Company Introduction, Market Segmentation, and Product Repositioning Research Paper

Company Introduction, Market Segmentation, and Product Repositioning - Research Paper Example Strategic Mission Statement The mission of Holden Trucking Services is to be preferred trucking firm by being able to deliver the most affordable, high quality and efficient trucking services to the customers. According to Radhakrishnan (2001), trucking services form a very important part of the supply chain for many business and it is critical that it is efficient in terms of service as well as cost. This is what Holden Trucking Services will seek to be doing, that is, provide efficient and reliable services to customers at affordable prices. In its growth outlook, Holden Trucking Services looks to serve the African market. The African market is the most underserved market in this sector of the global economy. Africa is expected to be next big economy in the next twenty years. According to market experts, the current fast growing markets such as India and China will have reached their optimum growth by the year 2050. At the current moment, every firm including trucking firms are con centrating their foreign market growth in the BRICS market. As the African market is being ignored, it is going to be easy for Holden Trucking Services to establish itself as the trucking firm of choice and be able to take advantage when the opportune e time comes. The African market is already a ripe market and is underserved and even without having to wait for the opportunities time. Most African countries don’t have dependable trucking services of their own and therefore depend on foreign firms. None of these foreign firms have been gracious enough to offer localised trucking services. This means that the services are too expensive for the local African market. The services are also inefficient and not dependable especially where time of delivery is critical. Holden Trucking Services will be the trucking firm to fill this gap to make sure that the local market is well served. Marketing Plan Holden Trucking Services will reach the market by personalising the services. The m arket will be divided into smaller cells with each cell being given as much autonomy as possible. This will make sure that every area can be served individually and this will increase the quality of the service to the customers. Holden Trucking Services will also seek to be a low-price leader. The modern trucking business is too expensive for most customers an this always has a negative implication of the customers because most of the customers are businesses which would benefit a lot if they could find a cheaper way to deliver their goods so that they can expand their profit margins (Kendall, 2005). Offering low prices and high quality of service to the customer will be an easy way to enter in the market and Holden Trucking Services seeks to use this as a way to make sure that it curves a market share for itself. Segmentation of the Market Holden Trucking Services will seek to serve the underserved market. Such underserved market include the small scale businesses which usually can not afford to have their own trucks but at the same time find trucking services prohibitively high. In this regard, to be able to serve this market, Holden Trucking Services will use two main strategies. First, it will include smaller trucks rather than having only large trucks. These smaller trucks will help in making sure that the firm is able to dispatch customer’

Philosophy and theory of architecture Essay Example | Topics and Well Written Essays - 3500 words - 1

Philosophy and theory of architecture - Essay Example In so doing, it discusses the roots of this phenomenon, and surveys the different phases it has been and is going through and its physical spread and influence as well. That is, it takes a tour through both changes over time as well as spatially. The focus is mainly on the architecture of Buddhist temples, particularly those found in China. However, as the reader will come to know, if not known already, in Buddhism there is a variety of buildings that are considered as religious or spiritual spaces besides temples. A case study is made of the Baima Si, which is the White Horse Temple in the Henan province of China. This temple (Si) was chosen for its historical significance, as will be explained later, as well as the fact that it represents a unique amalgamation