"Antibacteriaw" redirects here. For oder uses, see Antibacteriaw (disambiguation).
This articwe is about treatment of bacteriaw infection, uh-hah-hah-hah. For anti-tumor antibiotics, see Chemoderapy § Cytotoxic antibiotics.
Testing de susceptibiwity of Staphywococcus aureus to antibiotics by de Kirby-Bauer disk diffusion medod – antibiotics diffuse from antibiotic-containing disks and inhibit growf of S. aureus, resuwting in a zone of inhibition, uh-hah-hah-hah.
An antibiotic is a type of antimicrobiaw substance active against bacteria and is de most important type of antibacteriaw agent for fighting bacteriaw infections. Antibiotic medications are widewy used in de treatment and prevention of such infections. They may eider kiww or inhibit de growf of bacteria. A wimited number of antibiotics awso possess antiprotozoaw activity. Antibiotics are not effective against viruses such as de common cowd or infwuenza; drugs which inhibit viruses are termed antiviraw drugs or antiviraws rader dan antibiotics.
Sometimes, de term antibiotic which means "opposing wife", based on Greek roots, (ἀντι-) anti: "against" and (βίος-) biotic: "wife", is broadwy used to refer to any substance used against microbes, but in de usuaw medicaw usage, antibiotics (such as peniciwwin) are dose produced naturawwy (by one microorganism fighting anoder), whereas nonantibiotic antibacteriaws (such as suwfonamides and antiseptics) are fuwwy syndetic. However, bof cwasses have de same goaw of kiwwing or preventing de growf of microorganisms, and bof are incwuded in antimicrobiaw chemoderapy. "Antibacteriaws" incwude antiseptic drugs, antibacteriaw soaps, and chemicaw disinfectants, whereas antibiotics are an important cwass of antibacteriaws used more specificawwy in medicine and sometimes in wivestock feed.
There's evidence of antibiotic use since ancient times. Many civiwizations used topicaw appwication of mouwdy bread, wif many references to its beneficiaw effects arising from ancient Egypt, China, Serbia, Greece and Rome. The first person to directwy document de use of mouwds to treat infections was John Parkinson (1567–1650). Antibiotics truwy revowutionized medicine in de 20f century. Awexander Fweming (1881–1955) discovered modern day peniciwwin in 1928. After reawizing de great potentiaw dere was in peniciwwin, Fweming pursued de chawwenge of how to market it and transwate it to commerciaw use. Wif hewp from oder biochemists, peniciwwin was finawwy avaiwabwe for widespread use. This was significantwy beneficiaw during wartime. Unfortunatewy, it didn't take wong for resistance to begin, uh-hah-hah-hah.   Effectiveness and easy access have awso wed to deir overuse and some bacteria have devewoped resistance. This has wed to widespread probwems, and de Worwd Heawf Organization have cwassified antimicrobiaw resistance as a "serious dreat [dat] is no wonger a prediction for de future, it is happening right now in every region of de worwd and has de potentiaw to affect anyone, of any age, in any country".
Antibiotics are used to treat or prevent bacteriaw infections, and sometimes protozoan infections. (Metronidazowe is effective against a number of parasitic diseases). When an infection is suspected of being responsibwe for an iwwness but de responsibwe padogen has not been identified, an empiric derapy is adopted. This invowves de administration of a broad-spectrum antibiotic based on de signs and symptoms presented and is initiated pending waboratory resuwts dat can take severaw days.
When de responsibwe padogenic microorganism is awready known or has been identified, definitive derapy can be started. This wiww usuawwy invowve de use of a narrow-spectrum antibiotic. The choice of antibiotic given wiww awso be based on its cost. Identification is criticawwy important as it can reduce de cost and toxicity of de antibiotic derapy and awso reduce de possibiwity of de emergence of antimicrobiaw resistance. To avoid surgery, antibiotics may be given for non-compwicated acute appendicitis.
Antibiotics may be given as a preventive measure and dis is usuawwy wimited to at-risk popuwations such as dose wif a weakened immune system (particuwarwy in HIV cases to prevent pneumonia), dose taking immunosuppressive drugs, cancer patients, and dose having surgery. Their use in surgicaw procedures is to hewp prevent infection of incisions. They have an important rowe in dentaw antibiotic prophywaxis where deir use may prevent bacteremia and conseqwent infective endocarditis. Antibiotics are awso used to prevent infection in cases of neutropenia particuwarwy cancer-rewated.
There are many different routes of administration for antibiotic treatment. Antibiotics are usuawwy taken by mouf. In more severe cases, particuwarwy deep-seated systemic infections, antibiotics can be given intravenouswy or by injection, uh-hah-hah-hah. Where de site of infection is easiwy accessed, antibiotics may be given topicawwy in de form of eye drops onto de conjunctiva for conjunctivitis or ear drops for ear infections and acute cases of swimmer's ear. Topicaw use is awso one of de treatment options for some skin conditions incwuding acne and cewwuwitis. Advantages of topicaw appwication incwude achieving high and sustained concentration of antibiotic at de site of infection; reducing de potentiaw for systemic absorption and toxicity, and totaw vowumes of antibiotic reqwired are reduced, dereby awso reducing de risk of antibiotic misuse. Topicaw antibiotics appwied over certain types of surgicaw wounds have been reported to reduce de risk of surgicaw site infections. However, dere are certain generaw causes for concern wif topicaw administration of antibiotics. Some systemic absorption of de antibiotic may occur; de qwantity of antibiotic appwied is difficuwt to accuratewy dose, and dere is awso de possibiwity of wocaw hypersensitivity reactions or contact dermatitis occurring.
Antibiotic consumption varies widewy between countries. The 'WHO report on surveiwwance of antibiotic consumption' pubwished in 2018 anawysed 2015 data from 65 countries. As measured in defined daiwy doses per 1,000 inhabitants per day. Mongowia had de highest consumption wif a rate of 64.4. Burundi had de wowest at 4.4. Amoxiciwwin and Amoxiciwwin/cwavuwanic acid were de most freqwentwy consumed.
Heawf advocacy messages such as dis one encourage patients to tawk wif deir doctor about safety in using antibiotics.
Antibiotics are screened for any negative effects before deir approvaw for cwinicaw use, and are usuawwy considered safe and weww towerated. However, some antibiotics have been associated wif a wide extent of adverse side effects ranging from miwd to very severe depending on de type of antibiotic used, de microbes targeted, and de individuaw patient. Side effects may refwect de pharmacowogicaw or toxicowogicaw properties of de antibiotic or may invowve hypersensitivity or awwergic reactions. Adverse effects range from fever and nausea to major awwergic reactions, incwuding photodermatitis and anaphywaxis. Safety profiwes of newer drugs are often not as weww estabwished as for dose dat have a wong history of use.
Common side-effects incwude diarrhea, resuwting from disruption of de species composition in de intestinaw fwora, resuwting, for exampwe, in overgrowf of padogenic bacteria, such as Cwostridium difficiwe. Antibacteriaws can awso affect de vaginaw fwora, and may wead to overgrowf of yeast species of de genus Candida in de vuwvo-vaginaw area. Additionaw side-effects can resuwt from interaction wif oder drugs, such as de possibiwity of tendon damage from de administration of a qwinowone antibiotic wif a systemic corticosteroid.
Exposure to antibiotics earwy in wife is associated wif increased body mass in humans and mouse modews. Earwy wife is a criticaw period for de estabwishment of de intestinaw microbiota and for metabowic devewopment. Mice exposed to subderapeutic antibiotic treatment (STAT)– wif eider peniciwwin, vancomycin, or chwortetracycwine had awtered composition of de gut microbiota as weww as its metabowic capabiwities. One study has reported dat mice given wow-dose peniciwwin (1 μg/g body weight) around birf and droughout de weaning process had an increased body mass and fat mass, accewerated growf, and increased hepatic expression of genes invowved in adipogenesis, compared to controw mice. In addition, peniciwwin in combination wif a high-fat diet increased fasting insuwin wevews in mice. However, it is uncwear wheder or not antibiotics cause obesity in humans. Studies have found a correwation between earwy exposure of antibiotics (<6 monds) and increased body mass (at 10 and 20 monds). Anoder study found dat de type of antibiotic exposure was awso significant wif de highest risk of being overweight in dose given macrowides compared to peniciwwin and cephawosporin. Therefore, dere is correwation between antibiotic exposure in earwy wife and obesity in humans, but wheder or not dere is a causaw rewationship remains uncwear. Awdough dere is a correwation between antibiotic use in earwy wife and obesity, de effect of antibiotics on obesity in humans needs to be weighed against de beneficiaw effects of cwinicawwy indicated treatment wif antibiotics in infancy.
There are few weww-controwwed studies on wheder antibiotic use increases de risk of oraw contraceptive faiwure. The majority of studies indicate antibiotics do not interfere wif birf controw piwws, such as cwinicaw studies dat suggest de faiwure rate of contraceptive piwws caused by antibiotics is very wow (about 1%). Situations dat may increase de risk of oraw contraceptive faiwure incwude non-compwiance (missing taking de piww), vomiting, or diarrhea. Gastrointestinaw disorders or interpatient variabiwity in oraw contraceptive absorption affecting edinywestradiow serum wevews in de bwood. Women wif menstruaw irreguwarities may be at higher risk of faiwure and shouwd be advised to use backup contraception during antibiotic treatment and for one week after its compwetion, uh-hah-hah-hah. If patient-specific risk factors for reduced oraw contraceptive efficacy are suspected, backup contraception is recommended.
In cases where antibiotics have been suggested to affect de efficiency of birf controw piwws, such as for de broad-spectrum antibiotic rifampicin, dese cases may be due to an increase in de activities of hepatic wiver enzymes' causing increased breakdown of de piww's active ingredients. Effects on de intestinaw fwora, which might resuwt in reduced absorption of estrogens in de cowon, have awso been suggested, but such suggestions have been inconcwusive and controversiaw. Cwinicians have recommended dat extra contraceptive measures be appwied during derapies using antibiotics dat are suspected to interact wif oraw contraceptives. More studies on de possibwe interactions between antibiotics and birf controw piwws (oraw contraceptives) are reqwired as weww as carefuw assessment of patient-specific risk factors for potentiaw oraw contractive piww faiwure prior to dismissing de need for backup contraception, uh-hah-hah-hah.
Interactions between awcohow and certain antibiotics may occur and may cause side-effects and decreased effectiveness of antibiotic derapy. Whiwe moderate awcohow consumption is unwikewy to interfere wif many common antibiotics, dere are specific types of antibiotics, wif which awcohow consumption may cause serious side-effects. Therefore, potentiaw risks of side-effects and effectiveness depend on de type of antibiotic administered.
Antibiotics such as metronidazowe, tinidazowe, cephamandowe, watamoxef, cefoperazone, cefmenoxime, and furazowidone, cause a disuwfiram-wike chemicaw reaction wif awcohow by inhibiting its breakdown by acetawdehyde dehydrogenase, which may resuwt in vomiting, nausea, and shortness of breaf. In addition, de efficacy of doxycycwine and erydromycin succinate may be reduced by awcohow consumption, uh-hah-hah-hah. Oder effects of awcohow on antibiotic activity incwude awtered activity of de wiver enzymes dat break down de antibiotic compound. However, red wine wif a high degree of powyphenows demonstrates in-vitro antibacteriaw properties.
The successfuw outcome of antimicrobiaw derapy wif antibacteriaw compounds depends on severaw factors. These incwude host defense mechanisms, de wocation of infection, and de pharmacokinetic and pharmacodynamic properties of de antibacteriaw. A bactericidaw activity of antibacteriaws may depend on de bacteriaw growf phase, and it often reqwires ongoing metabowic activity and division of bacteriaw cewws. These findings are based on waboratory studies, and in cwinicaw settings have awso been shown to ewiminate bacteriaw infection, uh-hah-hah-hah. Since de activity of antibacteriaws depends freqwentwy on its concentration, in vitro characterization of antibacteriaw activity commonwy incwudes de determination of de minimum inhibitory concentration and minimum bactericidaw concentration of an antibacteriaw. To predict cwinicaw outcome, de antimicrobiaw activity of an antibacteriaw is usuawwy combined wif its pharmacokinetic profiwe, and severaw pharmacowogicaw parameters are used as markers of drug efficacy.
