Antibiotics
Antibiotics are substances that inhibit the growth of or destroy bacteria that cause infection. Antibiotics do not work against viral diseases such as thecommon cold or influenza. The word "antibiotics" comes from the Greek anti("against") and bios("life"). Antibiotics have been used since the 1930s to prevent or treat a wide variety of infections in plants, animals,and humans. Before that time, there were few effective ways of combating microbial infections (infections caused by microorganisms). Illnesses such as pneumonia, tuberculosis, and typhoid fever were essentially untreatable. Even minor infections could be deadly.
The years between 1928 and 1940 were the most productive in the discovery anddevelopment of antimicrobial drugs. In 1928 Sir Alexander Fleming, a Scottish physician, was working on ways to kill bacteria isolated from infected wounds. He observed that a mold growing in a laboratory culture was able to destroy that culture's bacteria. Since the mold that produced the bacteria-killingsubstance was a species of Penicillium, Fleming named the substance penicillin.
It is not known when the first antibiotic was used; folk medicine has used various molds to fight infections for centuries. In 1935 a German chemist namedGerhard Domagk discovered the first class of antibacterial agents, the sulfonamides. Sulfanilamide (the parent compound of the sulfonamides) was originally part of a leather dye compound that was being screened for its potential ability to kill bacteria. It was found to be relatively nontoxic and when thedye was broken down in the body, it was converted to the compound sulfanilamide.
By 1941 penicillin had been tested in humans and was being used to treat serious infections. The results were dramatic; patients who received the drug made rapid and complete recoveries. Bacitracin, chlortetracycline, and streptomycin, naturally occurring antibiotics, were discovered by 1948. The penicillinring (chemical structure) was finally isolated in 1959 by scientists from Britain and the United States, and the door was open for the development of made-made (synthetic) antibiotics. Since 1948, a wide variety of substances thatinhibit or kill bacteria have been discovered.
How Antibiotics Are Made
The overwhelming majority of antibiotics are made from living organisms suchas bacteria about 90% of antibiotics are isolated from bacteria fungi, and molds. Others are produced synthetically, either in whole or in part.
At one time all antibiotics were made from living organisms. This process, known as biosynthesis, is still used in the manufacture of a number of antibiotics. In this method, it is actually the organisms themselves that manufacturethe antibiotic. The laboratory technician merely provides favorable conditions for the organisms to multiply, and then extracts the drug. For example, mold organisms are placed in a medium (a substance used for the growth of microorganisms) such as corn liquor to which milk sugar has been added. This mixture forms a liquid that is put into a tank, which is kept at a temperature of25 degrees Centigrade (77 degrees Fahrenheit) and shaken for over 100 hours.The mold organisms multiply rapidly in this warm liquid, producing penicillinin the process.
All types of penicillin have an identical ring. However, in each type of penicillin, the chemical chain attached to the ring is different. By modifying the molecules of the chain, scientists are able to create drugs with a wide range of effects on a variety of organisms. Some of these drugs are useful in treating infections.
Pharmaceutical companies use computer-generated images of the rings and experiment with a countless variety of possible chains. Researchers have developedantibiotics with long half-lives (period of effectiveness), which means thatthe medication can be taken every 24 hours instead of every few hours. The newer antibiotics are also more effective against a wider range of infectionsthan were earlier drugs.
How Antibiotics Work
The body's balance between health and illness is called homeostasis. Homeostasis largely depends on the relationship of the body to the bacteria with which it lives. For example, bacteria are always present on human skin. When theskin is cut, the bacteria are able to enter the body and may cause infection.The invading bacteria are usually destroyed by blood cells called phagocytesand by various actions of the immune system. However, when there are too many bacteria for the system to handle, illness results and antibiotics are needed to help restore homeostasis.
Antiobiotics can be bacteriostatic (prevent bacteria from multiplying) or bactericidal (kill bacteria). For most infections, these two types of antibiotics appear to be equally effective, but if if the immune system is impaired orthe individual has a severe infection, a bactericidal antibiotic is usually more effective. Bactericidal drugs, however, may be bacteriostatic against certain microorganisms, and vice versa.
In most infections, including certain types of pneumonia (pneumococcal) and urinary tract infections, there seems to be no advantage of bactericidal overbacteriostatic drugs. However, bactericidal activity seems to be necessary ininfections in which host (the organism from which the bacteria obtains its nourishment) defense mechanisms are at least partially lacking locally or systemically (in the whole system), for example, endocarditis (inflammation of the lining membrane of the heart), meningitis (inflammation of the membranes ofthe spinal cord or brain), or serious staphylococcal infections.
Each of the various types of antibiotics kill microorganisms in a unique way.Some disturb the structure of the bacterial cell wall; others interfere withthe production of essential proteins; and still others interfere with the transformation (metabolism) of nucleic acid (substances found in the cells of all living things).