of architectural styles. It also functioned as a model for other such buildings and thereby played a pivotal role in moulding a special wave of thinking on architecture, which makes it deserve serious attention. For contrasti ve purposes, important comparisons are also drawn with architectural features belonging to Buddhist temples elsewhere in the world, especially in other Far Eastern countries that are heartlands of Buddhism. In addition, some comparisons are also highlighted between Buddhist architecture and what is found in other religious architectural expressions, especially of Christian, Hindu and Islamic origin. After the distinguishing and other special features are identified for Chinese Buddhist temples, an attempt is then made to explain these and the philosophy behind them. Buddhist architecture In Buddhism, although the temple is the main place for spiritual practices, there are also other spiritual spaces. These are the pagodas, which are towers like broader based minarets, stupas, which are dome shaped monuments, and grottos, which are caves used for specific spiritual practices within a more isolated environment. They are all holy and made to be serene and tranquil. The temples function more as monasteries for collective practices. As far as Chinese temples are concerned, Buddhist philosophy has been described as the greatest impetus behind religious art and architecture in China (Phuoc, 2010). Initially, Buddhism was practised in ordinary settings in China, such as people’s houses, but as demand grew, then special buildings were constructed. These buildings proved to be far more interesting than the Confucian and Taoist places and rich in architectural detail reflecting an equally richer philosophy. Hindu and Islamic philosophies of architecture share some commonality with Buddhist architecture. The Hindu influence is mostly evident in the early temples. Thus, there is a direct connection with Hindu architecture as they gave roots to Buddhist architecture. Connections with other religions are more indirect. A prominent style of Christian architecture was Gothic architecture during the medieval period. This was related with scholastic philosophy (Radding & Clark, 1994) in which there was an attempt to develop a comprehensive and integrated solution for various tasks including the construction of churches. An interesting parallel is drawn between the ideas of St. Thomas Aquinas who was one of these aforementioned philosophers and Buddhist architecture in that he saw churches as symbolising heaven on earth. This is similar in some ways to the Buddhist concept of heaven but with some fundamental differences. Whereas only one heaven is envisaged in Christianity

Romantic Imagination Essay Example for Free

Romantic Imagination Essay â€Å"The Creation of Adam† painted by Michelangelo in 1510, is one of the most beautiful and famous painting representing the Creation. It was painted on the ceiling of the Papal Sistine Chapel and is a masterpiece of High Renaissance art. It is a part of a larger scheme of decoration within the chapel, including various elements like a large fresco of The Last Judgement. Michelangelo demonstrated his skill in creating a huge variety of poses for the human figure, providing an influential pattern for other artists ever since. So at the time, it was not conventional. The technique employed was fresco. The colours are beautiful. It represents a metaphor of Humankind’s need for a covenant (accordo, convenzione) with God. Elohim creating Adam by William Blake is a colour print finished in pen and watercolour. It represents God creating the first human being. God is a supernatural being with wings, white hair and beard. He is bigger and stronger than him and very powerful. Adam, instead, seems a very weak and suffering creature. He is stretched on the ground. In the picture there is also a great worm that entwines Adam and symbolizes the world of pain and sorrow, the devils temptations and also the fact that the human being is linked to sin and corruption. Blake uses cold colours, dull, dismal and gloomy. The atmosphere is very sad. The shapes of the protagonists are distinct and sharp. All these things suggest the tension of the creation and also the energy of God. For Blake the creation is a suffering moment for the creature, a moment of tension, because the author has a pessimistic view of life. Adam is innocent, weak and destined to sin.

