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Key Terms: Gram-negative, Gram-positive, Mycobacteria, Pneumocystis carinii pneumonia, Protozoa, Toxoplasmosis.
Definition
Antibiotics are drugs that are used to treat infections caused by bacteria and other organisms, including protozoa, parasites, and fungi.
Purpose
Many treatments for cancer destroy disease-fighting white blood cells, thereby reducing the body's ability to fight infection. For example, bladder, pulmonary, and urinary tract infections may occur with chemotherapy. Single-celled organisms called protozoa are rarely a problem for healthy individuals. However, they can cause serious infections in individuals with low white blood cell counts. Because of the dangers that infections present for cancer patients, antibiotic treatment often is initiated before the exact nature of the infection has been determined; instead, the choice of antibiotic may depend on the site of the infection and the organism that is likely to be the cause. Often, an antibiotic that kills a broad spectrum of bacteria is chosen and several antibiotics may be used together.
Description
The common antibiotics that are used during cancer treatment include:
Most of these antibiotics kill bacteria by preventing them from making protein for their cell walls. Ciprofloxacin and metronidazole prevent bacteria from reproducing by interfering with their ability to make new DNA. All of these drugs are approved for prescription by the U.S. Food and Drug Administration.
Recommended Dosage
Dosages of antibiotics depend on the individual, the infection that is being treated, and the presence of other medical conditions. For children, the dosage usually is based on body weight and is lower than the adult dosage. To be effective, an entire treatment with antibiotics must be completed, even if the symptoms of infection have disappeared. Furthermore, it is important to keep the level of antibiotic in the body at a constant level during treatment. Therefore, the drug should be taken on a regular schedule. If a dose is missed, it should be taken as soon as possible. If it is almost time for the next dose, the missed dose should be skipped. Doubling up doses is generally not recommended.
Average adult dosages of common antibiotics for cancer patients are as follows:
Precautions
Stomach or intestinal problems or colitis (inflammation of the colon) may affect the use of:
Kidney or liver disease may affect the use of:
Central nervous system or seizure disorders may affect the use of:
Anemia (low red blood cell count) or other blood disorders may affect the use of:
Ciprofloxacin may not be suitable for individuals with tendinitis or with skin sensitivities to sunlight. Gentamicin may not be suitable for people with hearing problems, myasthenia gravis, or Parkinson's disease. Metronidazole may not be suitable for individuals with heart disease, oral or vaginal yeast infections, or a history of alcoholism. Pentamidine may not be suitable for individuals with heart disease, bleeding disorders, or low blood pressure. Pentamidine may affect blood sugar levels, making control of diabetes mellitus or hypoglycemia (low blood sugar) difficult. Vancomycin may not be appropriate for individuals with hearing problems.
Many antibiotics should not be taken during pregnancy or while breast-feeding. Older individuals may be more susceptible to the side effects of sulfadiazine, SMZ-TMP, or trimethoprim.
Side Effects
Some individuals may have allergic reactions to antibiotics. If symptoms of an allergic reaction (such as rash, shortness of breath, swelling of the face and neck), severe diarrhea, or abdominal cramping occur, the antibiotic should be stopped and the individual should seek medical advice.
Because antibiotics can affect bacteria that are beneficial, as well as those that are harmful, women may become susceptible to infections by fungi when taking antibiotics. Vaginal itching or discharge may be symptoms of such infections. All patients may develop oral fungal infections of the mouth, indicated by white plaques in the mouth.
Injected antibiotics may result in irritation, pain, tenderness, or swelling in the vein used for injection. Antibiotics used in cancer patients may have numerous side effects, both minor and severe; however, most side effects are uncommon or rare.
The more common side effects of atovaquone, aztreonam, cephalosporins, ciprofloxacin, clindamycin, gentamicin, metronidazole, and SMZ-TMP include:
Other side effects of atovaquone may include:
Other side effects of ciprofloxacin may include:
Other common side effects of clindamycin include abdominal pain and fever. Side effects may occur up to several weeks after treatment with this medicine.
Gentamicin and vancomycin may cause serious side effects, particularly in elderly individuals and newborn infants. These include kidney damage and damage to the auditory nerve that controls hearing. Other, more common side effects of gentamicin may include:
When gentamicin is injected into a muscle, vein, or the spinal fluid, the following side effects may occur:
More common side effects of metronidazole include:
Pentamidine, pyrimethamine, sulfonamides, SMZTMP, and trimethoprim can lower the number of white blood cells, resulting in an increased risk of infection. These drugs also can lower the number of blood platelets that are important for blood clotting. Thus, there is an increased risk of bleeding or bruising while taking these drugs.
Serious side effects of pentamidine may include:
Pyrimethamine and trimethoprim may lower the red blood cell count, causing anemia. Leucovorin or the vitamin folic acid may be prescribed for anemia.
Some individuals become more sensitive to sunlight when taking sulfonamides, SMZ-TMP, or trimethoprim. Other common side effects of sulfonamides and SMZTMP include:
If vancomycin is injected into a vein too quickly, it can cause flushing and a rash over the neck, face, and chest, wheezing or difficulty breathing, and a dangerous decrease in blood pressure.
Interactions
Many prescription and non-prescription medicines can interact with these antibiotics. Therefore, it is important to consult a complete list of known drug interactions. Among the more common or dangerous interactions:
Many medicines can increase the risk of hearing or kidney damage from gentamicin. These include:
The following drugs may increase the risk of liver effects with sulfadiazine or SMZ-TMP:
Resources
Books
American Cancer Society. Consumers Guide to Cancer Drugs. Atlanta: Jones and Bartlett, 2000.
Other
American Cancer Society. Cancer Drugs. Cancer Resource Center. 2000. [cited May 27, 2001].
American Cancer Society. Infections in Individuals with Cancer. Cancer Resource Center. 30 Sep. 1999. [cited May 27, 2001].
MEDLINEplus Drug Information. U.S. National Library of Medicine. 24 Jan. 2001. [cited May 22, 2001].
—Margaret Alic, Ph.D.
Antibiotics are chemical substances that can inhibit the growth of, and even destroy, harmful microorganisms. They are derived from special microorganisms or other living systems, and are produced on an industrial scale using a fermentation process. Although the principles of antibiotic action were not discovered until the twentieth century, the first known use of antibiotics was by the Chinese over 2,500 years ago. Today, over 10,000 antibiotic substances have been reported. Currently, antibiotics represent a multibillion dollar industry that continues to grow each year.
Background
Antibiotics are used in many forms—each of which imposes somewhat different manufacturing requirements. For bacterial infections on the skin surface, eye, or ear, an antibiotic may be applied as an ointment or cream. If the infection is internal, the antibiotic can be swallowed or injected directly into the body. In these cases, the antibiotic is delivered throughout the body by absorption into the bloodstream.
Antibiotics differ chemically so it is under-standable that they also differ in the types of infections they cure and the ways in which they cure them. Certain antibiotics destroy bacteria by affecting the structure of their cells. This can occur in one of two ways. First, the antibiotic can weaken the cell walls of the infectious bacteria, which causes them to burst. Second, antibiotics can cause the contents of the bacterial cells to leak out by damaging the cell membranes. Another way in which antibiotics function is by interfering with the bacteria's metabolism. Some antibiotics such as tetracycline and erythromycin interfere with protein synthesis. Antibiotics like rifampin inhibit nucleic acid biosynthesis. Still other antibiotics, such as sulfonamide or trimethoprim have a general blocking effect on cell metabolism.
The commercial development of an antibiotic is a long and costly proposal. It begins with basic research designed to identify organisms, which produce antibiotic compounds. During this phase, thousands of species are screened for any sign of antibacterial action. When one is found, the species is tested against a variety of known infectious bacteria. If the results are promising, the organism is grown on a large scale so the compound responsible for the antibiotic effect can be isolated. This is a complex procedure because thousands of antibiotic materials have already been discovered. Often, scientists find that their new antibiotics are not unique. If the material passes this phase, further testing can be done. This typically involves clinical testing to prove that the antibiotic works in animals and humans and is not harmful. If these tests are passed, the Food and Drug Administration (FDA) must then approve the antibiotic as a new drug. This whole process can take many years.
The large-scale production of an antibiotic depends on a fermentation process. During fermentation, large amounts of the antibiotic-producing organism are grown. During fermentation, the organisms produce the antibiotic material, which can then be isolated for use as a drug. For a new antibiotic to be economically feasible, manufacturers must be able to get a high yield of drug from the fermentation process, and be able to easily isolate it. Extensive research is usually required before a new antibiotic can be commercially scaled up.
