document_title: The Phantom of the Opera

question_text: when did the phantom of the opera take place

text: The Phantom of the Opera

text: History behind the novel[edit]

text: Leroux first decided he would become a lawyer, but after he spent his inheritance gambling, he became a reporter for L’Echo de Paris. When he had this job, he was asked to write about and critique dramas in the area as well as being a reporter in a courtroom. With his job, he was able to travel frequently, but then he came back to Paris where he became a writer. Because of his fascination with both Edgar Allen Poe and Sir Arthur Conan Doyle, he wrote a mystery with a detective called The Mystery of the Yellow Room in 1907 and four years later he published Le Fantôme de l’Opéra.[3] The novel was first published within newspapers before finally being published as a novel in 1911.[4]

text: The Phantom of the Opera's origins came from Leroux's curiosity with the phantom being real. In the prologue he tells the readers about the phantom and the research that he did to prove the truth of the ghost. His detailed account tells the audience of why he believes this phantom and the in-depth research he did to uncover what he believed to be the truth. His findings connected the corpse from the opera house to the Persian phantom himself. [5] The claims from the prologue of his novel were ones that Leroux held onto even up until his death in 1927. [6]

text: The setting of The Phantom of the Opera came from an actual opera house that Leroux had heard the rumors about from the time the opera house was finished. The details about the Palais Garnier and the rumors surrounding it are ones that are closely linked in Leroux's writing. The underground water tank that he had written about is one that is accurate to this opera house and is used only today by firefighters training. The mystery that Leroux uses in his novel about the phantom are ones that still are a mystery to this day. [6]

text: Plot summary[edit]

text: In Paris in the 1890s, the Palais Garnier opera house is believed to be haunted by an entity known as the Phantom of the Opera, or simply the Opera Ghost. A stagehand named Joseph Buquet is found hanged and the rope around his neck goes missing. At a gala performance for the retirement of the opera house's two managers, a young little-known Swedish soprano, Christine Daaé, is called upon to sing in the place of the Opera's leading soprano, Carlotta, who is ill, and her performance is an astonishing success. The Vicomte Raoul de Chagny, who was present at the performance, recognizes her as his childhood playmate and recalls his love for her. He attempts to visit her backstage, where he hears a man complimenting her from inside her dressing room. He investigates the room once Christine leaves, only to find it empty.

text: At Perros-Guirec, Christine meets with Raoul, who confronts her about the voice he heard in her room. Christine tells him she has been tutored by the Angel of Music, whom her father used to tell them about. When Raoul suggests that she might be the victim of a prank, she storms off. Christine visits her father's grave one night, where a mysterious figure appears and plays the violin for her. Raoul attempts to confront it but is attacked and knocked out in the process.

text: Back at the Palais Garnier, the new managers receive a letter from the Phantom demanding that they allow Christine to perform the lead role of Marguerite in Faust, and that box 5 be left empty for his use, lest they perform in a house with a curse on it. The managers ignore his demands as a prank, resulting in disastrous consequences: Carlotta ends up croaking like a toad, and the chandelier suddenly drops into the audience, killing a spectator. The Phantom, having abducted Christine from her dressing room, reveals himself as a deformed man called Erik. Erik intends to keep her in his lair with him for a few days, but she causes him to change his plans when she unmasks him and, to the horror of both, beholds his noseless, lipless, sunken-eyed face, which resembles a skull dried up by the centuries, covered in yellowed dead flesh.

text: Fearing that she will leave him, he decides to keep her with him forever, but when Christine requests release after two weeks, he agrees on the condition that she wear his ring and be faithful to him. On the roof of the opera house, Christine tells Raoul about her abduction and makes Raoul promise to take her away to a place where Erik can never find her, even if she resists. Raoul tells Christine he will act on his promise the next day, to which she agrees. However, Christine sympathizes with Erik and decides to sing for him one last time as a means of saying goodbye. Unbeknownst to Christine and Raoul, Erik has been watching them and overheard their whole conversation.

text: The following night, the enraged and jealous Erik abducts Christine during a production of Faust and tries to force her to marry him. Raoul is led by a mysterious opera regular known as "The Persian" into Erik's secret lair deep in the bowels of the opera house, but they end up trapped in a mirrored room by Erik, who threatens that unless Christine agrees to marry him, he will kill them and everyone in the Opera House by using explosives. Christine agrees to marry Erik. Erik initially tries to drown Raoul and the Persian, using the water which would have been used to douse the explosives, but Christine begs and offers to be his "living bride", promising him not to kill herself after becoming his bride, as she had both contemplated and attempted earlier in the novel. Erik eventually releases Raoul and the Persian from his torture chamber.

text: When Erik is alone with Christine, he lifts his mask to kiss her on her forehead and is given a kiss back. Erik reveals that he has never received a kiss, not even from his own mother, nor has been allowed to give one and is overcome with emotion. He and Christine then cry together and their tears "mingle". Erik later says that he has never felt so close to another human being. He allows the Persian and Raoul to escape, though not before making Christine promise that she will visit him on his death day, and return the gold ring he gave her. He also makes the Persian promise that afterward he will go to the newspaper and report his death, as he will die soon and will die "of love". Indeed, sometime later Christine returns to Erik's lair, buries him somewhere he will never be found (by Erik's request) and returns the gold ring. Afterward, a local newspaper runs the simple note: "Erik is dead". Christine and Raoul (who finds out that Erik has killed his older brother) elope together, never to return.

text: Passages narrated directly by the Persian and the final chapter piece together Erik's life: the son of a construction business owner deformed from birth, he ran away from his native Normandy to work in fairs and in caravans, schooling himself in the arts of the circus across Europe and Asia, and eventually building trick palaces in Persia and Turkey. Eventually, he returned to France and, wearing a mask, started his own construction business. After being subcontracted to work on the foundations of the Palais Garnier, Erik had discreetly built himself a lair to disappear in, complete with hidden passages and other tricks that allowed him to spy on the managers.

text: Characters[edit]

text:
Erik: The Phantom of the Opera, a deformed former conjuror also referred to as the Angel of Music and the Opera Ghost. He tutors and eventually becomes obsessed with Christine Daaé.
Christine Daaé: A young Swedish soprano at the Paris Opera House with whom the Phantom falls in love.
Vicomte Raoul de Chagny: Christine's childhood friend and love interest.
The Persian: A mysterious man from Erik's past.
Comte Phillipe de Chagny: Raoul's older brother.
Armand Moncharmin and Firmin Richard: The new managers of the opera house.
Madame Giry: The opera's box keeper.
Meg Giry: Often referred to as "Little Meg", Madame Giry's only daughter, a ballet girl.
Debienne and Poligny: The previous managers of the opera house
Carlotta: A spoiled prima donna; the lead soprano of the Paris Opera House.
Madame Valérius: Christine's elderly guardian.

text: Themes[edit]

text: Music[edit]

text: Leroux uses the operatic setting in The Phantom of the Opera to use music as a device for foreshadowing.[7] Ribière makes note that Leroux was once a theatre critic and his brother was a musician, so he was knowledgeable about music and how to use it as a framing device. She uses the example of how Leroux introduces the song Danse Macabre which means "dance of death" in the gala scene which foreshadows the graveyard scene that comes later where the Phantom plays the fiddle for Christine and attacks Raoul when he tries to intervene.

text: Drumright points out that music is evident throughout the novel in that it is the basis for Christine and Erik's relationship. Christine sees Erik as her Angel of Music that her father promised would come to her one day. The Phantom sees Christine as his musical protege, and he uses his passion for music to teach her everything he knows.[4]

text: Mystery[edit]

text: Stylistically, the novel is framed as a mystery novel as it is narrated through a detective pulling his information from various forms of research.[8] The mystery being uncovered is the Phantom who lurks through the opera house, seemingly appearing in places out of nowhere as if by magic.[9]

text: Gothic horror[edit]

text: In his article, Fitzpatrick compares the Phantom to other monsters featured in Gothic horror novels such as Frankenstein, Dr. Jekyll, Dorian Gray, and Dracula. The Phantom has a torture chamber where he kidnaps and kills people, and the walls of the chapel in the graveyard are lined with human bones.[9] Indeed, Drumright notes that The Phantom of the Opera checks off every trope necessary to have a Gothic novel according to the Encyclopedia of Literature's description which says, “Such novels were expected to be dark and tempestuous and full of ghosts, madness, outrage, superstition, and revenge.”[10] Although the Phantom is really just a disfigured man, he has ghost-like qualities in that no one can ever find him or his lair and he is seen as a monster. People are frightened by him because of his deformities and the acts of violence he commits.[4]

text: Romance[edit]

text: The novel features a love triangle between the Phantom, Christine, and Raoul. Raoul is seen as Christine's childhood love whom she is familiar with and has affection for. He is rich and therefore offers her security as well as a wholesome, Christian marriage. The Phantom, on the other hand, is not familiar. He is dark, ugly, and dangerous and therefore represents the forbidden love. However, Christine is drawn to him because she sees him as her Angel of Music, and she pities his existence of loneliness and darkness.[4]

text: Critical reception[edit]

text: By the time Leroux published The Phantom of the Opera, he had already gained credibility as a crime mystery author in both French and English speaking countries. He had written six novels prior, two of which had garnered substantial popularity within their first year of publication called The Mystery of the Yellow Room and The Perfume of the Lady in Black.[7] The Phantom of the Opera, however, did not attain as much success as these previous novels, being particularly unpopular in France where it was first published.[11] One book review from the New York Times expressed a disappointment in the way the phantom was portrayed, saying that the feeling of suspense and horror is lost once it is found out that the phantom is just a man and not a real ghost.[12]The majority of the notability that the novel acquired early on was due to its publication in a series of installments in French, American, and English newspapers. This serialized version of the story became important when it was read and sought out by Universal Pictures to be adapted into a movie in 1925.[11]

text: Based on the critical reviews of two modern day readers of the book, Sean Fitzpatrick and Cathleen Myers, the novel is praiseworthy for its drama, but overall it does not rise to the standards of great literature. Fitzpatrick claims that "The Phantom of the Opera is not a great book, but it is a great read."[9] He digresses that even though the book is not good enough to be in the canon of great literature, there are many aspects of it that make it fun to read such as the drama of the "whodunnit" plot, the investigative styling of the book which pretends to pull from real life newspaper articles and interviews relating to the Paris Opera House, and the character Erik (the phantom) who fills the roles of the "mad genius", disfigured monster, and one of three in a love triangle all at once. Fitzpatrick argues that all of these elements make the book good for light reading.[9] Myers agrees that the novel makes for a good "airplane read", but says that it fails in terms of being a good mystery novel. She claims that one of the book's downfalls is that one of the important characters - the mysterious Persian - is introduced too late in the storyline. Another glaring omission that she sees in the book is that the Phantom is left unexplained. Myers also criticizes Christine's love for Raoul whom she claims is an idiot, saying he "makes Jonathon Harker and Lord Godalming in Dracula look like rocket scientists."[8]

text: Adaptations[edit]

text: There have been many literary and other dramatic works based on Leroux's novel, ranging from stage musicals to films to children's books. Some well known stage and screen adaptations of the novel are the 1925 film and the Andrew Lloyd Webber musical. In Webber's musical, he was focused on writing more of a romance piece and found the book and the musical took off from there. Leroux's novel was more than just a mystery and had romance and other genres, that would appeal to more audiences. [13] Webber used accounts from within the novel in the musical as well such as the real-life event of the chandelier falling. [14] This musical even after being produced in the mid-80s, has still remained popular with people today. The musical has received more than fifty awards and is seen by many as being the most popular musical on Broadway. [13]

text: Leroux’s novel was created into two silent films during the history and adaptations of the novel. The first production of the novel into a silent film was produced by German adaptation called, Das Gespenst im Opernhaus. This film though has no living proof left and is lost due to no pictures being taken or an actual copy of the film is preserved. The last living knowledge of the film is that it was made in 1916 and was directed by Ernest Matray. [15]

text: The next adaptation or silent film was made in 1925 by Universal Studios. This version starred Lon Chaney Sr. as the phantom. Due to tensions on the set, there was a switch in directors and Edward Sedgwick finished the film while changing the direction the movie was going to take. His take on the novel and making it a dark romantic movie with comedy wasn’t popular by audiences. [15]Finally, the film was adapted one last time by Maurice Pivar and Louis Weber where they took out most of Sedgwick’s adaptation and stuck to the original film. This time, the movie was a success with audiences in 1925. [15]


document_title: Antibiotics

question_text: when were the first antibiotics used to treat diseases

root

text: Antibiotics

text: Medical uses[edit]

text: Antibiotics are used to treat or prevent bacterial infections,[15] and sometimes protozoan infections. (Metronidazole is effective against a number of parasitic diseases). When an infection is suspected of being responsible for an illness but the responsible pathogen has not been identified, an empiric therapy is adopted.[16] This involves the administration of a broad-spectrum antibiotic based on the signs and symptoms presented and is initiated pending laboratory results that can take several days.[15][16]

tag: p

text: When the responsible pathogenic microorganism is already known or has been identified, definitive therapy can be started. This will usually involve the use of a narrow-spectrum antibiotic. The choice of antibiotic given will also be based on its cost. Identification is critically important as it can reduce the cost and toxicity of the antibiotic therapy and also reduce the possibility of the emergence of antimicrobial resistance.[16] To avoid surgery, antibiotics may be given for non-complicated acute appendicitis.[17]

text: Antibiotics may be given as a preventive measure (prophylactic) and this is usually limited to at-risk populations such as those with a weakened immune system (particularly in HIV cases to prevent pneumonia), those taking immunosuppressive drugs, cancer patients and those having surgery.[15] Their use in surgical procedures is to help prevent infection of incisions. They have an important role in dental antibiotic prophylaxis where their use may prevent bacteremia and consequent infective endocarditis. Antibiotics are also used to prevent infection in cases of neutropenia particularly cancer-related.[18][19]

text: Administration[edit]

text: There are many different routes of administration for antibiotic treatment. Antibiotics are usually taken by mouth. In more severe cases, particularly deep-seated systemic infections, antibiotics can be given intravenously or by injection.[2][16] Where the site of infection is easily accessed, antibiotics may be given topically in the form of eye drops onto the conjunctiva for conjunctivitis or ear drops for ear infections and acute cases of swimmer's ear. Topical use is also one of the treatment options for some skin conditions including acne and cellulitis.[20] Advantages of topical application include achieving high and sustained concentration of antibiotic at the site of infection; reducing the potential for systemic absorption and toxicity, and total volumes of antibiotic required are reduced, thereby also reducing the risk of antibiotic misuse.[21] Topical antibiotics applied over certain types of surgical wounds have been reported to reduce the risk of surgical site infections.[22] However, there are certain general causes for concern with topical administration of antibiotics. Some systemic absorption of the antibiotic may occur; the quantity of antibiotic applied is difficult to accurately dose, and there is also the possibility of local hypersensitivity reactions or contact dermatitis occurring.[21]

text: Side-effects[edit]

text: Antibiotics are screened for any negative effects before their approval for clinical use, and are usually considered safe and well tolerated. However, some antibiotics have been associated with a wide extent of adverse side effects ranging from mild to very severe depending on the type of antibiotic used, the microbes targeted, and the individual patient.[23][24] Side effects may reflect the pharmacological or toxicological properties of the antibiotic or may involve hypersensitivity or allergic reactions.[5] Adverse effects range from fever and nausea to major allergic reactions, including photodermatitis and anaphylaxis.[25] Safety profiles of newer drugs are often not as well established as for those that have a long history of use.[23]

text: Common side-effects include diarrhea, resulting from disruption of the species composition in the intestinal flora, resulting, for example, in overgrowth of pathogenic bacteria, such as Clostridium difficile.[26] Antibacterials can also affect the vaginal flora, and may lead to overgrowth of yeast species of the genus Candida in the vulvo-vaginal area.[27] Additional side-effects can result from interaction with other drugs, such as the possibility of tendon damage from the administration of a quinolone antibiotic with a systemic corticosteroid.[28]

text: Correlation with obesity[edit]

text: Exposure to antibiotics early in life is associated with increased body mass in humans and mouse models.[29] Early life is a critical period for the establishment of the intestinal microbiota and for metabolic development.[30] Mice exposed to subtherapeutic antibiotic treatment (STAT)– with either penicillin, vancomycin, or chlortetracycline had altered composition of the gut microbiota as well as its metabolic capabilities.[31] One study has reported that mice given low-dose penicillin (1 μg/g body weight) around birth and throughout the weaning process had an increased body mass and fat mass, accelerated growth, and increased hepatic expression of genes involved in adipogenesis, compared to control mice.[32] In addition, penicillin in combination with a high-fat diet increased fasting insulin levels in mice.[32] However, it is unclear whether or not antibiotics cause obesity in humans. Studies have found a correlation between early exposure of antibiotics (<6 months) and increased body mass (at 10 and 20 months).[33] Another study found that the type of antibiotic exposure was also significant with the highest risk of being overweight in those given macrolides compared to penicillin and cephalosporin.[34] Therefore, there is correlation between antibiotic exposure in early life and obesity in humans, but whether or not there is a causal relationship remains unclear. Although there is a correlation between antibiotic use in early life and obesity, the effect of antibiotics on obesity in humans needs to be weighed against the beneficial effects of clinically indicated treatment with antibiotics in infancy.[30]

text: Interactions[edit]

text: Birth control pills[edit]

text: Well controlled studies on the effect of oral contraceptive failure and antibiotics are very limited.[35] The majority of studies indicate antibiotics do not interfere with birth control pills,[36] such as clinical studies that suggest the failure rate of contraceptive pills caused by antibiotics is very low (about 1%).[37] Situations that may increase the risk of oral contraceptive failure include non-compliance (missing taking the pill), vomiting or diarrhea. Gastrointestinal disorders or interpatient variability in oral contraceptive absorption affecting ethinylestradiol serum levels in the blood.[35] Women with menstrual irregularities may be at higher risk of failure and should be advised to use backup contraception during antibiotic treatment and for one week after its completion. If patient-specific risk factors for reduced oral contraceptive efficacy are suspected, backup contraception is recommended.[35]

text: In cases where antibiotics have been suggested to affect the efficiency of birth control pills, such as for the broad-spectrum antibiotic rifampicin, these cases may be due to an increase in the activities of hepatic liver enzymes' causing increased breakdown of the pill's active ingredients.[36] Effects on the intestinal flora, which might result in reduced absorption of estrogens in the colon, have also been suggested, but such suggestions have been inconclusive and controversial.[38][39] Clinicians have recommended that extra contraceptive measures be applied during therapies using antibiotics that are suspected to interact with oral contraceptives.[36] More studies on the possible interactions between antibiotics and birth control pills (oral contraceptives) are required as well as careful assessment of patient-specific risk factors for potential oral contractive pill failure prior to dismissing the need for backup contraception.[35]

text: Alcohol[edit]

text: Interactions between alcohol and certain antibiotics may occur and may cause side-effects and decreased effectiveness of antibiotic therapy.[40][41] While moderate alcohol consumption is unlikely to interfere with many common antibiotics, there are specific types of antibiotics,with which alcohol consumption may cause serious side-effects.[42] Therefore, potential risks of side-effects and effectiveness depend on the type of antibiotic administered.[43]