Non-standard English: Usage and attitudes

Non-standard English: Usage and attitudes Introduction Spoken language is a powerful method of communication that conveys more than intended referential information. Depending on the listeners attitude, a speakers accent or dialect may imply a number of characteristics such as social class and professionalism. Examples of non-standard linguistic features are discussed under Task 1; followed by summaries of two studies under Task 2, which focus on attitudes towards West Indian Patois (Edwards, 1986) and the Cockney accent (Giles Sassoon, 1982). Task 1 Thats the girl he gave the bracelet to. This sentence contains a grammatical, non-standard linguistic feature because it ends with the preposition to. In Standard English, a preposition usually proceeds a noun, hence the sentence should read: Thats the girl to whom he gave the bracelet. However, there are cases where sentences sound unnatural if they are arranged in a way that avoids a final proposition. This is usually seen in conversational English, for example: in relative clauses and questions which feature phrasal verbs, passive constructions, and short sentences which feature an infinitive or verbal noun. Nonetheless, in formal writing, it is considered better practice to avoid placing a preposition at the end of a sentence where it may seem stranded. (Preposition, 2008) Buffy the vampire slayer is dead cool. This sentence contains a lexical, non-standard linguistic feature because dead functions as an adverb of degree, such as very; the sentence should read, Buffy the vampire slayer is very cool, or of a similar effect. Dead typically functions as an adjective, meaning no longer alive, and is used in contexts such as a dead bodyor a dead issue. It has therefore undergone semantic change, and its meaning has been broadened. (Dead, 2017) My old man gave me a set of wheels for my birthday. This sentence contains lexical, non-standard linguistic features because slang is used. My old man is a colloquial, informal noun phrase meaning ones father or a womans husband or boyfriend; set of wheels is also a colloquial, informal noun phrase meaning a motor vehicle, as opposed to a literal set of wheels. According to Standard English, the sentence should read: My father gave me a motor vehicle for my birthday. The phrases have thus undergone semantic change. (Old man, 2017) The guy that works in the bar is really nice. This sentence contains a lexical, non-standard linguistic feature due to the use of the informal noun, guy, meaning man (Guy, 2017). There is also a grammatical, nonstandard linguistic feature because, in Standard English, that should not be used as a relative pronoun when the antecedent is personal. A human antecedent is typically proceeded by who in a defining clause. An inanimate antecedent or a human but representative of a class is followed by that; for example, the chair that collapsed / the baby that laughed. In Standard English, the sentence should therefore read: The man who works in the bar is really nice. (That, 1998) Who did you see? This sentence contains a grammatical, non-standard linguistic feature because who is used in place of whom. In Standard English, who is a relative pronoun or an interrogative when it refers to the subject (who is there?). Whom is the objective form, hence the sentence should read: Whom did you see? However, the use of whom is declining and is often replaced by who in modern usage. (Who and whom, 2017) Task 2 A study of West Indian Patois, conducted by Viv Edwards (1986) A study of 45 British-born black adolescents in a West Midlands community (Edwards 1997: 409) reveals the attitudes of teachers and pupils towards West Indian Patois. Attitudes to Patois in the educational world are generally negative. The Association of Teachers of English to Pupils from Overseas (ATEPO 1970) describe West Indian language as babyish and lacking proper grammar (Edwards 1986: 25); the National Association of School Masters (1969) refer to West Indian language as a plantation English which is socially unacceptable and inadequate for communication (Edwards 1986: 25). These negative attitudes reflect some of the findings of Edwards (1986) West Midlands study. Conducted in Dudley, the study consisted of a judgement sample and comprised of 3 measures which were applied to the speech of 21 women and 24 men, aged between 16 and 23: frequency of Patois features, competence in Patois, and patterns of Patois usage. (Edwards 1997: 410). The studys findings are presented in 3 sets of interactions, as summarised below: Classroom Interaction, Pupil-Pupil Interactions and Pupil-Teacher Interactions. Classroom Interaction The stereotype that Patois speakers are limited to monolingualism was opposed by recordings of Black pupils using different language patterns in the classroom. Pupil-Pupil Interactions Contrary to the beliefs of the White community, Black pupils, who reduced the frequency and range of their nonstandard linguistic features, made a marked choice not to speak Standard English (despite their competence to speak both varieties). The use of Patois in the classroom was rare but virtually all black pupils could understand it, and used features in at least some situations. Within Black peer groups, it marked solidarity and acceptance; in mixed-raced groups, it functioned to exclude the White outsider. However, a few White pupils sought acceptance from Black friendship groups by using Patois, but their degree of competence varied. Some Black pupils responded with amusement and approval; most responded negatively to the White community for using a variety of English that was distinctively Black. Pupil-Teacher Interactions Black pupils used Patois to exclude their White teacher as means of defiance. Teachers then felt threatened when Patois was used in a confrontational way. Teachers who responded punitively elicited negative attitudes towards Patois. Other reports of teacher responses included learning nonstandard linguistic features in an attempt to understand Black dialect. Edwards (1997) concludes that teachers punitive responses and the use of Patois to exclude the White community are a reflection of the issues caused by negative attitudes towards nonstandard varieties of English. A study of Cockney, conducted by Howard Giles and Caroline Sassoon (1982) A study of a speakers accent and social class reveals the attitudes of 120 undergraduate listeners towards Cockney, in comparison to Received Pronunciation (RP). Based, on Ryan Sebastians (1980) study of the attitudes of middle class listeners towards Mexican-American in the USA, both studies were reminiscent of Lamberts (1967) matched-guise test and consisted of a tape-recording, followed by a questionnaire. Ryan Sebastian (1980) found that by disconfirming the listeners assumption of the accented speakers social class, their evaluations improved. Giles Sassoon (1982) referred to this as the Ryan Sebastian effect, which they later opposed in their hypothesis: awareness of a Cockney speakers social class would not attenuate significantly the unfavourable status associations commonly levied against nonstandard speech (pp. 306). The participants of the study (Ss) consisted of 63 males and 57 females, aged between 18 and 23. Ss heard 1 combination of a male students voice and social class information who was recorded reading two stimulus passages using RP and Cockney accents. The legitimacy of his bidialectal skills was assessed in a pilot study by 24 undergraduates. The studys dependant measures involved 5 small questionnaires, each consisting of 7-point rating scales and instructions. The questionnaires were: measures of Ss perception of the speakers social class, accent and formality of speech; social evaluation scales based on the speakers intelligence, success, friendliness and trustworthiness; belief similarity items which measured the extent that Ss agree[d] with the speaker on social issues such as the legislation of marijuana; social distance items which measured how close a relationship Ss were willing to have with the speaker; and social role items which determined Ss willingness to work with the speaker as subordinate to, superior over, or colleague with them (pp. 307). Ss were recorded in groups of up to 6 other undergraduates; they were handed the 5 questionnaires in the format of a response booklet with the social class information facing upwards. Once they had completed the task, they were debriefed and engaged in discussion. The results proved Giles Sassoons hypothesis; the awareness of the speakers middle class background did not prevent Ss from perceiving him as a low status evaluation when he used Cockney. Accent influenced the ratings on only 1 of 4 social issues; listeners shared more beliefs on the legislation of marijuana with the speaker when he used an RP accent; accent had no effect on social distance items; but the findings from the social role items showed that Ss preferred an RP speaker as their superordinate, and as a subordinate too (pp. 311). Giles Sassoon conclude that the awareness of a Cockney speakers middle class background does not prevent the stereotyped negative attitudes towards low status ratings (pp. 311). Conclusion