antibiotic(redirected from Antibiotic resistance)
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antibiotic,any of a variety of substances, usually obtained from microorganisms, that inhibit the growth of or destroy certain other microorganisms.
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. Tetracyclinestetracycline
, any of a group of antibiotics produced by bacteria of the genus Streptomyces. They are effective against a wide range of Gram positive and Gram negative bacteria, interfering with protein synthesis in these microorganisms (see Gram's stain).
..... Click the link for more information. , 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 stainGram's stain,
laboratory staining technique that distinguishes between two groups of bacteria by the identification of differences in the structure of their cell walls. The Gram stain, named after its developer, Danish bacteriologist Christian Gram, has become an important tool
..... Click the link for more information. ). Ciprofloxacin (Cipro) is another broad-spectrum antibiotic, effective in the treatment of mild infections of the urinary tract and sinuses. The medium-spectrum antibiotics bacitracinbacitracin
, antibiotic produced by a strain of the bacterial species Bacillus subtilis. It is widely used for topical therapy such as for skin and eye infections; it is effective against gram-positive bacteria, including strains of staphylococcus that are resistant to
..... Click the link for more information. , the erythromycinserythromycin
, any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). Erythromycin is most effective against gram-positive bacteria such as pneumococci, streptococci, and some staphylococci (see Gram's stain).
..... Click the link for more information. , penicillin, and the cephalosporinscephalosporin
, any of a group of more than 20 antibiotics derived from species of fungi of the genus Cephalosporium and closely related chemically to penicillin. Cephalosporins, e.g.
..... Click the link for more information. are effective primarily against Gram-positive bacteria, although the streptomycinstreptomycin
, antibiotic produced by soil bacteria of the genus Streptomyces and active against both gram-positive and gram-negative bacteria (see Gram's stain), including species resistant to other antibiotics, e.g.
..... Click the link for more information. 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. Chloramphenicolchloramphenicol
, antibiotic effective against a wide range of gram-negative and gram-positive bacteria (see Gram's stain). It was originally isolated from a species of Streptomyces bacteria.
..... Click the link for more information. , 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 resistancedrug resistance,
condition in which infecting bacteria can resist the destructive effects of drugs such as antibiotics and sulfa drugs. Drug resistance has become a serious public health problem, since many disease-causing bacteria are no longer susceptible to previously
..... Click the link for more information. ).
Antibiotics have found wide nonmedical use. Some are used in animal husbandry, along with vitamin B12, to enhance the weight gain of livestock. 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. In 2013 the Food and Drug Administration moved to restrict the use of antibiotics in livestock, calling for labeling changes that would bar their use to promote growth and requirements for veterinarian supervision when antibiotics are used. The use of antibiotics for disease prevention (as opposed to disease treatment) was not, however, banned. 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.
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 a common mold (genus Penicillium) 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 gramicidingramicidin
, antibiotic obtained from the bacterial species Bacillus brevis, which is found in soil. Gramicidin is particularly effective against gram-positive bacteria (see Gram's stain).
..... Click the link for more information. 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. Penicillinpenicillin,
any of a group of chemically similar substances obtained from molds of the genus Penicillium that were the first antibiotic agents to be used successfully in the treatment of bacterial infections in humans.
..... Click the link for more information. was finally isolated in 1939, and in 1944 Selman Waksman and Albert Schatz, American microbiologists, isolated streptomycinstreptomycin
, antibiotic produced by soil bacteria of the genus Streptomyces and active against both gram-positive and gram-negative bacteria (see Gram's stain), including species resistant to other antibiotics, e.g.
..... Click the link for more information. and a number of other antibiotics from Streptomyces griseus.
See also actinomycinactinomycin
, any one of a group of antibiotics produced by bacteria of the genus Streptomyces. Actinomycin was the first antibiotic reported to be able to halt cancer; however, it is not widely used to treat cancers because it is highly toxic to humans, interfering with
..... Click the link for more information. , amphotericin Bamphotericin B
, antibiotic that halts the growth of several disease-causing fungi. Discovered in 1956, it is produced by bacteria of the genus Streptomyces. It is used in lotion or ointment form to treat fungal infections of the skin and is given internally only to
..... Click the link for more information. , ampicillinampicillin
, a penicillin-type antibiotic that is effective against both gram-negative microorganisms and gram-positive microorganisms such as Escherichia coli. It is often used in the treatment of urinary tract infections, but resistant organisms are increasingly common
..... Click the link for more information. , lincomycinlincomycin
, antibiotic isolated from bacteria of the genus Streptomyces. Similar in activity to erythromycin, it is effective against most gram-positive organisms including staphylococci, some streptococci, and anaerobic bacteria of the genus Clostridium
..... Click the link for more information. , neomycinneomycin
, broad spectrum antibiotic effective against both gram positive and gram negative bacteria (see Gram's stain). It interferes with protein synthesis in sensitive bacterial cells such as species of Proteus and Staphylococcus.
..... Click the link for more information. , rifampinrifampin
, antibiotic used in the treatment of tuberculosis. It is also used to eliminate the meningococcus microorganism from carriers and to treat leprosy, or Hansen's disease.
..... Click the link for more information. , and vancomycinvancomycin
, antibiotic resembling penicillin in the way it acts. It is derived from the bacterium Streptomyces orientalis, which was isolated from soil of India and Indonesia.
..... Click the link for more information. .
See H. M. Böttcher, Wonder Drugs (1964); T. Korzybski, Antibiotics (2 vol., 1967); L. P. Garrod et al., Antibiotics and Chemotherapy (3d ed. 1971); M. J. Blaser, Missing Microbes (2014).
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.
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 Bacterial physiology and metabolism, Fermentation
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 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 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 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 Acquired immune deficiency syndrome (AIDS), Medical parasitology, Protozoa
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.
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 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 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 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.
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.
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 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.
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 Plant pathology