text: Antibiotics such as metronidazole, tinidazole, cephamandole, latamoxef, cefoperazone, cefmenoxime, and furazolidone, cause a disulfiram-like chemical reaction with alcohol by inhibiting its breakdown by acetaldehyde dehydrogenase, which may result in vomiting, nausea, and shortness of breath.[42] In addition, the efficacy of doxycycline and erythromycin succinate may be reduced by alcohol consumption.[44] Other effects of alcohol on antibiotic activity include altered activity of the liver enzymes that break down the antibiotic compound.[45]

text: Pharmacodynamics[edit]

text: The successful outcome of antimicrobial therapy with antibacterial compounds depends on several factors. These include host defense mechanisms, the location of infection, and the pharmacokinetic and pharmacodynamic properties of the antibacterial.[46] A bactericidal activity of antibacterials may depend on the bacterial growth phase, and it often requires ongoing metabolic activity and division of bacterial cells.[47] These findings are based on laboratory studies, and in clinical settings have also been shown to eliminate bacterial infection.[46][48] Since the activity of antibacterials depends frequently on its concentration,[49] in vitro characterization of antibacterial activity commonly includes the determination of the minimum inhibitory concentration and minimum bactericidal concentration of an antibacterial.[46][50] To predict clinical outcome, the antimicrobial activity of an antibacterial is usually combined with its pharmacokinetic profile, and several pharmacological parameters are used as markers of drug efficacy.[51]

text: Combination therapy[edit]

text: In important infectious diseases, including tuberculosis, combination therapy (i.e., the concurrent application of two or more antibiotics) has been used to delay or prevent the emergence of resistance. In acute bacterial infections, antibiotics as part of combination therapy are prescribed for their synergistic effects to improve treatment outcome as the combined effect of both antibiotics is better than their individual effect.[52][53] Methicillin-resistant Staphylococcus aureus infections may be treated with a combination therapy of fusidic acid and rifampicin.[52] Antibiotics used in combination may also be antagonistic and the combined effects of the two antibiotics may be less than if the individual antibiotic was given as part of a monotherapy.[52] For example, chloramphenicol and tetracyclines are antagonists to penicillins and aminoglycosides. However, this can vary depending on the species of bacteria.[54] In general, combinations of a bacteriostatic antibiotic and bactericidal antibiotic are antagonistic.[52][53]

text: Classes[edit]

text: Antibiotics are commonly classified based on their mechanism of action, chemical structure, or spectrum of activity. Most target bacterial functions or growth processes.[55] Those that target the bacterial cell wall (penicillins and cephalosporins) or the cell membrane (polymyxins), or interfere with essential bacterial enzymes (rifamycins, lipiarmycins, quinolones, and sulfonamides) have bactericidal activities. Protein synthesis inhibitors (macrolides, lincosamides and tetracyclines) are usually bacteriostatic (with the exception of bactericidal aminoglycosides).[56] Further categorization is based on their target specificity. "Narrow-spectrum" antibiotics target specific types of bacteria, such as gram-negative or gram-positive, whereas broad-spectrum antibiotics affect a wide range of bacteria. Following a 40-year break in discovering new classes of antibacterial compounds, four new classes of antibiotics have been brought into clinical use in the late 2000s and early 2010s: cyclic lipopeptides (such as daptomycin), glycylcyclines (such as tigecycline), oxazolidinones (such as linezolid), and lipiarmycins (such as fidaxomicin).[57][58]

text: Production[edit]

text: With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds.[59] These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis.[59] Many antibacterial compounds are relatively small molecules with a molecular weight of less than 1000 daltons.[60]

text: Since the first pioneering efforts of Howard Florey and Chain in 1939, the importance of antibiotics, including antibacterials, to medicine has led to intense research into producing antibacterials at large scales. Following screening of antibacterials against a wide range of bacteria, production of the active compounds is carried out using fermentation, usually in strongly aerobic conditions.[citation needed]

text: Resistance[edit]

text: The emergence of resistance of bacteria to antibiotics is a common phenomenon. Emergence of resistance often reflects evolutionary processes that take place during antibiotic therapy. The antibiotic treatment may select for bacterial strains with physiologically or genetically enhanced capacity to survive high doses of antibiotics. Under certain conditions, it may result in preferential growth of resistant bacteria, while growth of susceptible bacteria is inhibited by the drug.[61] For example, antibacterial selection for strains having previously acquired antibacterial-resistance genes was demonstrated in 1943 by the Luria–Delbrück experiment.[62] Antibiotics such as penicillin and erythromycin, which used to have a high efficacy against many bacterial species and strains, have become less effective, due to the increased resistance of many bacterial strains.[63]

text: Resistance may take the form of biodegredation of pharmaceuticals, such as sulfamethazine-degrading soil bacteria introduced to sulfamethazine through medicated pig feces.[64] The survival of bacteria often results from an inheritable resistance,[65] but the growth of resistance to antibacterials also occurs through horizontal gene transfer. Horizontal transfer is more likely to happen in locations of frequent antibiotic use.[66]

text: Antibacterial resistance may impose a biological cost, thereby reducing fitness of resistant strains, which can limit the spread of antibacterial-resistant bacteria, for example, in the absence of antibacterial compounds. Additional mutations, however, may compensate for this fitness cost and can aid the survival of these bacteria.[67]

text: Paleontological data show that both antibiotics and antibiotic resistance are ancient compounds and mechanisms.[68] Useful antibiotic targets are those for which mutations negatively impact bacterial reproduction or viability.[69]

text: Several molecular mechanisms of antibacterial resistance exist. Intrinsic antibacterial resistance may be part of the genetic makeup of bacterial strains.[70][71] For example, an antibiotic target may be absent from the bacterial genome. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extra-chromosomal DNA.[70] Antibacterial-producing bacteria have evolved resistance mechanisms that have been shown to be similar to, and may have been transferred to, antibacterial-resistant strains.[72][73] The spread of antibacterial resistance often occurs through vertical transmission of mutations during growth and by genetic recombination of DNA by horizontal genetic exchange.[65] For instance, antibacterial resistance genes can be exchanged between different bacterial strains or species via plasmids that carry these resistance genes.[65][74] Plasmids that carry several different resistance genes can confer resistance to multiple antibacterials.[74] Cross-resistance to several antibacterials may also occur when a resistance mechanism encoded by a single gene conveys resistance to more than one antibacterial compound.[74]

