%). Trimethoprim resistance = one of first exhaustively studied. Lay off antibiotic long time = resurgence of the wild type.
Immunoassays: fates differ with age, metabolic vigor. Not just "Serum killing-power test".Urine, blood, etc.
Therapeutic index: Min. toxic dose/min. effective dose. Decreases with use. Darwinian selection.
Antibacterials:
penicillins(pen. V, K, etc.), cephalosporins(1st, 2nd, 3rd generations), sulfonamides(sulfa), aminoglycosides(streptomycin), Chloramphenicol(synthetically made), Tetracyclines (broad spectrum, provoke colitis?), macrolides (erythromycin), quinolones (topoisomerase hit), naldixic acid, nitrofuran (DNA synthesis), vancomycin (last-ditch for S. aureus), bacitracin and polymyxin (topical)
Antimycobacterials (must take for long time), antifungals (therapeutic indices very low), antiparasitics (great potential, unaffordable?) The Health and Wealth of Nations (Hopeful spiral) Antivirals (rapid resistance, so, cocktails. Earlier, so unaffordable, "...like a dog viewing a 747; curious, but no way!" However, Brazil broke patent rights, costs plummeted from $15,000 to $300 per patient/ year)
First use of penicillin: http://info.med.yale.edu/external/pubs/ym_su00/letters.htm
The early days of antibiotics To the editor:
I read with great interest John Curtis' recent article on the first use of penicillin in this country ["Fulton, Penicillin and Chance," Capsule, Fall 1999/Winter 2000]. It brought back memories of my own role in that event.Mrs. Miller was a private patient of Dr. John Bumstead in the old Isolation Building of the New Haven Hospital. As such she was under the direct care of Dr. Bumstead, assisted by the junior intern assigned to the isolation service. I was that low man on the house-staff totem pole. The more senior members of the house staff were not involved with the care of a private patient.I remember Dr. Bumstead giving me the small bottle of penicillin--a yellow powder--with instructions to take it over to Dr. Morris Tager's laboratory in the bacteriology department of the medical school and dissolve it in saline solution and pass it through a Seitz filter. This removed bacteria but not viruses. I then returned to the patient's bedside and under Dr. Bumstead's supervision gave her 5,000 Oxford units of penicillin intravenously. This dose was repeated every four hours for the rest of her hospital stay. Mrs. Miller said she liked my "needlework" and Dr. Bumstead asked me to continue to give her the injections every four hours around the clock including days and nights when I was otherwise off duty. The intravenous route was chosen because, in our ignorance, we were afraid that intramuscular injections might cause a sterile abscess.As Mr. Curtis reported, all of Mrs. Miller's urine was sent to Merck in Rahway, N.J., so that the penicillin could be recovered and returned to us in New Haven. After Mrs. Miller had recovered and was discharged, we had enough penicillin left to treat and cure a man with septicemia due to Staphylococcus aureus. Finally we had enough penicillin to start treating a young man with subacute bacterial endocarditis due to Streptococcus viridans. At that time this was a uniformly fatal disease. He improved, his blood cultures became sterile, but we ran out of penicillin completely and he relapsed and died.In the early 1970s the School of Medicine sponsored a documentary film on the first use of penicillin in this country at the New Haven Hospital. It featured an interview with Mrs. Miller and the film crew visited my office in Washington, D.C., and interviewed me regarding the events I described above. I was then chief of gastroenterology and clinical professor of medicine at George Washington University School of Medicine as well as in private practice.Thomas S. Sappington Sr., M.D., HS '45 Randolph, N.H.
The Health and Wealth of Nations: http://www.riverpath.com/library/pdf/HEALTH%20AND%20WEALTH%20RPA%20FEB00.PDF
The Health and Wealth of Nations
From health to income
The positive correlation between health and income per capita is one of the best-known relationships in international development (see figure 1). This correlation is commonly thought to reflect a causal link running from income to health. Higher income gives greater command over many of the goodsand services that promote good health, such as better nutrition and access to safe water, sanitation,and good quality health services.
Recently, however, another intriguing possibility has emerged: that the health-income correlation is partly explained by a causal link running the other way - from health to income. Several mechanisms, falling into four main categories, could account for this relationship: