Question:

What is white oblong pill with 1174 on one side and 93 on other?

Answer:

The pill you are most likely referring to is a 500 mg penicillin V potassium, which is an antibiotic.

More Info:


Penicillin
Penicillin (sometimes abbreviated PCN or pen) is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V. Penicillin antibiotics are historically significant because they are the first drugs that were effective against many previously serious diseases, such as syphilis, and infections caused by staphylococci and streptococci. Penicillins are still widely used today, though many types of bacteria are now resistant. All penicillins are β-lactam antibiotics and are used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The term "penicillin" is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V). Procaine penicillin and benzathine penicillin have the same antibacterial activity as benzylpenicillin but act for a longer time span. Phenoxymethylpenicillin is less active against Gram-negative bacteria than benzylpenicillin. Benzylpenicillin, procaine penicillin and benzathine penicillin are given by injection (parenterally), but phenoxymethylpenicillin is given orally. Common adverse drug reactions (≥ 1% of patients) associated with use of the penicillins include diarrhoea, hypersensitivity, nausea, rash, neurotoxicity, urticaria, and superinfection (including candidiasis). Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in people with epilepsy), and pseudomembranous colitis. Bacteria constantly remodel their peptidoglycan cell walls, simultaneously building and breaking down portions of the cell wall as they grow and divide. -Lactam antibioticsβ inhibit the formation of peptidoglycan cross-links in the bacterial cell wall; this is achieved through binding of the four-membered β-lactam ring of penicillin to the enzyme DD-transpeptidase. Consequently, DD-transpeptidase cannot catalyze formation of these cross-links, and an imbalance between cell wall production and degradation develops, causing the cell to rapidly die. More specifically, the enzymes that hydrolyze the peptidoglycan cross-links continue to function, even while those that form such cross-links do not. This weakens the cell wall of the bacterium, and osmotic pressure continues to rise—eventually causing cell death (cytolysis). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolases and autolysins, which further digest the cell wall's peptidoglycans. The small size of the penicillins increases their potency, by allowing them to penetrate the entire depth of the cell wall. This is in contrast to the glycopeptide antibiotics vancomycin and teicoplanin, which are both much larger than the penicillins. Gram-positive bacteria are called protoplasts when they lose their cell walls. Gram-negative bacteria do not lose their cell walls completely and are called spheroplasts after treatment with penicillin.][ Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing their disruption of bacterial protein synthesis within the cell. This results in a lowered MBC for susceptible organisms. Penicillins, like other β-lactam antibiotics, block not only the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, they have no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory of the evolution of plastid division in land plants. The term "penam" is used to describe the common core skeleton of a member of the penicillins. This core has the molecular formula R-C9H11N2O4S, where R is the variable side chain that differentiates the penicillins from one another. The penam core has a molecular weight of 243 g/mol, with larger penicillins having molecular weights near 450—for example, cloxacillin has a molecular weight of 436 g/mol. The key structural feature of the penicillins is the four-membered β-lactam ring; this structural moiety is essential for penicillin's antibacterial activity. The β-lactam ring is itself fused to a five-membered thiazolidine ring. The fusion of these two rings causes the β-lactam ring to be more reactive than monocyclic β-lactams because the two fused rings distort the β-lactam amide bond and therefore remove the resonance stabilisation normally found in these chemical bonds. Overall, there are three main and important steps to the biosynthesis of penicillin G (benzylpenicillin). Penicillin is a secondary metabolite of certain species of Penicillium and is produced when growth of the fungus is inhibited by stress. It is not produced during active growth. Production is also limited by feedback in the synthesis pathway of penicillin. The by-product, -lysine, inhibits the production of homocitrate, so the presence of exogenous lysine should be avoided in penicillin production. The Penicillium cells are grown using a technique called fed-batch culture, in which the cells are constantly subject to stress, which is required for induction of penicillin production. The available carbon sources are also important: Glucose inhibits penicillin production, whereas lactose does not. The pH and the levels of nitrogen, lysine, phosphate, and oxygen of the batches must also be carefully controlled. The biotechnological method of directed evolution has been applied to produce by mutation a large number of Penicillium strains. These techniques include error-prone PCR, DNA shuffling, ITCHY, and strand-overlap PCR. Semisynthetic penicillins are prepared starting from the penicillin nucleus 6-APA. The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in 1928. He showed that, if Penicillium rubens were grown in the appropriate substrate, it would exude a substance with antibiotic properties, which he dubbed penicillin. This serendipitous observation began the modern era of antibiotic discovery. The development of penicillin for use as a medicine is attributed to the Australian Nobel laureate Howard Walter Florey, together with the German Nobel laureate Ernst Chain and the English biochemist Norman Heatley. The first published reference appears in the publication of the Royal Society in 1875, by John Tyndall. Joaquim Monteiro Caminhoá, Professor of Botany and Zoology of the Faculty of Medicine of the Federal University of Rio de Janeiro in Brazil, also recognised the antibiotic activity of Penicillium and other fungi in 1877. In his book, Elements of General and Medical Botany (under a section titled "Useful fungi, harmful and curious"), he stated: "The mould (Penicillium infestans, Penicillium glaucum, figure 1680, Ascophora and many others) is useful because it feeds on decaying organic matter and destroys putrifaction so that, as a rule, the odour of infection does not occur, or is produced in infinitely smaller amounts." In 1895, Vincenzo Tiberio, physician of the University of Naples published a research about a mold (Penicillium) in a water well that had an antibacterial action. Ernest Duchesne documented it in an 1897 paper, which was not accepted by the Institut Pasteur because of his youth. In March 2000, doctors at the San Juan de Dios Hospital in San José, Costa Rica, published the manuscripts of the Costa Rican scientist and medical doctor Clodomiro (Clorito) Picado Twight (1887–1944). They reported Picado's observations on the inhibitory actions of fungi of the genus Penicillium between 1915 and 1927. Picado reported his discovery to the Paris Academy of Sciences, yet did not patent it, even though his investigations started years before Fleming's. Joseph Lister was experimenting with Penicillum in 1871 for his aseptic surgery. He found that it weakened the microbes, but then he dismissed the fungi. These early investigations did not lead to the use of antibiotics to treat infection because they took place in obscure circumstances, and the idea that infections were caused by transmissible agents was not widely accepted at the time. Sterilization measures had been shown to limit the outbreak and spread of disease; however, the mechanism of transmission of disease by parasites, bacteria, viruses and other agents was unknown. In the late 19th century, knowledge was increasing of the mechanisms by which living organisms become infected, how they manage infection once it has begun and, most importantly in the case of penicillin, the effect that natural and man-made agents could have on the progress of infection. Fleming recounted that the date of his discovery of penicillin was on the morning of Friday, September 28, 1928. It was a fortuitous accident: in his laboratory in the basement of St. Mary's Hospital in London (now part of Imperial College), Fleming noticed a Petri dish containing Staphylococcus plate culture he mistakenly left open, was contaminated by blue-green mould, which formed a visible growth. There was a halo of inhibited bacterial growth around the mould. Fleming concluded the mould released a substance that repressed the growth and lysing the bacteria. He grew a pure culture and discovered it was a Penicillium mould, now known to be Penicillium notatum. Charles Thom, an American specialist working at the U.S. Department of Agriculture, was the acknowledged expert, and Fleming referred the matter to him. Fleming coined the term "penicillin" to describe the filtrate of a broth culture of the Penicillium mould. Even in these early stages, penicillin was found to be most effective against Gram-positive bacteria, and ineffective against Gram-negative organisms and fungi. He expressed initial optimism that penicillin would be a useful disinfectant, being highly potent with minimal toxicity compared to antiseptics of the day, and noted its laboratory value in the isolation of Bacillus influenzae (now Haemophilus influenzae). After further experiments, Fleming was convinced penicillin could not last long enough in the human body to kill pathogenic bacteria, and stopped studying it after 1931. He restarted clinical trials in 1934, and continued to try to get someone to purify it until 1940. In 1930, Cecil George Paine, a pathologist at the Royal Infirmary in Sheffield, attempted to use penicillin to treat sycosis barbae, eruptions in beard follicles, but was unsuccessful, probably because the drug did not penetrate the skin deeply enough. Moving on to ophthalmia neonatorum, a gonococcal infection in infants, he achieved the first recorded cure with penicillin, on November 25, 1930. He then cured four additional patients (one adult and three infants) of eye infections, and failed to cure a fifth. In 1939, Australian scientist Howard Florey (later Baron Florey) and a team of researchers (Ernst Boris Chain, Arthur Duncan Gardner, Norman Heatley, M. Jennings, J. Orr-Ewing and G. Sanders) at the Sir William Dunn School of Pathology, University of Oxford made significant progress in showing the in vivo bactericidal action of penicillin. Their attempts to treat humans failed because of insufficient volumes of penicillin (the first patient treated was Reserve Constable Albert Alexander), but they proved it harmless and effective on mice. Some of the pioneering trials of penicillin took place at the Radcliffe Infirmary in Oxford, England. These trials continue to be cited by some sources as the first cures using penicillin, though the Paine trials took place earlier. On March 14, 1942, John Bumstead and Orvan Hess saved a dying patient's life using penicillin. Notably, survivors of the November 28, 1942 Cocoanut Grove fire in Boston, which killed 492 people, were treated with penicillin. Merck and Company rushed a 32-liter supply of the drug, in the form of culture liquid in which the Penicillium mold had been grown, from New Jersey to Boston in early December. The drug was crucial in combating staphylococcus bacteria which typically infect skin grafts. As a result of the success of penicillin in preventing infections, the US Government decided to support the production and distribution of penicillin to the armed forces. The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945. Penicillin has since become the most widely used antibiotic to date, and is still used for many Gram-positive bacterial infections. A team of Oxford research scientists led by Australian Howard Florey and including Ernst Boris Chain and Norman Heatley devised a method of mass-producing the drug. Florey and Chain shared the 1945 Nobel Prize in Medicine with Fleming for their work. After World War II, Australia was the first country to make the drug available for civilian use. The challenge of mass-producing this drug was daunting. On March 14, 1942, the first patient was treated for streptococcal septicemia with US-made penicillin produced by Merck & Co. Half of the total supply produced at the time was used on that one patient. By June 1942, just enough US penicillin was available to treat ten patients. In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin stocks to Allied troops fighting in Europe. The results of fermentation research on corn steep liquor at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the United States to produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. After a worldwide search in 1943, a mouldy cantaloupe in a Peoria, Illinois market was found to contain the best strain of penicillin for production via the corn steep liquor process. Large-scale production resulted from the development of deep-tank fermentation by chemical engineer Margaret Hutchinson Rousseau. As a direct result of the war and the War Production Board, by June 1945, over 646 billion units per year were being produced. G. Raymond Rettew made a significant contribution to the American war effort by his techniques to produce commercial quantities of penicillin. During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds among Allied forces, saving an estimated 12%–15% of lives.][ Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug, necessitating frequent dosing. Penicillin is actively excreted, and about 80% of a penicillin dose is cleared from the body within three to four hours of administration. Indeed, during the early penicillin era, the drug was so scarce and so highly valued that it became common to collect the urine from patients being treated, so that the penicillin in the urine could be isolated and reused. This was not a satisfactory solution, so researchers looked for a way to slow penicillin excretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for excretion, such that the transporter would preferentially excrete the competing molecule and the penicillin would be retained. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are administered together, probenecid competitively inhibits the excretion of penicillin, increasing penicillin's concentration and prolonging its activity. Eventually, the advent of mass-production techniques and semi-synthetic penicillins resolved the supply issues, so this use of probenecid declined. Probenecid is still useful, however, for certain infections requiring particularly high concentrations of penicillins. In a 1946 to 1948 study in Guatemala, U.S. researchers used prostitutes to infect prison inmates, insane asylum patients, and Guatemalan soldiers with syphilis and other sexually transmitted diseases (STDs), to test the effectiveness of penicillin in treating such diseases. They later tried infecting people with "direct inoculations made from syphilis bacteria poured into the men's penises and on forearms and faces that were slightly abraded ... or in a few cases through spinal punctures". Approximately 1300 people were infected as part of the study (including orphaned children). The study was sponsored by the Public Health Service, the National Institutes of Health and the Pan American Health Sanitary Bureau (now the World Health Organization's Pan American Health Organization) and the Guatemalan government. The team was led by John Charles Cutler, who later participated in the Tuskegee syphilis experiments. Cutler chose to do the study in Guatemala because he would not have been permitted to do it in the United States. The Presidential Commission for the Study of Bioethical Issues determined that 83 people died; however, it was not possible to determine whether the experiments were the direct cause of death. Chemist John C. Sheehan at the Massachusetts Institute of Technology (MIT) completed the first chemical synthesis of penicillin in 1957. Sheehan had started his studies into penicillin synthesis in 1948, and during these investigations developed new methods for the synthesis of peptides, as well as new protecting groups—groups that mask the reactivity of certain functional groups. Although the synthesis developed by Sheehan was not appropriate for mass production of penicillins, one of the intermediate compounds in Sheehan's synthesis was 6-aminopenicillanic acid (6-APA), the nucleus of penicillin. Attaching different groups to the 6-APA 'nucleus' of penicillin allowed the creation of new forms of penicillin. The narrow range of treatable diseases or "spectrum of activity" of the penicillins, along with the poor activity of the orally active phenoxymethylpenicillin, led to the search for derivatives of penicillin that could treat a wider range of infections. The isolation of 6-APA, the nucleus of penicillin, allowed for the preparation of semisynthetic penicillins, with various improvements over benzylpenicillin (bioavailability, spectrum, stability, tolerance). The first major development was ampicillin, which offered a broader spectrum of activity than either of the original penicillins. Further development yielded β-lactamase-resistant penicillins, including flucloxacillin, dicloxacillin, and methicillin. These were significant for their activity against β-lactamase-producing bacterial species, but were ineffective against the Staphylococcus aureusmethicillin-resistant (MRSA) strains that subsequently emerged. Another development of the line of true penicillins was the antipseudomonal penicillins, such as carbenicillin, ticarcillin, and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the β-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most important, the cephalosporins, still retain it at the center of their structures. M: BAC bact (clas) gr+f/gr+a (t)/gr-p (c)/gr-o drug (J1p, w, n, m, vacc) Note: See the receptor PAMsAGABA navbox for a full list of GABAA positive allosteric modulators.