text: Antibacterial-resistant strains and species, sometimes referred to as "superbugs", now contribute to the emergence of diseases that were for a while well controlled. For example, emergent bacterial strains causing tuberculosis that are resistant to previously effective antibacterial treatments pose many therapeutic challenges. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide.[75] For example, NDM-1 is a newly identified enzyme conveying bacterial resistance to a broad range of beta-lactam antibacterials.[76] The United Kingdom's Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."[77] On 26 May 2016 an E coli bacteria "superbug" was identified in the United States resistant to colistin, "the last line of defence" antibiotic.[78][79]

text: Misuse[edit]

text: Per The ICU Book "The first rule of antibiotics is try not to use them, and the second rule is try not to use too many of them."[80] Inappropriate antibiotic treatment and overuse of antibiotics have contributed to the emergence of antibiotic-resistant bacteria. Self prescription of antibiotics is an example of misuse.[81] Many antibiotics are frequently prescribed to treat symptoms or diseases that do not respond to antibiotics or that are likely to resolve without treatment. Also, incorrect or suboptimal antibiotics are prescribed for certain bacterial infections.[23][81] The overuse of antibiotics, like penicillin and erythromycin, has been associated with emerging antibiotic resistance since the 1950s.[63][82] Widespread usage of antibiotics in hospitals has also been associated with increases in bacterial strains and species that no longer respond to treatment with the most common antibiotics.[82]

text: Common forms of antibiotic misuse include excessive use of prophylactic antibiotics in travelers and failure of medical professionals to prescribe the correct dosage of antibiotics on the basis of the patient's weight and history of prior use. Other forms of misuse include failure to take the entire prescribed course of the antibiotic, incorrect dosage and administration, or failure to rest for sufficient recovery. Inappropriate antibiotic treatment, for example, is their prescription to treat viral infections such as the common cold. One study on respiratory tract infections found "physicians were more likely to prescribe antibiotics to patients who appeared to expect them".[83] Multifactorial interventions aimed at both physicians and patients can reduce inappropriate prescription of antibiotics.[84][85]

text: Several organizations concerned with antimicrobial resistance are lobbying to eliminate the unnecessary use of antibiotics.[81] The issues of misuse and overuse of antibiotics have been addressed by the formation of the US Interagency Task Force on Antimicrobial Resistance. This task force aims to actively address antimicrobial resistance, and is coordinated by the US Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and the National Institutes of Health (NIH), as well as other US agencies.[86] An NGO campaign group is Keep Antibiotics Working.[87] In France, an "Antibiotics are not automatic" government campaign started in 2002 and led to a marked reduction of unnecessary antibiotic prescriptions, especially in children.[88]

text: The emergence of antibiotic resistance has prompted restrictions on their use in the UK in 1970 (Swann report 1969), and the EU has banned the use of antibiotics as growth-promotional agents since 2003.[89] Moreover, several organizations (including the World Health Organization, the National Academy of Sciences, and the U.S. Food and Drug Administration) have advocated restricting the amount of antibiotic use in food animal production.[90] However, commonly there are delays in regulatory and legislative actions to limit the use of antibiotics, attributable partly to resistance against such regulation by industries using or selling antibiotics, and to the time required for research to test causal links between their use and resistance to them. Two federal bills (S.742[91] and H.R. 2562[92]) aimed at phasing out nontherapeutic use of antibiotics in US food animals were proposed, but have not passed.[91][92] These bills were endorsed by public health and medical organizations, including the American Holistic Nurses' Association, the American Medical Association, and the American Public Health Association (APHA).[93]

text: Despite pledges by food companies and restaurants to reduce or eliminate meat that comes from animals treated with antibiotics, the purchase of antibiotics for use on farm animals has been increasing every year.[94]

text: There has been extensive use of antibiotics in animal husbandry. In the United States, the question of emergence of antibiotic-resistant bacterial strains due to use of antibiotics in livestock was raised by the US Food and Drug Administration (FDA) in 1977. In March 2012, the United States District Court for the Southern District of New York, ruling in an action brought by the Natural Resources Defense Council and others, ordered the FDA to revoke approvals for the use of antibiotics in livestock, which violated FDA regulations.[95]

text: History[edit]

text: Before the early 20th century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.[96] Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections.[97][98]

text: The use of antibiotics in modern medicine began with the discovery of synthetic antibiotics derived from dyes.[55][99][100][101][102]

text: Synthetic antibiotics derived from dyes[edit]

text: Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s.[55] Ehrlich noted certain dyes would color human, animal, or bacterial cells, whereas others did not. He then proposed the idea that it might be possible to create chemicals that would act as a selective drug that would bind to and kill bacteria without harming the human host. After screening hundreds of dyes against various organisms, in 1907, he discovered a medicinally useful drug, the first synthetic antibacterial salvarsan[55][99][100] now called arsphenamine.

text: The era of antibacterial treatment began with the discoveries of arsenic-derived synthetic antibiotics by Alfred Bertheim and Ehrlich in 1907.[103][102] Ehrlich and Bertheim experimented with various chemicals derived from dyes to treat trypanosomiasis in mice and spirochaeta infection in rabbits. While their early compounds were too toxic, Ehrlich and Sahachiro Hata, a Japanese bacteriologist working with Erlich in the quest for a drug to treat syphilis, achieved success with the 606th compound in their series of experiments. In 1910 Ehrlich and Hata announced their discovery, which they called drug "606", at the Congress for Internal Medicine at Wiesbaden.[104] The Hoechst company began to market the compound toward the end of 1910 under the name Salvarsan. This drug is now known as arsphenamine.[104] The drug was used to treat syphilis in the first half of the 20th century. In 1908, Ehrlich received the Nobel Prize in Physiology or Medicine for his contributions to immunology.[105] Hata was nominated for the Nobel Prize in Chemistry in 1911 and for the Nobel Prize in Physiology or Medicine in 1912 and 1913.[106]

text: The first sulfonamide and the first systemically active antibacterial drug, Prontosil, was developed by a research team led by Gerhard Domagk in 1932 or 1933 at the Bayer Laboratories of the IG Farben conglomerate in Germany,[102][107][100] for which Domagk received the 1939 Nobel Prize in Physiology or Medicine.[108] Sulfanilamide, the active drug of Prontosil, was not patentable as it had already been in use in the dye industry for some years.[107] Prontosil had a relatively broad effect against Gram-positive cocci, but not against enterobacteria. Research was stimulated apace by its success. The discovery and development of this sulfonamide drug opened the era of antibacterials.[109][110]

text: Penicillin and other natural antibiotics[edit]

text: Observations about the growth of some microorganisms inhibiting the growth of other microorganisms have been reported since the late 1800s. These observations of antibiosis between microorganisms led to the discovery of natural antibacterials. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics".[111]

text: In 1874, physician Sir William Roberts noted that cultures of the mold Penicillium glaucum that is used in the making of some types of blue cheese did not display bacterial contamination.[112] In 1876, physicist John Tyndall also contributed to this field.[113] Pasteur conducted research showing that Bacillus anthracis would not grow in the presence of the related mold Penicillium notatum.

