ANTIBIOTICS AND FEVER

Question: Antibiotics can kill gram-negative bacteria, but symptoms of fever and low blood pressure can persist. Why?
Answer: The antibiotics kill the the bacteria, but they do not eliminate the dead parts of the bacteria. Although the bacteria is dead, the endotoxic lipopolysaccharide membrane remains in the body for some time. Fever and low blood pressure are signs that the immune system is still functioning at a high level, being triggered by the bacterial membrane. The immune system will continue its work until that foreign material has been excreted from the body.

PENICILLIN THE MIRACLE DRUG

Antibiotics are chemicals, effective at very low concentrations, created as part of the life process of one organism, which can kill or stop the growth of a disease-causing microbe--a germ. Penicillin was among the first of these created. When penicillin was developed in the 1940s, it was called a "miracle drug." This is because it targeted bacterial infections that had previously been very difficult to treat. Penicillin has saved countless lives since it was developed. The ability of this drug to cure people of many once-fatal bacterial infections has saved so many lives that it is easy to understand why it was once called a "miracle drug".

HISTORY OF PENICILLIN
In 1929, Alexander Fleming, a doctor and researcher at St. Mary's Hospital in London, England, published a paper on a chemical he called "penicillin", which he had isolated from from a mold, Penicillium notatum. Penicillin, Fleming wrote, had prevented the growth of a neighboring colony of germs in the same petri dish. Dr. Fleming was never able to purify his samples of penicillin, but he became the first person to publish the news of its germ-killing power. Later researchers found methods that made large-scale production efficient, and this work was especially important because of the many deaths from bacterial infections experienced by soldiers during WW2. Over time, researchers continued to find higher-yielding Penicillium molds, and also produced higher yielding strains by exposing molds to x-rays or ultraviolet light.

HOW PENICILLIN WORKS

Penicillin kills by preventing some bacteria from forming new cell walls. One by one, the bacteria die because they cannot complete the process of division that produces two new "daughter" bacteria from a single "parent" bacterium. The new cell wall that needs to be made to separate the "daughters" is never formed.

SELECTIVE TOXICITY
Several hundreds of compounds with antibiotic activity have been isolated from microorganisms over the years, but only a few of them are clinically-useful. The reason for this is that only compounds with selective toxicity can be used clinically. The selective toxicity of antibiotics means that they must be highly effective against the microbe but have minimal or no toxicity to humans. In practice, this is expressed by a drug's therapeutic index. This is the ratio of the toxic dose (to the patient) to the therapeutic dose (to eliminate the infection). The larger the index, the safer is the drug (antibiotic) for human use.

HOW SELECTIVE TOXICITY WORKS

Selective toxicity means that the agent acts in some way that inhibits or kills bacterial pathogens but has little or no toxic effect on the patient. The selective toxicity of antibiotics is brought about by finding vulnerable targets for the drug in the microbe that do not exist in the animal (eucaryote) that is given the drug. Most antibiotics in clinical usage are directed against bacterial cell wall synthesis, bacterial protein synthesis, or bacterial nucleic acid synthesis, which are unique in some ways to bacteria. For example, the beta lactam antibiotics (penicillin and its relatives) inhibit peptidoglycan synthesis in the cell wall. Humans have neither a cell wall nor peptidoglycan and so are unaffected by the action of the drug.

CHARACTERISTICS OF ANTIBIOTICS
Antibiotics may have a cidal (killing) effect or a static (inhibitory) effect on a range of microbes. The range of bacteria or other microorganisms that is affected by a certain antibiotic is expressed as its spectrum of action. Antibiotics effective against procaryotes that kill or inhibit a wide range of Gram-positive and Gram-negative bacteria are said to be broad spectrum. If effective mainly against Gram-positive or Gram-negative bacteria, they are narrow spectrum. If effective against a single organism or disease, they are referred to as limited spectrum.

IMPORTANT QUALITIES OF ANTIBIOTICS

A clinically-useful antibiotic should have as many of these qualities as possible: -It should have a wide spectrum of activity with the ability to destroy or inhibit many different species of pathogenic organisms. -It should be nontoxic to the host and without undesirable side effects. -It should be nonallergenic to the host. -It should not eliminate the normal flora of the host. -It should be able to reach the part of the human body where the infection is occurring. -It should be inexpensive and easy to produce. -It should be chemically-stable (have a long shelf-life). -Microbial resistance is uncommon and unlikely to develop.

CHEMOTHERAPY
Chemotherapy is the treatment of cancer with one or more cytotoxic antineoplastic drugs as part of a standardized regimen. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms. It is often used in conjunction with other cancer treatments, such as radiation therapy or surgery. Certain chemotherapeutic agents also have a role in the treatment of other conditions, including multiple sclerosis, Crohn's disease, psoriasis, psoriatic arthritis and rheumatoid arthritis. Traditional chemotherapeutic agents act by killing cells that divide rapidly, one of the main properties of most cancer cells. This means that chemotherapy also harms cells that divide rapidly under normal circumstances: cells in the bone marrow, digestive tract, and hair follicles.

BACTERIAL RESISTANCE
Some bacteria are able to resist the action of antibiotic drugs, including penicillin. Antibiotic resistance occurs because not all bacteria of the same species are alike, just as people in your own family are not exactly alike. Eventually, the small differences among the bacteria often mean that some will be able to resist the attack of an antibiotic. If the sick person's own defenses can not kill off these resistant bacteria, they will multiply. This antibioticresistant form of a disease can re-infect the patient, or be passed on to another person. Taking antibiotics for viral illnesses like colds can also cause antibiotic resistant bacteria to develop. Antibiotics have no effect on viruses, but it will kill off harmless and even the beneficial bacteria living in the patient's body. The surviving resistant bacteria, free from competition, will live and multiply and may eventually cause disease.

HOW RESISTANCE DEVELOPS

Patients with bacterial infections, who don't finish their antibiotic prescriptions completely, also allow resistant bacteria to develop. This happens because a small number of semi-resistant bacteria, which needed the full course of antibiotics to kill them, survive. Instead of being a small part of the bacteria causing an infection, the more resistant bacteria take over when sensitive bacteria are killed by the antibiotic. Humans can slow the creation of antibiotic resistant diseases by understanding the uses and limits of antibiotics. Take all of an antibiotic, and only take them when prescribed by a doctor. Research to develop new antibiotics to treat resistant bacteria continues, but research takes time. Time is running out because the world's biodiversity is decreasing--the source of half of our disease-fighting chemicals.