Doxycycline
InChI=1S/C22H24N2O8.H2O/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29;/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31);1H2/t7-,10+,14+,15-,17-,22-;/m0./s1Yes 
Key:XQTWDDCIUJNLTR-CVHRZJFOSA-NYes  Doxycycline is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Vibramycin received US Food and Drug Administration approval in 1967,][. Other brand names include Monodox, Microdox, Periostat, Vibra-Tabs, Oracea, Doryx, Vibrox, Adoxa, Doxyhexal, Doxylin, Doxoral, Doxy-1 and Atridox (topical doxycycline hyclate for periodontitis). In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease, acne, rosacea, and rickettsial infections. It is used in prophylaxis against malaria. It should not be used alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed. This delay is related to its mechanism of action, which is to specifically impair the progeny of the apicoplast genes, resulting in their abnormal cell division. It can be used in a treatment plan in combination with other agents, such as quinine. Branhamella catarrhalis, Brucella melitensis, Chlamydia pneumoniae, and Mycoplasma pneumoniae are generally susceptible to doxycycline, while some Haemophilus spp., Mycoplasma hominis, and Pseudomonas aeruginosa have developed resistance to varying degrees. It is used in the treatment and prophylaxis of anthrax (caused by Bacillus anthracis) and Leptospirosis. It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease, ehrlichiosis and Rocky Mountain spotted fever. In fact, because doxycycline is one of the few medications shown to be effective in treating Rocky Mountain spotted fever (with the next-best alternative being chloramphenicol), doxycycline is indicated even for use in children for this illness. Otherwise, it is not indicated for use in children under the age of eight years. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat and prevent: Doxycycline kills the symbiotic Wolbachia bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis. Field trials in 2005 showed an eight-week course of doxycycline almost completely eliminates the release of microfilariae. Cautions and side effects are similar to those of other members of the tetracycline antibiotic group. An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug. Unlike some other members of the tetracycline group, it may be used in those with renal impairment. The combination of doxycycline with dairy, antacids, calcium supplements, iron products, and laxatives containing magnesium is not inherently dangerous, but any of these foods and supplements may decrease doxycycline's effectiveness.][ Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to CYP450 induction. Recent research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy. Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption compared with the earlier tetracycline compounds. In addition, food has less effect on absorption than on absorption of earlier drugs with doxycycline serum concentrations being reduced by ∼20% by test meals compared with 50% for tetracycline. Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with precaution in patients with kidney injury, as they can worsen azotemia due to catabolic effects. At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions. Doxycycline has been demonstrated to reduce the in vitro growth of human breast and prostate cancer cells, possibly through phase1G cell cycle arrest. Doxycycline and other tetracyclines are also highly osteotropic, and in animal models of breast cancer bone metastases, doxycycline treatments have reduced the growth of breast cancer tumours in the bone. Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease. It has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension. In chronic obstructive pulmonary disease, doxycycline has been shown to improve lung functions in patients with stable symptoms. Doxycycline is also used in "Tet-on" and "Tet-off" tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures. Other experimental applications include treating: Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc.][ and marketed under the brand name Vibramycin.][ M: MOU anat/devp noco/cofa (c)/cogi/tumr, sysi proc (peri), drug (A1) M: BAC bact (clas) gr+f/gr+a (t)/gr-p (c)/gr-o drug (J1p, w, n, m, vacc) Chagas disease: nitroimidazole (Benznidazole#) Pentavalent antimonials (Meglumine antimoniate#, Sodium stibogluconate) M: PRO ambz, excv, chrm (strc) ambz, excv, chrm ambz, excv, chrm M: PRO ambz, excv, chrm (strc) ambz, excv, chrm ambz, excv, chrm