text: In 1895 Vincenzo Tiberio, Itallian physician, published a paper on the antibacterial power of some extracts of mold.[114]

text: In 1897, doctoral student Ernest Duchesne submitted a dissertation, "Contribution à l'étude de la concurrence vitale chez les micro-organismes: antagonisme entre les moisissures et les microbes" (Contribution to the study of vital competition in micro-organisms: antagonism between molds and microbes),[115] the first known scholarly work to consider the therapeutic capabilities of molds resulting from their anti-microbial activity. In his thesis, Duchesne proposed that bacteria and molds engage in a perpetual battle for survival. Duchesne observed that E. coli was eliminated by Penicillium glaucum when they were both grown in the same culture. He also observed that when he inoculated laboratory animals with lethal doses of typhoid bacilli together with Penicillium glaucum, the animals did not contract typhoid. Unfortunately Duchesne's army service after getting his degree prevented him from doing any further research.[116] Duchesne died of tuberculosis, a disease now treated by antibiotics.[116]

text: In 1928, Sir Alexander Fleming postulated the existence of penicillin, a molecule produced by certain molds that kills or stops the growth of certain kinds of bacteria. Fleming was working on a culture of disease-causing bacteria when he noticed the spores of a green mold, Penicillium chrysogenum, in one of his culture plates. He observed that the presence of the mold killed or prevented the growth of the bacteria.[117] Fleming postulated that the mold must secrete an antibacterial substance, which he named penicillin in 1928. Fleming believed that its antibacterial properties could be exploited for chemotherapy. He initially characterized some of its biological properties, and attempted to use a crude preparation to treat some infections, but he was unable to pursue its further development without the aid of trained chemists.[118][119]

text: Ernst Chain, Howard Florey and Edward Abraham succeeded in purifying the first penicillin, penicillin G, in 1942, but it did not become widely available outside the Allied military before 1945. Later, Norman Heatley developed the back extraction technique for efficiently purifying penicillin in bulk. The chemical structure of penicillin was first proposed by Abraham in 1942[120] and then later confirmed by Dorothy Crowfoot Hodgkin in 1945. Purified penicillin displayed potent antibacterial activity against a wide range of bacteria and had low toxicity in humans. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic sulfonamides. (see below) The development of penicillin led to renewed interest in the search for antibiotic compounds with similar efficacy and safety.[121] For their successful development of penicillin, which Fleming had accidentally discovered but could not develop himself, as a therapeutic drug, Chain and Florey shared the 1945 Nobel Prize in Medicine with Fleming.

text: Florey credited Rene Dubos with pioneering the approach of deliberately and systematically searching for antibacterial compounds, which had led to the discovery of gramicidin and had revived Florey's research in penicillin.[122] In 1939, coinciding with the start of World War II, Dubos had reported the discovery of the first naturally derived antibiotic, tyrothricin, a compound of 20% gramicidin and 80% tyrocidine, from B. brevis. It was one of the first commercially manufactured antibiotics and was very effective in treating wounds and ulcers during World War II.[122] Gramicidin, however, could not be used systemically because of toxicity. Tyrocidine also proved too toxic for systemic usage. Research results obtained during that period were not shared between the Axis and the Allied powers during World War II and limited access during the Cold War.[123]

text: Etymology[edit]

text: The term 'antibiosis', meaning "against life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs.[55][124][125] Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis.[124][126] These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942.[55][124][127]

text: The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.[124][127] This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. In current usage, the term "antibiotic" is applied to any medication that kills bacteria or inhibits their growth, regardless of whether that medication is produced by a microorganism or not.[128][129]

text: The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for life, lively",[130] which comes from βίωσις (biōsis), "way of life",[131] and that from βίος (bios), "life".[45][132] The term "antibacterial" derives from Greek ἀντί (anti), "against"[133] + βακτήριον (baktērion), diminutive of βακτηρία (baktēria), "staff, cane",[134] because the first bacteria to be discovered were rod-shaped.[135]

text: Research[edit]

text: Alternatives[edit]

text: The increase in bacterial strains that are resistant to conventional antibacterial therapies together with decreasing number of new antibiotics currently being developed in the drug pipeline has prompted the development of bacterial disease treatment strategies that are alternatives to conventional antibacterials.[136][137] Non-compound approaches (that is, products other than classical antibacterial agents) that target bacteria or approaches that target the host including phage therapy and vaccines are also being investigated to combat the problem.[138]

text: Resistance-modifying agents[edit]

text: One strategy to address bacterial drug resistance is the discovery and application of compounds that modify resistance to common antibacterials. Resistance modifying agents are capable of partly or completely suppressing bacterial resistance mechanisms.[139] For example, some resistance-modifying agents may inhibit multidrug resistance mechanisms, such as drug efflux from the cell, thus increasing the susceptibility of bacteria to an antibacterial.[139][140] Targets include:

text:
The efflux inhibitor Phe-Arg-β-naphthylamide.[140]
Beta-lactamase inhibitors, such as clavulanic acid and sulbactam[141]

tag: ul

text: Metabolic stimuli such as sugar can help eradicate a certain type of antibiotic-tolerant bacteria by keeping their metabolism active.[142]

text: Vaccines[edit]

text: Vaccines rely on immune modulation or augmentation. Vaccination either excites or reinforces the immune competence of a host to ward off infection, leading to the activation of macrophages, the production of antibodies, inflammation, and other classic immune reactions. Antibacterial vaccines have been responsible for a drastic reduction in global bacterial diseases.[143] Vaccines made from attenuated whole cells or lysates have been replaced largely by less reactogenic, cell-free vaccines consisting of purified components, including capsular polysaccharides and their conjugates, to protein carriers, as well as inactivated toxins (toxoids) and proteins.[144]

text: Phage therapy[edit]

