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An antibiotic is a type of
antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All orga ...
substance active against
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
. It is the most important type of
antibacterial agent Antiseptics (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") are antimicrobial substances that are applied to living tissue/skin Skin is the layer of usually soft, flexible outer tissue covering th ...
for fighting
bacterial infections Pathogenic bacteria are bacteria that can cause disease. This article deals with human pathogenic bacteria. Although most bacteria are harmless or often beneficial, some are pathogenic, with the number of species estimated as fewer than a hundre ...
, and antibiotic
medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medicine, prevent disease. Drug therapy (pharmacotherapy) ...

medication
s are widely used in the
treatment Treatment may refer to: * Treatment (song), "Treatment" (song), a 2012 song by * Film treatment, a prose telling of a story intended to be turned into a screenplay * Medical treatment or therapy * Sewage treatment * Surface treatment or surface fi ...
and
prevention Prevention may refer to: Health and medicine * Preventive healthcare Preventive healthcare, or prophylaxis, consists of measures taken for disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, ...
of such infections. They may either
kill Kill often refers to: *Homicide, one human killing another Kill may also refer to: Media *''Kill!'', a 1968 film directed by Kihachi Okamoto *Kill (Cannibal Corpse album), ''Kill'' (Cannibal Corpse album), 2006 *Kill (Electric Six album), ''Kill' ...
or inhibit the growth of bacteria. A limited number of antibiotics also possess
antiprotozoal Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceutical A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug File:Aspirine macro shot.jpg, Uncoated aspirin Tablet (p ...
activity. Antibiotics are not effective against
virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecu ...

virus
es such as the
common cold The common cold, also known simply as a cold, is a viral infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (b ...
or
influenza Influenza, commonly known as "the flu", is an infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), ...

influenza
; drugs which inhibit viruses are termed
antiviral drug Antiviral drugs are a class of medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug Uncoated tablets, consisting of about 90% acetylsalicylic acid, along with a mino ...
s or antivirals rather than antibiotics. Sometimes, the term ''antibiotic''—literally "opposing life", from the
Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 million as of ...
roots ἀντι ''anti'', "against" and βίος ''bios'', "life"—is broadly used to refer to any substance used against
microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms ar ...
s, but in the usual medical usage, antibiotics (such as
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
) are those produced naturally (by one
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes ...
fighting another), whereas nonantibiotic antibacterials (such as
sulfonamide In chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they undergo during ...

sulfonamide
s and
antiseptic Antiseptics (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") are antimicrobial, antimicrobial substances that are applied to living biological tissue, tissue/skin to reduce the possibility of infection ...

antiseptic
s) are fully synthetic. However, both classes have the same goal of killing or preventing the growth of microorganisms, and both are included in
antimicrobial chemotherapyAntimicrobial chemotherapy is the clinical application of antimicrobial agents to treat infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, an ...
. "Antibacterials" include
antiseptic Antiseptics (from Greek ἀντί ''anti'', "against" and σηπτικός ''sēptikos'', "putrefactive") are antimicrobial, antimicrobial substances that are applied to living biological tissue, tissue/skin to reduce the possibility of infection ...

antiseptic
drugs,
antibacterial soap Antibacterial soap is a soap which contains chemical ingredients that purportedly assist in killing bacteria. The majority of antibacterial soaps contain triclosan, though other chemical additives are also common. The effectiveness of products brand ...
s, and chemical
disinfectant A disinfectant is a chemical A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ...
s, whereas antibiotics are an important class of antibacterials used more specifically in medicine and sometimes in livestock feed. Antibiotics have been used since ancient times. Many civilizations used topical application of mouldy bread, with many references to its beneficial effects arising from ancient Egypt, Nubia, China, Serbia, Greece, and Rome. The first person to directly document the use of molds to treat infections was John Parkinson (1567–1650). Antibiotics revolutionized medicine in the 20th century.
Alexander Fleming Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist, best known for discovering the enzyme lysozyme and the world's first broadly effective antibiotic substance which he named penicillin. He dis ...

Alexander Fleming
(1881–1955) discovered modern day
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
in 1928, the widespread use of which proved significantly beneficial during wartime. However, the effectiveness and easy access to antibiotics have also led to their overuse and some bacteria have evolved
resistance Resistance may refer to: Arts, entertainment, and media Comics * Either of two similarly named but otherwise unrelated comic book series, both published by Wildstorm: ** ''Resistance'' (comics), based on the video game of the same title ** ''Th ...

resistance
to them. The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United Nations and each other through the co-ordinating machinery of the Unit ...
has classified antimicrobial resistance as a widespread "serious threat
hat A collection of 18th and 19th century men's beaver felt hats A hat is a head covering which is worn for various reasons, including protection against weather conditions, ceremonial reasons such as university graduation, religious reasons, safet ...

hat
is no longer a prediction for the future, it is happening right now in every region of the world and has the potential to affect anyone, of any age, in any country".


Medical uses

Antibiotics are used to treat or prevent bacterial infections, and sometimes protozoan infections. (
Metronidazole Metronidazole, marketed under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ...

Metronidazole
is effective against a number of
parasitic disease A parasitic disease, also known as parasitosis, is an infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), ...
s). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an
empiric therapy Empiric therapy or empirical therapy is medical treatment or therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health Health is a state of physical, mental and social well-being Well ...
is adopted. This involves the administration of a
broad-spectrum antibiotic A broad- spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial inf ...
based on the signs and symptoms presented and is initiated pending laboratory results that can take several days. When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance. To avoid surgery, antibiotics may be given for non-complicated acute
appendicitis Appendicitis is inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a pr ...

appendicitis
. Antibiotics may be given as a preventive measure and this is usually limited to at-risk populations such as those with a
weakened immune system Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
(particularly in
HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus ''Lentivirus'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, inc ...

HIV
cases to prevent
pneumonia Pneumonia is an inflammatory Inflammatory may refer to: * Inflammation, a biological response to harmful stimuli * The word ''inflammatory'' is also used to refer literally to fire and flammability, and figuratively in relation to comments t ...

pneumonia
), those taking
immunosuppressive drug Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs Uncoated tablets, consisting of about 90% acetylsalicylic acid, along with a minor amount of inert fillers and bind ...
s,
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumor A benign tumor is a mass of cells Cell most often refers to: * Cell (biolo ...

cancer
patients, and those having
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical or dental specialty that uses operative manual and instrumental techniques on a person to investigate or t ...
. Their use in surgical procedures is to help prevent infection of incisions. They have an important role in
dental antibiotic prophylaxis Dental antibiotic prophylaxis is the administration of antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biologica ...
where their use may prevent
bacteremia Bloodstream infections (BSIs), which include bacteremias when the Bacterial infection, infections are bacterial and fungemias when the infections are Fungal infection, fungal, are infections present in the blood. Blood is normally a Asepsis, steri ...
and consequent
infective endocarditis Infective endocarditis is an infection An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), host tissues to the infectious ag ...
. Antibiotics are also used to prevent infection in cases of
neutropenia Neutropenia is an abnormally low concentration of neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cell White blood cells (WBCs), also c ...

neutropenia
particularly cancer-related.


Administration

There are many different
routes of administration Route or routes may refer to: * Route (gridiron football) Route or routes may refer to: * Route (gridiron football), a path run by a wide receiver * route (command), a program used to configure the routing table * Route, County Antrim, an area ...
for antibiotic treatment. Antibiotics are usually . In more severe cases, particularly deep-seated systemic infections, antibiotics can be given
intravenously Intravenous therapy (abbreviated as IV therapy) is a medical technique that delivers fluids, medications and nutrition directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrition ...
or by injection. Where the site of infection is easily accessed, antibiotics may be given
topically A topical medication is a medication that is applied to a particular place on or in the body. Most often topical administration means application to body surface area, body surfaces such as the human skin, skin or mucous membranes to treat ailme ...
in the form of
eye drop Eye drops or eyedrops are liquid drops applied directly to the surface of the eye Eyes are organs of the visual system The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina conta ...

eye drop
s onto the
conjunctiva The conjunctiva is a tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubit ...
for
conjunctivitis Conjunctivitis, also known as pink eye, is inflammation Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irri ...

conjunctivitis
or
ear drop Ear drops are a form of medicine used to help treat or prevent ear infections, especially infections of the outer ear and ear canal (otitis externa). It is also used to help remove ear wax. It is used for short-term treatment and can be purchase ...
s for ear infections and acute cases of
swimmer's ear Otitis externa, also called swimmer's ear, is inflammation of the ear canal. It often presents with ear pain, swelling of the ear canal, and occasionally Hearing loss, decreased hearing. Typically there is pain with movement of the outer ear. A hi ...

swimmer's ear
. Topical use is also one of the treatment options for some skin conditions including
acne Acne, also known as acne vulgaris, is a long-term skin condition A skin condition, also known as cutaneous condition, is any medical condition A disease is a particular abnormal condition that negatively affects the structure or ...

acne
and
cellulitis Cellulitis is a bacterial infection involving the inner layers of the skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Ot ...

cellulitis
. Advantages of topical application include achieving high and sustained concentration of antibiotic at the site of infection; reducing the potential for systemic absorption and toxicity, and total volumes of antibiotic required are reduced, thereby also reducing the risk of antibiotic misuse. Topical antibiotics applied over certain types of surgical wounds have been reported to reduce the risk of surgical site infections. However, there are certain general causes for concern with topical administration of antibiotics. Some systemic absorption of the antibiotic may occur; the quantity of antibiotic applied is difficult to accurately dose, and there is also the possibility of local
hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune sy ...
reactions or
contact dermatitis Contact dermatitis is a type of inflammation of the skin. Some symptoms of contact dermatitis can include itchy or dry skin, a red rash, bumps, blisters, and swelling. The rash isn't contagious or life-threatening, but it can be very uncomfortabl ...

contact dermatitis
occurring. It is recommended to administer antibiotics as soon as possible, especially in life-threatening infections. Many emergency departments stock antibiotics for this purpose.


Prevalence

Antibiotic consumption varies widely between countries. The
WHO The World Health Organization (WHO) is a specialized agency of the United Nations United Nations Specialized Agencies are autonomous organizations working with the United Nations and each other through the co-ordinating machinery of the Unite ...

WHO
report on surveillance of antibiotic consumption’ published in 2018 analysed 2015 data from 65 countries. As measured in defined daily doses per 1,000 inhabitants per day. Mongolia had the highest consumption with a rate of 64.4. Burundi had the lowest at 4.4.
Amoxicillin Amoxicillin is an antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is ...

Amoxicillin
and
amoxicillin/clavulanic acid Amoxicillin/clavulanic acid, also known as co-amoxiclav, is an antibiotic medication used for the treatment of a number of bacterial infections. It is a combination consisting of amoxicillin, a β-lactam antibiotic, and potassium clavulanate, a ...
were the most frequently consumed.


Side effects

Antibiotics are screened for any negative effects before their approval for clinical use, and are usually considered safe and well tolerated. However, some antibiotics have been associated with a wide extent of adverse
side effect In medicine Medicine is the science Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity, awareness, or understanding of someone or something, such as facts ( descriptive knowledge) ...
s ranging from mild to very severe depending on the type of antibiotic used, the microbes targeted, and the individual patient. Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity or
allergic Allergies, also known as allergic diseases, are a number of conditions caused by hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, i ...

allergic
reactions. Adverse effects range from fever and nausea to major allergic reactions, including and
anaphylaxis Anaphylaxis is a serious allergic reaction Allergies, also known as allergic diseases, are a number of conditions caused by hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable rea ...
. Safety profiles of newer drugs are often not as well established as for those that have a long history of use. Common side-effects include
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery defecation, bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration of ...
, resulting from disruption of the species composition in the
intestinal flora Gut microbiota, gut flora, or microbiome are the microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any indivi ...
, resulting, for example, in overgrowth of pathogenic bacteria, such as '' Clostridium difficile''. Taking
probiotics Probiotics are live microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that e ...
during the course of antibiotic treatment can help prevent antibiotic-associated diarrhea. Antibacterials can also affect the
vaginal flora Lactobacilli and a vaginal squamous cell. Vaginal flora, vaginal microbiota or vaginal microbiome are the microorganisms A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós' ...
, and may lead to overgrowth of
yeast Yeasts are eukaryotic Eukaryotes () are organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular ...

yeast
species of the genus '' Candida'' in the vulvo-vaginal area. Additional side effects can result from
interaction Interaction is a kind of action that occurs as two or more objects have an effect upon one another. The idea of a two-way effect is essential in the concept of interaction, as opposed to a one-way causal effect. Closely related terms are interac ...
with other drugs, such as the possibility of
tendon A tendon or sinew is a tough, high-tensile-strength band of dense fibrous connective tissue that connects muscle Skeletal muscles (commonly referred to as muscles) are organs An organ is a group of tissues with similar functions. Plant ...

tendon
damage from the administration of a
quinolone antibiotic A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria Bacteria (; common noun bacteria, singular bacterium) ar ...
with a systemic
corticosteroid Corticosteroids are a class of steroid hormone A steroid hormone is a steroid A steroid is a biologically active organic compound In , organic compounds are generally any s that contain - . Due to carbon's ability to (form chains w ...
. Some antibiotics may also damage the
mitochondrion A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

mitochondrion
, a bacteria-derived organelle found in eukaryotic, including human, cells. Mitochondrial damage cause
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen ...
in cells and has been suggested as a mechanism for side effects from
fluoroquinolone A quinolone antibiotic is a member of a large group of broad-spectrum antibiotic, broad-spectrum bacteriocidals that share a bicyclic molecule, bicyclic core structure related to the substance 4-Quinolone, 4-quinolone. They are used in human and ...
s. They are also known to affect
chloroplast A chloroplast is a type of membrane-bound organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structure ...

chloroplast
s.


Correlation with obesity

Exposure to antibiotics early in life is associated with increased body mass in humans and mouse models. Early life is a critical period for the establishment of the
intestinal microbiota Gut microbiota, gut flora, or microbiome The word microbiome (from the Greek ''micro'' meaning "small" and ''bíos'' meaning "life") was first used by J.L. Mohr in 1952 in The Scientific Monthly to mean the microorganisms found in a specific ...
and for
metabolic Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main purposes of metabolism are: the conversion of the energy in food to energy available to run cell ...

metabolic
development. Mice exposed to subtherapeutic antibiotic treatment – with either penicillin,
vancomycin Vancomycin is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large doma ...

vancomycin
, or
chlortetracycline Chlortetracycline (trade name Aureomycin, Lederle Laboratories) is a Tetracycline antibiotics, tetracycline antibiotic, the first tetracycline to be identified. It was discovered in 1945 at Lederle Laboratories under the supervision of scientist Ye ...

chlortetracycline
had altered composition of the gut microbiota as well as its metabolic capabilities. One study has reported that mice given low-dose penicillin (1 μg/g body weight) around birth and throughout the
weaning Weaning is the process of gradually introducing an infant An infant (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is the more formal or specialised synonym for the common term ''baby'', meaning the very y ...
process had an increased body mass and fat mass, accelerated growth, and increased
hepatic The liver is an Organ (anatomy), organ of the digestive system only found in vertebrates which detoxification, detoxifies various metabolites, Protein biosynthesis, synthesizes proteins and produces biochemicals necessary for digestion and growth ...
expression of
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s involved in
adipogenesis Adipogenesis is the formation of adipocytes (fat cells) from stem cells. It involves 2 phases, determination, and terminal differentiation. Determination is mesenchymal stem cells committing to the adipocyte precursor cells, also known as preadipocy ...
, compared to control mice. In addition, penicillin in combination with a high-fat diet increased fasting
insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the main Anabolism, anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and p ...

insulin
levels in mice. However, it is unclear whether or not antibiotics cause
obesity Obesity is a medical condition A disease is a particular abnormal condition that negatively affects the structure or function (biology), function of all or part of an organism, and that is not due to any immediate external injury. ...

obesity
in humans. Studies have found a correlation between early exposure of antibiotics (<6 months) and increased body mass (at 10 and 20 months). Another study found that the type of antibiotic exposure was also significant with the highest risk of being overweight in those given
macrolide The macrolides are a class of natural products that consist of a large macrocycle, 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-memb ...
s compared to penicillin and
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorga ...
. Therefore, there is correlation between antibiotic exposure in early life and obesity in humans, but whether or not there is a causal relationship remains unclear. Although there is a correlation between antibiotic use in early life and obesity, the effect of antibiotics on obesity in humans needs to be weighed against the beneficial effects of clinically indicated treatment with antibiotics in infancy.


Interactions


Birth control pills

There are few well-controlled studies on whether antibiotic use increases the risk of
oral contraceptiveOral contraceptives, abbreviated OCPs, also known as birth control pills, are medication A medication (also referred to as medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therap ...
failure. The majority of studies indicate antibiotics do not interfere with
birth control pillsOral contraceptives, abbreviated OCPs, also known as birth control pills, are medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, t ...
, such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%). Situations that may increase the risk of oral contraceptive failure include non-compliance (missing taking the pill), vomiting, or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting
ethinylestradiol Ethinylestradiol (EE) is an estrogen Estrogen, or oestrogen, is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous e ...

ethinylestradiol
serum levels in the blood. Women with
menstrual irregularities Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods). Irregular cycles or periods Irregular cycles or irregular periods is an abnor ...
may be at higher risk of failure and should be advised to use backup contraception during antibiotic treatment and for one week after its completion. If patient-specific risk factors for reduced oral contraceptive efficacy are suspected, backup contraception is recommended. In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic
rifampicin Rifampicin, also known as rifampin, is an antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biol ...