Ciprofloxacin
InChI=1S/C17H18FN3O3/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24/h7-10,19H,1-6H2,(H,23,24)Yes 
Key:MYSWGUAQZAJSOK-UHFFFAOYSA-NYes  Ciprofloxacin (INN) is a second-generation fluoroquinolone antibiotic. Its spectrum of activity includes most strains of bacterial pathogens responsible for respiratory, urinary tract, gastrointestinal, and abdominal infections, including Gram-(-) (Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa), and Gram-(+) (methicillin-sensitive but not methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, Enterococcus faecalis, and Streptococcus pyogenes) bacterial pathogens. Ciprofloxacin and other fluoroquinolones are valued for this broad spectrum of activity, excellent tissue penetration, and for their availability in both oral and intravenous formulations. Ciprofloxacin is used alone or in combination with other antibacterial drugs in the empiric treatment of infections for which the bacterial pathogen has not been identified, including urinary tract infections and abdominal infections among others. It is also used for the treatment of infections caused by specific pathogens known to be sensitive. In 2010 over 20 million outpatient prescriptions were written for ciprofloxacin, making it the 35th most commonly prescribed drug, and the 5th most commonly prescribed antibacterial, in the US. It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of protein. Ciprofloxacin was first patented in 1983 by Bayer A.G. and subsequently approved by the US Food and Drug Administration (FDA) in 1987. Ciprofloxacin has 12 FDA-approved human uses and other veterinary uses, but it is often used for unapproved uses (off-label). Ciprofloxacin is used to treat a number of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid, as well as: Ciprofloxacin is not recommended for the treatment of tuberculosis. It is also used in combination with other specific drugs: Oral and intravenous fluoroquinolones are approved by the FDA for use in children for only two indications due to the risk of permanent injury to the musculoskeletal system. Indications include: Ciprofloxacin is not recommended to treat community-acquired pneumonia (CAP) as a stand-alone first-line agent due to its modest activity against Streptococcus pneumoniae, a common causative pathogen. "Respiratory quiniolones" such as levofloxacin, having greater activity against this pathogen, are recommended as first line agents for the treatment of CAP in patients with important co-morbidities and in patients requiring hospitalization (Infectious Diseases Society of America 2007). The guidelines include a warning that "Data exist suggesting that resistance to macrolides and older fluoroquinolones (ciprofloxacin and levofloxacin) results in clinical failure. Other studies have shown that repeated use of fluoroquinolones predicts an increased risk of infection with fluoroquinolone-resistant pneumococci...." Ciprofloxacin may be approved for other uses, or restricted, by the various regulatory agencies worldwide. Ciprofloxacin is available as tablets, syrups, intravenous solutions, and eye and ear drops. Only four contraindications are found within the 2009 package insert: Ciprofloxacin is also considered to be contraindicated within the pediatric population (except for the indications outlined above), pregnancy, nursing mothers, and in patients with epilepsy or other seizure disorders. Ciprofloxacin is Pregnancy Category C. This category includes drugs for which there are no adequate and well-controlled studies in human pregnancy, but for which animal studies have suggested the potential for harm to the fetus. The label further states, "Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother." A controlled prospective observational study followed 200 women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first-trimester exposures) during gestation. In utero exposure to fluoroquinolones during embryogenesis was not associated with increased risk of major malformations. Rates of spontaneous abortions, prematurity and low birth weight did not differ between the groups, and there were no clinically significant musculoskeletal dysfunctions up to one year of age in the ciprofloxacin-exposed children. Similar results were obtained in a second study of 549 pregnancies with fluoroquinoline exposure, of which 70 involved ciprofloxacin. The label notes, however, "these small post-marketing epidemiology studies, of which most experience is from short term, first trimester exposure, are insufficient to evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the safety of ciprofloxacin in pregnant women and their developing fetuses." The fluoroquinolones rapidly cross the blood-placenta and blood-milk barriers, and are extensively distributed into the fetal tissues. The fluoroquinolones have also been reported as being present in the mother's milk and are passed on to the nursing child. Fluoroquinolones are approved by the FDA for use in children for only limited indications. Ciprofloxacin is approved for the treatment of complicated urinary tract infections and pyelonephritis due to Escherichia coli, and inhalational anthrax (postexposure), and levofloxacin was recently licensed for the treatment of inhalational anthrax (postexposure). In the UK, fluoroquinolones are approved for the treatment lower respiratory infections in children with cystic fibrosis. The risks associated with the use of ciprofloxacin in pediatric patients were recently evaluated in a systematic review of 105 research publications describing the use of ciprofloxacin in 16,184 patients 17 years and younger. The most frequently reported adverse events (AEs) were musculoskeletal AEs, abnormal liver tests, nausea, changes in white blood cell counts, and vomiting. Twenty-three patients discontinued treatment due to AEs (0.1%). A single death occurred in a neonate who experienced an anaphylactic reaction. Forty-eight patients (0.3%) experienced a joint or tendon disorder. Current recommendations by the American Academy of Pediatrics note the systemic use of ciprofloxacin in children should be restricted to infections caused by multidrug-resistant pathogens or when no safe or effective alternatives are available. Ciprofloxacin should not be used in infants as they have not developed sufficient enzymes to metabolize the drug.][ Severe adverse reaction may occur in this patient group. The status of the patient's renal and hepatic functions must also be taken into consideration to avoid an accumulation that may lead to an overdose and the development of toxicity. Ciprofloxacin is eliminated primarily by renal excretion. However, the drug is also metabolized and partially cleared through the liver and the intestines. Modification of the dosage is 'recommended' using the table found within the package insert for those with impaired liver or kidney function. However, since the drug is known to be substantially excreted by the kidneys, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. The duration of treatment depends upon the severity of infection, and is usually seven to 14 days. The safety of fluoroquinolones is similar to that of other antibiotics. In most, adverse reactions are mild to moderate; but serious adverse effects occur on occasion. 49,038 patients received courses of ciprofloxacin in pre-approval clinical trials. Most of the adverse events reported were described as only mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Ciprofloxacin was discontinued because of an adverse event in 1% of orally treated patients. The most frequently reported drug-related events, from clinical trials of all formulations, all dosages, all drug-therapy durations, and for all indications of ciprofloxacin therapy, were nausea (2.5%), diarrhea (1.6%), abnormal liver function tests (1.3%), vomiting (1%), and rash (1%). Other adverse events occurred at rates of <1%. A number of regulatory actions have been taken as a result of such adverse reactions, which included published warnings, additional warnings and safety information added to the package inserts together with the issuance of "Dear Doctor Letters" concerning the recent addition of black box warnings. See the Quinolones article for a discussion of the history of these warnings and the role of public advocacy groups in their inclusion in the product label. As of 2011, the FDA has added two black box warnings for this drug in reference to spontaneous tendon ruptures and because ciprofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and potentially life-threatening breathing problems. A case control study performed using a UK medical care database found that fluoroquinolone use was associated with a 1.9-fold increase in tendon problems. The relative risk increased to 3.2 in those over 60 years of age and to 6.2 in those over the age of 60 who were also taking corticosteroids. Among the 46,766 quinolone users in the study, 38 (0.1%) cases of Achilles tendon rupture were identified. A study performed using an Italian healthcare database reached qualitatively similar conclusions. Tendonitis and other forms of tendon damage may manifest during fluoroquinolone therapy, and long after it had been discontinued. Ciprofloxacin is active in six of eight in vitro assays used as rapid screens for the detection of genotoxic effects, but is not active in in vivo assays of genotoxicity including the rat hepatocyte DNA repair assay, micronucleus test (mice) or the dominant lethal test (mice). Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 and 750 mg/kg to rats and mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose based upon mg/m2). Results from photo co-carcinogenicity testing indicate ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours, five times every two weeks, for up to 78 weeks, while concurrently being administered ciprofloxacin. The time to development of the first skin tumors was 50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately equal to maximum recommended human dose based upon mg/m2), as opposed to 34 weeks when animals were treated with both UVA and vehicle. The administration of Ciprofloxacin has been associated with a number of rare but serious side effects, including SIADHperipheral neuropathy acute liver failure or serious liver injury (hepatitis), QTc prolongation/torsades de pointes, toxic epidermal necrolysis (TEN), and Stevens–Johnson syndrome, severe central nervous system disorders (CNS) and Clostridium difficile associated disease (CDAD: pseudomembranous colitis), as well as photosensitivity/phototoxicity reactions. Psychotic reactions and confusional states, acute pancreatitis, interstitial nephritis, and hemolytic anemia may also occur during ciprofloxacin therapy. Additional serious adverse reactions include temporary loss of vision, double vision, drug induced psychosis, impaired color vision, exanthema, abdominal pain, malaise, drug fever, dysaesthesia, and eosinophilia. Children and the elderly are at a much greater risk of experiencing such adverse reactions. Ciprofloxacin interacts with other drugs and herbal and natural supplements, a characteristic it shares with other widely used antibacterial drugs, such as amoxicillin, trimethoprim, azithromycin, cephalexin, and doxycycline. Concurrent administration of ciprofloxacin with magnesium or aluminium antacids, sucralfate, or products containing calcium, iron, or zinc (including multivitamins or other dietary supplements) may substantially decrease the absorption of ciprofloxacin, resulting in serum and urine levels considerably lower than desired. Serum levels of certain drugs metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones. Coadministration may dangerously increase coumadin (warfarin) activity; INR should be monitored closely. Levels of tizanidine and methylxanthines (for example, theophylline and caffeine) may be increased due to ciprofloxacin's interaction with the cytochrome P-450 enzyme CYP1A2. The Committee on the Safety of Medicines and the FDA warn that central nervous system (CNS) adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones. The interaction between quinolones and NSAIDs is important, because it has the potential for considerable CNS toxicity. The mechanism for this interaction is believed to be due to a synergistic increased antagonism of GABA neurotransmission. Ciprofloxacin's renal clearance may affect other drugs subject to renal clearance or otherwise affecting the kidney. The use of ciprofloxacin concomitantly with cyclosporine has also been associated with transient elevations in serum creatinine. Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and risk of methotrexate toxicity. Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in serum. Altered serum levels of the anti-epileptic drugs phenytoin and carbamazepine (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin. Current or past treatment with oral corticosteroids is associated with an increased risk of Achilles tendon rupture, especially in elderly patients who are also taking the fluoroquinolones. This is the subject of Black box warnings in FDA and BNF labeling for quinolones. Overdose of ciprofloxacin may result in reversible renal toxicity. Treatment of overdose includes emptying of the stomach by induced vomiting or gastric lavage. Careful monitoring and supportive treatment, monitoring of renal function, and maintaining adequate hydration is recommended by the manufacturer. Administration of magnesium-, aluminium-, or calcium-containing antacids can reduce the absorption of ciprofloxacin. Hemodialysis or peritoneal dialysis removes only less than 10% of ciprofloxacin. Ciprofloxacin may be quantified in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims. Ciprofloxacin is a broad-spectrum antibiotic active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV, enzymes necessary to separate bacterial DNA, thereby inhibiting cell division. Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid. Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 g/mol. It is a faintly yellowish to light yellow crystalline substance. Ciprofloxacin hydrochloride (USP) is the monohydrochloride monohydrate salt of ciprofloxacin. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. Its empirical formula is C17H18FN3O3HCl•H2O. The effects of 200–400 mg of ciprofloxacin given intravenously are linear; drug accumulation does not occur when administered at 12-hour intervals. Bioavailability is approximately 70-80%, with no significant first pass effect. IV administration produces a similar serum levels as those achieved with administration of 500 mg administered orally. IV administration over 60 min given every 8 h produces similar serum levels of the drug as 750 mg administered orally every 12 h. Biotransformation is hepatic. The elimination half life is 4 h. The patent history for ciprofloxacin makes reference to a 1982 European patent (patent number 0049355), as well a German patent dated 21 January 1986. Bayer introduced ciprofloxacin in 1987 and it was later approved by the US FDA on 22 October 1987 for use in the United States to treat specific bacterial infections. In 1991, the intravenous formulation was introduced. The current US patent appears to be held by Bayer, being the assignee. The United States patent was applied for in January 1987, but was not approved until 1996 according to the patent history. In 2004, ciprofloxacin and levofloxacin together commanded 65% ($3.3 billion) of the global sales of the fluoroquinolone class. The first 9 months of 2008 sales for ciprofloxacin were $242 million, as compared to $324 million for Bayer aspirin. Ciprofloxacin has been a highly successful drug for Bayer A. G., generating billions of dollars in revenue. "In 1999, Cipro was the eleventh most prescribed drug in the United States based on new prescriptions, and ranked twentieth in total United States sales. In 1999, Bayer's gross sales of Cipro in the United States were approximately $1.04 billion." The sale of ciprofloxacin increased dramatically following the anthrax scare of 2001. On 24 October 2002, the Bush administration (2001–2009) announced a deal between the government and Bayer Pharmaceuticals to purchase 100 million tablets of ciprofloxacin at a reduced price of $0.95 per pill. On 24 October 2001, The Prescription Access Litigation (PAL) filed suit to dissolve an agreement between Bayer and three of its competitors which produced generic versions of drugs (Barr Laboratories, Rugby Laboratories, and Hoechst-Marion-Roussel) that PAL claimed was blocking access to adequate supplies and cheaper, generic versions of ciprofloxacin. The plaintiffs charged that Bayer Corporation, a unit of Bayer AG, had unlawfully paid the three competing companies a total of $200 million to prevent cheaper, generic versions of ciprofloxacin from being brought to the market, as well as manipulating its price and supply. Numerous other consumer advocacy groups joined the lawsuit. On 15 October 2008, five years after Bayer's patent had expired, the United States District Court for the Eastern District of New York granted Bayer's and the other defendants' motion for summary judgment, holding that any anticompetitive effects caused by the settlement agreements between Bayer and its codefendants were within the exclusionary zone of the patent and thus could not be redressed by federal antitrust law, in effect upholding Bayer's agreement with its competitors. Ciprofloxacin is commonly used for urinary tract and intestinal infections (traveler's diarrhea), and was once considered a powerful antibiotic of last resort, used to treat especially tenacious infections. Not all physicians agreed with this assessment, as evidenced by its widespread use to treat minor infections, as well as unapproved uses. As a result, many bacteria have developed resistance to this drug in recent years, leaving it significantly less effective than it would have been otherwise. Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, Streptococcus pyogenes and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance worldwide. Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated. Meanwhile, some Burkholderia cepacia, Clostridium innocuum and Enterococcus faecium strains have developed resistance to ciprofloxacin to varying degrees. Fluoroquinolones had become the most commonly prescribed class of antibiotics to adults in 2002. Nearly half (42%) of those prescriptions were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study supported in part by the Agency for Healthcare Research and Quality. Additionally, they were commonly prescribed for medical conditions that were not even bacterial to begin with, such as viral infections, or those to which no proven benefit existed. Bayer AG A class action was filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the US Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who alleged they suffered serious adverse effects from taking ciprofloxacin (Cipro) in the aftermath of the anthrax attacks in 2001. The action alleged Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. According to the allegations within the complaint, exposed individuals were not informed of the true safety profile of ciprofloxacin, the high rate of adverse events associated with its use, or the availability of safer and equally effective alternative drugs. The class action was defeated and the litigation abandoned by the plaintiffs. A similar action had been filed in New Jersey to cover New Jersey postal workers. Final disposition of that lawsuit is unknown. Following the addition of the black box warning in 2008, regarding tendon damage, product liability law firms began soliciting clients who have suffered a spontaneous tendon rupture following fluoroquinolone therapy. Ciprofloxacin is marketed worldwide with over 300 different brand names. In the United States, Canada, and the UK, it is marketed as Baycip, Ciloxan, Ciflox, Ciplox, Cipro, Cipro XR, Cipro XL, Ciproxin, Prociflor, and most recently, Proquin. It is also marketed as Neofloxin and Cipro-A in Bangladesh; in India it is marketed as Alcipro, in Russia as Ciprex, and as Cetraxal in Spain. In Pakistan, it is marketed as Ciproheim. In addition, ciprofloxacin is available as a generic drug under a variety of different brand names and is also available for limited use in veterinary medicine.
M: BAC bact (clas) gr+f/gr+a (t)/gr-p (c)/gr-o drug (J1p, w, n, m, vacc) M: EAR anat (e/p)/phys/devp noco/cong, epon proc, drug (S2)