text: Phage therapy is another method for treating antibiotic-resistant strains of bacteria. Phage therapy infects pathogenic bacteria with their own viruses, bacteriophages and their host ranges are extremely specific for certain bacteria, thus they do not disturb the host organism and intestinal microflora unlike antibiotics.[145] Bacteriophages, also known simply as phages, infect and can kill bacteria and affect bacterial growth primarily during lytic cycles.[145][146] Phages insert their DNA into the bacterium, where it is transcribed and used to make new phages, after which the cell will lyse, releasing new phage able to infect and destroy further bacteria of the same strain.[146] The high specificity of phage protects "good" bacteria from destruction. However, some disadvantages to use of bacteriophages also exist. Bacteriophages may harbour virulence factors or toxic genes in their genomes and identification of genes with similarity to known virulence factors or toxins by genomic sequencing may be prudent prior to use. In addition, the oral and IV administration of phages for the eradication of bacterial infections poses a much higher safety risk than topical application, and there is the additional concern of uncertain immune responses to these large antigenic cocktails. There are considerable regulatory hurdles that must be cleared for such therapies.[145] The use of bacteriophages as a replacement for antimicrobial agents against MDR pathogens no longer respond to conventional antibiotics remains an attractive option despite numerous challenges.[145][147]

text: Phytochemicals[edit]

text: Plants are an important source of antimicrobial compounds and traditional healers have long used plants to prevent or cure infectious diseases.[148][149] There is a recent renewed interest into the use of natural products for the identification of new members of the 'antibiotic-ome' (defined as natural products with antibiotic activity), and their application in antibacterial drug discovery in the genomics era.[136][150] Phytochemicals are the active biological component of plants and some phytochemicals including tannins, alkaloids, terpenoids and flavonoids possess antimicrobial activity.[148][151][152] Some antioxidant dietary supplements also contain phytochemicals (polyphenols), such as grape seed extract, and demonstrate in vitro anti-bacterial properties.[153][154][155] Phytochemicals are able to inhibit peptidoglycan synthesis, damage microbial membrane structures, modify bacterial membrane surface hydrophobicity and also modulate quorum-sensing.[151] With increasing antibiotic resistance in recent years, the potential of new plant-derived antibiotics is under investigation.[150]

text: Development of new antibiotics[edit]

text: In April 2013, the Infectious Disease Society of America (IDSA) reported that the weak antibiotic pipeline does not match bacteria's increasing ability to develop resistance. Since 2009, only 2 new antibiotics were approved in the United States. The number of new antibiotics approved for marketing per year declines continuously. The report identified seven antibiotics against the Gram-negative bacilli (GNB) currently in phase 2 or phase 3 clinical trials. However, these drugs do not address the entire spectrum of resistance of GNB.[156][157] Some of these antibiotics are combination of existent treatments:[citation needed]

text:
Ceftolozane/tazobactam (CXA-201; CXA-101/tazobactam): Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor). FDA approved on 19 December 2014.
Ceftazidime/avibactam (ceftazidime/NXL104): Antipseudomonal cephalosporin/β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 3.
Ceftaroline/avibactam (CPT-avibactam; ceftaroline/NXL104): Anti-MRSA cephalosporin/ β-lactamase inhibitor combination (cell wall synthesis inhibitor)
Imipenem/MK-7655: Carbapenem/ β-lactamase inhibitor combination (cell wall synthesis inhibitor). In phase 2.
Plazomicin (ACHN-490): Aminoglycoside (protein synthesis inhibitor). New Drug Application is under Priority Review by U.S. FDA.
Eravacycline (TP-434): Synthetic tetracycline derivative / protein synthesis inhibitor targeting the ribosome. Development by Tetraphase, Phase 2 trials complete.[158]
Brilacidin (PMX-30063): Peptide defense protein mimetic (cell membrane disruption). In phase 2.

text: Streptomyces research is expected to provide new antibiotics, including treatment against MRSA and infections resistant to commonly used medication. Efforts of John Innes Centre and universities in the UK, supported by BBSRC, resulted in the creation of spin-out companies, for example Novacta Biosystems, which has designed the type-b lantibiotic-based compound NVB302 (in phase 1) to treat Clostridium difficile infections.[159][160] Possible improvements include clarification of clinical trial regulations by FDA. Furthermore, appropriate economic incentives could persuade pharmaceutical companies to invest in this endeavor.[157] In the US, the Antibiotic Development to Advance Patient Treatment (ADAPT) Act was introduced with the aim of fast tracking the drug development of antibiotics to combat the growing threat of 'superbugs'. Under this Act, FDA can approve antibiotics and antifungals treating life-threatening infections based on smaller clinical trials. The CDC will monitor the use of antibiotics and the emerging resistance, and publish the data. The FDA antibiotics labeling process, 'Susceptibility Test Interpretive Criteria for Microbial Organisms' or 'breakpoints', will provide accurate data to healthcare professionals.[161][162] According to Allan Coukell, senior director for health programs at The Pew Charitable Trusts, "By allowing drug developers to rely on smaller datasets, and clarifying FDA's authority to tolerate a higher level of uncertainty for these drugs when making a risk/benefit calculation, ADAPT would make the clinical trials more feasible."[163]


document_title: Mr. Bean (animated TV series)

question_text: who voices mr bean in the animated series

text: Mr. Bean (animated TV series)

text: Main Characters[edit]

text:
Mr. Bean (voiced by Rowan Atkinson) – the title character who serves as the protagonist of the series. He wants every environment around him to be clean and out of trouble.
Teddy – Mr Bean's lifelong best friend. Mr. Bean often pretends Teddy is alive.
Mrs. Julia Wicket (voiced by Sally Grace) – Mr. Bean's landlady, an old woman who occasionally serves as the antagonist. She owns a one-eyed cat named Scrapper. She gets angry at Bean quite easily; however, they occasionally have a good relationship.
Irma Gobb (voiced by Matilda Ziegler) – Mr. Bean's girlfriend.
Lottie – Irma's teddy bear. She looks almost identical to Mr. Bean's Teddy, except she has eyelashes, a red bow and a red skirt. She is sometimes portrayed as Teddy's girlfriend, but Bean dislikes this relationship.
The Burglars – a duo of thieves, one stocky and the other small, who commit crimes while in various disguises.
The Bruisers – Mr. Bean's neighbours, a working-class family made up of a father, mother and three children, with a dog named Tutati.