History
While our scientific knowledge of antibiotics has only recently been developed, the practical application of antibiotics has existed for centuries. The first known use was by the Chinese about 2,500 years ago. During this time, they discovered that applying the moldy curd of soybeans to infections had certain therapeutic benefits. It was so effective that it became a standard treatment. Evidence suggests that other cultures used antibiotic-type substances as therapeutic agents. The Sudanese-Nubian civilization used a type of tetracycline antibiotic as early as 350 A.D. In Europe during the Middle Ages, crude plant extracts and cheese curds were also used to fight infection. Although these cultures used antibiotics, the general principles of antibiotic action were not understood until the twentieth century.
The development of modern antibiotics depended on a few key individuals who demonstrated to the world that materials derived from microorganisms could be used to cure infectious diseases. One of the first pioneers in this field was Louis Pasteur. In 1877, he and an associate discovered that the growth of disease-causing anthrax bacteria could be inhibited by a saprophytic bacteria. They showed that large amounts of anthrax bacilli could be given to animals with no adverse affects as long as the saprophytic bacilli were also given. Over the next few years, other observations supported the fact that some bacterially derived materials could prevent the growth of disease-causing bacteria.
In 1928, Alexander Fleming made one of the most important contributions to the field of antibiotics. In an experiment, he found that a strain of green Penicillium mold inhibited the growth of bacteria on an agar plate. This led to the development of the first modern era antibiotic, penicillin. A few years later in 1932, a paper was published which suggested a method for treating infected wounds using a penicillin preparation. Although these early samples of penicillin were functional, they were not reliable and further refinements were needed. These improvements came in the early 1940s when Howard Florey and associates discovered a new strain of Penicillium, which produced high yields of penicillin. This allowed large-scale production of penicillin, which helped launch the modern antibiotics industry.
After the discovery of penicillin, other antibiotics were sought. In 1939, work began on the isolation of potential antibiotic products from the soil bacteria streptomyces. It was around this time that the term antibiotic was introduced. Selman Waxman and associates discovered streptomycin in 1944. Subsequent studies resulted in the discovery of a host of new, different antibiotics including actinomycin, streptothricin, and neomycin all produced by Streptomyces. Other antibiotics that have been discovered since include bacitracin, polymyxin, viomycin, chloramphenicol and tetracyclines. Since the 1970s, most new antibiotics have been synthetic modifications of naturally occurring antibiotics.
Raw Materials
The compounds that make the fermentation broth are the primary raw materials required for antibiotic production. This broth is an aqueous solution made up of all of the ingredients necessary for the proliferation of the microorganisms. Typically, it contains a carbon source like molasses, or soy meal, both of which are made up of lactose and glucose sugars. These materials are needed as a food source for the organisms. Nitrogen is another necessary compound in the metabolic cycles of the organisms. For this reason, an ammonia salt is typically used. Additionally, trace elements needed for the proper growth of the antibiotic-producing organisms are included. These are components such as phosphorus, sulfur, magnesium, zinc, iron, and copper introduced through water soluble salts. To prevent foaming during fermentation, anti-foaming agents such as lard oil, octadecanol, and silicones are used.
The Manufacturing
Process
Although most antibiotics occur in nature, they are not normally available in the quantities necessary for large-scale production. For this reason, a fermentation process was developed. It involves isolating a desired microorganism, fueling growth of the culture and refining and isolating the final antibiotic product. It is important that sterile conditions be maintained throughout the manufacturing process, because contamination by foreign microbes will ruin the fermentation.
Starting the culture
Fermentation
Isolation and purification
Refining
Quality Control
Quality control is of utmost importance in the production of antibiotics. Since it involves a fermentation process, steps must be taken to ensure that absolutely no contamination is introduced at any point during production. To this end, the medium and all of the processing equipment are thoroughly steam sterilized. During manufacturing, the quality of all the compounds is checked on a regular basis. Of particular importance are frequent checks of the condition of the microorganism culture during fermentation. These are accomplished using various chromatography techniques. Also, various physical and chemical properties of the finished product are checked such as pH, melting point, and moisture content.
In the United States, antibiotic production is highly regulated by the Food and Drug Administration (FDA). Depending on the application and type of antibiotic, more or less testing must be completed. For example, the FDA requires that for certain antibiotics each batch must be checked by them for effectiveness and purity. Only after they have certified the batch can it be sold for general consumption.
The Future
Since the development of a new drug is a costly proposition, pharmaceutical companies have done very little research in the last decade. However, an alarming development has spurred a revived interest in the development of new antibiotics. It turns out that some of the disease-causing bacteria have mutated and developed a resistance to many of the standard antibiotics. This could have grave consequences on the world's public health unless new antibiotics are discovered or improvements are made on the ones that are available. This challenging problem will be the focus of research for many years to come.
Where to Learn More
Books
Crueger, W. Biotechnology: A Textbook of Industrial Microbiology. Sunderland: Sinauer Associates, Inc., 1989.
Kirk Othmer Encyclopedia of Chemical Technology. New York: John Wiley & Sons, 1992.
Periodicals
Morell, Virginia. "Antibiotic Resistance: Road of No Return." Science 278 (October 24, 1997): 575-576.
Stinson, Stephen. "Drug Firms Restock Antibacterial Arsenal." Chemical & Engineering News (September 23,1996): 75-100.
[Article by: Perry Romanowski]
The original definition of an antibiotic was a chemical substance that is produced by a microorganism and, in dilute solutions, can inhibit the growth of, and even destroy, other microorganisms. This definition has been expanded to include similar inhibitory substances that are produced by plants, marine organisms, and total- or semisynthetic procedures. Since the discovery of penicillin by A. Fleming in 1928, thousands of antibiotics have been isolated and identified; some have been found to be of value in the treatment of infectious disease. They differ markedly in physicochemical and pharmacological properties, antimicrobial spectra, and mechanisms of action.
Production
Penicillin is produced by strains of the fungus Penicillium notatum and P. chrysogenum. Most of the other antibiotics in clinical use are produced by actinomycetes, particularly streptomycetes (natural antibiotics). Other antibiotics are produced by chemical synthesis (synthetic antibiotics). Based on structure, the major antibiotic classes are the β-lactams (penicillins and cephalosporins), aminoglycosides, macrolides, tetracyclines, quinolones, rifamycins, polyenes, azoles, glycopeptides, and polypeptides.
The key step in the production of natural antibiotics is a fermentation process. Strains of microorganisms, selected by elaborate screening procedures from randomly isolated pure cultures, are inoculated into sterile nutrient medium in large vats and incubated for varying periods of time. Different strains of a single microbial species may differ greatly in the amounts of antibiotics they produce. Strain selection is thus the most powerful tool in effecting major improvements in antibiotic yield. In addition, variations in culturing conditions often markedly affect the amount of antibiotic that is produced by a given strain. Chemical modifications of antibiotics produced by fermentation processes have led to semisynthetic ones with improved antimicrobial activity or pharmacological properties. See also Bacterial physiology and metabolism; Fermentation.
Antimicrobial activity
All microorganisms can cause infectious diseases in animals and humans, though the majority of infections are caused by bacteria. Most antibiotics are active against bacteria. Although for the proper treatment of serious infections cultures and antibiotic sensitivities are required, antibiotic therapy is often empiric, with etiology being inferred from the clinical features of a disease.
Bacteria are divided into the gram positive and the gram negative; each group comprises a wide variety of different species. Staphylococci, pneumococci, and streptococci are the more common gram-positive organisms, while enterobacteria, Pseudomonas, and Hemophilus are the most common gram negative. Certain antibiotics are effective only against gram-positive bacteria. Others are effective against both gram-positive and gram-negative bacteria and are referred to as broad-spectrum antibiotics. See also Bacteria; Medical bacteriology.
Pathogenic fungi may be divided on the basis of their pathogenicity into true pathogens and opportunistic pathogens. The opportunistic occur mainly in debilitated and immunocompromised patients. Clinically useful antibiotics include amphotericin B, nystatin, griseofulvin and the azole antifungals. See also Fungi; Medical mycology; Opportunistic infections.
With some viruses that cause mild infections, such as the common-cold viruses (rhinoviruses), treatment is symptomatic. With others, such as the polio, smallpox (now eradicated), and hepatitis B viruses, the only way to prevent disease is by vaccination. With still other viruses, antibiotics, mostly synthetic, are the appropriate treatment. Clinically useful antibiotics are ribavirin, acyclovir, and zidovudine, which are active against, respectively, respiratory, herpes, and human immunodeficiency viruses. See also Animal virus; Vaccination.