It is believed that antibiotics interfere with the surface of bacteria cells,causing a change in their ability to reproduce. Testing the action of an antibiotic in the laboratory shows how much exposure to the drug is necessary todecrease reproduction or to kill the bacteria. Although a large dose of an antibiotic taken at one time might kill the bacteria causing an illness, the dose would most likely cause severe side effects. Therefore, antibiotics are given in a series of smaller doses. This method assures that the bacteria areeither killed or reduced enough in number so that the body can repel them. Onthe other hand, when too little antibiotic is taken, bacteria can develop methods to protect themselves against it. Thus the next time the antibiotic isneeded against these bacteria, it will not be effective.
Classes of Antibiotics
Although there are thousands of antibiotic substances that have been producednaturally or synthetically, relatively few varieties have been proven safe and effective. Sulfonamides, the earliest drugs to be used as antibacterial agents, have largely the same effects as those of the later-developed penicillins. However, sulfa drugs can have harmful effects on the kidneys, although they are effective in combating kidney infections. Thus, the sulfa drugs are always taken with large quantities of water to prevent the formation of drug crystals. Gantrisin is among the most useful of the sulfa drugs.
Although there are 160 varieties available, the following are the most commonly used types of antibiotics:
- penicillins
- cephalosporins
- fluoroquinolones
- aminoglycosides
- tetracyclines
- macrolides
- polypeptides
Penicillins encompass a large group of bactericidal agents. They include:
- penicillin G
- penicillin V
- cloxacillin
- nafcillin
- oxacillin
- ampicillin
- amoxicillin
- ticarcillin
Penicillins work by damaging the cell walls of the invading bacteria as the bacteria are in the process of reproduction. Penicillin G and V, for example,are widely used for streptococcal infections as well as for other types of bacterial infection.
Antibiotics are classified as narrow-spectrum drugs when they work against only a few types of bacteria. Broad-spectrum antibiotics, on the other hand, attack many types of bacteria. However, the danger with broad-spectrum antibiotics is that they are more likely to promote antibiotic resistance. For that reason, narrow-spectrum antibiotics, which often cost less, are used wheneverpossible. Broad-spectrum antibiotics are generally reserved for infections that are unresponsive to narrow-spectrum drugs.
Broad-spectrum penicillins, such as ampicillin and amoxicillin, are used on infections caused by what are called gram-negative organisms. In Gram's method(named after Hans C.J. Gram, a Danish physician), bacteria are identified bystaining them with dye and placed them on slides. Gram-negative bacteria take up a red color; gram-positive bacteria retain the gentian violet stain.
Hypersensitivity reactions (such as rash or fever) to penicillin are relatively common side effects. However, severe life-threatening allergic reactions (such as anaphylactic shock) are rare. Penicillins are often given in combination with other types of antibiotics.
Cephalosporins are broad-spectrum antibiotics. They include:
- cefadroxil
- cefazolin
- cephalexin
- cephalothin
- cephapirin
- cephradine
Like penicillins, the cephalosporins work by interfering with bacterial cellwall formation. The cephalosporin cefotaxime sodium is particularly effectivein treating deep infections such as those occurring in bones or resulting from surgery. The cephalosporins are often administered when a sensitivity to penicillin is known or suspected. Occasionally, however, individuals allergicto penicillins will also be allergic to the cephalosporins. Adverse side effects of the cephalosporins may include rash or fever.
Fluoroquinolones are the newest class of antibiotics. They include:
- ciprofloxacin
- enoxacin
- levofloxacin
- norfloxacin
- ofloxacin
The fluoroquinolones are well absorbed, have a broad spectrum of attack, andare considered relatively safe. These antibiotics interfere with bacterial enzymes and are most often used for treating urinary tract infections. Since fluoroquinolones may affect bone growth, however, the use of this class of antibiotics is not recommended in children or pregnant women.
Aminoglycosides work by impeding the protein formation of bacteria in invading cells. This class of antibiotics includes:
- gentamicin
- streptomycin
- neomycin
The aminoglycosides are effective against a wide variety of bacteria and other organisms and are believed to prevent the production of proteins in the invading bacterial cells. These drugs are effective against pneumonia, typhus, and other bacteria-caused illnesses but can impair liver and kidney function.Thus they are usually administered with caution. Tetracycline in a special gel base is used to treat a number of eye infections.
Tetracyclines include:
- tetracyline
- doxycycline
- minocycline
The macrolides also interfere with the protein formation of invading bacteria. The macrolides are often used in patients who are known or suspected to besensitive to penicillin. Some of the side effects of the macrolides are gastrointestinal discomfort.
The macrolides include:
- azithromycin
- clarithromycin
- erythromycin
Polypeptides are a class of antibiotics that is quite toxic and is used primarily on the skin surface. These drugs include:
- bacitracin
- colistin
- polymyxin B
Choosing an Antibiotic
Physicians are usually able to determine the type of organism responsible forcausing the most commonly seen infections and know which class of antibioticwill be the most effective in combating it. If the agent causing illness isnot known, a culture from the infection is usually examined under a microscope to identify the invading organism. However, even when the bacteria have been identified and their sensitivity to antibiotics have been determined, the choice of antibiotic is not always an easy one.