In important infectious diseases, incwuding tubercuwosis, combination derapy (i.e., de concurrent appwication of two or more antibiotics) has been used to deway or prevent de emergence of resistance. In acute bacteriaw infections, antibiotics as part of combination derapy are prescribed for deir synergistic effects to improve treatment outcome as de combined effect of bof antibiotics is better dan deir individuaw effect. Mediciwwin-resistant Staphywococcus aureus infections may be treated wif a combination derapy of fusidic acid and rifampicin, uh-hah-hah-hah. Antibiotics used in combination may awso be antagonistic and de combined effects of de two antibiotics may be wess dan if de individuaw antibiotic was given as part of a monoderapy. For exampwe, chworamphenicow and tetracycwines are antagonists to peniciwwins and aminogwycosides. However, dis can vary depending on de species of bacteria. In generaw, combinations of a bacteriostatic antibiotic and bactericidaw antibiotic are antagonistic.
Antibiotics are commonwy cwassified based on deir mechanism of action, chemicaw structure, or spectrum of activity. Most target bacteriaw functions or growf processes. Those dat target de bacteriaw ceww waww (peniciwwins and cephawosporins) or de ceww membrane (powymyxins), or interfere wif essentiaw bacteriaw enzymes (rifamycins, wipiarmycins, qwinowones, and suwfonamides) have bactericidaw activities. Protein syndesis inhibitors (macrowides, wincosamides, and tetracycwines) are usuawwy bacteriostatic (wif de exception of bactericidaw aminogwycosides). Furder categorization is based on deir target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as gram-negative or gram-positive, whereas broad-spectrum antibiotics affect a wide range of bacteria. Fowwowing a 40-year break in discovering new cwasses of antibacteriaw compounds, four new cwasses of antibiotics have been brought into cwinicaw use in de wate 2000s and earwy 2010s: cycwic wipopeptides (such as daptomycin), gwycywcycwines (such as tigecycwine), oxazowidinones (such as winezowid), and wipiarmycins (such as fidaxomicin).
Wif advances in medicinaw chemistry, most modern antibacteriaws are semisyndetic modifications of various naturaw compounds. These incwude, for exampwe, de beta-wactam antibiotics, which incwude de peniciwwins (produced by fungi in de genus Peniciwwium), de cephawosporins, and de carbapenems. Compounds dat are stiww isowated from wiving organisms are de aminogwycosides, whereas oder antibacteriaws—for exampwe, de suwfonamides, de qwinowones, and de oxazowidinones—are produced sowewy by chemicaw syndesis. Many antibacteriaw compounds are rewativewy smaww mowecuwes wif a mowecuwar weight of wess dan 1000 dawtons.
Since de first pioneering efforts of Howard Fworey and Chain in 1939, de importance of antibiotics, incwuding antibacteriaws, to medicine has wed to intense research into producing antibacteriaws at warge scawes. Fowwowing screening of antibacteriaws against a wide range of bacteria, production of de active compounds is carried out using fermentation, usuawwy in strongwy aerobic conditions.
The emergence of resistance of bacteria to antibiotics is a common phenomenon, uh-hah-hah-hah. Emergence of resistance often refwects evowutionary processes dat take pwace during antibiotic derapy. The antibiotic treatment may sewect for bacteriaw strains wif physiowogicawwy or geneticawwy enhanced capacity to survive high doses of antibiotics. Under certain conditions, it may resuwt in preferentiaw growf of resistant bacteria, whiwe growf of susceptibwe bacteria is inhibited by de drug. For exampwe, antibacteriaw sewection for strains having previouswy acqwired antibacteriaw-resistance genes was demonstrated in 1943 by de Luria–Dewbrück experiment. Antibiotics such as peniciwwin and erydromycin, which used to have a high efficacy against many bacteriaw species and strains, have become wess effective, due to de increased resistance of many bacteriaw strains.
Resistance may take de form of biodegredation of pharmaceuticaws, such as suwfamedazine-degrading soiw bacteria introduced to suwfamedazine drough medicated pig feces. The survivaw of bacteria often resuwts from an inheritabwe resistance, but de growf of resistance to antibacteriaws awso occurs drough horizontaw gene transfer. Horizontaw transfer is more wikewy to happen in wocations of freqwent antibiotic use.
Antibacteriaw resistance may impose a biowogicaw cost, dereby reducing fitness of resistant strains, which can wimit de spread of antibacteriaw-resistant bacteria, for exampwe, in de absence of antibacteriaw compounds. Additionaw mutations, however, may compensate for dis fitness cost and can aid de survivaw of dese bacteria.
Paweontowogicaw data show dat bof antibiotics and antibiotic resistance are ancient compounds and mechanisms. Usefuw antibiotic targets are dose for which mutations negativewy impact bacteriaw reproduction or viabiwity.
Severaw mowecuwar mechanisms of antibacteriaw resistance exist. Intrinsic antibacteriaw resistance may be part of de genetic makeup of bacteriaw strains. For exampwe, an antibiotic target may be absent from de bacteriaw genome. Acqwired resistance resuwts from a mutation in de bacteriaw chromosome or de acqwisition of extra-chromosomaw DNA. Antibacteriaw-producing bacteria have evowved resistance mechanisms dat have been shown to be simiwar to, and may have been transferred to, antibacteriaw-resistant strains. The spread of antibacteriaw resistance often occurs drough verticaw transmission of mutations during growf and by genetic recombination of DNA by horizontaw genetic exchange. For instance, antibacteriaw resistance genes can be exchanged between different bacteriaw strains or species via pwasmids dat carry dese resistance genes. Pwasmids dat carry severaw different resistance genes can confer resistance to muwtipwe antibacteriaws. Cross-resistance to severaw antibacteriaws may awso occur when a resistance mechanism encoded by a singwe gene conveys resistance to more dan one antibacteriaw compound.
Antibacteriaw-resistant strains and species, sometimes referred to as "superbugs", now contribute to de emergence of diseases dat were for a whiwe weww controwwed. For exampwe, emergent bacteriaw strains causing tubercuwosis dat are resistant to previouswy effective antibacteriaw treatments pose many derapeutic chawwenges. Every year, nearwy hawf a miwwion new cases of muwtidrug-resistant tubercuwosis (MDR-TB) are estimated to occur worwdwide. For exampwe, NDM-1 is a newwy identified enzyme conveying bacteriaw resistance to a broad range of beta-wactam antibacteriaws. The United Kingdom's Heawf Protection Agency has stated dat "most isowates wif NDM-1 enzyme are resistant to aww standard intravenous antibiotics for treatment of severe infections." On 26 May 2016 an E cowi bacteria "superbug" was identified in de United States resistant to cowistin, "de wast wine of defence" antibiotic.
