Which Was the First Penicillin and Continues to Be the Drug of Choice for Many Infections Quizlet
Why Penicillin Continues To Grow in Importance
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February 6, 1979
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ALTHOUGH it kills guinea pigs and thus might never have been approved for use on humans if it were developed under modern regulations, penicillin, which revolutionized the practice of medicine when it was introduced in World War II, remains a "wonder drug" almost 90 years later, and its importance is still growing.
Almost overnight, the antibiotic tamed a host of infectious diseases that had killed and crippled since ancient times. It is still the drug of choice for a long list of infections — among them gonorrhea, syphilis, impetigo, "strep" throats, pneumococcal pneumonia, sinusitis, childbirth fever, lung abscesses and spinal meningitis.
Most experts believe that in the treatment of streptococcal infections penicillin, a natural substance produced by molds, has greatly reduced the incidence of rheumatic fever, once a common complication of streptococcal infections.
Doctors have learned that penicillin can be given in almost unlimited doses without injuring the patient; some specialists say they prescribe it in amounts up to 20 million units day — and sometimes in even larger doses — to treat the severest problems.
And the impact of penicillin has gone far beyond its usefulness in treating certain diseases. It was one of the few drugs discovered in a university laboratory. It took more than a decade to unlock the secret of preparing large amounts for commercial production, but then penicillin helped to make the drug industry a potent economic force.
It ushered in a series of other "wonder drugs," and when chemical mastery of the molecule gave rise to semi‐synthetic penicillins — derivatives created by chemically manipulating portions of the basic natural molecule — they became a symbol of modem therapeutics.
Many of the other so‐called wonder drugs disappointed original boosters because their effects proved temporary or were offset by serious complications or toxic reactions that showed up only with long‐term use.
The penicillin antibiotic family now includes at least 11 drugs that can treat a much wider range of infections than penicillin itself. And, although there is a wide range in costs, the members of the family are considered among the cheapest, least toxic and most effective drugs known, according to experts such as Dr. H. Sherwood Lawrence, the chief of infectious diseases at New York University Medical School.
Penicillin's impact, beyond having been sustained in virtually all fields of medicine for almost four decades, continues to grow.
Recently, a substance that is formed naturally in the body as a degradation product of penicillin was licensed for the treatment of cases of severe rheumatoid arthritis that do not respond to conventional measures.
The substance, manufactured as a drug called penicillamine, has been used for several years in the treatment of two rare hereditary disorders called Wilson's Disease and cystinuria and has been presCribed in some poisonings to promote the excretion of heavy metals like lead and mercury. It is, however, much more toxic than penicillin.
Penicillin's special ability is that it affects only actively multiplying bacteria without harming human cells. In bacteria, it thwarts multiplication by preventing the formation of new cell walls. Other antibiotics, such as amphotericin, interfere with the biochemistry of human cells as much as that of offending organisms. The chief role of antibiotics is to prepare organisms for easier destruction by the body's immunological defense system, according to infectious‐disease experts like Dr. Louis Weinstein of the Peter Bent Brigham Hospital in Boston.
Early Obstacles
Despite its huge impact, penicillin has had to overcome a series of obstacles since 1928, when it was accidentally discovered in a British laboratory by Sir Alexander Fleming. Although scientists had been searching in vain for a "magic bullet" since the late 19th century, the significance of Dr, Fleming's observations was not immediately appreciated.
But the discovery of sulfa drugs in the 1930's renewed interest in "magic bullets," and the pressing needs of World War II led to the applied research that produced the first batches of penicillin.
Its value has since been threatened several times by the sudden appearance of strains of bacteria that were resistant to the antibiotic. For example, penicillin‐resistant staphylococci caused infections in many hospitals beginning in the late 1950's.
Soon Methicillin was marketed, becoming the first of a series of semisynthetic penicillins that can treat staphylococci resistant to penicillin itself. More recently, public health officials have been concerned about the discovery of penicillin‐resistant strains of the bacteria that cause gonorrhea and pneumococcal pneumonia.
Still, the bulk of infections that doctors treat every day are caused by strains that succumb to penicillin therapy. In fact, Dr. Mercedes Albuerne of the Food and Drug Administration said, doctors each year write more than 80 million prescriptions for the pencillins, making them the most widely used class of antibiotics.
That situation markedly contrasts to the earliest days of penicillin therapy, when the antibiotic's developers could make just a few thousand units at a time from Fleming's original strain. Because the British lacked the apparatus to make penicillin during wartime, they grew the mold in bedpans. When doctors learned that penicillin was excreted unchanged in the urine,they recovered it from those under treatment, purified it and gave it to others.
The first patient treated, an Oxford policeman who had streptococcal and staphylococcal infections, responded to penicillin therapy initially but died after the supply ran out, leading an Oxford professor to define penicillin as "a remarkable substance grown in bedpans and purified by passage through the Oxford Police Force."
The mass production of penicillin was accomplished in this country using fermentation techniques. To increase production for commercial purposes, scientists selected fast‐growing strains, then irradiated them to produce faster‐growing mutants. One of the best strains came from a mold on a cantaloupe.
Although penicillin is much less toxic than most other drugs, it can kill. Each year, experts estimate, a few hundred people die, chiefly through reactions that usually occur within minutes after an injection. Rashes and hives are less severe but more frequent manifestations of penicillin allergy. Dr. Weinstein estimates that 2 percent of the population is allergic to penicillin.
And humans are not the only species with a sometimes‐violent reaction to the antibiotic. It has been said that penicillin, if it were discovered today, would not pass the extensive animal research tests that are a prerequisite to marketing a drug because it kills guinea pigs.
Just why it does so is a mystery. Scientific literature is filled with references to the variability of the phenomenom and, for the last 10 years, Dr. Lewis Thomas, president of the Memorial Sloan‐Kettering Cancer Center, has been studying it in unpublished experiments in New York, in New Haven and in Edinburgh, Scotland.
He said he had collected guinea pigs from breeders in different parts of the world and that they had been kept under identical climatic and housing conditions. For unknown reasons, Dr. Thomas said, penicillin Is lethal for guinea pigs only in the winter, not during other seasons.
Like penicillin itself, the usefulness of penicillamine, the substance formed naturally in the body, in treating rare hereditary disorders was found accidentally. The discovery was made by British scientist, Dr. John Walshe, who was working on problems of liver disease at the Boston City Hospital in the early 1950's.
Through a series of observations and deductions, Dr. Walshe learned that penicillamine would promote the excretion of heavy metals from the body. He found that it worked in Wilson's Disease, in which a biochemical defect causes abnormally high amounts of copper to accumulate.
Another unplanned discovery was that penicillamine, which has no antibiotic properties and is much more toxic than penicillin, could be used in treating rheumatoid arthritis. That finding was made when Dr. Israeli A. Jaffe tried to determine the role of substance called rheumatoid factor in patients with the disease.
Because penicillamine was known to have an effect on rheumatoid factor in test tubes, Dr. Jaffe studied it on a few patients and learned that some of them showed beneficial effects. Further studies in Britain and this country have confirmed the findings.
Although many health officials remain concerned that the appearance of new penicillin‐resistant strains of bacteria may herald serious problems for the antibiotic, others — among them, Dr. Weinstein — point out that it took more than 30 years for these strains to appear, so they are cautiously optimistic that penicillin will be the dominant antibiotic for many years
Source: https://www.nytimes.com/1979/02/06/archives/why-penicillin-continues-to-grow-in-importance-rheumatic-fever-was.html
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