History and Development of Antimicrobial Drugs

To appreciate the unique antibiotic era in which we now live, it is helpful to understand the history and development of these life-saving remedies.

Discovery of Antimicrobial Drugs

The development of Salvarsan by Paul Ehrlich was the first documented example of a chemical used successfully as an antimicrobial medication. The next breakthrough in the developing science of antimicrobial chemotherapy came almost 25 years

508 Chapter 21 Antimicrobial Medications

Table 21.1 Terms that Relate to Antimicrobial Medications

Term

Definition

Acquired resistance

Resistance that develops through mutation or acquisition of new genes.

Antibacterial drug

An antimicrobial drug used to treat a disease caused by bacteria.

Antibiotic

A compound naturally produced by certain molds and bacteria that inhibits the growth of or kills other microorganisms.

Antimicrobial drug (or antimicrobial)

A chemical that inhibits the growth of or kills microorganisms.This term encompasses antibiotics and chemically synthesized drugs.

Antiviral drug

A drug that interferes with the replication of viruses. All antiviral drugs are chemically synthesized; none are antibiotics.

Bactericidal drug

An antimicrobial drug that kills bacteria.

Bacteriostatic drug

An antimicrobial drug that inhibits the growth of bacteria.

Broad-spectrum antimicrobial

An antimicrobial that is effective against a wide range of microorganisms, often including both Gram-positive and Gram-negative bacteria.

Chemotherapeutic agent

A chemical used to treat a disease.

Intrinsic resistance

Resistance due to an inherent characteristic of the microorganism.

Narrow-spectrum antimicrobial

An antimicrobial that is effective against a limited range of microorganisms.

R plasmid

A plasmid that encodes resistance to one or more antimicrobial drugs.

Therapeutic index

A measure expressing the relative toxicity of a chemotherapeutic drug. It is the lowest dose toxic to the patient divided by the dose used for therapy.

later. In 1932, the German chemist Gerhard Domagk, using the same dogged persistence demonstrated by Erlich, discovered that a red dye called Prontosil was dramatically effective in treating streptococcal infections in animals. Surprisingly, Prontosil had no effect on streptococci growing in test tubes. It was later discovered that enzymes in the blood of the animal split the Prontosil molecule, producing a smaller molecule called sul-fanilamide; this breakdown product acted against the infecting streptococci. Thus, the discovery of sulfanilamide, the first sulfa drug, was based on luck as well as scientific effort. If Prontosil had only been screened against bacteria in test tubes and not given to infected animals, its effectiveness might never have been discovered.

Salvarsan and Prontosil were the first documented examples of chemicals used successfully as antimicrobial medications. Any chemical that is used to treat a disease is called a chemotherapeutic agent. One used to treat microbial infections can also be called an antimicrobial drug or, more simply, an antimicrobial. Antimicrobials can also be referred to by terms that indicate the type of microorganisms they kill or inhibit. For example, one that is used to treat bacterial infections is called an antibacterial drug. These and other definitions are summarized in table 21.1.

Discovery of Antibiotics

Alexander Fleming, a British scientist, was working with cultures of Staphylococcus when he noticed that colonies growing near a contaminating mold looked odd, as if they were dissolving. Recognizing that the mold might be secreting a substance that killed the bacteria, he proceeded to study it more carefully. He identified the mold as a species of Pénicillium and showed that it was indeed producing a bacteria-killing substance; he called this penicillin. Even though Fleming was unable to purify penicillin, he showed that it was remarkably effective in killing many different kinds of bacteria and could be injected into rabbits and mice without adverse effects. Although Fleming recognized the potential medical significance of his discovery, he became discouraged with his inability to purify the compound and eventually abandoned his study of it.

Ten years after Fleming's discovery, two other scientists in Britain, Ernst Chain and Howard Florey, were successful in their attempts to purify penicillin. In 1941, the drug was tested for the first time on a police officer with a life-threatening Staphylococcus aureus infection. He improved so dramatically that within 24 hours his illness seemed under control. Unfortunately, the supply of purified penicillin ran out, and the man eventually died of the infection. Later, with greater supplies of the drug, the experiment was repeated and two deathly ill patients were successfully cured. World War II spurred a cooperation of British and American scientists to determine the chemical structure of penicillin and to develop the means for its large-scale production so that it could be used to treat infected soldiers and workers. Several different penicillins were found in the mold cultures, and were designated alphabetically. Penicillin G (or benzyl penicillin)

was found to be the most suitable for treating infections. This was the first of what we now call antibiotics, antimicrobial drugs naturally produced by microorganisms.

Soon after the discovery of penicillin, Selman Waksman isolated a bacterium from soil, Streptomyces griseus, that produced an antibiotic he called streptomycin. The realization that bacteria as well as molds could produce medically useful antimicrobial drugs prompted researchers to begin laboriously screening hundreds of thousands of different strains of microorganisms for antibiotic production. Even today, pharmaceutical companies examine soil samples from around the world for organisms that produce novel antibiotics.

Development of New Generations of Drugs

In the 1960s scientists discovered that they could alter the chemical structure of drugs such as penicillin G, and give them new properties. For example, penicillin G, which is mostly active against Gram-positive bacteria, can be altered to produce ampicillin, a drug that kills additional Gramnegative species as well. Other changes to penicillin created the drug methicillin, which is less susceptible to enzymes used by some bacteria to inactivate penicillin. Thus, methicillin can be used to treat infections caused by certain penicillin-resistant organisms. Today a variety of penicillin-like medications exist, making up what is referred to as the family of penicillins (figure 21.1). Other unrelated antimicrobial drugs have also been altered to give them new characteristics.

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  • mandy
    What is the history and development of antimicrobial drug?
    3 years ago
  • zahra
    What are the History and Development of Antimicrobial Drugs?
    2 years ago

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