Protozoa may be divided, on the basis of the site of infection, into intestinal, urogenital, blood, and tissue. Protozoan diseases such as malaria, trypanosomiasis, and amebiasis are particularly common in the tropics, in populations living under poor housing and sanitary conditions. In the developed countries, P. carinii is the most important opportunistic pathogen, being associated almost exclusively with acquired immune deficiency syndrome (AIDS). Antibiotics active against protozoa include metronidazole, trimethoprim-sulfamethoxazole, and quinine. See also Acquired immune deficiency syndrome (AIDS); Medical parasitology; Protozoa.
Antitumor activity
The observation of the antitumor activity of actinomycin sparked an intensive search for antitumor antibiotics in plants and microorganisms. Among the antibiotics used clinically against certain forms of cancer are daunorubicin, doxorubicin, mitomycin C, and bleomycin. See also Cancer (medicine).
Mechanism of action
Antibiotics active against bacteria are bacteriostatic or bacteriocidal; that is, they either inhibit growth of susceptible organisms or destroy them. On the basis of their mechanism of action, antibiotics are classified as (1) those that affect bacterial cell-wall biosynthesis, causing loss of viability and often cell lysis (penicillins and cephalosporins, bacitracin, cycloserine, vancomycin); (2) those that act directly on the cell membrane, affecting its barrier function and leading to leakage of intracellular components (polymyxin); (3) those that interfere with protein biosynthesis (chloramphenicol, tetracyclines, erythromycin, spectinomycin, streptomycin, gentamycin); (4) those that affect nucleic acid biosynthesis (rifampicin, novobiocin, quinolones); and (5) those that block specific steps in intermediary metabolism (sulfonamides, trimethoprim). See also Enzyme; Sulfonamide.
Antibiotics active against fungi are fungistatic or fungicidal. Their mechanisms of action include (1) interaction with the cell membrane, leading to leakage of cytoplasmic components (amphotericin, nystatin); (2) interference with the synthesis of membrane components (ketoconazole, fluconazole); (3) interference with nucleic acid synthesis (5-fluorocytosine); and (4) interference with microtubule assembly (griseofulvin). See also Fungistat and fungicide.
For an antibiotic to be effective, it must first reach the target site of action on or in the microbial cell. It must also reach the body site at which the infective microorganism resides in sufficient concentration, and remain there long enough to exert its effect. The concentration in the body must remain below that which is toxic to the human cells. The effectiveness of an antibiotic also depends on the severity of the infection and the immune system of the body, being significantly reduced when the immune system is impaired. Complete killing or lysis of the microorganism may be required to achieve a successful outcome. See also Immunity.
Antibiotics may be given by injection, orally, or topically. When given orally, they must be absorbed into the body and transported by the blood and extracellular fluids to the site of the infecting organisms. When they are administered topically, such absorption is rarely possible, and the antibiotics then exert their effect only against those organisms present at the site of application.
Microbial resistance
The therapeutic value of every antibiotic class is gradually eroded by the microbial resistance that invariably follows broad clinical use.
Some bacteria are naturally resistant to certain antibiotics (inherent resistance). Clinical resistance is commonly due to the emergence of resistant organisms following antibiotic treatment (acquired resistance). This emergence, in turn, is due to selection of resistant mutants of the infective species (endogenous resistance) or, usually, to transfer of resistance genes from other, naturally resistant species (exogenous resistance). A major challenge in antimicrobial chemotherapy is the horizontal spread of resistance genes and resistant strains, mostly in the hospital but also in the community. The consequences are increased patient morbidity and mortality, reduced drug options, and more expensive and toxic antibiotics.
Rapid detection of resistance and pathogen identification are critical for the rational use of antibiotics and implementation of infection control measures. In the absence of such information, treament is empiric, usually involving broad-spectrum agents, which exacerbates resistance development. Inadequate infection control measures encourage dissemination of resistant strains.
Importance
It is estimated that the average duration of many infectious diseases and the severity of certain others have decreased significantly since the introduction of antibiotic therapy. The dramatic drop in mortality rates for such dreaded diseases as meningitis, tuberculosis, and septicemia offers striking evidence of the effectiveness of these agents. Bacterial pneumonia, bacterial endocarditis, typhoid fever, and certain sexually transmitted diseases are also amenable to treatment with antibiotics. So are infections that often follow viral or neoplastic diseases, even though the original illness may not respond to antibiotic therapy. See also Epidemiology.
Antibiotics in small amounts are widely used as feed supplements to stimulate growth of livestock and poultry. They probably act by inhibiting organisms responsible for low-grade infections and by reducing intestinal epithelial inflammation. Many experts believe that this use of antibiotics contributes to the emergence of antibiotic-resistant bacteria that could eventually pose a public health problem.
In cattle, sheep, and swine, antibiotics are effective against economically important diseases. The use of antibiotics in dogs and cats closely resembles their use in human medical practice. In fish farms, antibiotics are usually added to the food or applied to the fish by bathing. The incidence of infections in fish, and animals in general, may be reduced by the use of disease-resistant stock, better hygiene, and better diet. See also Aquaculture.
Although effective against many microorganisms causing disease in plants, antibiotics are not widely used to control crop and plant diseases. Some of the limiting factors are instability of the antibiotic under field conditions, the possibility of harmful residues, and expense. Nevertheless, antibiotic control of some crop pathogens is being practiced, as is true of the rice blast in Japan, for example. See also Plant pathology.
Substances produced by living organisms which inhibit the growth of other organisms. The first antibiotic to be discovered was penicillin, which is produced by the mould Penicillium notatum and inhibits the growth of sensitive bacteria. Many antibiotics are used to treat bacterial infections in human beings and animals; different compounds affect different bacteria. Small amounts of antibiotics may be added to animal feed (a few grams/tonne), resulting in improved growth, possibly by controlling mild infections or changing the population of intestinal bacteria and so altering the digestion and absorption of food, but their use as growth promoters is banned in the EU.
A substance secreted by a micro-organism (e.g. bacterium or fungus) that can inhibit or kill other microorganisms. The fungus Penicillium nodosum, for example, secretes penicillin that kills some bacteria.
Many people are concerned about the inclusion of antibiotics in animal feedstuffs to accelerate the animals' growth and protect them against disease. Although the antibiotics used in these feedstuffs are not those used in human medicine, some people still fear that antibiotics may be transferred to humans and destroy beneficial bacteria normally resident in the gut. This is not likely.
Indiscriminate use of antibiotics (e.g. not taking a full course) can encourage the development of antibiotic-resistant strains of bacteria. Hence, a particular antibiotic used successfully in the past to treat a disease may no longer be effective.
Antibiotics have come to be regarded in the minds of most people as substances used to combat infection. In fact they are both more and less than that; more because they are increasingly important in the chemotherapy of cancer, and less because not all drugs used to treat microbial infections are actually antibiotics. Antibiotics are substances of natural origin, and their name derives from the ecological relationship between the organism which produces them and the microbe or living tissue whose growth is inhibited by them: antibiosis — the exact antithesis of symbiosis (living together for mutual benefit). Antibiosis as a biological phenomenon was known in the nineteenth century, but the scientific term ‘antibiotic’ was only coined much later, after the young physician Alexander Fleming (later Sir Alexander) had made his seminal observations which led to the discovery of penicillin and ushered in the era of modern chemotherapy. As the story goes, in 1929 Fleming was working at St Mary's Hospital in Paddington with cultures of pathogenic bacteria (staphylococci), when one day there blew in through the partially open window of his laboratory above Praed Street a fungal spore, which landed on one of his agar plates and grew up to produce a large clump of the mould. For an ordinary microbiologist this could have been regarded as a minor inconvenience, the sort of contamination which happens from time to time if one is not super-meticulous about sterile precautions, and calls for nothing more demanding than the disposal of the contaminated plate and inoculation of a fresh one. To his credit, Fleming noticed that not only was the growth of the bacteria inhibited in the vicinity of the mould, but the colonies of staphylococci were actually disappearing or lysing. He showed that the effect was due to a substance secreted by the mould, and attempted to purify it — but it proved unstable.
It took the outbreak of World War II to galvanize the scientific community into action and exploit the discovery of penicillin for widespread clinical benefit. The problems of producing the material on an industrial scale were solved, and for the first time many infectious diseases were brought under effective control. But not all. In general, infections caused by ‘Gram positive’ bacteria (categorized by Gram's staining process) proved curable by penicillin, but treatment of those caused by ‘Gram negative’ organisms (such as dysentery, cholera, and the like) had to await the discovery of other antibiotics by screening methods which are still largely in use today. Streptomycin, tetracyclines, and numerous macrolide (‘large-ring’) antibiotics were found whose activities complemented those of penicillin. In parallel with screening approaches the chemists succeeded in creating a whole family of semi-synthetic derivatives of penicillin (generically known as β-lactam antibiotics, because they all contain the essential 4-membered β-lactam ring). These semi-synthetic drugs have extended the antibacterial spectrum of ‘natural’ penicillin, and have helped to counter the emergence of antibiotic-resistant strains of pathogenic bacteria.
