Antibiotic

Antibiotic

Overview
An antibacterial is a compound or substance that kills or slows down the growth of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

.
The term is often used synonym
Synonym
Synonyms are different words with almost identical or similar meanings. Words that are synonyms are said to be synonymous, and the state of being a synonym is called synonymy. The word comes from Ancient Greek syn and onoma . The words car and automobile are synonyms...

ously 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
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...

 compounds, including antifungal and other compounds.

The term antibiotic was coined by Selman Waksman
Selman Waksman
Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics...

 in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.
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Unanswered Questions
Encyclopedia
An antibacterial is a compound or substance that kills or slows down the growth of bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

.
The term is often used synonym
Synonym
Synonyms are different words with almost identical or similar meanings. Words that are synonyms are said to be synonymous, and the state of being a synonym is called synonymy. The word comes from Ancient Greek syn and onoma . The words car and automobile are synonyms...

ously 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
Antimicrobial
An anti-microbial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Antimicrobial drugs either kill microbes or prevent the growth of microbes...

 compounds, including antifungal and other compounds.

The term antibiotic was coined by Selman Waksman
Selman Waksman
Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics...

 in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria, but are not produced by microorganisms (such as gastric juices and hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...

). It also excluded synthetic
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...

 antibacterial compounds such as the sulfonamides
Sulfonamide (medicine)
Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...

. Many antibacterial compounds are relatively small molecule
Small molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...

s with a molecular weight of less than 2000 atomic mass unit
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

s.

With advances in medicinal chemistry
Medicinal chemistry
Medicinal chemistry and pharmaceutical chemistry are disciplines at the intersection of chemistry, especially synthetic organic chemistry, and pharmacology and various other biological specialties, where it is involved with design, chemical synthesis and development for market of pharmaceutical...

, most of today's antibacterials chemically are semisynthetic
Semisynthetic
"Semisynthesis" or partial chemical synthesis is a type of chemical synthesis that uses compounds isolated from natural sources as starting materials. These natural biomolecules are usually large and complex molecules...

 modifications of various natural compounds. These include, for example, the beta-lactam
Beta-lactam antibiotic
β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-lactam nucleus in its molecular structure. This includes penicillin derivatives , cephalosporins , monobactams, and carbapenems...

 antibacterials, which include the penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

s (produced by fungi in the genus Penicillium
Penicillium
Penicillium is a genus of ascomycetous fungi of major importance in the natural environment as well as food and drug production. Members of the genus produce penicillin, a molecule that is used as an antibiotic, which kills or stops the growth of certain kinds of bacteria inside the body...

), the cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...

s, and the carbapenem
Carbapenem
Carbapenems are a class of β-lactam antibiotics with a broad spectrum of antibacterial activity. They have a structure that renders them highly resistant to most β-lactamases...

s. Compounds that are still isolated from living organisms are the aminoglycoside
Aminoglycoside
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...

s, whereas other antibacterials—for example, the sulfonamides, the quinolone
Quinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....

s, and the oxazolidinones—are produced solely by chemical synthesis. Accordingly, many antibacterial compounds are classified on the basis of chemical/biosynthetic
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

 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 agent
Bacteriostatic agent
A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily harming them otherwise. Depending on their application, bacteriostatic antibiotics, disinfectants, antiseptics and preservatives can be...

s slow down or stall bacterial growth.

History



Before the early 20th century, treatments for infections were based primarily on medicinal folklore
Folk medicine
-Description:Refers to healing practices and ideas of body physiology and health preservation known to a limited segment of the population in a culture, transmitted informally as general knowledge, and practiced or applied by anyone in the culture having prior experience.All cultures and societies...

. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago. Many ancient cultures, including the ancient Egyptians
Ancient Egyptian medicine
The medicine of the ancient Egyptians is some of the oldest documented. From the beginnings of the civilization in the until the Persian invasion of 525 BC, Egyptian medical practice went largely unchanged and was highly advanced for its time, including simple non-invasive surgery, setting of...

 and ancient Greeks, used specially selected mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

 and plant materials and extracts to treat infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s. More recent observations made in the laboratory of antibiosis between micro-organisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...

 observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".

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. Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....

 observed that an airborne bacillus could inhibit the growth of Bacillus anthracis
Bacillus anthracis
Bacillus anthracis is the pathogen of the Anthrax acute disease. It is a Gram-positive, spore-forming, rod-shaped bacterium, with a width of 1-1.2µm and a length of 3-5µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.It is one of few bacteria known to...

. These drugs were later renamed antibiotics by Selman Waksman
Selman Waksman
Selman Abraham Waksman was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics...

