A brief history of antibiotics (Part 2)
Recently I talked about how some antibiotics were discovered. Here I bring you the rest of the list. In the past, people were screening soil for antimicrobial compounds; most of todays agents are designed in silico. Not bad for just half a century.
This class of antibiotics originated in 1957 from cultures of Amycolatopsis mediterranei (baptized as Streptomyces mediterranei first, reclassified as Nocardia species, then as the actinomycete Amycolatopsis truly confusing, but there are more important things to worry about). These bacteria were obtained by Italian researchers at Gruppo Lepetit SpA in Milan from a pine forest near the French city of Nice. They named the compound "rifomycin" (with an o), inspired by the popular French gangster movie "Rififi" of 1955. The first compound, rifomycin B, was not well absorbed orally or very effective. These difficulties were overcome in 1966 by the semisynthetic derivative rifampin. Save yourself a call by telling your patient and nurses about the orange urine and body fluids.
One could say that these were the first antibiotics ever. The chemical company I. G. Farbenindustrie (now Bayer and Sanofi) was in the business of dyes. In 1908, the compound sulphonamide was turned into a red dye.
With the introduction of the microscope, it was possible to demonstrate that bacteria uptake some dyes differentially from human cells. The goal was to find a dye that would not kill human cells. If it could be given systemically, even better. Headed by Dr. Gerhard Domagk, two chemists tried several derivates of sulphonamide for the treatment of mice infected with 25 different bacteria (tuberculosis, gonococcus, pneumococcus, meningococcus, streptococcus, etc).
On Christmas, 1932, mice and rabbits given "sulphanilamide" survived, leading to the patenting of prontosil. Domagks own daughter fell ill with a streptococcal infection, and he secretly gave her prontosil, after which she recovered. Subsequently, in 1933, a 10-month-old infant with Staphylococcal septicemia was successfully treated with prontosil (first contemporaneous antibiotic treatment reported in the medical literature). Sulfas were coming to stay, and Domagk was awarded in 1947 the Nobel Prize in Medicine for 1938.
The first tetracyclines were discovered in the late 1940s by screening organisms obtained from the soil for their antimicrobial properties. Benjamin Duggar at Lederle laboratories (now part of the giant Wyeth) found that the golden-colored colonies of Streptomyces aureofaciens released an antibacterial product that he named aureomycin (chlortetracycline). Oxytetracycline was isolated in 1950 from Streptomyces rimosus, and tetracycline was synthesized by dehalogenation of chlortetracycline in 1953. If you were a child at that time, you would probably receive several courses of aureomycin or oxytetracycline (they were really broad spectrum agents) for ear infections (bad idea, since teeth calcify mostly between 2 months and 5 years; but they didnt know about the brown dental discoloration) or for bronchiolitis (bad idea too, but the role of a virus such as respiratory syncytial virus in children with bronchiolitis remained unknown until 1962).
To finish our antibiotic voyage around the globe, I will mention that vancomycin was isolated from Amycolatopsis orientalis. Sounds familiar? Yes, as with the ryfamicins, the species changed names: Streptomyces orientalis, then Nocardia orientalis. Vancomycin was isolated from a soil sample from Borneo in the mid 1950s. It came timely as the incipient rise of penicillin-resistant Staphylococcus aureus was causing therapeutic failures, and it was before the appearance of the preferred semi-synthetic penicillins. Vancomycin, in its earlier preparations, was labeled as Mississippi mud because of its threatening brownish, muddy appearance and unpleasant infusion reactions: high fevers, hypotension, severe phlebitis and nephrotoxicity. With better purification in manufacturing, vanc was beefed up to recover its dignity. Adulated by many, despised by others, vancomycin is a forever blockbuster.