Antibiotics work by selectively inhibiting processes which are peculiar to microbial cells, often ones associated with a unique structural feature, enzyme, or organelle not present in human cells. A prime example is the bacterial cell wall, the composition of which is unique in several respects. Penicillins are selectively toxic because they mimic a particular dipeptide sequence present in cell wall precursors. This molecular mimicry inactivates a crucial enzyme needed to form cross-links between the peptidoglycan chains which impart mechanical strength to the bacterial cell wall. Other antibiotics prevent protein synthesis in the bacterial cell, or inactivate enzymes concerned with the complicated processes of nucleotide and nucleic acid biosynthesis.
— M. J. Waring
See also chemotherapy; infection.
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Definition
Antibiotics are used for treatment or prevention of bacterial infection. They may be informally defined as the subgroup of anti-infectives that are derived from bacterial sources and are used to treat bacterial infections. Other classes of drugs, most notably the sulfonamides, may be effective antibacterials. Similarly, some antibiotics may have secondary uses, such as the use of demeclocycline (Declomycin, a tetracycline derivative) to treat the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Other antibiotics may be useful in treating protozoal infections.
Description
Classifications
Although there are several classification schemes for antibiotics, based on bacterial spectrum (broad versus narrow) or route of administration (injectable versus oral versus topical), or type of activity (bactericidal versus bacteriostatic), the most useful is based on chemical structure. Antibiotics within a structural class will generally show similar patterns of effectiveness, toxicity, and allergic potential.
PENICILLINS. The penicillins are the oldest class of antibiotics and have a common chemical structure that they share with the cephalosporins. Classed as the betalactam antibiotics, the two groups are generally bacteriocidal, which means that they kill bacteria rather than simply inhibit its growth. The penicillins can be further subdivided. The natural penicillins are based on the original penicillin G structure; penicillinase-resistant penicillins, notably methicillin and oxacillin, are active even in the presence of the bacterial enzyme that inactivates most natural penicillins. Aminopenicillins such as ampicillin and amoxicillin have an extended spectrum of action compared with the natural penicillins; extended spectrum penicillins are effective against a wider range of bacteria. These generally include coverage for Pseudomonas aeruginosa.
CEPHALOSPORINS. Cephalosporins and the closely related cephamycins and carbapenems, like the penicillins, contain a beta-lactam chemical structure. Consequently, there are patterns of cross-resistance and cross-allergenicity among the drugs in these classes. The "cepha" drugs are among the most diverse classes of antibiotics and are themselves subdivided into first, second, and third generations. Each generation has a broader spectrum of activity than the one before. In addition, cefoxitin, a cephamycin, is highly active against anaerobic bacteria, which offers utility in treatment of abdominal infections. The third generation drugs, cefotaxime, ceftizoxime, ceftriaxone, and others, cross the blood-brain barrier and may be used to treat meningitis and encephalitis. Cephalosporins are the usually preferred agents for surgical prophylaxis.
FLUOROQUINOLONES. The fluoroquinolones are synthetic antibacterial agents and not derived from bacteria. They are included here because they can be readily interchanged with traditional antibiotics. An earlier, related class of antibacterial agents, the quinolones, drugs that were not well absorbed, could be used only to treat urinary tract infections. The fluoroquinolones, which are based on the older group, are broad-spectrum bacteriocidal drugs that are chemically unrelated to the penicillins or the cephalosporins. They are well distributed into bone tissue and so well absorbed that in general they are as effective by the oral route as by intravenous infusion.
TETRACYCLINES Tetracyclines got their name from the fact that they share a chemical structure that has four rings. They are derived from a species of Streptomyces bacteria. Broad-spectrum bacteriostatic agents, the tetracyclines may be effective against a wide variety of microorganisms, including rickettsia and amoebic parasites.
MACROLIDES. The macrolide antibiotics are derived from Streptomyces bacteria. Erythromycin, the prototype of this class, has a spectrum and use similar to penicillin. Newer members of the group, azithromycin and clarithromycin, are particularly useful for their high level of lung penetration. Clarithromycin has been widely used to treat Helicobacter pylori infections, the cause of stomach ulcers.
OTHERS. Other classes of antibiotics include the aminoglycosides, which are particularly useful for their effectiveness in treating Pseudomonas aeruginosa infections, and the lincosamide drugs clindamycin and lincomycin, which are highly active against anaerobic pathogens. There are other, individual drugs which may have utility in specific infections.
General Use
Antibiotics are used for treatment or prevention of bacterial infections. In most cases, they are prescribed for a short period of time to treat a specific infection. This period may range from three days to 10 days or more. More serious infections may require longer periods of treatment, up to several months or longer. Lower doses may be used over a long period of time to prevent the return of a serious infection.
Precautions
All antibiotics should be used as prescribed. These drugs will degrade over time and lose their potency. Not completing a prescribed course of treatment increases the probability that drug-resistant strains of organisms will develop.
Side Effects
All antibiotics cause risk of overgrowth by non-susceptible bacteria. Manufacturers list other major hazards by class; however, the healthcare provider should review each drug individually to assess the degree of risk. Generally, breastfeeding may be continued while taking antibiotics, but nursing mothers should always check with their physician first. Excessive or inappropriate use may promote growth of resistant pathogens.
Hypersensitivity to penicillins may be common, and cross allergenicity with cephalosporins has been reported. (That is, those who are allergic to penicillin may also be allergic to cephalosporins.) Penicillins are classed as category B during pregnancy.
Several cephalosporins and related compounds have been associated with seizures. Cefmetazole, cefoperazone, cefotetan, and ceftriaxone may be associated with problems in poor blood clotting. Pseudomembranous colitis (an intestinal disorder) has been reported with cephalosporins and other broad spectrum antibiotics. Some drugs in this class may cause kidney toxicity. Cephalosporins are classed as category B during pregnancy.
Regarding fluoroquinolones, lomefloxacin has been associated with increased sensitivity to light. All drugs in this class have been associated with convulsions. Fluoroquinolones are classed as category C during pregnancy.
Of the tetracyclines, demeclocycline may cause increased photosensitivity. Minocycline may cause dizziness. Healthcare providers do not prescribe tetracyclines in children under the age of eight, and they specifically avoid doing so during periods of tooth development. Oral tetracyclines bind to anions such as calcium and iron. Although doxycycline and minocycline may be taken with meals, people must be advised to take other tetracycline antibiotics on an empty stomach and not to take the drugs with milk or other calcium-rich foods. Expired tetracycline should never be administered. These drugs have a pregnancy category D. Use during pregnancy may cause alterations in fetal bone development.
Of the macrolides, erythromycin may aggravate the weakness of people with myasthenia gravis. Azithromycin has, rarely, been associated with allergic reactions, including angioedema (swelling), anaphylaxis, and severe skin reactions. Oral erythromycin may be highly irritating to the stomach and when given by injection may cause severe phlebitis (inflammation of the veins). These drugs should be used with caution in people with liver dysfunction. Azithromycin and erythromycin are pregnancy category B. Clarithromycin, dirithromycin, and troleandomycin are pregnancy category C.
The aminoglycosides class of drugs causes kidney and ear problems. These problems can occur even with normal doses. Dosing should be based on kidney function, with periodic testing of both kidney function and hearing. These drugs are pregnancy category D.
Parental Concerns
Parents should be sure to follow all dosage and label directions. This includes using all of a prescription at the time it is prescribed. Parents should also ensure that children cannot ingest any prescription medications by accident.
Resources
Books
Antibiotics: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego, CA: ICON Health Publications, 2003.
Archer, Gordon, and Ronald E. Polk. "Treatment and Prophylaxis of Bacterial Infections." In Harrison's Principles of Internal Medicine, 15th ed. Edited by Eugene Braunwald, et al. New York: McGraw-Hill, 2001, pp. 867-81.
Diasio, Robert B. "Principles of Drug Therapy." In Cecil Textbook of Medicine, 22nd ed. Edited by Lee Goldman, et al. Philadelphia: Saunders, 2003, pp. 124-34.
Scott, Geoffrey M. Handbook of Essential Antibiotics. New York: Gordon & Breach Publishing Group, 2004.
Sherman, Josepha. War against Germs. New York: Rosen Publishing Group, 2004.
Periodicals
Ashworth, M., et al. "Why has antibiotic prescribing for respiratory illness declined in primary care?" Journal of Public Health (Oxford) 26, no. 3 (2004): 268–74.
Carrat, F., et al. "Antibiotic treatment for influenza does not affect resolution of illness, secondary visits or lost workdays." European Journal of Epidemiology 19, no. 7 (2004): 703-5.