The nonstandard linguistic features in Task 1 and the studies summarised in Task 2 portray several varieties of English. The mixed attitudes towards the widespread use of nonstandard linguistic features are a clear reflection of an ever-changing language. Word count: 1500 words References Allen, R. Fowler, H. (2008). Preposition. Pocket Fowlers Modern English Usage. Oxford: Oxford University Press. Retrieved from http://www.oxfordreference.com.idpproxy.reading.ac.uk/view/10.1093/acref/9780199232581.001.0001/acref-9780199232581-e-3016?rskey=4f5JCxresult=1 Allen, R. Fowler, H. (2008). Who and whom. Pocket Fowlers Modern English Usage. Oxford: Oxford University Press. Retrieved from http://www.oxfordreference.com.idpproxy.reading.ac.uk/view/10.1093/acref/9780199232581.001.0001/acref-9780199232581-e-4155?rskey=ducoglresult=2 Dead. (2017). Oxford English Dictionary. Oxford. Retrieved from https://en.oxforddictionaries.com/definition/dead Edwards, V. (1986). Language In A Black Community. Clevedon: Multilingual Matters Edwards, V. (2007). Patois and the Politics of Protest: Black English in British Classrooms. In Coupland, N. Jaworski, A. Sociolinguistics: A Reader and Coursebook. (408-415). London: MacMillan Press. Fowler, H. Burchfield, R. (1998). That. The new Fowlers Modern English usage. Oxford: Oxford University Press. Giles, H. Sassoon, C. (1983). The effect of speakers accent, social class background and message style on British listeners social judgements. Language Communication, 3(3), 305-313. http://dx.doi.org/10.1016/0271-5309(83)90006-x Guy. (2017). Oxford English Dictionary. Oxford. Retrieved from https://en.oxforddictionaries.com/definition/guy Lambert, W. E. (1967). A social psychology of bilingualism. Journal of Social Issues. 23, 91- 109. Old man. (2017). Oxford English Dictionary. Oxford. Retrieved from https://en.oxforddictionaries.com/definition/old_man

Free Essays on Terrorism: Europes Contempt Toward the U.S :: Exploratory Essays Research Papers

September 11 and Europe's Contempt Toward the U.S Lest we forget the heroic resolve of our many European "allies," the French surged forward into the fray last week. Well, perhaps "surging" isn't quite the word, and the "fray" has become a meager affair as of late. Their token gesture to join the U.S. and Great Britain in orchestrating a Northern Alliance victory amounts to little more than tactical cowardice, a dashing display of minced words and foot-dragging that only the French seem capable of. However symbolic the gesture, the French and their European counterparts tend to deliver such offerings of goodwill sealed with the usual stamp of anti-Americanism. The irritating Euro-superiority complex recently surfaced over the issue of extraditing captured terrorists to the United States. In September, Spanish authorities infiltrated the Soldiers of Allah, a radical Islamic group based in Madrid with links to al Qaeda. The operation led to 14 arrests of key al Qaeda operatives and shed new light on the financing of bin Laden's operations preceding the September 11 attacks. Hundreds of millions of pesetas (i.e. millions of dollars) flowed through this unit of al Qaeda's financial network. Despite this damning evidence, Spain still sniffs at the thought of extraditing the detainees to the U.S. And what is the source of Spain's moral indigestion? The "backward" American justice system, of course. After all, the U.S. still employs such barbaric anachronisms as the death penalty (and even worse, a solid majority of Americans seem to support it). As evidenced by the continual stalling of Spanish diplomats, the moral burden of any extradition to a country as primitive as the United States is simply too much for the collective Spanish conscience to bear. The fate of al Qaeda operatives must not be abandoned to the crude methods of American jurisprudence. Instead of rejecting such anti-Americanism, the 15 members of the European Union echoed Spain's sentiments in their sanctimonious reports to the press. The Bush administration's establishment of military tribunals further inflamed the E.U.'s righteous indignation. Several countries kindly reminded the U.S. that sending the al Qaeda henchmen across the pond would violate the EU's extradition ban against countries that use the death penalty. This was consistent with what seems to be the E.U.'s role of the meddling whiner, seizing some disputable moral high ground to voice complaints instead of solutions. Perhaps the most annoying aspect of most European indignation is its paternalistic tone, as if the Americans were still reckless colonies in need of a scolding.