text: Episodes[edit]

text:
Series
Episodes
Originally aired

First aired
Last aired

1
18
5 January 2002
26 March 2002

2
16
16 February 2003
5 April 2003

3
18
6 May 2004
2 June 2004

4
52
16 February 2015
10 March 2016

tag: table

text: The programme originally lasted for three series, which contained a total of 52 episodes. The first two series in 2002 to 2003 were broadcast in a prime time Saturday night slot on ITV, and featured two back to back episodes in a half hour segment. However, the third series in 2004 was broadcast daily on CITV, and the series was run as twenty single episodes, rather than back to back segments. The final episode of the third series was titled "Double Trouble", and it was aired on 2 June 2004.

text: In January 2014, CITV announced that a new animated series would be made, with Rowan Atkinson once again providing his voice for the role. 52 new episodes, each lasting twelve minutes were recorded during 2014, and began airing on 16 February 2015 on CITV.

text: DVD releases[edit]

text: The animated version has been re-released on DVD by A&E Home Video in Region 1 (actually are Region Free), and Universal Pictures in Regions 2 and 4. In the United States, all 52 episodes were released on six volumes. However, in the United Kingdom and Australia, the six volumes only contained 47 of the 52 episodes, with the other five episodes appearing each as extras on the DVD releases of the live action series.

text: The reason for this is that when the episodes were classified by the BBFC in the United Kingdom, they were given a PG certificate rather than a U certificate. It was decided that the DVDs of the animated series should have a U certificate so the five PG episodes were not included.

text: Region 1[edit]

text:
DVD name
# of episodes
Release date

Mr. Bean The Animated Series – Volume 1: Bean There, Done That
10
30 September 2003

Mr. Bean The Animated Series – Volume 2: Whatever Will Bean, Will Bean
10
30 March 2004

Mr. Bean The Animated Series – Volume 3: It's All Bean to Me
8
30 March 2004

Mr. Bean The Animated Series – Volume 4: Grin and Bean It
8
28 September 2004

Mr. Bean The Animated Series – Volume 5: The Ends Justify the Beans
8
28 September 2004

Mr. Bean The Animated Series – Volume 6: It's Not Easy Being Bean
10
October 29, 2004 (2004-10-29)

Mr. Bean The Animated Series – Volume 1 and 2: It's Not Easy Being Bean & Bean There, Done That
18
September 2004

Mr. Bean The Animated Series Volume 3 and 4: Whatever Will Bean, Will Bean & It's All Bean to Me
16
September 2004

Mr. Bean The Animated Series – Volume 5 and 6: Grin and Bean It & The Ends Justify the Beans
18
September 2004

text: Region 2[edit]

text:
DVD name
# of episodes
Release date

Mr. Bean The Animated Series – Number 1: Eight Amazing Adventures
8
29 August 2005; 20th Anniversary Re-release: 6 September 2010; 25th Anniversary Re-release: 20 July 2015

Mr. Bean The Animated Series – Number 2: Eight Exciting Escapades
8
27 March 2006; 20th Anniversary Re-release: 6 September 2010

Mr. Bean The Animated Series – Number 3: Eight Terrific Tales
8
31 July 2006; 20th Anniversary Re-release: 6 September 2010

Mr. Bean The Animated Series – Number 4: Seven Smashing Stories
7
13 November 2006; 20th Anniversary Re-release: 6 September 2010

Mr. Bean The Animated Series – Number 5: Eight Eventful Escapades
8
19 March 2007; 20th Anniversary Re-release: 9 September 2010

Mr. Bean The Animated Series – Number 6: Eight Sticky Scrapes
8
22 November 2007; 20th Anniversary Re-release: 9 September 2010

Mr. Bean The Animated Series: The Bean Boxset! (Numbers 1–6)
47
18 March 2008; 20th Anniversary Re-release: 6 September 2010

Mr. Bean The Animated Series – Number 7: Nine Tremendous Tales
9
7 September 2015

Mr. Bean The Animated Series - Number 7: Home Movie & MORE Tremendous Tales! (2017 New Cover Re-release)
9
7 September 2015

Mr. Bean The Animated Series – Number 8: Nine Splendid Stories
9
19 October 2015

Mr. Bean The Animated Series - Number 8: Holiday For Teddy & MORE Tantalising Tales! (2017 New Cover Re-release)
9
19 October 2015

Mr. Bean The Animated Series – Number 9: Racing Adventures & MORE Exciting Escapades!
8
23 May 2016

Mr. Bean The Animated Series: Cat Sitting & MORE Paw-some Adventures! (Re release of Episodes)
9
29 August 2016

Mr. Bean The Animated Series – Number 10: HallowBean & MORE Awesome Stories!
9
3 October 2016

Mr. Bean The Animated Series – Number 11: SuperBean & OTHER Splendid Stories!
8
30 January 2017

Mr. Bean The Animated Series: Egg & Bean & OTHER Springtime Surprises! (Re-release of Episodes)
8
3 April 2017

Mr. Bean The Animated Series – Number 12: Birthday Bean & FRIENDS!
9
24 July 2017

Mr. Bean The Animated Series: On Thin Ice & OTHER Winter Wonders! (Re-release of Episodes)
7
2 October 2017

text: Region 4[edit]

text: Season 2 Volume 3 was an exclusive for Big W, which is no longer available.

text:
DVD name
# of episodes
Release date

Mr. Bean The Animated Series – Number 1: Eight Amazing Adventures
8
18 August 2004

Mr. Bean The Animated Series – Number 2: Eight Exciting Escapades
8
4 July 2007

Mr. Bean The Animated Series – Number 3: Eight Terrific Tales
8
28 October 2009

Mr. Bean The Animated Series – Number 4: Seven Smashing Stories
7
28 October 2009

Mr. Bean The Animated Series – Number 5: Eight Eventful Escapades
8
28 October 2009

Mr. Bean The Animated Series – Number 6: Eight Sticky Scrapes
8
28 October 2009

Mr. Bean The Animated Series – Season 2 Vol.1: Nine Tremendous Tales
9
24 September 2015

Mr. Bean The Animated Series – Season 2 Vol.2: Nine Splendid Stories
9
24 September 2015

Mr. Bean The Animated Series – Season 2 Vol.3: Silly Stories
9
13 September 2017

Mr. Bean The Animated Series – Season 2 Vol.4: Halloween & MORE Awesome Stories!
9
2017 (2017)

text: Merchandising[edit]

text: Two Mr. Bean games based on the animated series have been released: Mr. Bean: Around the World[6] and Mr. Bean: Flying Teddy.[citation needed] Both are available globally on iOS, Android and Amazon mobile devices.[citation needed]