Dancer, S. J. "How antibiotics can make us sick: the less obvious adverse effects of antimicrobial chemotherapy." Lancet Infectious Diseases 4, no. 10 (2004): 611–9.
Simoes, J. A., et al. "Antibiotic resistance patterns of group B streptococcal clinical isolates." Infectious Diseases in Obstetrics and Gynecology 12, no. 1 (2004): 1–8.
Organizations
American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Web site: www.aafp.org/.
American Academy of Pediatrics. 141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098. Web site: www.aap.org/.
American College of Emergency Physicians. PO Box 619911, Dallas, TX 75261-9911. Web site: www.acep.org/.
Web Sites
"Antibiotic Guide." Johns Hopkins Point of Care Information Technology. Available online at
"Antibiotics: When They Can and Can't Help." American Academy of Family Physicians. Available online at
[Article by: L. Fleming Fallon, Jr., MD, DrPH]
Antibiotics represent a class of drugs used in the treatment of infections and infectious diseases caused by bacteria. These bacteria possess unique features (e.g., a cell wall, proteins, enzymes) that differentiate them from animal cells. Antibiotics interfere with the production of these bacterial characteristics, resulting in selective killing or growth inhibition of susceptible microorganisms. For example, prior to 1990, infections caused by Streptococcus pneumoniae (e.g., pneumonia, bronchitis, ear infections), were usually treated with penicillin or amoxicillin. Streptococcus pneumoniae possess a cell wall that acts as a protective barrier— a unique feature not found on animal or human cells. Penicillin or amoxicillin, two common antibiotics, bind to that cell wall as it is produced, causing it to weaken and "leak," eventually killing the bacteria without harming the animal host cells.
Antibiotics can be further described by the number of bacteria covered (narrow-spectrum antibiotics versus broad-spectrum antibiotics), and by how strongly the antibiotics work against the bacteria (bactericidal activity versus bacteriostatic activity). Narrow-spectrum antibiotics are used to treat infections limited to a few families and types of bacteria, while broad-spectrum antibiotics are useful to treat infections caused by multiple families of bacteria. An antibiotic that exhibits bactericidal activity will kill bacteria when it comes into contact with it (e.g., S. pneumoniae). Bacteriostatic activity, on the other hand, occurs when an antibiotic inhibits the growth of bacteria, without necessarily killing it.
(SEE ALSO: Communicable Disease Control; Drug Resistance; Pathogenic Organisms; Penicillin; Pharmaceutical Industry)
— MEGANNE S. KANATANI
From antiquity people have tried to find substances that would cure disease or heal wounds. Most of the recipes called for exotic ingredients, such as eye of newt. Folk wisdom and early doctors occasionally knew of something that seemed to work some of the time -- garlic, molds, herbs, even soil -- but most of the time the substances were ineffective. This did not stop people from looking for what we now think of as "wonder drugs."
In the 16th century, Paracelsus advocated strong chemicals to cure disease, including mercury compounds and other poisons. At the end of the 19th century, medical researchers had identified several microorganisms responsible for diseases such as syphilis, anthrax, tuberculosis, and cholera. To observe these bacteria under the microscope, one had to stain them. German bacteriologist Paul Ehrlich began to search for dyes that might kill bacteria on the theory that such dyes could destroy bacteria without affecting animal cells. In 1907 he discovered that Trypan red, a dye that stains trypanosomes, the organisms that cause African sleeping sickness, also kills them. Ehrlich then started tests with arsenic compounds. His student Sahachiro Hata discovered in 1909 that one of these compounds, number 606, introduced in 1910 and trademarked as Salvarsan, kills the bacterium that causes syphilis. Ehrlich called these compounds "magic bullets" because they kill harmful pathogens without affecting the patient.
Unfortunately, very few new magic bullets for the treatment of other infections were found during the next years. In 1932 German biochemist Gerhard Domagk discovered that a dye containing the sulfonamide radical, called Prontosil Rubrum, was effective against streptococcal infections. Strangely enough, Prontosil did not kill streptococci in the test tube, but did so when injected into a mouse. Domagk had not tested Prontosil on humans, but when his daughter contracted streptococcal blood poisoning by pricking herself with a needle, and was near death, Domagk injected her with Prontosil Rubrum and saved her life.
Chemists discovered that Prontosil changed in the body and produced a fragment called sulfanilamide, the active agent against certain bacteria. They then started looking for other compounds that would chemically resemble sulfanilamide and kill a wider range of bacteria. Several such sulfa drugs were found. They were effective against a series of diseases that formerly had been treatable only with difficulty.
Before then, however, scientists had learned that looking for inorganic compounds was not the best way to solve the problem. The strongest agents against microbes had always existed in nature, just as traditional healers believe. Louis Pasteur and Jules François Joubert observed in 1877 that anthrax bacilli are killed by bacteria from the air. They also knew that soil, which is filled with many harmless bacteria and fungi, does not harbor most disease-causing bacteria. Substances in soil, probably produced by common soil bacteria or fungi, seem to kill other bacteria. Searching for these substances might be more productive than searching for inorganic compounds that would do the same thing. After all, it was known that these substances in soil exist. However, there are so many different substances in soil that no one tried this approach for many years.
In the meantime, Alexander Fleming was seeking such a substance in a different known source. Tears contain something that kills bacteria and causes no physical damage to the body. In 1922 Fleming isolated the substance lysozyme from tears. Although lysozyme kills bacteria, it has no medical application. But Fleming continued to work on the problem of killing bacteria. Quite by accident he found another substance in 1928. This substance was produced by a mold that had somehow landed on one of his cultures of staphylococcus. It was evident in a ring of dead bacteria around each speck of mold. John Tyndall had observed the same effect while investigating bacteria and molds on airborne dust in the 19th century, but had not pursued it.
Fleming investigated and found that the substance produced by the mold, which he named penicillin, killed some bacteria, but not others. In addition, the substance did not damage white blood cells. He published a report on penicillin and went back to other work. Howard Florey and Ernst Chain, who were both experimenting with lysozyme, turned their attention to penicillin when World War II started, hoping to isolate the substance for use against war wounds. They succeeded, and scientists at the U.S. Northern Research Laboratory in Peoria, Illinois, found strains of mold that could be grown in large tanks to produce the new drug in quantity. Penicillin saved thousands of lives in World War II and continues to be, in one form or another, one of the most powerful and useful antibiotics.
Shortly before Florey and Chain began to work with penicillin, the first scientist to search for antibiotics in soil had achieved success. René Jules Dubos discovered two antibiotics, gramicidin and tyrocidin, in a substance produced by a soil bacterium. But it was the success of penicillin that started many teams of scientists searching soil samples. In 1943 Selman A. Waksman found streptomycin, an effective antibiotic for some bacteria although somewhat toxic to humans. Benjamin Duggar and coworkers found Aureomycin, the first tetracycline, in soil samples the following year. Since then, a variety of antibiotics have been found in soil samples and produced by various fungi. Mild antibiotics have even been found in garlic. By analyzing the structures of antibiotics and how they work, scientists have created many synthetic antibiotics.
While antibiotics have greatly reduced the effects of infectious disease, their very success has led to the problem of resistant bacteria. Bacteria can easily exchange genetic material through structures called plasmids. If a few bacteria are resistant to a particular antibiotic, they soon pass this trait on to others. Frequent use of antibiotics and sulfa drugs has created resistant populations of many disease-causing bacteria. The effectiveness of sulfa drugs against some diseases dropped by 50 percent over a 20-year period. Consequently, the search for new antibiotics continues, since bacteria resistant to one antibiotic may not be resistant to another that works by a different mechanism.
A substance that inhibits the growth of micro-organisms or kills them. The best-known is penicillin, originally obtained from the fungal mould Penicillum notatum. It kills some bacteria by preventing cell-wall synthesis. Some antibiotics (e.g. ciprofloxacin) have been used as a prophylactic treatment of traveller's diarrhoea by elite athletes travelling abroad to important competitions, but physicians are loath to encourage the widespread use of antibiotics for fear of the development of resistant micro-organisms.
Types of Antibiotics
The great number of diverse antibiotics currently available can be classified in different ways, e.g., by their chemical structure, their microbial origin, or their mode of action. They are also frequently designated by their effective range. Tetracyclines, the most widely used broad-spectrum antibiotics, are effective against both Gram-positive and Gram-negative bacteria, as well as against rickettsias and psittacosis-causing organisms (see Gram's stain). Ciprofloxacin (Cipro) is another broad-spectrum antibiotic, effective in the treatment of mild infections of the urinary tract and sinuses. The medium-spectrum antibiotics bacitracin, the erythromycins, penicillin, and the cephalosporins are effective primarily against Gram-positive bacteria, although the streptomycin group is effective against some Gram-negative and Gram-positive bacteria. Polymixins are narrow-spectrum antibiotics effective against only a few species of bacteria.