Margaret Laurences A Bird in the House Essay -- Laurence A Bird in th

Margaret Laurence's A Bird in the House Margaret Laurence's A Bird in the House differentiates itself from the four other novels that make up the 'Manawaka series' that has helped establish her as an icon of Canadian literature. It does not present a single story; instead, it is a compilation of eight well-crafted short stories (written between the years 1962 and 1970) that intertwine and combine into a single narrative, working as a whole without losing the essential independence of the parts. It tells - at least on a surface level - of the childhood of a young girl named Vanessa MacLeod , and of her trials and tribulations in the small Manitoban town of Manawaka. The narrative style of the stories is important, since it is through Vanessa's own eyes that we learn of her family and life - yet the eyes belong to an older, wiser Vanessa, remembering her own childhood from a future point years later. Laurence handles the narrative style quite cleverly; the experiences of the child-Vanessa are portrayed with all the innocence and naà ¯vety and shock that first accompanied them, yet are also tainted and clarified by the wisdom of the older-Vanessa. "... the narrator [becomes] Vanessa, the woman, who takes on the voice and attributes of the child she was and, at the same time, remains her present self, far older and wiser in compassion and understanding."1 It is the perspective of the older and wiser Vanessa that allows the reader to pick up on the important ideas, images, and themes that the author is trying to convey to us. A Bird in the House is far more than semi-autobiographical, is far more than the simple story of a young girl growing up in the prairies during the great Depression: it is a work of... ...e. The tightness of Laurence's weaving is remarkable: the symbols, the characters, and the characters are drawn together into a cohesive whole. "... the characters reflect the book's central metaphor and are thus symbolically interconnected [...] the stories chart how they are all caught up in parallel captivities and engaged in divergent flights." (Davidson 99) They are, indeed, all drawn together by the bird in the house. Works Cited 1. qtd. in Davidson, Arnold E. "Cages and Escapes in Margaret Laurence's A Bird in the House." University of Windsor Review 16 (1981): 95. 2.Margaret Laurence, A Bird in the House (Toronto: McClelland & Stewart Inc., 1970), 43. All further references are to this edition and are included in my text. 3. Jon Kertzer, "That House in Manawaka": Margaret Laurence's A Bird in the House (Toronto: ECW Press, 1992), 57.

The Rise of Antibiotics

The Rise of Antibiotic-Resistant Infections by_ Ricki Lewis, Ph. D. _ When penicillin became widely available during the second world war, it was a medical miracle, rapidly vanquishing the biggest wartime killer–infected wounds. Discovered initially by a French medical student, Ernest Duchesne, in 1896, and then rediscovered by Scottish physician Alexander Fleming in 1928, the product of the soil mold Penicillium crippled many types of disease-causing bacteria. But just four years after drug companies began mass-producing penicillin in 1943, microbes began appearing that could resist it. The first bug to battle penicillin was Staphylococcus aureus. This bacterium is often a harmless passenger in the human body, but it can cause illness, such as pneumonia or toxic shock syndrome, when it overgrows or produces a toxin. In 1967, another type of penicillin-resistant pneumonia, caused by Streptococcus pneumoniae and called pneumococcus, surfaced in a remote village in Papua New Guinea. At about the same time, American military personnel in southeast Asia were acquiring penicillin-resistant gonorrhea from prostitutes. By 1976, when the soldiers had come home, they brought the new strain of gonorrhea with them, and physicians had to find new drugs to treat it. In 1983, a hospital-acquired intestinal infection caused by the bacterium Enterococcus faecium joined the list of bugs that outwit penicillin. Antibiotic resistance spreads fast. Between 1979 and 1987, for example, only 0. 02 percent of pneumococcus strains infecting a large number of patients surveyed by the national Centers for Disease Control and Prevention were penicillin-resistant. CDC's survey included 13 hospitals in 12 states. Today, 6. 