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. Effects on the
intestinal flora Gut microbiota are the microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical str ...
, which might result in reduced absorption of
estrogen Estrogens or oestrogens, are a class of natural or synthetic sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid ho ...

estrogen
s in the colon, have also been suggested, but such suggestions have been inconclusive and controversial. Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral
contraceptive Birth control, also known as contraception, anticonception, and fertility control, is a method or device used to prevent pregnancy Pregnancy, also known as gestation, is the time during which one or more offspring develops inside a woman ...
s. More studies on the possible interactions between antibiotics and birth control pills (oral contraceptives) are required as well as careful assessment of patient-specific risk factors for potential oral contractive pill failure prior to dismissing the need for backup contraception.


Alcohol

Interactions between alcohol and certain antibiotics may occur and may cause side effects and decreased effectiveness of antibiotic therapy. While moderate alcohol consumption is unlikely to interfere with many common antibiotics, there are specific types of antibiotics, with which alcohol consumption may cause serious side effects. Therefore, potential risks of side effects and effectiveness depend on the type of antibiotic administered. Antibiotics such as
metronidazole Metronidazole, marketed under the brand name Flagyl among others, is an antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") an ...

metronidazole
,
tinidazole Tinidazole is a drug used against protozoan Protozoa (also protozoan, plural protozoans) is an informal term for a group of single-celled eukaryote Eukaryotes () are organisms whose Cell (biology), cells have a cell nucleus, nucleus enclo ...

tinidazole
, cephamandole,
latamoxef Latamoxef (or moxalactam) is an oxacephem antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They ...

latamoxef
,
cefoperazone Cefoperazone is a third-generation cephalosporin antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological ce ...

cefoperazone
,
cefmenoxime Cefmenoxime is a third-generation cephalosporin antibiotic. External links * * * * Acetaldehyde dehydrogenase inhibitors Thiazoles Tetrazoles Cephalosporin antibiotics Ketoximes {{antibiotic-stub ...

cefmenoxime
, and , cause a
disulfiram Disulfiram (sold under the trade name Antabuse) is a medication, drug used to support the treatment of chronic alcoholism by producing an acute sensitivity to ethanol (drinking alcohol). Disulfiram works by Enzyme inhibition, inhibiting the enzyme ...

disulfiram
-like chemical reaction with alcohol by inhibiting its breakdown by
acetaldehyde dehydrogenase Acetaldehyde dehydrogenases () are dehydrogenase A dehydrogenase is an enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called ...
, which may result in vomiting, nausea, and shortness of breath. In addition, the efficacy of doxycycline and
erythromycin Erythromycin is an antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () i ...

erythromycin
succinate may be reduced by alcohol consumption. Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.


Pharmacodynamics

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. The 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 concentrationIn microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible cell growth, growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being ( ...

minimum inhibitory concentration
and minimum bactericidal concentration of an antibacterial. To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its
pharmacokinetic Pharmacokinetics (from Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often roughly divided into the following peri ...

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


Combination therapy

In important infectious diseases, including tuberculosis,
combination therapy Combination therapy or polytherapy is therapy that uses more than one medication or modality . Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can a ...
(i.e., the concurrent application of two or more antibiotics) has been used to delay or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their
synergistic Synergy is an interaction or cooperation giving rise to a whole that is greater than the simple sum of its parts. The term ''synergy'' comes from the Attic Greek Attic Greek is the Greek language, Greek dialect of the regions of ancient Greec ...
effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect. Methicillin-resistant ''Staphylococcus aureus'' infections may be treated with a combination therapy of
fusidic acid Fusidic acid is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large doma ...
and rifampicin. Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if one of the antibiotics was given as a
monotherapy Combination therapy or polytherapy is therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health Health is a state of physical, mental and social well-being Well-being, also known as ' ...
. For example,
chloramphenicol Chloramphenicol is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medicat ...

chloramphenicol
and
tetracyclines Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. Tet ...

tetracyclines
are antagonists to
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
s. However, this can vary depending on the species of bacteria. In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic. In addition to combining one antibiotic with another, antibiotics are sometimes co-administered with resistance-modifying agents. For example, β-lactam antibiotics may be used in combination with β-lactamase inhibitors, such as
clavulanic acid Clavulanic acid is a β-lactam drug that functions as a mechanism-based β-lactamase inhibitor. While not effective by itself as an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; c ...

clavulanic acid
or
sulbactam Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics. It was patented in 1977 and approved for medical use in 19 ...

sulbactam
, when a patient is infected with a β-lactamase-producing strain of bacteria.


Classes

Antibiotics are commonly classified based on their
mechanism of action In pharmacology Pharmacology is a branch of , and concerned with or action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemical or physiological effect on the ...

mechanism of action
,
chemical structure A chemical structure determination includes a chemist A chemist (from Greek ''chēm(ía)'' alchemy; replacing ''chymist'' from Medieval Latin Medieval Latin was the form of Latin Latin (, or , ) is a classical language A class ...
, or spectrum of activity. Most target bacterial functions or growth processes. Those that target the bacterial cell wall (
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
s and
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorga ...
s) or the cell membrane (
polymyxin Image:Polymyxin B.svg, Polymyxin B (R=H is polymyxin B1, R=CH3 is polymyxin B2) Polymyxins are antibiotics. Polymyxins Polymyxin B">B and E (also known as colistin) are used in the treatment of Gram-negative bacterial infections. They work most ...
s), or interfere with essential bacterial enzymes (
rifamycin The rifamycins are a group of antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organ ...
s, s, quinolones, and
sulfonamides In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
) have
bactericidal A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), ...
activities.
Protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins Proteins are large biomolecule , showing alpha helices, repr ...
s (
macrolide The macrolides are a class of natural products that consist of a large macrocycle, 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-memb ...
s,
lincosamides Lincosamides are a class of antibiotics, which include lincomycin, clindamycin, and pirlimycin. Structure Lincosamides consist of a pyrrolidine ring linked to a pyranose moiety (methylthio-lincosamide) via an amide bond. Hydrolysis of lincosami ...
, and
tetracycline Tetracycline, sold under the brand name Sumycin among others, is an oral antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell ...