Erythromycin
InChI=1S/C37H67NO13/c1-14-25-37(10,45)30(41)20(4)27(39)18(2)16-35(8,44)32(51-34-28(40)24(38(11)12)15-19(3)47-34)21(5)29(22(6)33(43)49-25)50-26-17-36(9,46-13)31(42)23(7)48-26/h18-26,28-32,34,40-42,44-45H,14-17H2,1-13H3/t18-,19-,20+,21+,22-,23+,24+,25-,26+,28-,29+,30-,31+,32-,34+,35-,36-,37-/m1/s1Yes 
Key:ULGZDMOVFRHVEP-RWJQBGPGSA-NYes  Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often prescribed for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including Mycoplasma and legionellosis. It was first marketed by Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester prodrug that is commonly administered). It is also occasionally used as a prokinetic agent. In structure, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desosamine), making it a compound very difficult to produce via synthetic methods. Erythromycin is produced from a strain of the actinomycete Saccharopolyspora erythraea. Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate erythromycin from the metabolic products of a strain of Streptomyces erythreus (designation changed to "Saccharopolyspora erythraea") found in the samples. Lilly filed for patent protection of the compound and U.S. patent 2,653,899 was granted in 1953. The product was launched commercially in 1952 under the brand name Ilosone (after the Philippine region of Iloilo where it was originally collected). Erythromycin was formerly also called Ilotycin. In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at Harvard University (Cambridge, MA) Robert B. Woodward (posthumously), along with a large number of members from his research group, reported the first stereocontrolled asymmetric chemical synthesis of erythromycin A. The antibiotic clarithromycin was invented by scientists at the Japanese drug company Taisho Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of erythromycin. Scientists at Chugai Pharmaceuticals discovered an erythromycin-derived motilin agonist called mitemcinal that is believed to have strong prokinetic properties (similar to erythromycin) but lacking antibiotic properties. At the present time, erythromycin is commonly used off-label for gastric motility indications such as gastroparesis. If mitemcinal can be shown to be an effective a prokinetic agent, it would represent a significant advance in the GI field as treatment with this drug would not carry the risk of unintentional selection for antibiotic-resistant bacteria. Over the three decades after the discovery of erythromycin A and its activity as an antimicrobial, many attempts were made to synthesize it in the laboratory. However, the presence of ten stereospecific carbons and several points of distinct substitution has made the total synthesis of erythromycin A a formidable task. Complete syntheses of erythromycins’ related structures and precursors such as 6- deoxyerythronolide B have been accomplished, giving way to possible syntheses of different erythromycins and other macrolide antimicrobials. However, Woodward did successfully complete the synthesis of erythromycin A. This total synthesis begins with (7) and (8). After being coupled, the resulting structure is subjected to a series of reactions, including hydrolysis and stereospecific aldolization. The resulting pure enone is then converted to the desired dithiadecalin product (9) through a series of reduction and oxidation reactions. (9) is then converted to both a ketone (10) and an aldehyde (11). Step1erythromycin.jpg Figure 1 a) NaH, THF, Me2SO; b)AcOH, H2O; c)MsCL, Py; d)alumina, EtOAc; e)NaBH4, MeOH; f)MeOCH2I, KH, THF; g)OsO4, ether; NaHSO3, Py(aq); h)Me2C(OMe)2, TsOH, CH2Cl2; i)CF3COOH, CH2Cl2; j)(CF3CO)2O, Me2SO, CH2Cl2; (i-Pr)2NEt; k)Ra(Ni)-(W-2), EtOH, reflux; l)o-NO2C6H4SeCN, P(n-Bu)3, THF; m)O3, MeOH, CH2Cl2; Me2S, NaHCO3. With these two species, each of which resembling key segments of the erythronolide A seco acid, an aldol condensation is carried out to yield (12). (12) is put through several reactions, including the addition of benzyl thiol, the coupling of enolates, and stereospecific reduction to yield (13), which contains the carbon skeleton and stereocenters of the erythronolide A seco acid. Step2erythromycin.jpg Figure 2 a) Mesityllithium, THF; b)(CF3CO)2O, Me2SO, CH2Cl2; (i-Pr)2NEt; c), KH, HMPA, THF; AcCl; d)NaBH4, MeOH, CH2Cl2; e)MsCl, Py; DMAP, Py, MeOH; f)PhCH2SH, n-BuLi, THF; g)LAH, ether; h)Ac2O, DMAP, CH2Cl2; i)Ra(Ni)-(W-2), EtOH, DMF, reflux; j)o-NO2C6H4SeCN, P(n- Bu)3, THF; 30% H2O2, THF; k)O3, MeOH, CH2Cl2; Me2S, NaHCO3; l)EtCOSCMe3, LDA, THF; m)t-BuLi, (CH2NMe2)2, THF; AcOH. (13) is then subjected to a series of reactions including successive deprotections and acetylization to yield (14), a compound that is more likely to yield a lactone. Acetalization of (14) yields a precursor to the desired thioester (15), which was achieved by replacing the terminal methoxy group with the required thio group. (15) is then lactonized in 70% yield to give (16). Step3erythromycin.jpg Figure 3 a) Na2CO3, MeOH; b)(PhOCH2CO)2O, Py, DMAP, CH2Cl2; c)MsCl, Py; d)LiOH, 30% H2O2, THF; e)LiN3, HMPA(aq); f)H2(1 atm), PtO2, THF; g)ClCOOC6H4-p-NO2, CH2Cl2, NaHCO3(aq); h)NH2OH⋅HCl, KH2PO4, MeOH(aq), reflux; i)Et3N, CH2Cl2; j)mesitaldehyde dimethyl acetal, CF3COOH, CH2Cl2; k)EtSLi, HMPA; l)ClCOS-2-Py, Et3N, CH2Cl2. To complete the synthesis of erythromycin A, (16) is acylated with p-phenylbenzoyl chloride, undergoes hydrolysis, and is deprotected at its hydroxyl groups at carbons 3 and 5 to yield (17). After a series of glycosidation reactions, (17) is converted to (18). (18) is then subjected to a number of reactions, eventually converting carbon 9 from an amine to the ketone, yielding the final erythromycin A product (1). Step4erythromycin.jpg Figure 4 a) BPCOCl, Et3N, DMAP, CH2Cl2; b)NaOH(aq), THF, i-PrOH; c)SiO2, CF3COOH(aq), CH2Cl2; d)Na- Hg/MeOH; e)N-chlorosuccinimide, Py; f)AgF, HMPA; g)- H2O. Total yield for Woodward’s complete synthesis of erythromycin A was approximately 0.02%, leaving future scientists with a clear goal for improvement. Erythromycin is available in enteric-coated tablets, slow-release capsules, oral suspensions, ophthalmic solutions, ointments, gels, and injections. The following erythromycin combinations are available for oral dosage: For injection the available combinations are: Brand names include Robimycin, E-Mycin, E.E.S. Granules, E.E.S.-200, E.E.S.-400, E.E.S.-400 Filmtab, Erymax, Ery-Tab, Eryc, Ranbaxy, Erypar, EryPed, Eryped 200, Eryped 400, Erythrocin Stearate Filmtab, Erythrocot, E-Base, Erythroped, Ilosone, MY-E, Pediamycin, Zineryt, Abboticin, Abboticin-ES, Erycin, PCE Dispertab, Stiemycine, Acnasol and Tiloryth. Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very common because erythromycin is a motilin agonist. Because of this, erythromycin tends not to be prescribed as a first-line drug. However, erythromycin may be useful in treating gastroparesis due to this pro-motility effect. Intravenous erythromycin may also be used in endoscopy as an adjunct to clear gastric contents. More serious side-effects include arrhythmia with prolonged QTc intervals including Torsades de pointes and reversible deafness. Allergic reactions range from urticaria to anaphylaxis. Cholestasis, Stevens–Johnson syndrome, and toxic epidermal necrolysis are some other rare side-effects that may occur. Exposure to erythromycin (especially long courses at antimicrobial doses, and also through breastfeeding) has been linked to an increased probability of pyloric stenosis in young infants. Erythromycin used for feeding intolerance in young infants has not been associated with hypertrophic pyloric stenosis. Erythromycin estolate has been associated with reversible hepatotoxicity in pregnant women in the form of elevated serum glutamic-oxaloacetic transaminase and is not recommended during pregnancy. Some evidence suggests similar hepatotoxicity in other populations. It can also affect the central nervous system, causing psychotic reactions, nightmares and night sweats. It may also alter the effectiveness of combined oral contraceptive pills because of its effect on the gut flora. Erythromycin is an inhibitor of the cytochrome P450 system, which means that it can have a rapid effect on levels of other drugs metabolised by this system, e.g., warfarin. Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations, but the mechanism is not fully understood. By binding to the 50s subunit of the bacterial 70s rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited. Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Without this translocation, the A site remains occupied and, thus, the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action. Erythromycin is easily inactivated by gastric acid; therefore, all orally-administered formulations are given as either enteric-coated or more-stable salts or esters, such as erythromycin ethylsuccinate. Erythromycin is very rapidly absorbed, and diffuses into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where, during active phagocytosis, large concentrations of erythromycin are released. Most of erythromycin is metabolised by demethylation in the liver. Its main elimination route is in the bile. There is little renal excretion. Erythromycin's elimination half-life is 1.6 hours. Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular, by isozymes of the CYP3A superfamily, CYP3A (Hunt et al., 1992). The activity of the CYP3A enzymes can be induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates — drugs that are broken down by CYP3A - such as simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor)—are taken concomitantly with erythromycin, levels of the substrates will increase, often causing adverse effects. A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Another group of CYP3A4 substrates are drugs used for migraine such as ergotamine and dihydroergotamine; their adverse effects may be more pronounced if erythromycin is associated. Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4. Hence, erythromycin should not be administered to people using these drugs, or drugs that also prolong the QT interval. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Theophylline, which is used mostly in asthma, is also contraindicated. Erythromycin is not recommended when using clindamycin-containing products, even topical products such as Duac or BenzaClin. In general, the simultaneous use of two different erythromycin derivatives (such as clindamycin and Mitemcinal) should be avoided as drugs in this macrolide family possess a common mechanism of action. M: SKA anat/phys/devp noco/cong/tumr, sysi/epon proc, drug (D10) M: BAC bact (clas) gr+f/gr+a (t)/gr-p (c)/gr-o drug (J1p, w, n, m, vacc)