6 percent of pneumococcus strains are resistant, according to a report in the June 15, 1994, Journal of the American Medical Association by Robert F. Breiman, M. D. , and colleagues at CDC. The agency also reports that in 1992, 13,300 hospital patients died of bacterial infections that were resistant to antibiotic treatment. Why has this happened? â€Å"There was complacency in the 1980s. The perception was that we had licked the bacterial infection problem. Drug companies weren't working on new agents. They were concentrating on other areas, such as viral infections,† says Michael Blum, M. D. , medical officer in the Food and Drug Administration's division of anti-infective drug products. â€Å"In the meantime, resistance increased to a number of commonly used antibiotics, possibly related to overuse of antibiotics. In the 1990s, we've come to a point for certain infections that we don't have agents available. † According to a report in the April 28, 1994, New England Journal of Medicine, researchers have identified bacteria in patient samples that resist all currently available antibiotic drugs. Survival of the Fittest The increased prevalence of antibiotic resistance is an outcome of evolution. Any population of organisms, bacteria included, naturally includes variants with unusual traits–in this case, the ability to withstand an antibiotic's attack on a microbe. When a person takes an antibiotic, the drug kills the defenseless bacteria, leaving behind–or â€Å"selecting,† in biological terms–those that can resist it. These renegade bacteria then multiply, increasing their numbers a millionfold in a day, becoming the predominant microorganism. The antibiotic does not technically cause the resistance, but allows it to happen by creating a situation where an already existing variant can flourish. â€Å"Whenever antibiotics are used, there is selective pressure for resistance to occur. It builds upon itself. More and more organisms develop resistance to more and more drugs,† says Joe Cranston, Ph. D. , director of the department of drug policy and standards at the American Medical Association in Chicago. A patient can develop a drug-resistant infection either by contracting a resistant bug to begin with, or by having a resistant microbe emerge in the body once antibiotic treatment begins. Drug-resistant infections increase risk of death, and are often associated with prolonged hospital stays, and sometimes complications. These might necessitate removing part of a ravaged lung, or replacing a damaged heart valve. Bacterial Weaponry Disease-causing microbes thwart antibiotics by interfering with their mechanism of action. For example, penicillin kills bacteria by attaching to their cell walls, then destroying a key part of the wall. The wall falls apart, and the bacterium dies. Resistant microbes, however, either alter their cell walls so penicillin can't bind or produce enzymes that dismantle the antibiotic. In another scenario, erythromycin attacks ribosomes, structures within a cell that enable it to make proteins. Resistant bacteria have slightly altered ribosomes to which the drug cannot bind. The ribosomal route is also how bacteria become resistant to the antibiotics tetracycline, streptomycin and gentamicin. How Antibiotic Resistance Happens Antibiotic resistance results from gene action. Bacteria acquire genes conferring resistance in any of three ways. In spontaneous DNA mutation, bacterial DNA (genetic material) may mutate (change) spontaneously (indicated by starburst). Drug-resistant tuberculosis arises this way. In a form of microbial sex called transformation, one bacterium may take up DNA from another bacterium. Pencillin-resistant gonorrhea results from transformation. Most frightening, however, is resistance acquired from a small circle of DNA called a plasmid, that can flit from one type of bacterium to another. A single plasmid can provide a slew of different resistances. In 1968, 12,500 people in Guatemala died in an epidemic of Shigella diarrhea. The microbe harbored a plasmid carrying resistances to four antibiotics! A Vicious Cycle: More Infections and Antibiotic Overuse Though bacterial antibiotic resistance is a natural phenomenon, societal factors also contribute to the problem. These factors include increased infection transmission, coupled with inappropriate antibiotic use. More people are contracting infections. Sinusitis among adults is on the rise, as are ear infections in children. A report by CDC's Linda F. McCaig and James M. Hughes, M. D. , in the Jan. 18, 1995, Journal of the American Medical Association, tracks antibiotic use in treating common illnesses. The report cites nearly 6 million antibiotic prescriptions for sinusitis in 1985, and nearly 13 million in 1992. Similarly, for middle ear infections, the numbers are 15 million prescriptions in 1985, and 23. 