, an American microbiologist, in 1942.

Antagonistic activities by fungi against bacteria were first described in England by John Tyndall
John Tyndall
John Tyndall FRS was a prominent Irish 19th century physicist. His initial scientific fame arose in the 1850s from his study of diamagnetism. Later he studied thermal radiation, and produced a number of discoveries about processes in the atmosphere...

 in 1875. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich
Paul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...

 in the late 1880s. 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  now called Arsphenamine.

After this initial chemotherapeutic compound proved effective, others pursued similar lines of inquiry but it was not until in 1928 that Alexander Fleming
Alexander Fleming
Sir Alexander Fleming was a Scottish biologist and pharmacologist. He wrote many articles on bacteriology, immunology, and chemotherapy...

 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.

The first sulfonamide
Sulfonamide (medicine)
Sulfonamide or sulphonamide is the basis of several groups of drugs. The original antibacterial sulfonamides are synthetic antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame...

 and first commercially available antibacterial antibiotic, Prontosil
Prontosil
Prontosil, the first commercially available antibacterial antibiotic , was developed by a research team at the Bayer Laboratories of the IG Farben conglomerate in Germany...

, was developed by a research team led by Gerhard Domagk
Gerhard Domagk
Gerhard Johannes Paul Domagk was a German pathologist and bacteriologist credited with the discovery of Sulfonamidochrysoidine – the first commercially available antibiotic – for which he received the 1939 Nobel Prize in Physiology or Medicine.Domagk was born in Lagow, Brandenburg, the...

 in 1932 at the Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

 Laboratories of the IG Farben
IG Farben
I.G. Farbenindustrie AG was a German chemical industry conglomerate. Its name is taken from Interessen-Gemeinschaft Farbenindustrie AG . The company was formed in 1925 from a number of major companies that had been working together closely since World War I...

 conglomerate in Germany. Domagk received the 1939 Nobel Prize for Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

 for his efforts. Prontosil had a relatively broad effect against Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 cocci
Coccus
Coccus can be used to describe any bacterium that has a spherical shape. It is one of the three distinct types of bacteria shapes, the other two being bacillus and spirillum cells...

, but not against enterobacteria
Enterobacteriaceae
The Enterobacteriaceae is a large family of bacteria that includes many of the more familiar pathogens, such as Salmonella, Escherichia coli, Yersinia pestis, Klebsiella and Shigella. This family is the only representative in the order Enterobacteriales of the class Gammaproteobacteria in the...

. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...

 opened the era of antibacterial antibiotics. In 1939, coinciding with the start of World War II, Rene Dubos reported discovery of the first naturally derived antibiotic, gramicidin
Gramicidin
Gramicidin is a heterogeneous mixture of six antibiotic compounds, gramicidins A, B and C, making up 80%, 6%,and 14% respectively, all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramicidin D are linear pentadecapeptides; that is...

 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. Research results obtained during that period were not shared between the Axis and Allied powers during the war.

Florey and Chain succeeded in purifying the first penicillin, penicillin G procaine in 1942, which was not widely available outside the Allied military's needs 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. 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.

Indications

  • Treatment
    • Bacterial infection
    • Protozoan infection
      Protozoan infection
      Protozoan infections are parasitic diseases organisms formerly classified in the Kingdom Protozoa. They include organisms classified in Amoebozoa, Excavata, and Chromalveolata....

      , e.g. metronidazole
      Metronidazole
      Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....

       is effective against several parasitics
    • Immunomodulation, e.g. tetracycline which is effective in periodontal inflammation, and dapsone
      Dapsone
      Dapsone is a medication most commonly used in combination with rifampicin and clofazimine as multidrug therapy for the treatment of Mycobacterium leprae infections . It is also second-line treatment for prophylaxis against Pneumocystis pneumonia caused by Pneumocystis jiroveci Dapsone...

       which is effective in autoimmune diseases such as oral
      Mouth
      The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....

       mucous membrane pemphigoid
      Pemphigoid
      Pemphigoid is a group of uncommon and rare autoimmune blistering skin diseases. As its name indicates, pemphigoid is similar to pemphigus, but, unlike pemphigus, pemphigoid does not feature acantholysis....


  • Prevention
    Preventive medicine
    Preventive medicine or preventive care refers to measures taken to prevent diseases, rather than curing them or treating their symptoms...

     of infection
    • Surgical wound
    • Dental antibiotic prophylaxis
      Dental antibiotic prophylaxis
      Dental antibiotic prophylaxis is the admission of antibiotics to a dental patient for prevention of harmful consequences of bacteremia, that may be caused by invasion of the oral flora into an injured gingival or peri-apical vessel during dental treatment...