This poster from de US Centers for Disease Controw and Prevention "Get Smart" campaign, intended for use in doctors' offices and oder heawdcare faciwities, warns dat antibiotics do not work for viraw iwwnesses such as de common cowd.
Per The ICU Book "The first ruwe of antibiotics is try not to use dem, and de second ruwe is try not to use too many of dem." Inappropriate antibiotic treatment and overuse of antibiotics have contributed to de emergence of antibiotic-resistant bacteria. Sewf-prescribing of antibiotics is an exampwe of misuse. Many antibiotics are freqwentwy prescribed to treat symptoms or diseases dat do not respond to antibiotics or dat are wikewy to resowve widout treatment. Awso, incorrect or suboptimaw antibiotics are prescribed for certain bacteriaw infections. The overuse of antibiotics, wike peniciwwin and erydromycin, has been associated wif emerging antibiotic resistance since de 1950s. Widespread usage of antibiotics in hospitaws has awso been associated wif increases in bacteriaw strains and species dat no wonger respond to treatment wif de most common antibiotics.
Common forms of antibiotic misuse incwude excessive use of prophywactic antibiotics in travewers and faiwure of medicaw professionaws to prescribe de correct dosage of antibiotics on de basis of de patient's weight and history of prior use. Oder forms of misuse incwude faiwure to take de entire prescribed course of de antibiotic, incorrect dosage and administration, or faiwure to rest for sufficient recovery. Inappropriate antibiotic treatment, for exampwe, is deir prescription to treat viraw infections such as de common cowd. One study on respiratory tract infections found "physicians were more wikewy to prescribe antibiotics to patients who appeared to expect dem". Muwtifactoriaw interventions aimed at bof physicians and patients can reduce inappropriate prescription of antibiotics.
Severaw organizations concerned wif antimicrobiaw resistance are wobbying to ewiminate de unnecessary use of antibiotics. The issues of misuse and overuse of antibiotics have been addressed by de formation of de US Interagency Task Force on Antimicrobiaw Resistance. This task force aims to activewy address antimicrobiaw resistance, and is coordinated by de US Centers for Disease Controw and Prevention, de Food and Drug Administration (FDA), and de Nationaw Institutes of Heawf (NIH), as weww as oder US agencies. An NGO campaign group is Keep Antibiotics Working. In France, an "Antibiotics are not automatic" government campaign started in 2002 and wed to a marked reduction of unnecessary antibiotic prescriptions, especiawwy in chiwdren, uh-hah-hah-hah.
The emergence of antibiotic resistance has prompted restrictions on deir use in de UK in 1970 (Swann report 1969), and de EU has banned de use of antibiotics as growf-promotionaw agents since 2003. Moreover, severaw organizations (incwuding de Worwd Heawf Organization, de Nationaw Academy of Sciences, and de U.S. Food and Drug Administration) have advocated restricting de amount of antibiotic use in food animaw production, uh-hah-hah-hah. However, commonwy dere are deways in reguwatory and wegiswative actions to wimit de use of antibiotics, attributabwe partwy to resistance against such reguwation by industries using or sewwing antibiotics, and to de time reqwired for research to test causaw winks between deir use and resistance to dem. Two federaw biwws (S.742 and H.R. 2562) aimed at phasing out nonderapeutic use of antibiotics in US food animaws were proposed, but have not passed. These biwws were endorsed by pubwic heawf and medicaw organizations, incwuding de American Howistic Nurses' Association, de American Medicaw Association, and de American Pubwic Heawf Association (APHA).
Despite pwedges by food companies and restaurants to reduce or ewiminate meat dat comes from animaws treated wif antibiotics, de purchase of antibiotics for use on farm animaws has been increasing every year.
There has been extensive use of antibiotics in animaw husbandry. In de United States, de qwestion of emergence of antibiotic-resistant bacteriaw strains due to use of antibiotics in wivestock was raised by de US Food and Drug Administration (FDA) in 1977. In March 2012, de United States District Court for de Soudern District of New York, ruwing in an action brought by de Naturaw Resources Defense Counciw and oders, ordered de FDA to revoke approvaws for de use of antibiotics in wivestock, which viowated FDA reguwations.
Before de earwy 20f century, treatments for infections were based primariwy on medicinaw fowkwore. Mixtures wif antimicrobiaw properties dat were used in treatments of infections were described over 2,000 years ago. Many ancient cuwtures, incwuding de ancient Egyptians and ancient Greeks, used speciawwy sewected mowd and pwant materiaws and extracts to treat infections.
The use of antibiotics in modern medicine began wif de discovery of syndetic antibiotics derived from dyes.
Arsphenamine, awso known as sawvarsan, discovered in 1907 by Pauw Ehrwich.
Syndetic antibiotic chemoderapy as a science and devewopment of antibacteriaws began in Germany wif Pauw Ehrwich in de wate 1880s. Ehrwich noted certain dyes wouwd cowor human, animaw, or bacteriaw cewws, whereas oders did not. He den proposed de idea dat it might be possibwe to create chemicaws dat wouwd act as a sewective drug dat wouwd bind to and kiww bacteria widout harming de human host. After screening hundreds of dyes against various organisms, in 1907, he discovered a medicinawwy usefuw drug, de first syndetic antibacteriaw sawvarsan now cawwed arsphenamine.
The era of antibacteriaw treatment began wif de discoveries of arsenic-derived syndetic antibiotics by Awfred Berdeim and Ehrwich in 1907. Ehrwich and Berdeim experimented wif various chemicaws derived from dyes to treat trypanosomiasis in mice and spirochaeta infection in rabbits. Whiwe deir earwy compounds were too toxic, Ehrwich and Sahachiro Hata, a Japanese bacteriowogist working wif Erwich in de qwest for a drug to treat syphiwis, achieved success wif de 606f compound in deir series of experiments. In 1910 Ehrwich and Hata announced deir discovery, which dey cawwed drug "606", at de Congress for Internaw Medicine at Wiesbaden. The Hoechst company began to market de compound toward de end of 1910 under de name Sawvarsan, uh-hah-hah-hah. This drug is now known as arsphenamine. The drug was used to treat syphiwis in de first hawf of de 20f century. In 1908, Ehrwich received de Nobew Prize in Physiowogy or Medicine for his contributions to immunowogy. Hata was nominated for de Nobew Prize in Chemistry in 1911 and for de Nobew Prize in Physiowogy or Medicine in 1912 and 1913.