Antibiotic resistance
Antibiotic resistance is a form of drug resistance whereby some (or, less commonly, all) sub-populations of a microorganism, usually a bacterial species, are able to survive after exposure to one or more antibiotics; pathogens resistant to multiple antibiotics are considered multidrug resistant (MDR) or, more colloquially, superbugs. Microbes, rather than people, develop resistance to antibiotics. Antibiotic resistance is a serious and growing phenomenon in contemporary medicine and has emerged as one of the pre-eminent public health concerns of the 21st century, particularly as it pertains to pathogenic organisms (the term is especially relevant to organisms which cause disease in humans). In the simplest cases, drug-resistant organisms may have acquired resistance to first-line antibiotics, thereby necessitating the use of second-line agents. Typically, a first-line agent is selected on the basis of several factors including safety, availability and cost; a second-line agent is usually broader in spectrum, has a less favourable risk-benefit profile and is more expensive or, in dire circumstances, be locally unavailable. In the case of some MDR pathogens, resistance to second and even third-line antibiotics is thus sequentially acquired, a case quintessentially illustrated by Staphylococcus aureus in some nosocomial settings. Some pathogens, such as Pseudomonas aeruginosa, also possess a high level of intrinsic resistance. It may take the form of a spontaneous or induced genetic mutation, or the acquisition of resistance genes from other bacterial species by horizontal gene transfer via conjugation, transduction, or transformation. Many antibiotic resistance genes reside on transmissible plasmids, facilitating their transfer. Exposure to an antibiotic naturally selects for the survival of the organisms with the genes for resistance. In this way, a gene for antibiotic resistance may readily spread through an ecosystem of bacteria. Antibiotic-resistance plasmids frequently contain genes conferring resistance to several different antibiotics. This is not the case for Mycobacterium tuberculosis, the bacteria that causes Tuberculosis, since evidence is lacking for whether these bacteria have plasmids. Also. M. tuberculosis lack the opportunity to interact with other bacteria in order to share plasmids. Genes for resistance to antibiotics, like the antibiotics themselves, are ancient. However, the increasing prevalence of antibiotic-resistant bacterial infections seen in clinical practice stems from antibiotic use both within human medicine and veterinary medicine. Any use of antibiotics can increase selective pressure in a population of bacteria to allow the resistant bacteria to thrive and the susceptible bacteria to die off. As resistance towards antibiotics becomes more common, a greater need for alternative treatments arises. However, despite a push for new antibiotic therapies there has been a continued decline in the number of newly approved drugs. Antibiotic resistance therefore poses a significant problem. The growing prevalence and incidence of infections due to MDR pathogens is epitomised by the increasing number of familiar acronyms used to describe the causative agent and sometimes the infection generally; of these, MRSA is probably the most well-known, but others including VISA (vancomycin-intermediate S. aureus), VRSA (vancomycin-resistant S. aureus), ESBL (Extended spectrum beta-lactamase), VRE (Vancomycin-resistant Enterococcus) and MRAB (Multidrug-resistant A. baumannii) are prominent examples. Nosocomial infections overwhelmingly dominate cases where MDR pathogens are implicated, but multidrug-resistant infections are also becoming increasingly common in the community. Although there were low levels of preexisting antibiotic-resistant bacteria before the widespread use of antibiotics, evolutionary pressure from their use has played a role in the development of multidrug resistance varieties and the spread of resistance between bacterial species. In medicine, the major problem of the emergence of resistant bacteria is due to misuse and overuse of antibiotics. In some countries, antibiotics are sold over the counter without a prescription, which also leads to the creation of resistant strains. Other practices contributing towards resistance include the addition of antibiotics to livestock feed. Household use of antibacterials in soaps and other products, although not clearly contributing to resistance, is also discouraged (as not being effective at infection control). Unsound practices in the pharmaceutical manufacturing industry can also contribute towards the likelihood of creating antibiotic-resistant strains. The procedures and clinical practice during the period of drug treatment are frequently flawed — usually no steps are taken to isolate the patient to prevent re-infection or infection by a new pathogen, negating the goal of complete destruction by the end of the course. (see Healthcare-associated infections and Infection control) Certain antibiotic classes are highly associated with colonisation with "superbugs" compared to other antibiotic classes. A superbug, also called multiresistant, is a bacterium that carries several resistance genes. The risk for colonisation increases if there is a lack of sensitivity (resistance) of the superbugs to the antibiotic used and high tissue penetration, as well as broad-spectrum activity against "good bacteria". In the case of MRSA, increased rates of MRSA infections are seen with glycopeptides, cephalosporins and especially quinolones. In the case of colonisation with Clostridium difficile the high risk antibiotics include cephalosporins and in particular quinolones and clindamycin. Of antibiotics used in the United States in 1997, half were used in humans and half in animals. There is evidence that naturally occurring antibiotic resistance is common. The genes that confer this resistance are known as the environmental resistome. These genes may be transferred from non-disease-causing bacteria to those that do cause disease, leading to clinically significant antibiotic resistance. In 1952 an experiment conducted by Joshua and Esther Lederberg showed that penicillin-resistant bacteria existed before penicillin treatment. While experimenting at the University of Wisconsin-Madison, Joshua Lederberg and his graduate student Norton Zinder also demonstrated preexistent bacterial resistance to streptomycin. In 1962, the presence of penicillinase was detected in dormant Bacillus licheniformis endospores, revived from dried soil on the roots of plants, preserved since 1689 in the British Museum. Six strains of Clostridium, found in the bowels of William Braine and John Hartnell (members of the Franklin Expedition) showed resistance to cefoxitin and clindamycin. It was suggested that penicillinase may have emerged as a defense mechanism for bacteria in their habitats, such as the case of penicillinase-rich Staphylococcus aureus, living with penicillin-producing Trichophyton, however this was deemed circumstantial. Search for a penicillinase ancestor has focused on the class of proteins that must be a priori capable of specific combination with penicillin. The resistance to cefoxitin and clindamycin in turn was attributed to Braine's and Hartnell's contact with microorganisms that naturally produce them or random mutation in the chromosomes of Clostridium strains. Nonetheless there is evidence that heavy metals and some pollutants may select for antibiotic-resistant bacteria, generating a constant source of them in small numbers. The sheer volume of antibiotics prescribed is the major factor in the increasing rates of bacterial resistance rather than non-compliance with antibiotic protocol A single dose of antibiotics leads to a greater risk of resistant organisms to that antibiotic in the person for up to a year. Inappropriate prescribing of antibiotics has been attributed to a number of causes, including people who insist on antibiotics, physicians who simply prescribe them as they feel they do not have time to explain why they are not necessary, and physicians who do not know when to prescribe antibiotics or else are overly cautious for medical legal reasons. For example, a third of people believe that antibiotics are effective for the common cold, and the common cold is the most common reasons antibiotics are prescribed even though antibiotics are completely useless against viruses. Antibiotic resistance has been shown to increase with duration of treatment; therefore, as long as a clinically effective lower limit is observed (that depends upon the organism and antibiotic in question), the use by the medical community of shorter courses of antibiotics is likely to decrease rates of resistance, reduce cost, and have better outcomes due to fewer complications such as C. difficile infection and diarrhea. In some situations a short course is inferior to a long course. One study found that with one antibiotic a short course was more effective, but with a different antibiotic, a longer course was more effective. Advice to always complete a course of antibiotics is not based on strong evidence, and some researchers discourage the use of the prescription label “Finish all this medication unless otherwise directed by prescriber.” Often, antibiotics can be safely stopped 72 hours after symptoms resolve. However, some infections require treatment long after symptoms are gone, and in all cases, an insufficient course of antibiotics may lead to relapse (with an infection that is now more antibiotic resistant). Doctors must provide instructions to patients so they know when it is safe to stop taking a prescription since patients may feel better before the infection is eradicated. Some researchers advocate doctors' using a very short course of antibiotics, reevaluating the patient after a few days, and stopping treatment if there are no longer clinical signs of infection. A large number of people do not finish a course of antibiotics primarily because they feel better (varying from 10% to 44%, depending on the country). Compliance with once-daily antibiotics is better than with twice-daily antibiotics. Patients taking less than the required dosage or failing to take their doses within the prescribed timing results in decreased concentration of antibiotics in the bloodstream and tissues, and, in turn, exposure of bacteria to suboptimal antibiotic concentrations increases the frequency of antibiotic resistant organisms. Antibiotic-tolerant states may depend on physiological adaptations without direct connections to antibiotic target activity or to drug uptake, efflux, or inactivation. Identifying these adaptations, and targeting them to enhance the activity of existing drugs, is a promising approach to mitigate the public health crisis caused by the scarcity of new antibiotics.][ Poor hand hygiene by hospital staff has been associated with the spread of resistant organisms, and an increase in hand washing compliance results in decreased rates of these organisms. The improper use of antibiotics and therapeutic treatments can often be attributed to the presence of structural violence in particular regions. Socioeconomic factors such as race and poverty affect the accessibility of and adherence to drug therapy. The efficacy of treatment programs for these drug-resistant strains depends on whether or not programmatic improvements take into account the effects of structural violence. Drugs are used in animals that are used as human food, such as cattle, pigs, chickens, fish, etc. There has been extensive use of antibiotics in animal husbandry. Many of these drugs are not considered significant drugs for use in humans, either because of their lack of efficacy or purpose in humans, (such as the use of ionopores in ruminants) or because that drug has gone out of use in humans (such as the decline in use of Sulfonamide_(medicine) due to widespread allergic reactions and antibiotic resistance among human pathogens.) Historically, regulation of antibiotic use in food animals has been limited to limiting drug residues in meat, egg, and milk products, rather than concern over the development of antibiotic resistance. This mirrors the primary concerns in human medicine, where researchers and doctors were historically more concerned about effective but non-toxic doses of drugs rather than antibiotic resistance. Evidence for the transfer of so-called superbugs from animals to humans has been scant, and most evidence shows that pathogens of concern in human populations originated in humans and are maintained there, with rare cases of transference to humans. One of the pathogens most frequently cited in popular literature — MRSA — is largely maintained in the human population, often asyptomatically, and until recently has rarely been found in food or companion animals. More significantly, evidence for the transference of fluoroquinolone resistant genes in Camploybacteria strains through poultry was cited as justification for severely restricting veterinary use of fluoroquinolones in food animals in the USA. (Use in companion animals is still permitted, and fluoroquinolones are the most commonly prescribed antibiotic to adult humans in the United States, despite guidelines which recommend it only be used in severe infections.) In 1945, in his Nobel Lecture, "Penillin," Alexander Fleming warned against the use of sub‐therapeutic doses of antibiotics – “bought by anyone in the shops” without a prescription: “The time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non‐lethal quantities of the drug make them resistant. Here is a hypothetical illustration. Mr. X. has a sore throat. He buys some penicillin and gives himself, not enough to kill the streptococci but enough to educate them to resist penicillin. He then infects his wife. Mrs. X gets pneumonia and is treated with penicillin. As the streptococci are now resistant to penicillin the treatment fails. Mrs. X dies. Who is primarily responsible for Mrs. X’s death?” In defiance of Fleming's teaching, since the late 1950s, massive quantities of non-prescription antibiotics, bought in farm fodder supplier "shops," have been fed in subtherapeutic doses to very large numbers of healthy livestock (pigs, beef cattle and poultry), for the sole purpose of increasing he weight by about six percent. All bacteria remaining alive in the manure of these animals must be resistant to the antibiotics used. Not only are they antibiotic resistant, but some of these "superbugs" acquire the ability to produce toxins, with some C. difficile organisms producing neurotoxins related to tetanus and botulinum toxins, two of the most powerful organic toxins known to man. In 2001, the National Hog Farmer warned US producers that C. difficile “is sweeping the industry, killing many piglets” (Neutkens D; "New Clostridium Claiming Baby Pigs"). Thus, factory farms for antibiotic‐fed pigs are major reservoirs of C. difficile superbugs. Increasingly, C. difficile that has particularly afflicted hospitals in Quebec, a Canadian province with large numbers of pig factory farms. "Superbugs," just by coexisting in the same environment (manure piles, contaminated water, in the throats or colons of infected patients, or hospital staff carriers) have the ability to share antibiotic resistant genesby "gene jumping," a mechanism unknown by and unimaginable to Fleming (Google: "antibiotic resistance, gene jumping"). The resistant bacteria in animals due to antibiotic exposure can be transmitted to humans via three pathways, those being through the consumption of meat, from close or direct contact with animals, or through the environment./ However, complete cooking of meat inactivates bacteria, whether or not they are antibiotic-resistant. The World Health Organization concluded antibiotics as growth promoters in animal feeds should be prohibited, in the absence of risk assessments. In 1998, European Union health ministers voted to ban four antibiotics widely used to promote animal growth (despite their scientific panel's recommendations). Regulation banning the use of antibiotics in European feed, with the exception of two antibiotics in poultry feeds, became effective in 2006. In Scandinavia, there is evidence that the ban has led to a lower prevalence of antimicrobial resistance in (nonhazardous) animal bacterial populations. In the USA, federal agencies do not collect data on antibiotic use in animals, but animal-to-human spread of drug-resistant organisms has been demonstrated in research studies. Antibiotics are still used in U.S. animal feed, along with other ingredients that represent safety concerns. Growing U.S. consumer concern about using antibiotics in animal feed has led to a niche market of "antibiotic-free" animal products, but this small market is unlikely to change entrenched, industry-wide practices. In 2001, the Union of Concerned Scientists estimated that greater than 70% of the antibiotics used in the US are given to food animals (for example, chickens, pigs and cattle), in the absence of disease. Hence, the amounts given are termed "sub-therapeutic", i.e., insufficient to combat disease—because no demonstrable disease is present. Sub-therapeutic dosages kills some, but not all, of the bacterial organisms in the animal—leaving those that are naturally antibiotic-resistant. Studies have shown, however, that the overall population levels of bacteria are essentially unchanged; only the mix of bacteria is affected.][ Thus the actual mechanism by which sub-therapeutic antibiotic feed additives serve as growth promotors is unclear. Some people have speculated that animals and fowl in feedlot environments may have sub-clinical infections, which are cured by low levels of antibiotics in feed, thereby allowing the creatures to thrive; but no convincing evidence has been advanced for this theory. As the bacterial load in an animal is essentially unchanged by use of antibiotic feed additives, the mechanism of growth promotion is overwhelmingly likely to be something other than "killing off the bad bugs." In 2000, the US Food and Drug Administration (FDA) announced their intention to revoke approval of fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone-resistant Campylobacter infections in humans. The final decision to ban fluoroquinolones from use in poultry production was not made until five years later because of challenges from the food animal and pharmaceutical industries. During 2007, two federal bills (S. 549 and H.R. 962) aimed at phasing out "nontherapeutic" antibiotics in US food animal production. The Senate bill, introduced by Sen. Edward "Ted" Kennedy, died. The House bill, introduced by Rep. Louise Slaughter, died after being referred to Committee. In the United States, evidence of emergence of antibiotic-resistant bacterial strains due to wide use of antibiotics to promote weight gain in livestock was determined by the United States Food and Drug Administration in 1977, but nothing effective was done to prevent the practice. 