tetracycline
s) are usually
bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfecta ...
(with the exception of bactericidal
aminoglycoside Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ( ...
s). Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as
gram-negative Gram-negative bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typically a few microm ...
or
gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacte ...
, whereas
broad-spectrum antibiotics A broad-spectrum A spectrum (plural ''spectra'' or ''spectrums'') is a condition that is not limited to a specific set of values but can vary, without steps, across a Continuum (theory), continuum. The word was first used scientifically in optic ...
affect a wide range of bacteria. Following a 40-year break in discovering classes of antibacterial compounds, four new classes of antibiotics were introduced to clinical use in the late 2000s and early 2010s: cyclic
lipopeptide A lipopeptide is a molecule A scanning tunneling microscopy image of pentacene molecules, which consist of linear chains of five carbon rings. A molecule is an electrically Electricity is the set of physical phenomena associated wi ...
s (such as
daptomycin Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type o ...

daptomycin
), glycylcyclines (such as
tigecycline Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resista ...

tigecycline
),
oxazolidinone 2-Oxazolidone is a heterocyclic 125px, Pyridine, a heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic ...
s (such as
linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are antibiotic resistance, resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, includin ...

linezolid
), and s (such as ).


Production

With advances in
medicinal chemistry Medicinal chemistry is discipline at the intersection of chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or s ...
, most modern antibacterials are
semisynthetic Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds composed of atoms, molecules and ions ...
modifications of various natural compounds. These include, for example, the
beta-lactam antibiotics A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the Β carbon, β-carbon atom relative to the carbonyl. The simplest β-lactam pos ...
, which include the
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
s (produced by fungi in the genus ''
Penicillium ''Penicillium'' () is a genus of ascomycetous Ascomycota is a phylum of the kingdom Fungi that, together with the Basidiomycota, forms the subkingdom Dikarya. Its members are commonly known as the sac fungi or ascomycetes. It is the largest ...

Penicillium
''), the
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorga ...
s, and the
carbapenem Carbapenems are a class of highly effective antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, a ...

carbapenem
s. Compounds that are still isolated from living organisms are the
aminoglycoside Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ( ...
s, whereas other antibacterials—for example, the
sulfonamides In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
, the quinolones, and the
oxazolidinone 2-Oxazolidone is a heterocyclic 125px, Pyridine, a heterocyclic compound A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic ...
s—are produced solely by
chemical synthesis As a topic of chemistry Chemistry is the study of the properties and behavior of . It is a that covers the that make up matter to the composed of s, s and s: their composition, structure, properties, behavior and the changes they unde ...
. Many antibacterial compounds are relatively
small molecule Within the fields of molecular biology Molecular biology is the branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, molecular synthesis, mo ...
s with a molecular weight of less than 1000 dalton (unit), daltons. Since the first pioneering efforts of Howard Florey and Ernst Boris Chain, 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 Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
, production of the active compounds is carried out using industrial fermentation, fermentation, usually in strongly wikt:aerobic, aerobic conditions.


Resistance

The emergence of resistance of bacteria to antibiotics is a common phenomenon. Emergence of resistance often reflects evolutionary processes that take place during antibiotic therapy. The antibiotic treatment may natural selection, select for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibiotics. 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 for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment. Antibiotics such as penicillin and erythromycin, which used to have a high efficacy against many bacterial species and strains, have become less effective, due to the increased resistance of many bacterial strains. Resistance may take the form of biodegradation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces. The survival of bacteria often results from an inheritable resistance, but the growth of resistance to antibacterials also occurs through horizontal gene transfer. Horizontal transfer is more likely to happen in locations of frequent antibiotic use. Antibacterial resistance may impose a biological cost, thereby reducing biological fitness, 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. Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms. Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability. 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. 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 gene transfer, horizontal genetic exchange. 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 that were for a while well controlled. For example, emergent bacterial strains causing tuberculosis 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 antibacterials. The United Kingdom's Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections." On 26 May 2016, an ''Escherichia coli, E. coli'' "antimicrobial resistance, superbug" was identified in the United States resistant to colistin, drug of last resort, "the last line of defence" antibiotic.


Misuse

Per ''The ICU Book'' "The first rule of antibiotics is to try not to use them, and the second rule is try not to use too many of them." Inappropriate antibiotic treatment and overuse of antibiotics have contributed to the emergence of antibiotic-resistant bacteria. Self-prescribing of antibiotics is an example of misuse. Many antibiotics are frequently prescribed to treat symptoms or diseases that do not respond to antibiotics or that are likely to resolve without treatment. Also, incorrect or suboptimal antibiotics are prescribed for certain bacterial infections. The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s. Widespread usage of antibiotics in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibiotics. Common forms of antibiotic misuse include excessive use of prophylaxis, prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibiotics 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 antibiotic, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the
common cold The common cold, also known simply as a cold, is a viral infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (b ...
. One study on respiratory tract infections 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. The lack of rapid point of care diagnostic tests, particularly in resource-limited settings is considered as one of the drivers of antibiotic misuse. Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics. The issues of misuse and overuse of antibiotics have been addressed by the formation of the US 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, as well as other US agencies. A non-governmental organization 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 antibiotic prescriptions, especially in children. The emergence of antibiotic resistance has prompted restrictions on their use in the UK in 1970 (Swann report 1969), and the European Union has banned the use of antibiotics as growth-promotional agents since 2003. Moreover, several organizations (including the World Health Organization, the National Academy of Sciences, and the U.S. Food and Drug Administration) have advocated restricting the amount of antibiotic use in food animal production. However, commonly there are delays in regulatory and legislative actions to limit the use of antibiotics, attributable partly to resistance against such regulation by industries using or selling antibiotics, and to the time required for research to test causal links between their use and resistance to them. Two federal bills (S.742 and H.R. 2562) aimed at phasing out nontherapeutic use of antibiotics 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. Despite pledges by food companies and restaurants to reduce or eliminate meat that comes from animals treated with antibiotics, the purchase of antibiotics for use on farm animals has been increasing every year. 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 antibiotic use in livestock, use of antibiotics in livestock was raised by the US Food and Drug Administration (FDA) 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. Studies have shown that common misconceptions about the effectiveness and necessity of antibiotics to treat common mild illnesses contribute to their overuse.