The first suwfonamide and de first systemicawwy active antibacteriaw drug, Prontosiw, was devewoped by a research team wed by Gerhard Domagk in 1932 or 1933 at de Bayer Laboratories of de IG Farben congwomerate in Germany, for which Domagk received de 1939 Nobew Prize in Physiowogy or Medicine. Suwfaniwamide, de active drug of Prontosiw, was not patentabwe as it had awready been in use in de dye industry for some years. Prontosiw had a rewativewy broad effect against Gram-positive cocci, but not against enterobacteria. Research was stimuwated apace by its success. The discovery and devewopment of dis suwfonamide drug opened de era of antibacteriaws.
Observations about de growf of some microorganisms inhibiting de growf of oder microorganisms have been reported since de wate 19f century. These observations of antibiosis between microorganisms wed to de discovery of naturaw antibacteriaws. Louis Pasteur observed, "if we couwd intervene in de antagonism observed between some bacteria, it wouwd offer perhaps de greatest hopes for derapeutics".
In 1874, physician Sir Wiwwiam Roberts noted dat cuwtures of de mowd Peniciwwium gwaucum dat is used in de making of some types of bwue cheese did not dispway bacteriaw contamination, uh-hah-hah-hah. In 1876, physicist John Tyndaww awso contributed to dis fiewd. Pasteur conducted research showing dat Baciwwus andracis wouwd not grow in de presence of de rewated mowd Peniciwwium notatum.
In 1895 Vincenzo Tiberio, Itawian physician, pubwished a paper on de antibacteriaw power of some extracts of mowd.
In 1897, doctoraw student Ernest Duchesne submitted a dissertation, "Contribution à w'étude de wa concurrence vitawe chez wes micro-organismes: antagonisme entre wes moisissures et wes microbes" (Contribution to de study of vitaw competition in micro-organisms: antagonism between mowds and microbes), de first known schowarwy work to consider de derapeutic capabiwities of mowds resuwting from deir anti-microbiaw activity. In his desis, Duchesne proposed dat bacteria and mowds engage in a perpetuaw battwe for survivaw. Duchesne observed dat E. cowi was ewiminated by Peniciwwium gwaucum when dey were bof grown in de same cuwture. He awso observed dat when he inocuwated waboratory animaws wif wedaw doses of typhoid baciwwi togeder wif Peniciwwium gwaucum, de animaws did not contract typhoid. Unfortunatewy Duchesne's army service after getting his degree prevented him from doing any furder research. Duchesne died of tubercuwosis, a disease now treated by antibiotics.
In 1928, Sir Awexander Fweming postuwated de existence of peniciwwin, a mowecuwe produced by certain mowds dat kiwws or stops de growf of certain kinds of bacteria. Fweming was working on a cuwture of disease-causing bacteria when he noticed de spores of a green mowd, Peniciwwium chrysogenum, in one of his cuwture pwates. He observed dat de presence of de mowd kiwwed or prevented de growf of de bacteria. Fweming postuwated dat de mowd must secrete an antibacteriaw substance, which he named peniciwwin in 1928. Fweming bewieved dat its antibacteriaw properties couwd be expwoited for chemoderapy. He initiawwy characterized some of its biowogicaw properties, and attempted to use a crude preparation to treat some infections, but he was unabwe to pursue its furder devewopment widout de aid of trained chemists.
Ernst Chain, Howard Fworey and Edward Abraham succeeded in purifying de first peniciwwin, peniciwwin G, in 1942, but it did not become widewy avaiwabwe outside de Awwied miwitary before 1945. Later, Norman Heatwey devewoped de back extraction techniqwe for efficientwy purifying peniciwwin in buwk. The chemicaw structure of peniciwwin was first proposed by Abraham in 1942 and den water confirmed by Dorody Crowfoot Hodgkin in 1945. Purified peniciwwin dispwayed potent antibacteriaw activity against a wide range of bacteria and had wow toxicity in humans. Furdermore, its activity was not inhibited by biowogicaw constituents such as pus, unwike de syndetic suwfonamides. (see bewow) The devewopment of peniciwwin wed to renewed interest in de search for antibiotic compounds wif simiwar efficacy and safety. For deir successfuw devewopment of peniciwwin, which Fweming had accidentawwy discovered but couwd not devewop himsewf, as a derapeutic drug, Chain and Fworey shared de 1945 Nobew Prize in Medicine wif Fweming.
Fworey credited Rene Dubos wif pioneering de approach of dewiberatewy and systematicawwy searching for antibacteriaw compounds, which had wed to de discovery of gramicidin and had revived Fworey's research in peniciwwin, uh-hah-hah-hah. In 1939, coinciding wif de start of Worwd War II, Dubos had reported de discovery of de first naturawwy derived antibiotic, tyrodricin, a compound of 20% gramicidin and 80% tyrocidine, from B. brevis. It was one of de first commerciawwy manufactured antibiotics and was very effective in treating wounds and uwcers during Worwd War II. Gramicidin, however, couwd not be used systemicawwy because of toxicity. Tyrocidine awso proved too toxic for systemic usage. Research resuwts obtained during dat period were not shared between de Axis and de Awwied powers during Worwd War II and wimited access during de Cowd War.
The term 'antibiosis', meaning "against wife", was introduced by de French bacteriowogist Jean Pauw Vuiwwemin as a descriptive name of de phenomenon exhibited by dese earwy antibacteriaw drugs. Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed dat an airborne baciwwus couwd inhibit de growf of Baciwwus andracis. These drugs were water renamed antibiotics by Sewman Waksman, an American microbiowogist, in 1942.
The term antibiotic was first used in 1942 by Sewman Waksman and his cowwaborators in journaw articwes to describe any substance produced by a microorganism dat is antagonistic to de growf of oder microorganisms in high diwution, uh-hah-hah-hah. This definition excwuded substances dat kiww bacteria but dat are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It awso excwuded syndetic antibacteriaw compounds such as de suwfonamides. In current usage, de term "antibiotic" is appwied to any medication dat kiwws bacteria or inhibits deir growf, regardwess of wheder dat medication is produced by a microorganism or not.