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. On April 11, 2012 the FDA announced a voluntary program to phase out unsupervised use of drugs as feed additives and convert approved over-the-counter uses for antibiotics to prescription use only, requiring veterinarian supervision of their use and a prescription. Antibiotics have been polluting the environment since their introduction through human waste (medication, farming), animals, and the pharmaceutical industry. Along with antibiotic waste, resistant bacteria follow, thus introducing antibiotic resistant bacteria into the environment. As bacteria replicate quickly, the resistant bacteria that enter the environment replicate their resistance genes as they continue to divide. Additionally, bacteria carrying resistance genes have the ability to spread those genes to other species via horizontal gene transfer. Therefore, even if the specific antibiotic is no longer introduced into the environment, antibiotic resistance genes will persist through the bacteria that have since replicated without continual exposure. A study done of the Poudre River implicated wastewater treatment plants, as well as animal feeding operations in the dispersal of antibiotic resistance genes into the environment. This research was done using molecular signatures in order to determine the sources, and the location at the Poudre River was chosen due to lack of other anthropogenic influences upstream. The study indicates that monitoring of antibiotic resistance genes may be useful in determining not only the point of origin of their release, but also how these genes persist in the environment. Additionally, studying physical and chemical methods of treatment may alleviate pressure of antibiotic resistance genes in the environment, and thus their entry back into human contact. Antibiotic resistance can be a result of horizontal gene transfer, and also of unlinked point mutations in the pathogen genome at a rate of about 1 in 108 per chromosomal replication. The antibiotic action against the pathogen can be seen as an environmental pressure. Those bacteria with a mutation that allows them to survive live to reproduce. They then pass this trait to their offspring, which leads to the evolution of a fully resistant colony. The four main mechanisms by which microorganisms exhibit resistance to antimicrobials are: There are three known mechanisms of fluoroquinolone resistance. Some types of efflux pumps can act to decrease intracellular quinolone concentration. In Gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug's effectiveness. Research has shown the bacterial protein LexA may play a key role in the acquisition of bacterial mutations giving resistance to quinolones and rifampicin. Antibiotic resistance can also be introduced artificially into a microorganism through laboratory protocols, sometimes used as a selectable marker to examine the mechanisms of gene transfer or to identify individuals that absorbed a piece of DNA that included the resistance gene and another gene of interest. A recent study demonstrated that the extent of horizontal gene transfer among Staphylococcus is much greater than previously expected—and encompasses genes with functions beyond antibiotic resistance and virulence, and beyond genes residing within the mobile genetic elements. For a long time it has been thought that for a microorganism to become resistant to an antibiotic, it must be in a large population. However, recent findings show that there is no necessity of large populations of bacteria for the appearance of antibiotic resistance. We know now, that small populations of E.coli in an antibiotic gradient can become resistant. Any heterogeneous environment with respect to nutrient and antibiotic gradients may facilitate the development of antibiotic resistance in small bacterial populations and this is also true for the human body. Researchers hypothesize that the mechanism of resistance development is based on four SNP mutations in the genome of E.coli produced by the gradient of antibiotic. These mutations confer the bacteria emergence of antibiotic resistance. A common misconception is that a person can become resistant to certain antibiotics. It is a strain of microorganism that can become resistant, not a person's body. Staphylococcus aureus (colloquially known as "Staph aureus" or a "Staph infection") is one of the major resistant pathogens. Found on the mucous membranes and the human skin of around a third of the population, it is extremely adaptable to antibiotic pressure. It was one of the earlier bacteria in which penicillin resistance was found—in 1947, just four years after the drug started being mass-produced. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. Staphylococcus aureusMethicillin-resistant (MRSA) was first detected in Britain in 1961, and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of sepsis in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin. This left vancomycin as the only effective agent available at the time. However, strains with intermediate (4-8 μg/ml) levels of resistance, termed glycopeptide-intermediate Staphylococcus aureus (GISA) or vancomycin-intermediate Staphylococcus aureus (VISA), began appearing in the late 1990s. The first identified case was in Japan in 1996, and strains have since been found in hospitals in England, France and the US. The first documented strain with complete (>16 μg/ml) resistance to vancomycin, termed Staphylococcus aureusvancomycin-resistant (VRSA) appeared in the United States in 2002. However, in 2011 a variant of vancomycin has been tested that binds to the lactate variation and also binds well to the original target, thus reinstates potent antimicrobial activity. A new class of antibiotics, oxazolidinones, became available in the 1990s, and the first commercially available oxazolidinone, linezolid, is comparable to vancomycin in effectiveness against MRSA. Linezolid-resistance in S. aureus was reported in 2001. Community-acquired MRSA (CA-MRSA) has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases, including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. MRSA is the most frequently identified antimicrobial drug-resistant pathogen in US hospitals. The epidemiology of infections caused by MRSA is rapidly changing. In the past 10 years][, infections caused by this organism have emerged in the community. The two MRSA clones in the United States most closely associated with community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often contain Panton-Valentine leukocidin (PVL) genes and, more frequently, have been associated with skin and soft tissue infections. Outbreaks of CA-MRSA infections have been reported in correctional facilities, among athletic teams, among military recruits, in newborn nurseries, and among men who have sex with men. CA-MRSA infections now appear endemic in many urban regions and cause most CA-S. aureus infections. Streptococcus pyogenes (Group A Streptococcus: GAS) infections can usually be treated with many different antibiotics. Early treatment may reduce the risk of death from invasive group A streptococcal disease. However, even the best medical care does not prevent death in every case. For those with very severe illness, supportive care in an intensive care unit may be needed. For persons with necrotizing fasciitis, surgery often is needed to remove damaged tissue. Strains of S. pyogenes resistant to macrolide antibiotics have emerged; however, all strains remain uniformly sensitive to penicillin. Resistance of Streptococcus pneumoniae to penicillin and other beta-lactams is increasing worldwide. The major mechanism of resistance involves the introduction of mutations in genes encoding penicillin-binding proteins. Selective pressure is thought to play an important role, and use of beta-lactam antibiotics has been implicated as a risk factor for infection and colonization. S. pneumoniae is responsible for pneumonia, bacteremia, otitis media, meningitis, sinusitis, peritonitis and arthritis. Multidrug-resistant Enterococcus faecalis and Enterococcus faecium are associated with nosocomial infections. Among these strains, penicillin-resistant Enterococcus was seen in 1983, Enterococcusvancomycin-resistant in 1987, and linezolid-resistant Enterococcus in the late 1990s.][ Pseudomonas aeruginosa is a highly prevalent opportunistic pathogen. One of the most worrisome characteristics of P. aeruginosa is its low antibiotic susceptibility, which is attributable to a concerted action of multidrug efflux pumps with chromosomally encoded antibiotic resistance genes (for example, mexAB-oprM, mexXY, etc.) and the low permeability of the bacterial cellular envelopes. Pseudomonas aeruginosa has the ability to produce HAQs and it has been found that HAQs have prooxidant effects, and overexpressing modestly increased susceptibility to antibiotics. The study experimented with the Pseudomonas aeruginosa biofilms and found that a disruption of relA and spoT genes produced an inactivation of the Stringent response (SR) in cells who were with nutrient limitation which provides cells be more susceptible to antibiotics. Clostridium difficile is a nosocomial pathogen that causes diarrheal disease in hospitals world wide. Clindamycin-resistant C. difficile was reported as the causative agent of large outbreaks of diarrheal disease in hospitals in New York, Arizona, Florida and Massachusetts between 1989 and 1992. Geographically dispersed outbreaks of C. difficile strains resistant to fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, were also reported in North America in 2005. Infection with Escherichia coli and Salmonella can result from the consumption of contaminated food. When both bacteria are spread, serious health conditions arise. Many people are hospitalized each year after becoming infected, with some dying as a result. Since 1993, some strains of E. coli have become resistant to multiple types of fluoroquinolone antibiotics.][ On November 5, 2004, the Centers for Disease Control and Prevention (CDC) reported an increasing number of Acinetobacter baumannii bloodstream infections in patients at military medical facilities in which service members injured in the Iraq/Kuwait region during Operation Iraqi Freedom and in Afghanistan during Operation Enduring Freedom were treated. Most of these showed multidrug resistance (MRAB), with a few isolates resistant to all drugs tested. Tuberculosis is increasing across the globe, especially in developing countries, over the past few years. TB resistant to antibiotics is called MDR TB (Multidrug Resistant TB). The rise of the HIV/AIDS epidemic has contributed to this. TB was considered one of the most prevalent diseases, and did not have a cure until the discovery of Streptomycin by Selman Waksman in 1943. However, the bacteria soon developed resistance. Since then, drugs such as isoniazid and rifampin have been used. M. tuberculosis develops resistance to drugs by spontaneous mutations in its genomes. Resistance to one drug is common, and this is why treatment is usually done with more than one drug. Extensively Drug Resistant TB (XDR TB) is TB that is also resistant to the second line of drugs. Resistance of Mycobacterium tuberculosis to isoniazid, rifampin, and other common treatments has become an increasingly relevant clinical challenge. (For more on Drug Resistant TB, visit the Multi-drug resistant tuberculosis page.) Rational use of antibiotics may reduce the chances of development of opportunistic infection by antibiotic-resistant bacteria due to dysbacteriosis.Our immune systems will cure minor bacterial infections on their own. If we give it the chance without relying on antibiotics to cure a small infection, we will be less likely to become immune or resistant to the antibiotic. It is also important to note that antibiotics will not cure viral infections. Taking an antibiotic unnecessarily to treat a viral infection can lead to the resistance of antibiotics In one study, the use of fluoroquinolones is clearly associated with Clostridium difficile infection, which is a leading cause of nosocomial diarrhea in the United States, and a major cause of death, worldwide. Vaccines do not have the problem of resistance because a vaccine enhances the body's natural defenses, while an antibiotic operates separately from the body's normal defenses. Nevertheless, new strains may evolve that escape immunity induced by vaccines; for example an updated influenza vaccine is needed each year. While theoretically promising, antistaphylococcal vaccines have shown limited efficacy, because of immunological variation between Staphylococcus species, and the limited duration of effectiveness of the antibodies produced. Development and testing of more effective vaccines is under way. The Australian Commonwealth Scientific and Industrial Research Organization (CSIRO), realizing the need for the reduction of antibiotic use, has been working on two alternatives. One alternative is to prevent diseases by adding cytokines instead of antibiotics to animal feed. These proteins are made in the animal body "naturally" after a disease and are not antibiotics, so they do not contribute to the antibiotic resistance problem. Furthermore, studies on using cytokines have shown they also enhance the growth of animals like the antibiotics now used, but without the drawbacks of nontherapeutic antibiotic use. Cytokines have the potential to achieve the animal growth rates traditionally sought by the use of antibiotics without the contribution of antibiotic resistance associated with the widespread nontherapeutic uses of antibiotics currently used in the food animal production industries. Additionally, CSIRO is working on vaccines for diseases. Phage therapy, an approach that has been extensively researched and used as a therapeutic agent for over 60 years, especially in the Soviet Union, represents a potentially significant but currently underdeveloped approach to the treatment of bacterial disease. Phage therapy was widely used in the United States until the discovery of antibiotics, in the early 1940s. Bacteriophages or "phages" are viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse. Phage therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. Bacteriophage therapy is an important alternative to antibiotics in the current era of multidrug resistant pathogens. A review of studies that dealt with the therapeutic use of phages from 1966–1996 and few latest ongoing phage therapy projects via internet showed: phages were used topically, orally or systemically in Polish and Soviet studies. The success rate found in these studies was 80–95% with few gastrointestinal or allergic side effects. British studies also demonstrated significant efficacy of phages against Escherichia coli, Acinetobacter spp., Pseudomonas spp. and Staphylococcus aureus. US studies dealt with improving the bioavailability of phage. Phage therapy may prove as an important alternative to antibiotics for treating multidrug resistant pathogens. Discovery of the structure of the viral protein PlyC is allowing researchers to understand the way it kills a significant range of pathogenic bacteria. Until recently, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics. However: "The supply of new replacement antimicrobial agents has slowed dramatically and we face the prospect of a future where we have far fewer options in the treatment of infectious disease" The potential crisis at hand is the result of a marked decrease in industry R&D, and the increasing prevalence of resistant bacteria. Infectious disease physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future. Poor financial investment in antibiotic research has exacerbated the situation In research published on October 17, 2008 in Cell, a team of scientists pinpointed the place on bacteria where the antibiotic myxopyronin launches its attack, and why that attack is successful. The myxopyronin binds to and inhibits the crucial bacterial enzyme, RNA polymerase. The myxopyronin changes the structure of the switch-2 segment of the enzyme, inhibiting its function of reading and transmitting DNA code. This prevents RNA polymerase from delivering genetic information to the ribosomes, causing the bacteria to die. In 2012, a team of the University of Leipzig modified a peptide found in honeybees. It is effective against 37 types of bacteria. One major cause of antibiotic resistance is the increased pumping activity of microbial ABC transporters, which diminishes the effective drug concentration inside the microbial cell. ABC transporter inhibitors that can be used in combination with current antimicrobials are being tested in clinical trials and are available for therapeutic regimens. Antibiotic resistance is an important tool for genetic engineering. By constructing a plasmid that contains an antibiotic resistance gene as well as the gene being engineered or expressed, a researcher can ensure that when bacteria replicate, only the copies that carry the plasmid survive. This ensures that the gene being manipulated passes along when the bacteria replicates. The most commonly used antibiotics in genetic engineering are generally "older" antibiotics that have largely fallen out of use in clinical practice. These include: Industrially the use of antibiotic resistance is disfavored since maintaining bacterial cultures would require feeding them large quantities of antibiotics. Instead, the use of auxotrophic bacterial strains (and function-replacement plasmids) is preferred.