    • Conditions of neutropenia
      Neutropenia
      Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...

      , e.g. cancer
      Cancer
      Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

      -related

Pharmacodynamics



The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial. A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells. These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection. Since the activity of antibacterials depends frequently on its concentration, in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...

 and minimum bactericidal concentration of an antibacterial.
To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...

 profile, and several pharmacological parameters are used as markers of drug efficacy.

Classes



Antibacterial antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

s and cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...

s) or the cell membrane (polymixins), or interfere with essential bacterial enzymes (quinolone
Quinolone
The quinolones are a family of synthetic broad-spectrum antibiotics. The term quinolone refers to potent synthetic chemotherapeutic antibacterials....

s and sulfonamides) have bactericidal activities. Those that target protein synthesis (aminoglycoside
Aminoglycoside
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...

s, macrolide
Macrolide
The macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...

s, and tetracyclines) are usually bacteriostatic. Further categorization is based on their target specificity. "Narrow-spectrum" antibacterial antibiotics target specific types of bacteria, such as Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

 or Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 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
Daptomycin
Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections...

), glycylcyclines (such as tigecycline
Tigecycline
Tigecycline is a glycylcycline antibiotic developed by Francis Tally and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration fast-track approval and was approved on June 17, 2005...

), and oxazolidinones (such as linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...

).

Production


Since the first pioneering efforts of Florey and Chain
Ernst Boris Chain
Sir Ernst Boris Chain was a German-born British biochemist, and a 1945 co-recipient of the Nobel Prize for Physiology or Medicine for his work on penicillin.-Biography:...

 in 1939, the importance of antibiotics, including antibacterials, to medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

 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
Industrial fermentation
Industrial fermentation is the intentional use of fermentation by microorganisms such as bacteria and fungi to make products useful to humans. Fermented products have applications as food as well as in general industry.- Food fermentation :...

, usually in strongly aerobic conditions.

Administration


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 topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

ly, as with eye drop
Eye drop
Eye drops are saline-containing drops used as a route to administer medication in the eye. Depending on the condition being treated, they may contain steroids, antihistamines, sympathomimetics, beta receptor blockers, parasympathomimetics, parasympatholytics, prostaglandins, non-steroidal...

s or ointments.

Side effects


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.
Side effects range from mild to very serious depending on the antibiotics used, the microbial organisms targeted, and the individual patient. Safety profiles of newer drugs are often not as well established as for those that have a long history of use. Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis
Photodermatitis
Photodermatitis, sometimes referred to as "sun poisoning" or photoallergy is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure...

 and anaphylaxis. Common side effects include diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...

. Antibacterials can also affect the vaginal flora
Vaginal flora
The bacteria that colonize the vagina, collectively referred to as the vaginal microbiome, were discovered by the German gynecologist Albert Döderlein in 1892. The amount and type of bacteria present have significant implications for a woman's overall health...

, and may lead to overgrowth of yeast species of the genus Candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...

in the vulvo-vaginal area. Additional side effects can result from interaction with other drugs, such as elevated risk of tendon
Tendon
A tendon is a tough band of fibrous connective tissue that usually connects muscle to bone and is capable of withstanding tension. Tendons are similar to ligaments and fasciae as they are all made of collagen except that ligaments join one bone to another bone, and fasciae connect muscles to other...

 damage from administration of a quinolone antibiotic with a systemic corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

.

Contraceptive pills


The majority of studies indicate antibiotics do not interfere with contraceptive pills, such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). In cases where antibacterials have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibacterial rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

, these cases may be due to an increase in the activities of hepatic liver enzymes causing increased breakdown of the pill's active ingredients. 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. Clinicians have recommended that extra contraceptive measures are applied during therapies using antibacterials that are suspected to interact with oral contraceptives.

Alcohol


Interactions between alcohol and certain antibacterials may occur and may cause side effects and decreased effectiveness of antibacterial therapy.
"It is sensible to avoid drinking alcohol when taking medication. However, it is unlikely that drinking alcohol in moderation will cause problems if you are taking most common antibiotics. However, there are specific types of antibiotics with which alcohol should be avoided completely, because of serious side effects."

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
Metronidazole
Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....

, tinidazole
Tinidazole
Tinidazole is an anti-parasitic drug used against protozoan infections. It is widely known throughout Europe and the developing world as treatment for a variety of amoebic and parasitic infections...

, cephamandole, latamoxef
Latamoxef
Latamoxef is an oxacephem antibiotic usually grouped with the cephalosporins. In oxacephems such as latamoxef, the sulfur atom of the cephalosporin core is replaced with an oxygen atom....