The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for wife, wivewy", which comes from βίωσις (biōsis), "way of wife", and dat from βίος (bios), "wife". The term "antibacteriaw" derives from Greek ἀντί (anti), "against" + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane", because de first bacteria to be discovered were rod-shaped.
The increase in bacteriaw strains dat are resistant to conventionaw antibacteriaw derapies togeder wif decreasing number of new antibiotics currentwy being devewoped in de drug pipewine has prompted de devewopment of bacteriaw disease treatment strategies dat are awternatives to conventionaw antibacteriaws. Non-compound approaches (dat is, products oder dan cwassicaw antibacteriaw agents) dat target bacteria or approaches dat target de host incwuding phage derapy and vaccines are awso being investigated to combat de probwem.
Metabowic stimuwi such as sugar can hewp eradicate a certain type of antibiotic-towerant bacteria by keeping deir metabowism active.
Vaccines rewy on immune moduwation or augmentation, uh-hah-hah-hah. Vaccination eider excites or reinforces de immune competence of a host to ward off infection, weading to de activation of macrophages, de production of antibodies, infwammation, and oder cwassic immune reactions. Antibacteriaw vaccines have been responsibwe for a drastic reduction in gwobaw bacteriaw diseases. Vaccines made from attenuated whowe cewws or wysates have been repwaced wargewy by wess reactogenic, ceww-free vaccines consisting of purified components, incwuding capsuwar powysaccharides and deir conjugates, to protein carriers, as weww as inactivated toxins (toxoids) and proteins.
Phage derapy is anoder medod for treating antibiotic-resistant strains of bacteria. Phage derapy infects padogenic bacteria wif deir own viruses. Bacteriophages and deir host ranges are extremewy specific for certain bacteria, dus dey do not disturb de host organism and intestinaw microfwora unwike antibiotics. Bacteriophages, awso known simpwy as phages, infect and can kiww bacteria and affect bacteriaw growf primariwy during wytic cycwes. Phages insert deir DNA into de bacterium, where it is transcribed and used to make new phages, after which de ceww wiww wyse, reweasing new phage abwe to infect and destroy furder bacteria of de same strain, uh-hah-hah-hah. The high specificity of phage protects "good" bacteria from destruction, uh-hah-hah-hah. However, some disadvantages to use of bacteriophages awso exist. Bacteriophages may harbour viruwence factors or toxic genes in deir genomes and identification of genes wif simiwarity to known viruwence factors or toxins by genomic seqwencing may be prudent prior to use. In addition, de oraw and IV administration of phages for de eradication of bacteriaw infections poses a much higher safety risk dan topicaw appwication, and dere is de additionaw concern of uncertain immune responses to dese warge antigenic cocktaiws. There are considerabwe reguwatory hurdwes dat must be cweared for such derapies. The use of bacteriophages as a repwacement for antimicrobiaw agents against MDR padogens no wonger respond to conventionaw antibiotics remains an attractive option despite numerous chawwenges.
Pwants are an important source of antimicrobiaw compounds and traditionaw heawers have wong used pwants to prevent or cure infectious diseases. There is a recent renewed interest into de use of naturaw products for de identification of new members of de 'antibiotic-ome' (defined as naturaw products wif antibiotic activity), and deir appwication in antibacteriaw drug discovery in de genomics era. Phytochemicaws are de active biowogicaw component of pwants and some phytochemicaws incwuding tannins, awkawoids, terpenoids, and fwavonoids possess antimicrobiaw activity. Some antioxidant dietary suppwements awso contain phytochemicaws (powyphenows), such as grape seed extract, and demonstrate in vitro anti-bacteriaw properties. Phytochemicaws are abwe to inhibit peptidogwycan syndesis, damage microbiaw membrane structures, modify bacteriaw membrane surface hydrophobicity and awso moduwate qworum sensing. Wif increasing antibiotic resistance in recent years, de potentiaw of new pwant-derived antibiotics is under investigation, uh-hah-hah-hah.
Bof de WHO and de Infectious Disease Society of America (IDSA) reported dat de weak antibiotic pipewine does not match bacteria's increasing abiwity to devewop resistance. The IDSA report noted dat de number of new antibiotics approved for marketing per year had been decwining and identified seven antibiotics against de Gram-negative baciwwi (GNB) currentwy in phase 2 or phase 3 cwinicaw triaws. These drugs however, did not address de entire spectrum of resistance of GNB. According to de WHO fifty one new derapeutic entities (NTEs) - antibiotics (incwuding combinations), are in phase 1-3 cwinicaw triaws as of May 2017. Recent entries in de cwinicaw pipewine targeting muwtidrug-resistant Gram-positive padogens has improved de treatment options due to marketing approvaw of new antibiotic cwasses, de oxazowidinones and cycwic wipopeptides. However, resistance to dese antibiotics is certainwy wikewy to occur, de need for de devewopment new antibiotics against dose padogens stiww remains a high priority. Recent drugs in devewopment dat target Gram-negative bacteria have focused on re-working existing drugs to target specific microorganisms or specific types of resistance.
A few antibiotics have received marketing audorization in de wast seven years. The cephawosporin ceftarowine and de wipogwycopeptides oritavancin and tewavancin for de treatment of acute bacteriaw skin and skin structure infection and community-acqwired bacteriaw pneumonia. The wipogwycopeptide dawbavancin and de oxazowidinone tedizowid has awso been approved for use for de treatment of acute bacteriaw skin and skin structure infection, uh-hah-hah-hah. The first in a new cwass of narrow spectrum macrocycwic antibiotics, fidaxomicin, has been approved for de treatment of C. difficiwe cowitis. New cephawosporin-wactamase inhibitor combinations awso approved incwude ceftazidime-avibactam and ceftowozane-avibactam for compwicated urinary tract infection and intra-abdominaw infection, uh-hah-hah-hah.
Ceftowozane/tazobactam (CXA-201; CXA-101/tazobactam): Antipseudomonaw cephawosporin/β-wactamase inhibitor combination (ceww waww syndesis inhibitor). FDA approved on 19 December 2014.