Tetracycline
InChI=1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1Yes 
Key:OFVLGDICTFRJMM-WESIUVDSSA-NYes  Tetracycline (INN) is a broad-spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria, indicated for use against many bacterial infections. It is a protein synthesis inhibitor. It is commonly used to treat acne today, and, more recently, rosacea, and is historically important in reducing the number of deaths from cholera. Tetracycline is marketed under the brand names Sumycin, Tetracyn, and Panmycin, among others. Actisite is a thread-like fiber formulation used in dental applications. It is also used to produce several semisynthetic derivatives, which together are known as the tetracycline antibiotics. The term "tetracycline" is also used to denote the four-ring system of this compound; "tetracyclines" are related substances that contain the same four-ring system. Tetracycline binds to the 30S subunit of microbial ribosomes. It inhibits protein synthesis by blocking the attachment of charged aminoacyl-tRNA to the A site on the ribosome. Thus, it prevents introduction of new amino acids to the nascent peptide chain. The action is usually inhibitory and reversible upon withdrawal of the drug. Mammalian cells are less vulnerable to the effect of tetracyclines, as these contain no 30S ribosomal subunits (only prokaryotes have 30s subunit), but tetracycline also may bind to the eukaryotic 80S ribosome.][ Tetracyclines have a broad spectrum of antibiotic action. Originally, they possessed some level of bacteriostatic activity against almost all medically relevant aerobic and anaerobic bacterial genera, both Gram-positive and Gram-negative, with a few exceptions, such as Pseudomonas aeruginosa and Proteus spp., which display intrinsic resistance. However, acquired (as opposed to inherent) resistance has proliferated in many pathogenic organisms and greatly eroded the formerly vast versatility of this group of antibiotics. Resistance amongst Staphylococcus spp., Streptococcus spp., Neisseria gonorrhoeae, anaerobes, members of the Enterobacteriaceae and several other previously sensitive organisms is now quite common. Tetracyclines remain especially useful in the management of infections by certain obligately intracellular bacterial pathogens such as Chlamydia, Mycoplasma and Rickettsia. They are also of value in spirochaetal infections, such as syphilis, leptospirosis and Lyme disease. Certain rare or exotic infections, including anthrax, plague and brucellosis, are also susceptible to tetracyclines. These agents also have activity against certain eukaryotic parasites, including those responsible for diseases such as malaria and balantidiasis. Bacteria usually acquire resistance to tetracycline from horizontal transfer of a gene that either encodes an efflux pump or a ribosomal protection protein. Efflux pumps actively eject tetracycline from the cell, preventing the buildup of an inhibitory concentration of tetracycline in the cytoplasm. Ribosomal protection proteins interact with the ribosome and dislodge tetracycline from the ribosome, allowing for translation to continue. The tetracyclines, a large family of antibiotics, were discovered as natural products by Benjamin Minge Duggar in 1945 and first prescribed in 1948. Under Yellapragada Subbarao, Benjamin Duggar made his discovery of the first tetracycline antibiotic, chlorotetracycline (Aureomycin), at Lederle Laboratories in 1945. In 1950, Harvard University professor Robert Burns Woodward determined the chemical structure of the related substance, oxytetracycline (Terramycin); the patent protection for its fermentation and production was also first issued in 1950. A research team of seven scientists (K.J. Brunings, Francis A. Hochstein, C.R. Stephens, Lloyd Hillyard Conover, Abraham Bavley, Richard Pasternack, and Peter P. Regna) at Pfizer, in collaboration with Woodward, participated in the two-year research leading to the discovery. Pfizer was of the view that it deserved the right to a patent on tetracycline and filed its Conover application in October 1952. Cyanamid filed its Boothe-Morton application for similar rights in March 1953, while Heyden Chemicals filed its Minieri application in September 1953, named after scientist P. Paul Minieri, to obtain a patent on tetracycline and its fermentation process. This resulted in tetracycline litigation in which the winner would have to prove beyond reasonable doubt of priority invention and tetracycline’s natural state. Nubian mummies studied in the 1990s were found to contain significant levels of tetracycline; the beer brewed at the time could have been the source. Tetracycline sparked the development of many chemically altered antibiotics, so has proved to be one of the most important discoveries made in the field of antibiotics.][ It is used to treat many Gram-positive and Gram-negative bacteria.][ Like some other antibiotics, it is also used in the treatment of acne. Use of the tetracycline antibiotics group is problematic; they can:][ Caution should be exercised in long-term use with breastfeeding. Short-term use is safe; bioavailability in milk is low to nil. In 2010, the FDA added tetracycline to its Adverse Event Reporting System (AERS). The AERS contains a list of medications under investigation by the FDA for potential safety issues. The list is published quarterly and available online. The AERS cites a potential link between the use of tetracycline products and Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme. It is first-line therapy for Rocky Mountain spotted fever (Rickettsia), Lyme disease (B. burgdorferi), Q fever (Coxiella), psittacosis and lymphogranuloma venereum (Chlamydia), and to eradicate nasal carriage of meningococci. Tetracycline tablets were used in the plague outbreak in India in 1992. Since tetracycline is absorbed into bone, it is used as a marker of bone growth for biopsies in humans. Tetracycline labeling is used to determine the amount of bone growth within a certain period of time, usually a period of approximately 21 days. Tetracycline is incorporated into mineralizing bone and can be detected by its fluorescence. In "double tetracycline labeling", a second dose is given 11–14 days after the first dose, and the amount of bone formed during that interval can be calculated by measuring the distance between the two fluorescent labels. Tetracycline is also used as a biomarker in wildlife to detect consumption of medicine- or vaccine-containing baits. In genetic engineering, tetracycline is used in transcriptional activation. It is also one of the antibiotics used to treat ulcers caused by bacterial infections. In cancer research at Harvard Medical School, tetracycline has been used to switch off leukemia in genetically altered mice, and to do so reliably, when added to their drinking water. A technique being developed for the control of the mosquito species Aedes aegypti uses a strain that is genetically modified to require tetracycline to develop beyond the larval stage. Modified males raised in a laboratory will develop normally as they are supplied with this chemical and can be released into the wild. Their subsequent offspring will inherit this trait, but will find no tetracycline in their environment and so will never develop into adults. Tetracycline is used in cell biology as a selective agent in cell culture systems. It is toxic to prokaryotic and eukaryotic cells and selects for cells harboring the bacterial tetr gene, which encodes a 399-amino-acid, membrane-associated protein. This protein actively exports tetracycline from the cell, rendering cells harboring this gene more resistant to the drug. The yellow crystalline powder can be dissolved in water (20 mg/ml) or ethanol (5 mg/ml), and is routinely used at 10 mg/l in cell culture. In cell culture at 37°C (99°F), it is stable for days, with a half-life of approximately 24 hours. M: MOU anat/devp noco/cofa (c)/cogi/tumr, sysi proc (peri), drug (A1) Docosanol M: INT, SF, LCT anat/phys/devp noco (i/b/d/q/u/r/p/m/k/v/f)/cong/tumr (n/e/d), sysi/epon proc, drug (D2/3/4/5/8/11) M: SKA anat/phys/devp noco/cong/tumr, sysi/epon proc, drug (D10) M: BAC bact (clas) gr+f/gr+a (t)/gr-p (c)/gr-o drug (J1p, w, n, m, vacc) M: EAR anat (e/p)/phys/devp noco/cong, epon proc, drug (S2)