The effectiveness of the treatment depends on a variety of factors, such as how well the drug is absorbed into the bloodstream, how much drug reaches various body fluids, and how quickly the body eliminates the drug. Also, drugs selection must take into account the nature and seriousness of the illness, theside effects of the drug, the possibility of allergies or other serious reactions to the drug, as well as the cost of the drug.
Administering Antibiotics
To work against infecting organisms, an antibiotic can be applied externally,such as to a cut on the skin's surface, or administered internally, throughthe bloodstream. Antibiotics are manufactured in several forms and are administered in a variety of ways: topically, orally, or parenterally.
Topical application means "to a local area" such as on the skin, in the eyes,or on the mucous membrane. Antibiotics for topical use are available in theform of powders, ointments, drops, or creams.
Antibiotics in the form of tablets, liquids, and capsules are swallowed. Theantibiotic is released in the small intestine and absorbed into the bloodstream. Troches (lozenges) dissolve in the mouth, where the antibiotic is absorbed through the mucous membrane.
Applications outside the intestine are called parenteral. One form is an injection, which can be subcutaneous (under the skin), intramuscular (into a muscle), or intravenous (into a vein). Parenteral administration of an antibioticis used when a physician requires a strong, rapid concentration of the antibiotic into the bloodstream.
For severe bacterial infections, antibiotics are usually are given by injection first (typically intravenously). When the infection is under control, antibiotics can be taken orally. Antibiotics must be taken until the infecting organisms is eliminated from the body, which may be days after the symptoms disappear. Thus, stopping treatment too soon may result in a relapse or may encourage the development of resistant bacteria. For this reason, the antibioticis usually taken for several days after all evidence of the infection is gone.
Preventive Antibiotics
Antibiotics are used not only to treat infections but to prevent them (prophylactically). To be effective and to avoid the development of resistance in bacteria, preventive antibiotic therapy must be used for only a short duration,and the antibiotic must be potent against the particular type of bacteria involved. One example of preventive therapy is taking antibiotics before or during travel to foreign countries to prevent diarrhea. Also, preventive antibiotics are often used in people exposed to someone with meningitis (caused by meningococcus bacteria) because of the risk of infection.
Antibiotics are also used to prevent infections before, during, and after surgery. People with heart valve disorders routinely take antibiotics before surgery, including dental surgery (or even dental procedures such as cleaning).These people have increased risk of endocarditis from bacteria normally foundin the mouth and other parts of the body. Such bacteria may enter the bloodstream during the dental procedure and travel to the damaged heart valve. Preventive antibiotics may also be taken by people whose immune system is not fully functional, such as people with leukemia, people receiving chemotherapy for cancer, or people with AIDS. Otherwise healthy people undergoing those types of surgery that carry a high risk of infection (such as major orthopedic orintestinal surgery) may also take preventive antibiotics.
Side Effects
Allergic reactions to antibiotics are usually observed as skin rashes, but severe anemia (too few red blood cells), stomach disorders, and deafness can occasionally result. It was once thought that allergic reactions to antibioticspenicillin in particular were frequent and permanent. Later studies suggested, however, that many people outgrow their sensitivity or were never truly allergic. Since such a large number of antibiotics are available, in most casesallergy-causing drugs can be avoided.
People who have certain medical conditions may experience side effects when taking antibiotics. In addition, when people take antibiotics with certain foods or medications, the effects of the antibiotic or the risk of side effectsmay increase. After taking an antibiotic, any unusual symptoms should be reported to the physician immediately.
Antibiotic Resistance
An antibiotic limits or stops the growth of a specific microorganism by interfering with the wall of the bacterial cell at which it is targeted, while simultaneously having little effect on the body's normal cells.
However, when an individual takes an antibiotic for a long period of time, such as for an illness like rheumatic fever, the targeted bacteria may developtheir own defense against the drug. An enzyme (a complex protein capable of inducing chemical changes without being changed itself) that can destroy the drug may be produced by the bacteria, or the cell wall may become resistant tobeing broken by the action of the antibiotic. When this resistance occurs, as it does most often in response to long or frequent treatment with penicillin or streptomycin, an individual is said to be "fast" against the drug. For example, a person may be penicillin-fast, meaning penicillin is no longer ableto help fight the infection and another type of antibiotic must be administered.
Sometimes just a few bacteria in a population can resist the effects of an antibiotic. Because bacteria reproduce so quickly, the trait can be rapidly passed on through generations until almost all the bacteria of that species areimmune to a particular antibiotic. The more antibiotics are used, the more rapidly the process happens. As a result, almost every disease-causing bacterium is resistant to at least one antibiotic.
Health experts are particularly concerned about antibiotic resistance in bacteria that cause certain serious infections. For example, some strains of Staphylococcus aureus, that may cause pneumonia or bloodstream infections,are resistant to almost all antibiotics, making those conditions very difficult to treat. Many strains of tuberculosis, also an infectious disease, alsoare now resistant to one or more of the agents used to control tuberculosis.