Ceftazidime/avibactam (ceftazidime/NXL104): Antipseudomonaw cephawosporin/β-wactamase inhibitor combination (ceww waww syndesis inhibitor). In phase 3.
Imipenem/MK-7655: Carbapenem/ β-wactamase inhibitor combination (ceww waww syndesis inhibitor). In phase 2.
Pwazomicin (ACHN-490): Aminogwycoside (protein syndesis inhibitor). New Drug Appwication is under Priority Review by U.S. FDA.
Eravacycwine (TP-434): Syndetic tetracycwine derivative / protein syndesis inhibitor targeting de ribosome. Devewopment by Tetraphase, Phase 2 triaws compwete.
Briwacidin (PMX-30063): Peptide defense protein mimetic (ceww membrane disruption). In phase 2.
Streptomyces research is expected to provide new antibiotics, incwuding treatment against MRSA and infections resistant to commonwy used medication, uh-hah-hah-hah. Efforts of John Innes Centre and universities in de UK, supported by BBSRC, resuwted in de creation of spin-out companies, for exampwe Novacta Biosystems, which has designed de type-b wantibiotic-based compound NVB302 (in phase 1) to treat Cwostridium difficiwe infections.
Possibwe improvements incwude cwarification of cwinicaw triaw reguwations by FDA. Furdermore, appropriate economic incentives couwd persuade pharmaceuticaw companies to invest in dis endeavor. In de US, de Antibiotic Devewopment to Advance Patient Treatment (ADAPT) Act was introduced wif de aim of fast tracking de drug devewopment of antibiotics to combat de growing dreat of 'superbugs'. Under dis Act, FDA can approve antibiotics and antifungaws treating wife-dreatening infections based on smawwer cwinicaw triaws. The CDC wiww monitor de use of antibiotics and de emerging resistance, and pubwish de data. The FDA antibiotics wabewing process, 'Susceptibiwity Test Interpretive Criteria for Microbiaw Organisms' or 'breakpoints', wiww provide accurate data to heawdcare professionaws. According to Awwan Coukeww, senior director for heawf programs at The Pew Charitabwe Trusts, "By awwowing drug devewopers to rewy on smawwer datasets, and cwarifying FDA's audority to towerate a higher wevew of uncertainty for dese drugs when making a risk/benefit cawcuwation, ADAPT wouwd make de cwinicaw triaws more feasibwe."
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This page was wast edited on 20 Apriw 2019, at 20:02 (UTC).


text:
Best Mosques in Ho Chi Minh City
By: Rastian Gauna
Ho Chi Minh City has a healthy respect towards all religions. In fact, anywhere around Vietnam is generally accepting and courteous of other religions. It's simply never an issue here. Social and religious tolerance seems to be part of the Vietnamese psyche.
The earliest recorded introduction of Islam in the country is in the late 10th century. The main group of Muslim people in Vietnam are the Cham people, one of Vietnam's ethnic minority groups. These make up about 65% of the Muslim population. Almost 80% of Vietnam's Muslims live in the Southwest of the country.
Image source: Jamia Al Muslimin Mosque
If you go to visit a mosque remember that strict codes of dress and behaviour are demanded. Always dress modestly and keep legs and shoulders covered. It is important that you remove your shoes at the entrance. Also check times of certain important prayer meetings. These are fascinating buildings and an important part of the fabric of Ho Chi Minh City's society.
The city has Buddhists, Christians and Muslims in good numbers, all living in harmony with one another. The Buddhist temples and Christian Churches are dotted everywhere, it is hard to miss them. So, where are the mosques in Ho Chi Minh City?
Saigon Central Mosque (Jamia Al Muslimin Mosque)
66 Dong Du, D1
Opening Hours: 8:00 am to 9:00 pm every day
The most prominent mosque in Ho Chi Minh City is the Jamia Al Muslimin Mosque right in the centre of town. The mosque is located on Dong Du, a small street that runs between Hai Ba Trung and Dong Khoi. It is possible to walk past without noticing. Jamia Al Muslimin Mosque was built in the 1930s by South Indian Muslim expatriates, originally meant as a place of worship exclusively from Southern India. These days, Muslims around the globe are allowed to visit to worship and practice their belief. You may also pay a visit if you wish to learn more about Muslim culture as it also features beautiful architecture. Remember to be respectful when you visit as it is intended to be a solemn place for people to worship.
Image source: hochiminhcityhighlights.com
If you get hungry, you can also find halal food available right outside the mosque. There are also shaded verandah and stone floors, where you can sit, read or hang out with your family.
What people are saying: "This blessed place of worship gives off a peaceful and calming vibe. Love visiting here and would recommend it to anyone. Located next to sheraton hotel." - shereenkhan25 | trip advisor
Jamiul Islamiyah
495B Tran Hung Dao, Cau Kho, D1
Jamiul Islamiyah, or sometimes called the Nancy Mosque, is one of the primary mosques in Ho Chi Minh City. It was originally built in 1950 and was reconstructed between1980 and 2003. In 2004, the mosque opened its doors to other Muslim followers.
Image source: virtual-saigon.net
After your visit, you can go around the back alleyways for a meal. Here, you will find a halal restaurant called Pho Muslim which makes a perfect rest stop for a day of exploration.
What people are saying: "The architectural shape outside the façade is quite beautiful, looks different from the usual architecture, the roof has a dome structure, the whole building is painted green and looks cool and adds a special feature to the city." - Minh Tuyền Trần Trương | google.com
Al Rahim Mosque
45 Nam Ky Khoi Nghia, D1
Al Rahim was the first mosque in Vietnam. It was built in 1885 and mainly serves Malaysian and Indonesian groups every weekend. Here you will see pristine architecture and all the noticeable Muslim symbols decorated on its walls and all around the mosque.
Image source: xotourist.com
It is located near the center of the city which makes it easy to visit, and if you get hungry after worship, you can also find halal food nearby.
What people are saying: "Walking distance to Ben Thanh market. Such a pleasure to get to pray in a mosque amidst the shopping spree" - Norrulhuda Taib | google.com
Masjid Niamatul-Islamiyah
360 Cach Mang Thang Tam, D3
This mosque was built in 1952 and it used to accommodate the Vietnamese and Indian migrants. It also welcomes the Cham and Chinese people. Today, there are over 250 Muslims who visit each Friday to worship and perform their Muslim rituals.
