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Antibiotic


An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of "antimicrobials", a larger group which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term originally described only those formulations derived from living organisms, but is now applied also to synthetic antimicrobials, such as the sulfonamides. Antibiotics are small molecules with a molecular weight less than 2000 and they are not enzymes.

Unlike previous treatments for infections, which included poisons such as strychnine, antibiotics were labelled "magic bullets": drugs which targeted disease without harming the host. Antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual antibiotics vary widely in their effectiveness on various types of bacteria. Some specific antibiotics (called "narrow-spectrum antibiotics") target either gram-negative or gram-positive bacteria, and others are more wide-spectrum antibiotics. The effectiveness of individual antibiotics varies with the location of the infection and the ability of the antibiotic to reach this site. Oral antibiotics are the simplest approach when effective, with intravenous antibiotics reserved for more serious cases. Antibiotics may sometimes be administered topically, as with eyedrops or ointments.

Contents

History

Following earlier experiments that had demonstrated interesting anti-bacterial effects from various bacterial secretions, the German scientist E. de Freudenreich in 1888 isolated a bacterial secretion and noted its antibacterial properties. Pyocyanase, secreted by Bacillus pyocyaneus, retarded the growth of other bacteria in situ and was toxic to many disease-causing bacteria. Unfortunately, pyocyanase's own toxicity and unstable character prevented its use as an effective, safe antibiotic within the human body.

The first effective antibiotic discovered was penicillin. French physician Ernest Duchesne noted in his 1896 thesis that certain Penicillium molds killed bacteria. Duchesne died within a few years, and his research was forgotten for a generation, until an accident intervened. Alexander Fleming had been culturing bacteria on agar plates, one of which was ruined by an accidental fungal contamination. Rather than discarding the contaminated plate, Fleming noticed a clear zone surrounding the colony of mold. Having previously studied the ability of the enzyme lysozyme to kill bacteria, Fleming realized that the mold was secreting something that stopped bacterial growth. He knew that this substance might have enormous utility to medicine. Although he was unable to purify the compound (the beta-lactam ring in the penicillin molecule was not stable under the purification methods he tried), he reported it in the scientific literature. Since the mold was of the genus Penicillium, he named this compound penicillin.

This USPS stamps notes that during the 1940s, the improvement of antibiotics saved lives the world over.

In the 1930s German scientists investigated the antibacterial properties of certain dyes. One of these was a sulfonamide, prontosil, which was used to treat infections in humans, where its effect was found to be due to its conversion in the host to the active form, sulfanilimide. By today's more broad definition, this would likely qualify as the first successful use of an oral antibiotic. During the same era, Rene Dubos isolated tyrothricin , an antibiotic used topically for skin infections, from soil bacteria.

With the increased need for treating wound infections in World War II, resources were poured into investigating and purifying penicillin, and a team led by Howard Walter Florey succeeded in producing usable quantities of the purified active ingredient which were quickly tested on clinical cases. Physicians were exhilarated at the rapid and reliable cure of conditions which had, until then, been difficult to treat, terrible to endure, and frequently fatal. Observation of other species of mold and other organisms revealed a hitherto unknown level of chemical warfare being carried out against bacteria. New antibiotics were rapidly discovered and came into widespread use, and a new era of research into the possibility of similarly "magic" chemotherapeutic cures for other diseases eventually led to successes in the field of cancer chemotherapy.

The discovery of antibiotics, along with anesthesia and the adoption of hygienic practices by physicians (for example, washing hands and using sterilized instruments) revolutionized medicine. It has been said that this is the greatest advance in health since modern sanitation. People in developed countries now find it hard to imagine that a simple scratch once always carried the risk of infection and death.

See also Timeline of antibiotics.

Classes

There are many way to classify antibiotics.

One such classification is by chemical structure:

Another such classification is by their mechanism of action (that is, the mechanism by which they selectively poison bacterial cells):

  • Antibiotics which interfere with cell-wall synthesis
    • Beta-lactams, including penicillins and cephalosporins; mono-lactams, such as Imipenem; vancomycin, bacitracin
  • Antibiotics which interfere with bacterial protein synthesis
    • Antibiotics which bind to the 50S ribosomal unit
      • Lincosamides/lincosides including clindamycin and lincomycin; chloramphenicol, macrolides
    • Antibiotics which interfere the 30S ribosomal unit
      • Tetracyclines; aminoglycosides including gentamicin
  • Drugs which inhibit folate synthesis
    • Sulfonamides and trimethoprim
  • Drugs which interfere with DNA synthesis
    • Metronidazole, quinolones, novobiocin
  • Drugs which interfere with RNA synthesis
    • Rifampin (rifampicin)
  • Drugs which interfere with cell membrane function
    • Polymyxin B, gramicidin

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

Side effects

Side effects range from slight headache to a major allergic reaction. One of the more common side effects is diarrhea, which results from the antibiotic disrupting the balance of intestinal flora, the "good bacteria" that dwell inside the human digestive system. Other side effects can result from interaction between the antibiotic and other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.