Administration and Side Effects
Antibiotics are either injected, given orally, or applied to the skin in ointment form. Many, while potent anti-infective agents, also cause toxic side effects. Some, like penicillin, are highly allergenic and can cause skin rashes, shock, and other manifestations of allergic sensitivity. Others, such as the tetracyclines, cause major changes in the intestinal bacterial population and can result in superinfection by fungi and other microorganisms. Chloramphenicol, which is now restricted in use, produces severe blood diseases, and use of streptomycin can result in ear and kidney damage. Many antibiotics are less effective than formerly because antibiotic-resistant strains of microorganisms have emerged (see drug resistance).
Nonmedical Use
Antibiotics have found wide nonmedical use. Some are used in animal husbandry, along with vitamin B12, to enhance the weight gain of livestock. However, some authorities believe the addition of antibiotics to animal feeds is dangerous because continuous low exposure to the antibiotic can sensitize humans to the drug and make them unable to take the substance later for the treatment of infection. In addition low levels of antibiotics in animal feed encourage the emergence of antibiotic-resistant strains of microorganisms. Drug resistance has been shown to be carried by a genetic particle transmissible from one strain of microorganism to another, and the presence of low levels of antibiotics can actually cause an increase in the number of such particles in the bacterial population and increase the probability that such particles will be transferred to pathogenic, or disease-causing, strains. Antibiotics have also been used to treat plant diseases such as bacteria-caused infections in tomatoes, potatoes, and fruit trees. The substances are also used in experimental research.
Production of Antibiotics
The mass production of antibiotics began during World War II with streptomycin and penicillin. Now most antibiotics are produced by staged fermentations in which strains of microorganisms producing high yields are grown under optimum conditions in nutrient media in fermentation tanks holding several thousand gallons. The mold is strained out of the fermentation broth, and then the antibiotic is removed from the broth by filtration, precipitation, and other separation methods. In some cases new antibiotics are laboratory synthesized, while many antibiotics are produced by chemically modifying natural substances; many such derivatives are more effective than the natural substances against infecting organisms or are better absorbed by the body, e.g., some semisynthetic penicillins are effective against bacteria resistant to the parent substance.
History
Although for centuries preparations derived from living matter were applied to wounds to destroy infection, the fact that a microorganism is capable of destroying one of another species was not established until the latter half of the 19th cent. when Pasteur noted the antagonistic effect of other bacteria on the anthrax organism and pointed out that this action might be put to therapeutic use. Meanwhile the German chemist Paul Ehrlich developed the idea of selective toxicity: that certain chemicals that would be toxic to some organisms, e.g., infectious bacteria, would be harmless to other organisms, e.g., humans.
In 1928, Sir Alexander Fleming, a Scottish biologist, observed that Penicillium notatum, a common mold, had destroyed staphylococcus bacteria in culture, and in 1939 the American microbiologist René Dubos demonstrated that a soil bacterium was capable of decomposing the starchlike capsule of the pneumococcus bacterium, without which the pneumococcus is harmless and does not cause pneumonia. Dubos then found in the soil a microbe, Bacillus brevis, from which he obtained a product, tyrothricin, that was highly toxic to a wide range of bacteria. Tyrothricin, a mixture of the two peptides gramicidin and tyrocidine, was also found to be toxic to red blood and reproductive cells in humans but could be used to good effect when applied as an ointment on body surfaces. Penicillin was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycin and a number of other antibiotics from Streptomyces griseus.
See also actinomycin, amphotericin B, ampicillin, lincomycin, neomycin, rifampin, and vancomycin.
Bibliography
See H. M. Böttcher, Wonder Drugs (1964); T. Korzybski, Antibiotics (2 vol., 1967); L. P. Garrod et al., Antibiotics and Chemotherapy (3d ed. 1971).
The security and stability of a country depends in part on the health of its citizens. One of the factors that influence the health of people is infectious disease (a disease that can be spread from person to person or from another living being to a human). A variety of infectious diseases are caused by bacteria.
Some bacterial infections can be treated using compounds that are collectively known as antibiotics. Antibiotics can be naturally produced. For example, the first antibiotic discovered (penicillin; discovered in 1928 by Sir Alexander Fleming) is produced by a species of a mold microorganism. There are a variety of different naturally produced antibiotics, while many other antibiotics have been chemically produced. Finally, antibiotics act only on bacteria and are not effective against viruses.
Prior to the discovery of penicillin there were few effective treatments to battle or prevent bacterial infections. Pneumonia, tuberculosis, and typhoid fever were virtually untreatable. And, in those persons whose immune system was not functioning properly, even normally minor bacterial infections could prove to be be life-threatening.
In nature, antibiotics help protect a bacteria or eukaryotic cell (i.e., plant cell) from invading bacteria. In the laboratory, this is evident as the inhibition of growth of bacteria in the presence of the antibiotic-producing species. This screening can be automated so that thousands of samples can be processed each day.
The chemical synthesis of antibiotics is now very sophisticated. The antibiotic can be tailored to affect a specific target on the bacterial cell. Three-dimensional modeling of the bacterial surface and protein molecules is an important aid to antibiotic design.
Penicillin is in a class of antibiotics called beta-lactam antibiotics. The name refers to the chemical ring that is part of the molecule. Other classes of antibiotics include the tetracyclines, aminoglycosides, rifamycins, quinolones, and sulphonamides. The action of these antibiotics is varied. The targets of the antibiotics are different. Some antibiotics disrupt and weaken the cell wall of bacteria (i.e., beta-lactam antibiotics), which causes the bacteria to rupture and die. Other antibiotics disrupt enzymes that are vital for bacterial survival (aminoglycoside antibiotics). Still other antibiotics target genetic material and stop the replication of deoxyribonucleic acid (DNA) (i.e., quinolone antibiotics).
Antibiotics can also vary in the bacteria they affect. Some antibiotics kill only a few related types of bacteria and are referred to as narrow-spectrum antibiotics. Other antibiotics such as penicillin kill a variety of different bacteria. These are the broad-spectrum antibiotics.
Following the discovery of penicillin, many different naturally occurring antibiotics were discovered and still many others were synthesized. They were extremely successful in reducing many infectious diseases. Indeed, in the 1970s the prevailing view was that infectious diseases were a thing of the past. However, beginning in the 1970s and continuing to the present day, resistance to antibiotics is developing.
As of 2002, the problem of antibiotic resistance is so severe that many physicians and security analysts think that the twenty-first century will initiate the "post antibiotic era." In other words, the use of antibiotics to control infectious bacterial disease will no longer be an effective strategy.
Resistance to a specific antibiotic or a class of antibiotics can develop when an antibiotic is overused or misused. If an antibiotic is used properly to treat an infection, then all the infectious bacteria should be killed directly, or weakened such that the host's immune response will kill them. However, if the antibiotic concentration is too low, the bacteria may be weakened but not killed. The same thing can happen if antibiotic therapy is stopped too soon. The surviving bacteria may have acquired resistance, which can be genetically transferred to subsequent generations of bacteria. For example, many strains of Mycobacterium tuberculosis, the bacterium that causes tuberculosis, are resistant to one or more of the antibiotics used to treat the lung infection. Some strains of Staphylococcus aureus that can cause boils, pneumonia, or bloodstream infections, are resistant to most (and with one strain, all) antibiotics.
The increasing antibiotic resistance of bacteria, and the resulting increase in infectious diseases, is a security risk. Disease can decimate the population. The misery and economic hardship that results can cause political instability. In underdeveloped countries, this instability can lead to anger directed at developed countries such as the United States. Even in developed countries, the increasing numbers of people needing hospitalization and medical care can strain the health care system.
The availability of antibiotics to combat bacterial epidemics has always been challenging. The appearance and rapid increase in an infection can tax the ability of a healthcare system to respond with medicines including the appropriate antibiotics.
The threat of biological warfare, such as the aerial distribution of Bacillus anthracis, the agent of anthrax, has made the provision of large quantities of antibiotics a priority for the United States and other nations. Plants that manufacture antibiotics are designed with sterility of manufacture in mind, not security. Disabling an antibiotic manufacturing facility would be a crippling blow to any potential biowarfare response.
Even if a large supply of a particular antibiotic were available, the emergency response would be challenging, as the antibiotic would need to be distributed to many people (i.e., millions in the event of an aerial release of the anthrax bacterium) within hours.
Further Reading
Periodicals
Inglesby, Thomas V. "Bioterrorist Threats: What the Infectious Disease Community Should Know about Anthrax and Plague." Emerging Infections 5. Washington, DC: American Society for Microbiology Press, 2001.