Image source: urbanistnetwork.com
What people are saying: "A small mosque but the caretaker of the mosque Mr. ABDUL KAREEM is very kind and generous and also his wife Fatima is very loving and caring. Allah bless both of them Ameen" - Shah Jeeh | google.com
Cho Lon Mosque
641 Nguyen Trai Street, D5
Opening Hours: From Monday to Sunday
Cholon Mosque was built in 1932 and was initially exclusive to the Muslim communities from Southern India. In 1975, the mosque opened its doors to Malaysian and Indonesian Muslims who lived nearby.
Image source: i.pinimg.com
If you're visiting to see the Mihrab - the tiled niche in the wall that indicates the direction of prayer towards Mecca - with your own eyes or just to appreciate the architecture, the best time to go is around lunch or dinner time so you can enjoy tasty halal food at the restaurant on the grounds before or after visiting the mosque.
What people are saying: "Excellent Location! Centrally located in the heart of the city. Really clean and well kept. Makes travelling to the city really worthwhile." - Yusuff W | trip advisor
Masjid Jamiul Anwar
157 Duong Ba Trac, D8
District 8 is where the majority of the Cham people are located in Ho Chi Minh City. The mosque has a narrow alley and might be crowded especially on Fridays when large numbers of Muslims come to worship to the Pillar of Salat.
Image source: angelfire.com
What people are saying: "A nice mosque in a narrow alley. A lot of Muslims in this area, hence you can find many Muslim shops and restaurants." - Huseyin Kizil | google.com
Banner Image source: Jamia Al Muslimin Mosque
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redpajama_set_name: RedPajamaCommonCrawl


Researchers at Palo Alto Networks discovered new malware being used by the Kremlin-backed hacking group Fancy Bear.
Why it matters: The "cannon" malware uses email to communicate with its command and control server. That's not common in malware right now, says Jen Miller-Osborn, deputy director of threat Intelligence for the Palo Alto Networks Unit 42 research team, and doesn't appear to be something Fancy Bear has ever done before.
Details: Cannon is a new early phase of a multi-stage attack — it communicates basic information with command and control servers and downloads new malware.
It has only been observed in a single campaign. The malware was sent to government officials in North America, Europe and a former Soviet state, according to the Palo Alto Networks write-up.
The intrigue: "We don't know if this is a one-off, or a trojan we'll see again," said Miller-Osborn. "So we also don't know if the email technique is a one off, or something they are starting to use."


text:
1 And he made the altar of burnt offering of shittim wood: five cubits was the length thereof, and five cubits the breadth thereof; it was foursquare; and three cubits the height thereof.
2 And he made the horns thereof on the four corners of it; the horns thereof were of the same: and he overlaid it with brass.
3 And he made all the vessels of the altar, the pots, and the shovels, and the basons, and the fleshhooks, and the firepans: all the vessels thereof made he of brass.
4 And he made for the altar a brasen grate of network under the compass thereof beneath unto the midst of it.
5 And he cast four rings for the four ends of the grate of brass, to be places for the staves.
6 And he made the staves of shittim wood, and overlaid them with brass.
7 And he put the staves into the rings on the sides of the altar, to bear it withal; he made the altar hollow with boards.
8 And he made the laver of brass, and the foot of it of brass, of the lookingglasses of the women assembling, which assembled at the door of the tabernacle of the congregation.
9 And he made the court: on the south side southward the hangings of the court were of fine twined linen, an hundred cubits:
10 Their pillars were twenty, and their brasen sockets twenty; the hooks of the pillars and their fillets were of silver.
11 And for the north side the hangings were an hundred cubits, their pillars were twenty, and their sockets of brass twenty; the hooks of the pillars and their fillets of silver.
12 And for the west side were hangings of fifty cubits, their pillars ten, and their sockets ten; the hooks of the pillars and their fillets of silver.
13 And for the east side eastward fifty cubits.
14 The hangings of the one side of the gate were fifteen cubits; their pillars three, and their sockets three.
15 And for the other side of the court gate, on this hand and that hand, were hangings of fifteen cubits; their pillars three, and their sockets three.
16 All the hangings of the court round about were of fine twined linen.
17 And the sockets for the pillars were of brass; the hooks of the pillars and their fillets of silver; and the overlaying of their chapiters of silver; and all the pillars of the court were filleted with silver.
18 And the hanging for the gate of the court was needlework, of blue, and purple, and scarlet, and fine twined linen: and twenty cubits was the length, and the height in the breadth was five cubits, answerable to the hangings of the court.
19 And their pillars were four, and their sockets of brass four; their hooks of silver, and the overlaying of their chapiters and their fillets of silver.
20 And all the pins of the tabernacle, and of the court round about, were of brass.
21 This is the sum of the tabernacle, even of the tabernacle of testimony, as it was counted, according to the commandment of Moses, for the service of the Levites, by the hand of Ithamar, son to Aaron the priest.
22 And Bezaleel the son Uri, the son of Hur, of the tribe of Judah, made all that the LORD commanded Moses.
23 And with him was Aholiab, son of Ahisamach, of the tribe of Dan, an engraver, and a cunning workman, and an embroiderer in blue, and in purple, and in scarlet, and fine linen.
24 All the gold that was occupied for the work in all the work of the holy place, even the gold of the offering, was twenty and nine talents, and seven hundred and thirty shekels, after the shekel of the sanctuary.
25 And the silver of them that were numbered of the congregation was an hundred talents, and a thousand seven hundred and threescore and fifteen shekels, after the shekel of the sanctuary:
26 A bekah for every man, that is, half a shekel, after the shekel of the sanctuary, for every one that went to be numbered, from twenty years old and upward, for six hundred thousand and three thousand and five hundred and fifty men.
27 And of the hundred talents of silver were cast the sockets of the sanctuary, and the sockets of the vail; an hundred sockets of the hundred talents, a talent for a socket.
28 And of the thousand seven hundred seventy and five shekels he made hooks for the pillars, and overlaid their chapiters, and filleted them.
29 And the brass of the offering was seventy talents, and two thousand and four hundred shekels.
30 And therewith he made the sockets to the door of the tabernacle of the congregation, and the brasen altar, and the brasen grate for it, and all the vessels of the altar,
31 And the sockets of the court round about, and the sockets of the court gate, and all the pins of the tabernacle, and all the pins of the court round about.