History

Before the early 20th century, treatments for infections were based primarily on folk medicine, medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2,000 years ago. Many ancient cultures, including the Ancient Egyptian medicine, ancient Egyptians and Ancient Greek medicine, ancient Greeks, used specially selected Mold (fungus), mold and plant materials to treat infections. Nubian people, Nubian mummies studied in the 1990s were found to contain significant levels of
tetracycline Tetracycline, sold under the brand name Sumycin among others, is an oral antibiotic An antibiotic is a type of antimicrobial substance active against bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell ...

tetracycline
. The beer brewed at that time was conjectured to have been the source. The use of antibiotics in modern medicine began with the discovery of synthetic antibiotics derived from dyes.


Synthetic antibiotics derived from dyes

Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Ehrlich noted certain dyes would color human, animal, or bacterial cells, whereas 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, in 1907, he discovered a medicinally useful drug, the first synthetic antibacterial Organoarsenic chemistry, organoarsenic compound salvarsan, now called arsphenamine. This heralded the era of antibacterial treatment that was begun with the discovery of a series of arsenic-derived synthetic antibiotics by both Alfred Bertheim and Ehrlich in 1907. Ehrlich and Bertheim had experimented with various chemicals derived from dyes to treat trypanosomiasis in mice and spirochaeta infection in rabbits. While their early compounds were too toxic, Ehrlich and Sahachiro Hata, a Japanese bacteriologist working with Erlich in the quest for a drug to treat syphilis, achieved success with the 606th compound in their series of experiments. In 1910 Ehrlich and Hata announced their discovery, which they called drug "606", at the Congress for Internal Medicine at Wiesbaden. The Hoechst AG, Hoechst company began to market the compound toward the end of 1910 under the name Salvarsan, now known as arsphenamine. The drug was used to treat syphilis in the first half of the 20th century. In 1908, Ehrlich received the Nobel Prize in Physiology or Medicine for his contributions to immunology. Hata was nominated for the Nobel Prize in Chemistry in 1911 and for the Nobel Prize in Physiology or Medicine in 1912 and 1913. The first sulfonamide (medicine), sulfonamide and the first wikt:systemic, systemically active antibacterial drug, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 or 1933 at the Bayer Laboratories of the IG Farben conglomerate in Germany, for which Domagk received the 1939 Nobel Prize in Physiology or Medicine. Sulfanilamide, the active drug of Prontosil, was not patentable as it had already been in use in the dye industry for some years. Prontosil had a relatively broad effect against Gram-positive coccus, cocci, but not against Enterobacteriaceae, enterobacteria. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug opened the era of antibacterials.


Penicillin and other natural antibiotics

Observations about the growth of some microorganisms inhibiting the growth of other microorganisms have been reported since the late 19th century. These observations of antibiosis between microorganisms led to the discovery of natural antibacterials. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics". In 1874, physician Sir William Roberts (physician), William Roberts noted that cultures of the mold ''Penicillium glaucum'' that is used in the making of some types of blue cheese did not display bacterial contamination. In 1876, physicist John Tyndall also contributed to this field. Pasteur conducted research showing that ''Bacillus anthracis'' would not grow in the presence of the related mold ''Penicillium notatum''. In 1895 Vincenzo Tiberio, Italian physician, published a paper on the antibacterial power of some extracts of mold. In 1897, doctoral student Ernest Duchesne submitted a dissertation, "" (Contribution to the study of vital competition in micro-organisms: antagonism between molds and microbes), the first known scholarly work to consider the therapeutic capabilities of molds resulting from their anti-microbial activity. In his thesis, Duchesne proposed that bacteria and molds engage in a perpetual battle for survival. Duchesne observed that ''Escherichia coli, E. coli'' was eliminated by ''Penicillium glaucum'' when they were both grown in the same culture. He also observed that when he inoculation, inoculated laboratory animals with lethal doses of typhoid bacilli together with ''Penicillium glaucum'', the animals did not contract typhoid. Unfortunately Duchesne's army service after getting his degree prevented him from doing any further research. Duchesne died of tuberculosis, a disease now treated by antibiotics. In 1928, Sir
Alexander Fleming Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish physician and microbiologist, best known for discovering the enzyme lysozyme and the world's first broadly effective antibiotic substance which he named penicillin. He dis ...

Alexander Fleming
postulated the existence of
penicillin Penicillins (P, PCN or PEN) are a group of originally obtained from ' s, principally ' and '. Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins. A number of natural penicillins have been discov ...

penicillin
, a molecule produced by certain molds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of pathogen, disease-causing bacteria when he noticed the spores of a green mold, ''Penicillium chrysogenum'', in one of his agar plate, culture plates. He observed that the presence of the mold killed or prevented the growth of the bacteria. Fleming postulated that the mold must secrete an antibacterial substance, which he named penicillin in 1928. Fleming believed that its antibacterial properties could be exploited for chemotherapy. He initially characterized some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists. Ernst Chain, Howard Florey and Edward Abraham succeeded in purifying the first penicillin, penicillin G, in 1942, but it did not become widely available outside the Allied military before 1945. Later, Norman Heatley developed the back extraction technique for efficiently purifying penicillin in bulk. The chemical structure of penicillin was first proposed by Abraham in 1942 and then later confirmed by Dorothy Crowfoot Hodgkin in 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. (see below) The development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety. For their successful development of penicillin, which Fleming had accidentally discovered but could not develop himself, as a therapeutic drug, Chain and Florey shared the 1945 Nobel Prize in Medicine with Fleming. Florey credited Rene 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. In 1939, coinciding with the start of World War II, Dubos had reported the discovery of the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and 80% tyrocidine, from ''Bacillus brevis''. It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II. Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also proved too toxic for systemic usage. Research results obtained during that period were not shared between the Axis powers, Axis and the Allied powers of World War II, Allied powers during World War II and limited access during the Cold War.