Antibiotic misuse

Common forms of antibiotic misuse include taking an inappropriate antibiotic, in particular the use of antibacterials for viral infections like the common cold, and failure to take the entire prescribed course of the antibiotic, usually because the patient feels better before the infecting organism is completely eradicated. In addition to treatment failure, these practices can result in antibiotic resistance.

In the United States, a vast quantity of antibiotics is routinely included as low doses in the diet of healthy farm animals, as this practice has been proved to make animals grow faster. Opponents of this practice, however, point out the likelihood that it also leads to antibiotic resistance, frequently in bacteria that are known to also infect humans, although there has been little or no evidence as yet of such transfer of antibiotic resistance actually occurring.

Antibiotic resistance

Main article: Antibiotic resistance

One side effect of misusing antibiotics is the development of antibiotic resistance by the infecting organisms, similar to the development of pesticide resistance in insects. Evolutionary theory of genetic selection requires that as close as possible to 100% of the infecting organisms be killed off to avoid selection of resistance; if a small subset of the population survives the treatment and is allowed to multiply, the average susceptibility of this new population to the compound will be much less than that of the original population, since they have descended from those few organisms which survived the original treatment. This survival often results from an inheritable resistance to the compound, which was infrequent in the original population but is now much more frequent in the descendants thus selected entirely from those originally infrequent resistant organisms.

Antibiotic resistance has become a serious problem in both the developed and underdeveloped nations. By 1984 half the people with active tuberculosis in the United States had a strain that resisted at least one antibiotic. In certain settings, such as hospitals and some child-care locations, the rate of antibiotic resistance is so high that the normal, low cost antibiotics are virtually useless for treatment of frequently seen infections. This leads to more frequent use of newer and more expensive compounds, which in turn leads inexorably to the rise of resistance to those drugs, and a never-ending ever-spiraling race to discover new and different antibiotics ensues, just to keep us from losing ground in the battle against infection. The fear is that we will eventually fail to keep up in this race, and the time when people did not fear life-threatening bacterial infections will be just a memory of a golden era.

Another example of selection is Staphylococcus aureus, which could be treated successfully with penicillin in the 1940s and 1950s. At present, nearly all strains are resistant to penicillin, and many are resistant to nafcillin , leaving only a narrow selection of drugs such as vancomycin useful for treatment. The situation is worsened by the fact that genes coding for antibiotic resistance can be transferred between bacteria, making it possible for bacteria never exposed to an antibiotic to acquire resistance from those which have. The problem of antibiotic resistance is worsened when antibiotics are used to treat disorders in which they have no efficacy, such as the common cold or other viral complaints, and when they are used widely as prophylaxis rather than treatment (as in, for example, animal feeds), because this exposes more bacteria to selection for resistance.

Beyond antibiotics

Unfortunately, the comparative ease of finding compounds which safely cured bacterial infections proved much harder to duplicate with respect to fungal and viral infections. Antibiotic research led to great strides in our knowledge of basic biochemistry and to the current biological revolution; but in the process it was discovered that the susceptibility of bacteria to many compounds which are safe to humans is based upon significant differences between the cellular and molecular physiology of the bacterial cell and that of the mammalian cell. In contrast, despite the seemingly huge differences between fungi and humans, the basic biochemistries of the fungal cell and the mammalian cell are much more similar; so much so that there are few therapeutic opportunities for compounds to attack a fungal cell which will not harm a human cell. Similarly, we know now that viruses represent an incredibly minimal intracellular parasite, being stripped down to a few genes worth of DNA or RNA and the minimal molecular equipment needed to enter a cell and actually take over the machinery of the cell to produce new viruses. Thus, the great bulk of viral metabolic biochemistry is not merely similar to human biochemistry, it actually is human biochemistry, and the possible targets of antiviral compounds are restricted to the relatively very few components of the actual virus itself.

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