Electronic
Central Intelligence Agency. "The Global Infectious Disease Threat and Its Implications for the United States." January 2000.<http://www.cia.gov/cia/publications/nie/report/nie99–17d.html> (22 November 2002).
World Health Organization. "Strengthening Global Preparedness for Defense against Infectious Disease Threats." Statement to the United States Senate Committee on Foreign Relations Hearing on The Threat of Bioterrorism and the Spread of Infectious Diseases. 5 September 2001. <http://www.who.int/emc/pdfs/Senate_hearing.pdf>(24 November 2002).
A substance that destroys or inhibits the growth of microorganisms and is therefore used to treat some infections. One of the most familiar antibiotics is penicillin.
Patricia had to take an antibiotic to get rid of her infection.
LearnThatWord.com is a free vocabulary and spelling program where you only pay for results!
| antiarose, anti-messenger DNA, anti-inducer | |
| antibody, antibody-dependent cellular toxicity, antibody-mediated hypersensitivity |
1. destructive of life.
2. a chemical substance produced by a microorganism that has the capacity, in dilute solutions, to kill (biocidal activity) or inhibit the growth (biostatic activity) of other microorganisms. Antibiotics that are sufficiently nontoxic to the host are used as chemotherapeutic agents in the treatment of infectious diseases. See also antimicrobial.
3. used as feed additives to animals as growth promotants.
An organic substance produced by one of several microorganisms, especially certain molds, that is capable, in low concentration, of destroying or inhibiting the growth of certain other microorganisms.

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.[1] The term is often used synonymously with the term antibiotic(s); today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic(s) has come to denote a broader range of antimicrobial compounds, including antifungal and other compounds.[2]
The term antibiotic was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.[3] This definition excluded substances that kill bacteria, but are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.
With advances in medicinal chemistry, most of today's antibacterials chemically are semisynthetic modifications of various natural compounds.[4] These include, for example, the beta-lactam antibacterials, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms: bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.
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The term antibacterial derives from Greek ἀντί (anti), "against"[5] + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane",[6] because the first ones to be discovered were rod-shaped,[7] and the term antibiotic derives from anti + βιωτικός (biōtikos), "fil for life, lively",[8] which comes from βίωσις (biōsis), "way of life",[9] and that from βίος (bios), "life".[10]
Before the early 20th century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.[11] Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections.[12][13] More recent observations made in the laboratory of antibiosis between micro-organisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".[14]
The term antibiosis, meaning "against life," was introduced by the French bacteriologist Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs.[15][16] Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis.[17] These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942.[3][15]
John Tyndall first described antagonistic activities by fungi against bacteria in England in 1875.[14] Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s.[15] Ehrlich noted that certain dyes would color human, animal, or bacterial cells, while others did not. He then proposed the idea that it might be possible to create chemicals that would act as a selective drug that would bind to and kill bacteria without harming the human host. After screening hundreds of dyes against various organisms, he discovered a medicinally useful drug, the synthetic antibacterial Salvarsan [15][18][19] now called Arsphenamine.
In 1895, Vincenzo Tiberio, physician of the University of Naples discovered that a mold ( Penicillium ) in a water well has a antibacterial action.[20][21] After this initial chemotherapeutic compound proved effective, others pursued similar lines of inquiry but it was not until in 1928 that Alexander Fleming observed antibiosis against bacteria by a fungus of the genus Penicillium. Fleming postulated that the effect was mediated by an antibacterial compound named penicillin, and that its antibacterial properties could be exploited for chemotherapy. He initially characterized some of its biological properties, but he did not pursue its further development.[22][23]
The first sulfonamide and first commercially available antibacterial antibiotic, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 at the Bayer Laboratories of the IG Farben conglomerate in Germany.[19] Domagk received the 1939 Nobel Prize for Medicine for his efforts. Prontosil had a relatively broad effect against Gram-positive cocci, but not against enterobacteria. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug opened the era of antibacterial antibiotics. In 1939, coinciding with the start of World War II, Rene Dubos reported the discovery of the first naturally derived antibiotic, gramicidin from B. brevis. It was one of the first commercially manufactured antibiotics universally and very effectively used to treat wounds and ulcers during World War II.[24] Research results obtained during that period were not shared between the Axis and the Allied powers during the war.
Florey and Chain succeeded in purifying the first penicillin, penicillin G procaine in 1942, but it did not become widely available outside Allied military before 1945. Purified penicillin displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in humans. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic sulfonamides. The discovery of such a powerful antibiotic was unprecedented, and the development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety.[25] For their discovery and development of penicillin as a therapeutic drug, Ernst Chain, Howard Florey, and Alexander Fleming shared the 1945 Nobel Prize in Medicine. Florey credited Dubos with pioneering the approach of deliberately and systematically searching for antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's research in penicillin.[24]
The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial.[29] A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.[30] These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection.[29][31] Since the activity of antibacterials depends frequently on its concentration,[32] in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial.[29][33] To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile, and several pharmacological parameters are used as markers of drug efficacy.[34][35]
Antibacterial antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes.[15] Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymixins), or interfere with essential bacterial enzymes (quinolones and sulfonamides) have bactericidal activities. Those that target protein synthesis (aminoglycosides, macrolides, and tetracyclines) are usually bacteriostatic.[36] Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative or Gram-positive bacteria, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year hiatus in discovering new classes of antibacterial compounds, three new classes of antibacterial antibiotics have been brought into clinical use: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), and oxazolidinones (such as linezolid).[37]
Since the first pioneering efforts of Florey and Chain in 1939, the importance of antibiotics, including antibacterials, to medicine has led to intense research into producing antibacterials at large scales. Following screening of antibacterials against a wide range of bacteria, production of the active compounds is carried out using fermentation, usually in strongly aerobic conditions.[citation needed]
Oral antibacterials are orally ingested, whereas intravenous administration may be used in more serious cases, such as deep-seated systemic infections. Antibiotics may also sometimes be administered topically, as with eye drops or ointments.
Antibacterials are screened for any negative effects on humans or other mammals before approval for clinical use, and are usually considered safe and most are well-tolerated. However, some antibacterials have been associated with a range of adverse effects.[38] Side-effects range from mild to very serious depending on the antibiotics used, the microbial organisms targeted, and the individual patient.[citation needed] Safety profiles of newer drugs are often not as well established as for those that have a long history of use.[38] Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis.[citation needed] Common side-effects include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridium difficile.[39] Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area.[40] Additional side-effects can result from interaction with other drugs, such as elevated risk of tendon damage from administration of a quinolone antibiotic with a systemic corticosteroid.
The majority of studies indicate antibiotics do not interfere with contraceptive pills,[41] such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%).[42] In cases where antibacterials have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibacterial rifampicin, these cases may be due to an increase in the activities of hepatic liver enzymes causing increased breakdown of the pill's active ingredients.[41] Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial.[43][44] Clinicians have recommended that extra contraceptive measures be applied during therapies using antibacterials that are suspected to interact with oral contraceptives.[41]
Interactions between alcohol and certain antibacterials may occur and may cause side-effects and decreased effectiveness of antibacterial therapy.[45][46]
Therefore, potential risks of side-effects and effectiveness depend on the type of antibacterial administered. Despite the lack of a categorical counterindication, the belief that alcohol and antibacterials should never be mixed is widespread.