Late 20th century

During the mid-20th century, the number of new antibiotic substances introduced for medical use increased significantly. From 1935 to 1968, 12 new classes were launched. However, after this, the number of new classes dropped markedly, with only two new classes introduced between 1969 and 2003.


Etymology of the words 'antibiotic' and 'antibacterial'

The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist Jean Paul 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 observed that an airborne bacillus could inhibit the growth of ''Bacillus anthracis''. These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942. The term ''antibiotic'' was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is wikt:antagonism, antagonistic to the growth of other microorganisms in high dilution. This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded chemical synthesis, synthetic antibacterial compounds such as the
sulfonamides In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
. In current usage, the term "antibiotic" is applied to any medication that kills bacteria or inhibits their growth, regardless of whether that medication is produced by a microorganism or not. The term "antibiotic" derives from ''anti'' + βιωτικός (''biōtikos''), "fit for life, lively", which comes from βίωσις (''biōsis''), "way of life", and that from βίος (''bios''), "life". The term "antibacterial" derives from
Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approximately 10.7 million as of ...
ἀντί (''anti''), "against" + βακτήριον (''baktērion''), diminutive of βακτηρία (''baktēria''), "staff, cane", because the first bacteria to be discovered were rod.


Antibiotic pipeline

Both the WHO and the Infectious Disease Society of America report that the weak antibiotic pipeline does not match bacteria's increasing ability to develop resistance.Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, including tuberculosis. Geneva: World Health Organization; 2017 (WHO/EMP/IAU/2017.12). Licence: CC BY-NC-SA 3.0 IGO. The Infectious Disease Society of America report noted that the number of new antibiotics approved for marketing per year had been declining and identified seven antibiotics against the Gram-negative bacilli currently in phases of clinical research#Phase II, phase 2 or phases of clinical research#Phase III, phase 3 clinical trials. However, these drugs did not address the entire spectrum of resistance of Gram-negative bacilli. According to the WHO fifty one new therapeutic entities - antibiotics (including combinations), are in phase 1-3 clinical trials as of May 2017. Antibiotics targeting multidrug-resistant Gram-positive pathogens remains a high priority. A few antibiotics have received marketing authorization in the last seven years. The cephalosporin ceftaroline and the lipoglycopeptides oritavancin and telavancin for the treatment of acute bacterial skin and skin structure infection and community-acquired bacterial pneumonia. The lipoglycopeptide dalbavancin and the oxazolidinone tedizolid has also been approved for use for the treatment of acute bacterial skin and skin structure infection. The first in a new class of narrow spectrum macrocycle, macrocyclic antibiotics, fidaxomicin, has been approved for the treatment of ''C. difficile'' colitis. New cephalosporin-lactamase inhibitor combinations also approved include ceftazidime-avibactam and ceftolozane-avibactam for complicated urinary tract infection and intra-abdominal infection. Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor. In the US, the Antibiotic Development to Advance Patient Treatment (ADAPT) Act was introduced with the aim of fast tracking the drug development of antibiotics to combat the growing threat of 'superbugs'. Under this Act, FDA can approve antibiotics and antifungals treating life-threatening infections based on smaller clinical trials. The Centers for Disease Control and Prevention, CDC will monitor the use of antibiotics and the emerging resistance, and publish the data. The FDA antibiotics labeling process, 'Susceptibility Test Interpretive Criteria for Microbial Organisms' or 'breakpoints', will provide accurate data to healthcare professionals. According to Allan Coukell, senior director for health programs at The Pew Charitable Trusts, "By allowing drug developers to rely on smaller datasets, and clarifying FDA's authority to tolerate a higher level of uncertainty for these drugs when making a risk/benefit calculation, ADAPT would make the clinical trials more feasible."


Replenishing the antibiotic pipeline and developing other new therapies

Because antibiotic-resistant bacterial strains continue to emerge and spread, there is a constant need to develop new antibacterial treatments. Current strategies include traditional chemistry-based approaches such as natural product-based drug discovery, newer chemistry-based approaches such as drug design, traditional biology-based approaches such as immunoglobulin therapy, and experimental biology-based approaches such as phage therapy, fecal microbiota transplants, antisense RNA-based treatments, and CRISPR, CRISPR-Cas9-based treatments.


Natural product-based antibiotic discovery

Most of the antibiotics in current use are natural products or natural product derivatives, and
bacteria Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of prokaryotic microorganisms. Typ ...

bacteria
l, fungal, plant and animal extracts are being screened in the search for new antibiotics. Organisms may be selected for testing based on ecological, ethnomedical, genomic or historical rationales. Medicinal plants, for example, are screened on the basis that they are used by traditional healers to prevent or cure infection and may therefore contain antibacterial compounds. Also, soil bacteria are screened on the basis that, historically, they have been a very rich source of antibiotics (with 70 to 80% of antibiotics in current use derived from the actinomycetes). In addition to screening natural products for direct antibacterial activity, they are sometimes screened for the ability to suppress antimicrobial resistance, antibiotic resistance and antibiotic tolerance. For example, some secondary metabolites inhibit drug efflux pumps, thereby increasing the concentration of antibiotic able to reach its cellular target and decreasing bacterial resistance to the antibiotic. Natural products known to inhibit bacterial efflux pumps include the alkaloid lysergol, the carotenoids capsanthin and capsorubin, and the flavonoids rotenone and chrysin. Other natural products, this time primary metabolites rather than secondary metabolites, have been shown to eradicate antibiotic tolerance. For example, glucose, mannitol, and fructose reduce antibiotic tolerance in ''Escherichia coli'' and ''Staphylococcus aureus'', rendering them more susceptible to killing by
aminoglycoside Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ( ...
antibiotics. Natural products may be screened for the ability to suppress bacterial virulence factors too. Virulence factors are molecules, cellular structures and regulatory systems that enable bacteria to evade the body’s immune defenses (e.g. urease, staphyloxanthin), move towards, attach to, and/or invade human cells (e.g. type IV pili, Bacterial adhesin, adhesins, internalins), coordinate the activation of virulence genes (e.g. quorum sensing), and cause disease (e.g. exotoxins). Examples of natural products with antivirulence activity include the flavonoid epigallocatechin gallate (which inhibits listeriolysin O), the quinone tetrangomycin (which inhibits staphyloxanthin), and the sesquiterpene zerumbone (which inhibits ''Acinetobacter baumannii'' Bacteria#Movement, motility).


