Shortly after Domagk and Hörlein announced their discovery of the antibacterial properties of the dye sulfamidochrysoidine (Prontosil) in 1935, numerous chemical companies set out to modify the chemical structure. They soon recognized the sulfa component as the true antibacterial and produced an incredible number of derivatives (more than 5000 different compounds!!) by 1945.[1, 2] This effort was undoubtedly helped by the fact that Bayer had not patented the antibacterial sulfa pharmacophore but the dye part of the molecule instead. Big mistake!
In those early days drugs were tested without much regulatory oversight. Soon, impressive efficacy data were collected demonstrating clinical benefits in various tissue infectious caused by staphylococci and streptococci. While many trials were small and uncontrolled, some older studies provided important insights. For instance, the skin infection studies conducted by Snodgrass  are still often cited; indeed, they served as scientific basis for the most recent FDA guidelines for ABSSSI trials, providing efficacy comparisons to placebo and helping define non-inferiority margins.
There were some early warnings about drug safety and tolerability. Besides rashes and other allergic reaction, the practice of instillation, irrigation and insufflation of some very alkaline sulfa compounds into the nose, nasal sinuses and bronchial tree resulted in sloughing of epithelial layers and tissue necrosis. These AEs did not cause undue concerns as the treatment benefits were just so compelling.
1. Greenwood. Antimicrobial Drugs. Chronicle of a Twentieth Century Medical Triumph. Oxford University Press 2008
2. Northey. The Sulphonamides and Allied Compounds. Reinhold Pub. Corp.,1948
3. Snodgrass. BMJ, 2:101; 1937 and BMJ, 2:1159; 1937
4. FDA: Guidance for Industry. Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. 2013; http://www.fda.gov/downloads/Drugs/…/Guidances/ucm071185.pdf