Antibacterials such as metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase, which may result in vomiting, nausea, and shortness of breath.[47]
Other effects of alcohol on antibacterial activity include altered activity of the liver enzymes that break down the antibacterial compound.[48] In addition, serum levels of doxycycline and erythromycin succinate[clarification needed] two bacteriostatic antibacterials (see above) may be reduced by alcohol consumption, resulting in reduced efficacy and diminished pharmacotherapeutic effect.[49]
The emergence of resistance of bacteria to antibacterial drugs is a common phenomenon. Emergence of resistance often reflects evolutionary processes that take place during antibacterial drug therapy. The antibacterial treatment may select for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibacterials. Under certain conditions, it may result in preferential growth of resistant bacteria, while growth of susceptible bacteria is inhibited by the drug.[50] For example, antibacterial selection within whole bacterial populations for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment.[51] Survival of bacteria often results from an inheritable resistance.[52] Resistance to antibacterials also occurs through horizontal gene transfer. Horizontal transfer is more likely to happen in locations of frequent antibiotic use.[53] Antibacterials such as penicillin and erythromycin, which used to have high efficacy against many bacterial species and strains, have become less effective, because of increased resistance of many bacterial strains.[54] Antibacterial resistance may impose a biological cost, thereby reducing fitness of resistant strains, which can limit the spread of antibacterial-resistant bacteria, for example, in the absence of antibacterial compounds. Additional mutations, however, may compensate for this fitness cost and can aid the survival of these bacteria.[55]
Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains.[56] For example, an antibiotic target may be absent from the bacterial genome. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA.[56] Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains.[57][58] The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange.[52] For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes.[52][59] Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials.[59] Cross-resistance to several antibacterials may also occur when a resistance mechanism encoded by a single gene conveys resistance to more than one antibacterial compound.[59]
Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases that were for a while well-controlled. For example, emergent bacterial strains causing tuberculosis (TB) that are resistant to previously effective antibacterial treatments pose many therapeutic challenges. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.[60] For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials.[61] United Kingdom Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."[62]
The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them.[63]—Paul L. Marino, The ICU Book
Inappropriate antibacterial treatment and overuse of antibiotics have contributed to the emergence of antibacterial-resistant bacteria. Self prescription of antibacterials is an example of misuse.[64] Many antibacterials are frequently prescribed to treat symptoms or diseases that do not respond to antibacterial therapy or are likely to resolve without treatment, or incorrect or suboptimal antibacterials are prescribed for certain bacterial infections.[38][64] The overuse of antibacterials, like penicillin and erythromycin, have been associated with emerging antibacterial resistance since the 1950s.[54][65] Widespread usage of antibacterial drugs in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibacterials.[65]
Common forms of antibacterial misuse include excessive use of prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibacterials on the basis of the patient's weight and history of prior use. Other forms of misuse include failure to take the entire prescribed course of the antibacterial, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibacterial treatment, for example, is the prescription of antibacterials to treat viral infections such as the common cold. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them".[66] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.[67]
Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibacterials.[64] The issues of misuse and overuse of antibiotics have been addressed by the formation of the U.S. Interagency Task Force on Antimicrobial Resistance. This task force aims to actively address antimicrobial resistance, and is coordinated by the US Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and the National Institutes of Health (NIH), as well as other US agencies.[68] An NGO campaign group is Keep Antibiotics Working.[69] In France, an "Antibiotics are not automatic" government campaign started in 2002 and led to a marked reduction of unnecessary antibacterial prescriptions, especially in children.[70]
The emergence of antibacterial resistance has prompted restrictions on antibacterial use in the UK in 1970 (Swann report 1969), and the EU has banned the use of antibacterials as growth-promotional agents since 2003.[71] Moreover, several organizations (e.g., The American Society for Microbiology (ASM), American Public Health Association (APHA) and the American Medical Association (AMA)) have called for restrictions on antibiotic use in food animal production and an end to all nontherapeutic uses.[citation needed] However, commonly there are delays in regulatory and legislative actions to limit the use of antibacterials, attributable partly to resistance against such regulation by industries using or selling antibacterials, and to the time required for research to test causal links between antibacterial use and resistance. Two federal bills (S.742[72] and H.R. 2562[73]) aimed at phasing out nontherapeutic use of antibacterials in US food animals were proposed, but have not passed.[72][73] These bills were endorsed by public health and medical organizations, including the American Holistic Nurses’ Association, the American Medical Association, and the American Public Health Association (APHA).[74]
There has been extensive use of antibiotics in animal husbandry. In the United States the question of emergence of antibiotic-resistant bacterial strains due to use of antibiotics in livestock was raised by the United States Food and Drug Administration in 1977. In March, 2012 the United States District Court for the Southern District of New York, ruling in an action brought by the Natural Resources Defense Council and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock which violated FDA regulations.[75]
The increase in bacterial strains that are resistant to conventional antibacterial therapies has prompted the development of alternative strategies to treat bacterial diseases.
One strategy to address bacterial drug resistance is the discovery and application of compounds that modify resistance to common antibacterials. For example, some resistance-modifying agents may inhibit multidrug resistance mechanisms, such as drug efflux from the cell, thus increasing the susceptibility of bacteria to an antibacterial. Targets include:
Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic tolerant bacteria by keeping their metabolism active.[77]
Phage therapy is the use of viruses that infect bacteria (i.e. phages) for the treatment of bacterial infections.[78][79] Phages are common in bacterial populations and control the growth of bacteria in many environments, including in the intestine, the ocean, and the soil.[80] Phage therapy was in use in the 1920s and 1930s in the US, Western Europe, and Eastern Europe. However, success rates of this therapy have not been firmly established, because only a limited number of clinical trials testing the efficacy of phage therapy have been conducted.[79] These studies were performed mainly in the former Soviet Union, at the Eliava Institute of Bacteriophage, Microbiology and Virology, Republic of Georgia.[81] The development of antibacterial-resistant bacteria has sparked renewed interest in phage therapy in Western medicine.[82] Several companies (e.g., Intralytix, Novolytics, and Gangagen), universities, and foundations across the world now focus on phage therapies.[82][83][84][85] One concern with this therapeutic strategy is the use of genetically engineered viruses, which limits certain aspects of phage therapy.[79][86][87]
Bacteriocins are peptides that can be more readily engineered than small molecules,[88] and are possible alternatives to conventional antibacterial compounds.[89] Different classes of bacteriocins have different potential as therapeutic agents. Small-molecule bacteriocins (microcins and lantibiotics) are similar to the classic antibiotics; colicin-like bacteriocins possess a narrow spectrum, and require molecular diagnostics prior to therapy.[citation needed] Limitations of large-molecule antibacterials include reduced transport across membranes and within the human body. For this reason, they are usually applied topically or gastrointestinally.[90]
Chelation of micronutrients that are essential for bacterial growth to restrict pathogen spread in vivo might supplement some antibacterials. For example, limiting the iron availability in the human body restricts bacterial proliferation.[91][92] Many bacteria, however, possess mechanisms (such as siderophores) for scavenging iron within environmental niches in the human body, and experimental developments of iron chelators, therefore, aim to reduce iron availability specifically to bacterial pathogens.[93]
Vaccines rely on immune modulation or augmentation. Vaccination either excites or reinforces the immune competency of a host to ward off infection, leading to the activation of macrophages, the production of antibodies, inflammation, and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases.[citation needed] Vaccines made from attenuated whole cells or lysates have been replaced largely by less reactogenic, cell-free vaccines consisting of purified components, including capsular polysaccharides and their conjugates, to protein carriers, as well as inactivated toxins (toxoids) and proteins.[94]
Biotherapy may employ organisms, such as protozoa,[95] to consume the bacterial pathogens. Another such approach is maggot therapy.
Probiotics consist of a live culture of bacteria, which may become established as competing symbionts, and inhibit or interfere with colonization by microbial pathogens.[96]
An additional therapeutic agent is the enhancement of the multifunctional properties of natural anti-infectives, such as cationic host defense (antimicrobial) peptides (HDPs).[94]
Functionalization of antimicrobial surfaces can be used for sterilization, self-cleaning, and surface protection.
Copper-alloy surfaces have natural intrinsic properties to effectively and quickly destroy bacteria. The United States Environmental Protection Agency has approved the registration of 355 different antibacterial copper alloys that kill E. coli O157:H7, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus, Enterobacter aerogenes, and Pseudomonas aeruginosa in less than 2 hours of contact. As a public hygienic measure in addition to regular cleaning, antimicrobial copper alloys are being installed in healthcare facilities and in a subway transit system.[97][98][99]
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/ziz
This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)
Dansk (Danish)
n. - antibiotikum
adj. - antibiotisk
Nederlands (Dutch)
antibioticum, antibiotisch
Français (French)
n. - antibiotique
adj. - antibiotique
Deutsch (German)
n. - Antibiotikum
adj. - antibiotisch
Ελληνική (Greek)
n. - (βιολ.) αντιβιοτικό
adj. - αντιβιοτικός
Italiano (Italian)
antibiotico
Português (Portuguese)
n. - antibiótico (m) (Quím.)
adj. - antibiótico
Русский (Russian)
антибиотик, антибиотический
Español (Spanish)
n. - antibiótico
adj. - antibiótico
Svenska (Swedish)
n. - antibiotikum (med.)
adj. - antibiotisk (med.)
中文(简体)(Chinese (Simplified))
抗菌素, 抗生素, 抗生的, 抗菌的
中文(繁體)(Chinese (Traditional))
n. - 抗菌素, 抗生素
adj. - 抗生的, 抗菌的
한국어 (Korean)
n. - 항생물질
adj. - 항 생 작용의
日本語 (Japanese)
n. - 抗生物質
adj. - 抗生の
العربيه (Arabic)
(الاسم) مضاد حيوي (صفه) مضادات للجراثيم
עברית (Hebrew)
n. - חומרים שיוצרו ע"י חיידקים ומסוגלים להשמיד חיידקים הרגישים להם, אנטיביוטיקה
adj. - מתפקד כחומר אנטיביוטי
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