Pill (pharmacy)
A pill was originally defined as a small, round, solid pharmaceutical oral dosage form that was in use before the advent of tablets and capsules. Pills were made by mixing the active ingredients with an excipient such as glucose syrup in a mortar and pestle to form a paste, then rolling the mass into a long cylindrical shape (called a "pipe"), and dividing it into equal portions, which were then rolled into balls, and often coated with sugar to make them more palatable. Today, "pills" include tablets, capsules, and variants thereof like caplets -- essentially any directly ingestible oral dosage forms. Some pills are designed to contain sensory and communication elements that collect and wirelessly transmit physiological information after being swallowed.
penicillin V potassium Pharmacology Matter
Combined oral contraceptive pill

The combined oral contraceptive pill (COCP), often referred to as the birth-control pill or colloquially as "the Pill", is a birth control method that includes a combination of an estrogen (estradiol) and a progestogen (progestin). When taken by mouth every day, these pills inhibit female fertility. They were first approved for contraceptive use in the United States in 1960, and are a very popular form of birth control. They are currently used by more than 100 million women worldwide and by almost 12 million women in the United States. Use varies widely by country, age, education, and marital status: one third of women aged 16–49 in the United Kingdom currently use either the combined pill or a progestogen-only "minipill", compared to only 1% of women in Japan.

Combined oral contraceptive pills should be taken at the same time each day. If one or more tablets are forgotten for more than 12 hours, contraceptive protection will be reduced. Most brands of combined pills are packaged in one of two different packet sizes, with days marked off for a 28 day cycle. For the 21-pill packet, a pill is consumed daily for three weeks, followed by a week of no pills. For the 28-pill packet, 21 pills are taken, followed by week of placebo or sugar pills. A woman on the pill will have a withdrawal bleed sometime during the placebo week, and is still protected from pregnancy during this week. There are also two newer combination birth control pills (Yaz 28 and Loestrin 24 Fe) that have 24 days of active hormone pills, followed by 4 days of placebo.

Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original hormonal method—the combined oral contraceptive pill—was first marketed as a contraceptive in 1960. In the ensuing decades many other delivery methods have been developed, although the oral and injectable methods are by far the most popular. Altogether, 18% of the world's contraceptive users rely on hormonal methods. Hormonal contraception is highly effective: when taken on the prescribed schedule, users of steroid hormone methods experience pregnancy rates of less than 1% per year. Perfect-use pregnancy rates for most hormonal contraceptives are usually around the 0.3% rate or less. Currently available methods can only be used by women; the development of a male hormonal contraceptive is an active research area.

There are two main types of hormonal contraceptive formulations: combined methods which contain both an estrogen and a progestin, and progestogen-only methods which contain only progesterone or one of its synthetic analogues (progestins). Combined methods work by suppressing ovulation and thickening cervical mucus; while progestogen-only methods reduce the frequency of ovulation, most of them rely more heavily on changes in cervical mucus. The incidence of certain side effects is different for the different formulations: for example, breakthrough bleeding is much more common with progestogen-only methods. Certain serious complications occasionally caused by estrogen-containing contraceptives are not believed to be caused by progestogen-only formulations: deep vein thrombosis is one example of this.

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Just Like a Pill

"Just Like a Pill" is a pop rock song by American singer Pink. It was written and produced by Dallas Austin and Pink for her second studio album, Missundaztood. The lyrics of the song deal with getting out of painful relationships, with a subtheme about drug abuse.

The song was released worldwide as the third single from Missundaztood in June 2002 and was a commercial success, peaking at number eight on the Hot 100Billboard in the United States. It also performed well internationally, becoming her first number-one in the United Kingdom and reaching the top 10 in, amongst other countries, Ireland, France, the Netherlands and Sweden.


Beta-lactam antibiotics

β-Lactam antibiotics (beta-lactam antibiotics) are a broad class of antibiotics, consisting of als that contains a β-lactam ring in their molecular structures. This includes penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Up until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds.

Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-lactamase, an enzyme that attacks the β-lactam ring. To overcome this resistance, β-lactam antibiotics are often given with β-lactamase inhibitors such as clavulanic acid.

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