Antibiotics

Antibiotics: From Salvarsan to Broad-Spectrum Modern Agents

Definition. An antibiotic is a substance that, at low concentration, inhibits the growth of - or destroys - microorganisms by intervening in their metabolic processes. The modern definition has broadened beyond the historically original one (a compound produced only by microorganisms) to also include substances produced wholly or partly by chemical synthesis.

Historical development. The German bacteriologist Paul Ehrlich investigated a series of arsenic-based chemical structures while searching for a less-toxic treatment for syphilis, and this work led to arsphenamine (salvarsan) - toxic, but far more toxic to the causative spirochete bacterium than to the human patient - for which Ehrlich received the 1908 Nobel Prize in Medicine. Noticing a structural resemblance between salvarsan's $As=As$ linkage and the $N=N$ linkage found in azo dyes, Ehrlich went on to search systematically among dye-like compounds for antibacterial activity, and in 1932 this search yielded prontosil, the first effective antibacterial agent of this family. Prontosil itself is chemically converted inside the body into sulphanilamide, which is the true active compound - a discovery that launched the entire sulpha-drug class described earlier (section 16.1.1(c)).

The true revolution in antibacterial chemotherapy, however, followed Alexander Fleming's 1929 discovery of the antibacterial properties of a mould of the genus Penicillium. Isolating and purifying enough of the active compound for clinical trials took roughly thirteen further years of work, and Fleming shared the 1945 Nobel Prize in Medicine with H. W. Florey and colleagues for bringing penicillin to clinical use.

Modes of antibiotic action. Chemically, antibiotics act in one of two ways: bactericidal antibiotics (for example penicillin, the aminoglycosides, and ofloxacin) kill microbes outright, while bacteriostatic antibiotics (for example erythromycin, tetracycline, and chloramphenicol) only inhibit further microbial growth without necessarily killing existing organisms.

Spectrum of action. The range of organisms an antibiotic is effective against is called its spectrum of action:

• Broad-spectrum antibiotics act against a wide range of both Gram-positive and Gram-negative bacteria.
• Narrow-spectrum antibiotics act mainly against one of these two groups only.
• Limited-spectrum antibiotics act against a single organism or a single disease. …