Immunoglobulin therapy

Antibodies (anti-tetanus immunoglobulin) have been used in the treatment and prevention of tetanus since the 1910s, and this approach continues to be a useful way of controlling bacterial disease. The monoclonal antibody bezlotoxumab, for example, has been approved by the Food and Drug Administration, US FDA and European Medicines Agency, EMA for recurrent Clostridium difficile infection, ''Clostridium difficile'' infection, and other monoclonal antibodies are in development (e.g. AR-301 for the adjunctive treatment of ''S. aureus'' ventilator-associated pneumonia). Antibody treatments act by binding to and neutralizing bacterial exotoxins and other virulence factors.


Phage therapy

Phage therapy is under investigation as a method of treating antibiotic-resistant strains of bacteria. Phage therapy involves infecting bacterial pathogens with
virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecu ...

virus
es. Bacteriophages and their host ranges are extremely specific for certain bacteria, thus, unlike antibiotics, they do not disturb the host organism’s intestinal microbiota. Bacteriophages, also known simply as phages, infect and kill bacteria primarily during lytic cycles. Phages insert their DNA into the bacterium, where it is transcribed and used to make new phages, after which the cell will lyse, releasing new phage that are able to infect and destroy further bacteria of the same strain. The high specificity of phage protects Mutualism (biology), "good" bacteria from destruction. Some disadvantages to the use of bacteriophages also exist, however. Bacteriophages may harbour virulence factors or toxic genes in their genomes and, prior to use, it may be prudent to identify genes with similarity to known virulence factors or toxins by genomic sequencing. In addition, the oral and intravenous, IV administration of phages for the eradication of bacterial infections poses a much higher safety risk than topical application. Also, there is the additional concern of uncertain immune responses to these large antigenic cocktails. There are considerable Regulation of therapeutic goods, regulatory hurdles that must be cleared for such therapies. Despite numerous challenges, the use of bacteriophages as a replacement for antimicrobial agents against MDR pathogens that no longer respond to conventional antibiotics, remains an attractive option.


Fecal microbiota transplants

Fecal microbiota transplants involve transferring the full intestinal microbiota from a healthy human donor (in the form of feces, stool) to patients with Clostridium difficile infection, ''C. difficile'' infection. Although this procedure has not been officially approved by the Food and Drug Administration, US FDA, its use is permitted under some conditions in patients with antibiotic-resistant ''C. difficile'' infection. Cure rates are around 90%, and work is underway to develop stool biobank, banks, standardized products, and methods of Oral administration, oral delivery.


Antisense RNA-based treatments

Antisense RNA-based treatment (also known as gene silencing therapy) involves (a) identifying bacterial
gene In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mecha ...

gene
s that encode essential proteins (e.g. the ''Pseudomonas aeruginosa'' genes ''acpP'', ''lpxC'', and ''rpsJ''), (b) synthesizing single stranded RNA that is complementary to the messenger RNA, mRNA encoding these essential proteins, and (c) delivering the single stranded RNA to the infection site using cell-penetrating peptides or liposomes. The antisense RNA then Nucleic acid hybridization, hybridizes with the bacterial mRNA and blocks its Translation (biology), translation into the essential protein. Antisense RNA-based treatment has been shown to be effective in ''in vivo'' models of ''P. aeruginosa'' lung infection, pneumonia. In addition to silencing essential bacterial genes, antisense RNA can be used to silence bacterial genes responsible for antibiotic resistance. For example, antisense RNA has been developed that silences the ''S. aureus'' ''mecA'' gene (the gene that encodes modified penicillin-binding protein 2a and renders ''S. aureus'' strains Methicillin-resistant Staphylococcus aureus, methicillin-resistant). Antisense RNA targeting ''mecA'' mRNA has been shown to restore the susceptibility of methicillin-resistant staphylococci to oxacillin in both ''in vitro'' and ''in vivo'' studies.


CRISPR-Cas9-based treatments

In the early 2000s, a system was discovered that enables bacteria to defend themselves against invading viruses. The system, known as CRISPR-Cas9, consists of (a) an enzyme that destroys DNA (the nuclease Cas9) and (b) the DNA sequences of previously encountered viral invaders (CRISPR). These viral DNA sequences enable the nuclease to target foreign (viral) rather than self (bacterial) DNA. Although the function of CRISPR-Cas9 in nature is to protect bacteria, the DNA sequences in the CRISPR component of the system can be modified so that the Cas9 nuclease targets bacterial antimicrobial resistance, resistance genes or bacterial virulence genes instead of viral genes. The modified CRISPR-Cas9 system can then be administered to bacterial pathogens using plasmids or bacteriophages. This approach has successfully been used to Gene silencing, silence antibiotic resistance and reduce the virulence of Shigatoxigenic and verotoxigenic Escherichia coli, enterohemorrhagic ''E. coli'' in an ''in vivo'' model of infection.


Reducing the selection pressure for antibiotic resistance

In addition to developing new antibacterial treatments, it is important to reduce the selection pressure for the emergence and spread of antimicrobial resistance, antibiotic resistance. Strategies to accomplish this include well-established infection control measures such as infrastructure improvement (e.g. less crowded housing), better sanitation (e.g. safe drinking water and food) and vaccine development, other approaches such as antibiotic stewardship, and experimental approaches such as the use of Prebiotic (nutrition), prebiotics and
probiotics Probiotics are live microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organismos'') is any individual contiguous system that e ...
to prevent infection.


Vaccines

Vaccines rely on immune modulation or augmentation. Vaccination either excites or reinforces the immune competence of a host to ward off infection, leading to the activation of macrophages, the production of antibody, antibodies, inflammation, 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 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.


See also


References


Further reading


External links

* {{Authority control Antibiotics, Anti-infective agents Bactericides, .