, cefoperazone
Cefoperazone
Cefoperazone is a third generation cephalosporin antibiotic, marketed by Pfizer under the name Cefobid, and also marked by pharco B international under the name of Cefazoneand also marketed by "sigmatec " under the name " cefoperazone"...

, cefmenoxime
Cefmenoxime
Cefmenoxime is a third-generation cephalosporin antibiotic....

, and furazolidone
Furazolidone
Furazolidone is a nitrofuran antibacterial. It is marketed by Roberts Laboratories under the brand name Furoxone and by GlaxoSmithKline as Dependal-M.-Uses:It is used to treat diarrhoea and enteritis caused by bacteria or protozoan infections....

, cause a disulfiram
Disulfiram
Disulfiram is a drug discovered in the 1920s and used to support the treatment of chronic alcoholism by producing an acute sensitivity to alcohol. Trade names for disulfiram in different countries are Antabuse and Antabus manufactured by Odyssey Pharmaceuticals...

-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase
Acetaldehyde dehydrogenase
Acetaldehyde dehydrogenases are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows:...

, which may result in vomiting, nausea, and shortness of breath.

Other effects of alcohol on antibacterial activity include altered activity of the liver enzymes that break down the antibacterial compound. In addition, serum levels of doxycycline and erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

 succinate two bacteriostatic antibacterials (see above) may be reduced by alcohol consumption, resulting in reduced efficacy and diminished pharmacotherapeutic effect.

Resistance


The emergence of resistance of bacteria to antibacterial drugs is a common phenomenon. Emergence of resistance often reflects evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary 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. 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. Survival of bacteria often results from an inheritable resistance. Resistance to antibacterials also occurs through horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

. Horizontal transfer is more likely to happen in locations of frequent antibiotic use. 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. 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.

Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains. For example, an antibiotic target may be absent from the bacterial genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA. Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains. The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

. For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes. Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials. 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.

Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases which were for a while well-controlled. For example, emergent bacterial strains causing tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

 (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. For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam
Beta-lactam
A β-lactam ring, is a four-membered lactam. It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl...

 antibacterials. United Kingdom Health Protection Agency
Health Protection Agency
The Health Protection Agency, or, in Welsh, Yr Asiantaeth Diogelu Iechyd is a statutory corporation. It is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards...

 has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."

Misuse



Inappropriate antibacterial treatment and overuse of antibiotics have contributed to the emergence of antibacterial-resistant bacteria. Self prescription of antibacterials and their use as growth promoters in agriculture are additional examples of misuse. 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. The overuse of antibacterials, like penicillin and erythromycin, have been associated with emerging antibacterial resistance since the 1950s. 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.

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
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...

. One study on respiratory tract infection
Respiratory tract infection
Respiratory tract infection refers to any of a number of infectious diseases involving the respiratory tract. An infection of this type is normally further classified as an upper respiratory tract infection or a lower respiratory tract infection...

s found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them". Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.

Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibacterials. 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
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (FDA), and the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

 (NIH), as well as other US agencies. An NGO campaign group is Keep Antibiotics Working. 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.

In agriculture, antibacterials are often used to promote weight gain in livestock animals. More than 70% of the antibacterials used in U.S. are given to livestock animals in the absence of infectious diseases. This practice has been associated with the emergence of antibacterial-resistant strains of bacteria, including Salmonella spp., Campylobacter spp., Escherichia coli, and Enterococcus spp. 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. 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. However, commonly there are delays in regulatory and legislative actions to limit the use of antibacterials, partly attributable 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 and H.R. 2562) aimed at phasing out nontherapeutic use of antibacterials in US food animals were proposed, but have not passed. 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).

Alternatives


The increase in bacterial strains that are resistant to conventional antibacterial therapies has prompted the development of alternative strategies to treat bacterial diseases.

Resistance-modifying agents


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 a antibacterial. Targets include:
  • The efflux inhibitor
    Efflux (microbiology)
    Active efflux is a mechanism responsible for extrusion of toxic substances and antibiotics outside the cell; this is considered to be a vital part of xenobiotic metabolism...

     Phe-Arg-β-naphthylamide.
  • Beta-lactamase inhibitors, such as clavulanic acid
    Clavulanic acid
    Clavulanic acid is a competitive β-lactamase inhibitor combined with penicillin group antibiotics to overcome certain types of antibiotic resistance. It is used to overcome resistance in bacteria that secrete β-lactamase, which otherwise inactivates most penicillins...

     and sulbactam
    Sulbactam
    Sulbactam is a molecule that is given in combination with beta-lactam antibiotics to inhibit beta-lactamase, an enzyme produced by bacteria that destroys the antibiotics...

