Hans Christian Gram (1853–1938)
Bacteria are single-celled organisms surrounded by a protective cell wall. Faced with the challenge of visualizing bacteria under a microscope, in 1884 (one year after his graduation from medical school), Danish bacteriologist Hans Christian Gram devised a stain that has since been used to differentiate the two primary groups of bacteria. One group stains purple (Gram-positive), the other pink (Gram-negative). This difference is based on the chemical and physical properties of their cell walls, which in turn determines their sensitivity to different antibiotics.
The first penicillin, penicillin G, is active against most Gram-positive and many Gram-negative bacteria. This natural product, isolated from the Penicillium mold, kills bacteria by interfering with their ability to manufacture cell walls, which are essential for their survival. Penicillin is an unusual drug because, apart from allergic reactions (which affect one in ten of us), it produces very few toxic effects.
PENICILLIN BY MOUTH. Penicillin G is by no means perfect, however. When taken orally, it is inactivated by acids in the stomach and, therefore, can only be given by injection. By modifying its chemistry, in 1961 scientists at Beecham Laboratories in England produced ampicillin, one of the first penicillin derivatives able to withstand attack by these acids. In addition, ampicillin proved effective treating infections caused by a wider range of Gram-negative microbes than penicillin G, including many very common urinary-tract infections.
Notwithstanding ampicillin’s amazing success in the marketplace—where it has been sold as Penbritin, Omnipen, Polycillin, and Principen—it has one major shortcoming that it shared with many other penicillins. Ampicillin is susceptible to breakdown by penicillinase, an enzyme produced by some bacteria. Penicillinase is responsible for the resistance of these bacteria to many penicillins. To overcome this problem, ampicillin and its first cousin amoxicillin (Amoxil) have been packaged in combination with drugs (e.g., Augmentin) that can inactivate penicillinase.
The penicillins are the oldest group of antibiotics, but, with continual facelifts, they are looking as young as ever.
SEE ALSO Penicillin (1928), Tetracyclines (1948).
The Gram stain is used to stain and differentiate bacteria. The Gram-positive Bacillus cereus appears violet, while the Gram-negative Escherichia coli appear in small pink clusters in the background.