    .

Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic tolerant bacteria by keeping their metabolism active.

Phage therapy
Phage therapy
Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Although extensively used and developed mainly in former Soviet Union countries circa 1920, this method of therapy is still being tested for treatment of a variety of bacterial and poly-microbial...


Phage therapy is the use of viruses (called phages
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

) that infect bacteria for the treatment of bacterial infections. Phages are common in bacterial populations and control the growth of bacteria in many environments, including in the intestine, the ocean, and the soil. 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. These studies were performed mainly in the former Soviet Union, at the Eliava Institute of Bacteriophage, Microbiology and Virology
George Eliava Institute
The George Eliava Institute of Bacteriophage, Microbiology and Virology has been active since the 1930s in the field of phage therapy, which is used to combat microbial infection .- History :...

, Republic of Georgia
Georgia (country)
Georgia is a sovereign state in the Caucasus region of Eurasia. Located at the crossroads of Western Asia and Eastern Europe, it is bounded to the west by the Black Sea, to the north by Russia, to the southwest by Turkey, to the south by Armenia, and to the southeast by Azerbaijan. The capital of...

. The development of antibacterial-resistant bacteria has sparked renewed interest in phage therapy in Western medicine. Several companies (e.g., Intralytix
Intralytix
Intralytix is a biotechnology company based in Baltimore, Maryland. Intralytix specializes in bacteriophage-based products used to control bacterial pathogens in environmental, food processing, and medical settings.-ListShield:...

, Novolytics, and Gangagen), universities, and foundations across the world now focus on phage therapies. One concern with this therapeutic strategy is the use of genetically engineered
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...

 viruses, which limits certain aspects of phage therapy.

Bacteriocin
Bacteriocin
Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strain. They are typically considered to be narrow spectrum antibiotics, though this has been debated...

s


Bacteriocins are peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

s that can be more readily engineered than small molecules, and are possible alternatives to conventional antibacterial compounds. Different classes of bacteriocins have different potential as therapeutic agents. Small-molecule bacteriocins (microcins and lantibiotics) are similar to the classic antibiotics; colicin
Colicin
A colicin is a type of bacteriocin produced by and toxic to some strains of Escherichia coli. Colicins are released into the environment to reduce competition from other bacterial strains...

-like bacteriocins possess a narrow spectrum, and require molecular diagnostics prior to therapy. 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.

Chelation
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....


Chelation of micronutrients that are essential for bacterial growth to restrict pathogen spread in vivo might supplement some antibacterials. For example, limiting the iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 availability in the human body restricts bacterial proliferation. 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.

Vaccines


Vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

s 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
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

, inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

, and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases. Vaccines made from attenuated whole cells or lysates have been largely replaced 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.

Biotherapy
Biotherapy
Zootherapy is the use of living animals for medical treatment or as an adjunct to medical diagnosis.-Overview:Zootherapy is the use of living organisms to diagnose, treat or cure disease or disease symptoms...


Biotherapy may employ organisms, such as protozoa, to consume the bacterial pathogens. Another such approach is maggot therapy
Maggot therapy
Maggot therapy is a type of biotherapy involving the intentional introduction of live, disinfected maggots into the non-healing skin and soft tissue wound of a human or animal for the purpose of cleaning out the...

.

Probiotics


Probiotics consist of a live culture of bacteria, which may become established as competing symbionts
Competitive exclusion principle
In ecology, the competitive exclusion principle, sometimes referred to as Gause's law of competitive exclusion or just Gause's law, is a proposition which states that two species competing for the same resources cannot coexist if other ecological factors are constant...

, and inhibit or interfere with colonization by microbial pathogens.

Host defense peptides


An additional therapeutic agent is the enhancement of the multifunctional properties of natural anti-infectives, such as cationic host defense (antimicrobial) peptides (HDPs).

Antimicrobial coatings


Functionalization of antimicrobial surfaces can be used for sterilization, self-cleaning, and surface protection.

Antimicrobial copper alloy surfaces


Copper-alloy surfaces have natural intrinsic properties to effectively and quickly destroy bacteria. The United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 has approved the registration of 355 different antibacterial copper alloys that kill E. coli O157:H7, methicillin
Methicillin
Meticillin or methicillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.-History:Methicillin was developed by Beecham in 1959...

-resistant Staphylococcus aureus
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...

(MRSA), Staphylococcus
Staphylococcus
Staphylococcus is a genus of Gram-positive bacteria. Under the microscope they appear round , and form in grape-like clusters....

, 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.

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