6 million in 1992. Causes for the increase in reported infections are diverse. Some studies correlate the doubling in doctor's office visits for ear infections for preschoolers between 1975 and 1990 to increased use of day-care facilities. Homelessness contributes to the spread of infection. Ironically, advances in modern medicine have made more people predisposed to infection. People on chemotherapy and transplant recipients taking drugs to suppress their immune function are at greater risk of infection. â€Å"There are the number of immunocompromised patients, who wouldn't have survived in earlier times,† says Cranston. â€Å"Radical procedures produce patients who are in difficult shape in the hospital, and are prone to nosocomial [hospital-acquired] infections. Also, the general aging of patients who live longer, get sicker, and die slower contributes to the problem,† he adds. Though some people clearly need to be treated with antibiotics, many experts are concerned about the inappropriate use of these powerful drugs. â€Å"Many consumers have an expectation that when they're ill, antibiotics are the answer. They put pressure on the physician to prescribe them. Most of the time the illness is viral, and antibiotics are not the answer. This large burden of antibiotics is certainly selecting resistant bacteria,† says Blum. Another much-publicized concern is use of antibiotics in livestock, where the drugs are used in well animals to prevent disease, and the animals are later slaughtered for food. â€Å"If an animal gets a bacterial infection, growth is slowed and it doesn't put on weight as fast,† says Joe Madden, Ph. D. , strategic manager of microbiology at FDA's Center for Food Safety and Applied Nutrition. In addition, antibiotics are sometimes administered at low levels in feed for long durations to increase the rate of weight gain and improve the efficiency of converting animal feed to units of animal production. FDA's Center for Veterinary Medicine limits the amount of antibiotic residue in poultry and other meats, and the U. S. Department of Agriculture monitors meats for drug residues. According to Margaret Miller, Ph. D. , deputy division director at the Center for Veterinary Medicine, the residue limits for antimicrobial animal drugs are set low enough to ensure that the residues themselves do not select resistant bacteria in (human) gut flora. FDA is investigating whether bacteria resistant to quinolone antibiotics can emerge in food animals and cause disease in humans. Although thorough cooking sharply reduces the likelihood of antibiotic-resistant bacteria surviving in a meat meal to infect a human, it could happen. Pathogens resistant to drugs other than fluoroquinolones have sporadically been reported to survive in a meat meal to infect a human. In 1983, for example, 18 people in four midwestern states developed multi-drug-resistant Salmonella food poisoning after eating beef from cows fed antibiotics. Eleven of the people were hospitalized, and one died. A study conducted by Alain Cometta, M. D. , and his colleagues at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and reported in the April 28, 1994, New England Journal of Medicine, showed that increase in antibiotic resistance parallels increase in antibiotic use in humans. They examined a large group of cancer patients given antibiotics called fluoroquinolones to prevent infection. The patients' white blood cell counts were very low as a result of their cancer treatment, leaving them open to infection. Between 1983 and 1993, the percentage of such patients receiving antibiotics rose from 1. 4 to 45. During those years, the researchers isolated Escherichia coli bacteria annually from the patients, and tested the microbes for resistance to five types of fluoroquinolones. Between 1983 and 1990, all 92 E. coli strains tested were easily killed by the antibiotics. But from 1991 to 1993, 11 of 40 tested strains (28 percent) were resistant to all five drugs. Towards Solving the Problem Antibiotic resistance is inevitable, say scientists, but there are measures we can take to slow it. Efforts are under way on several fronts–improving infection control, developing new antibiotics, and using drugs more appropriately. Barbara E. Murray, M. D. , of the University of Texas Medical School at Houston writes in the April 28, 1994, New England Journal of Medicine that simple improvements in public health measures can go a long way towards preventing infection. Such approaches include more frequent hand washing by health-care workers, quick identification and isolation of patients with drug-resistant infections, and improving sewage systems and water purity in developing nations. Drug manufacturers are once again becoming interested in developing new antibiotics. These efforts have been spurred both by the appearance of new bacterial illnesses, such as Lyme disease and Legionnaire's disease, and resurgences of old foes, such as tuberculosis, due to drug resistance. FDA is doing all it can to speed development and availability of new antibiotic drugs. â€Å"We can't identify new agents–that's the job of the pharmaceutical industry. But once they have identified a promising new drug for resistant infections, what we can do is to meet with the company very early and help design the development plan and clinical trials,† says Blum. In addition, drugs in development can be used for patients with multi-drug-resistant infections on an â€Å"emergency IND (compassionate use)† basis, if the physician requests this of FDA, Blum adds. This is done for people with AIDS or cancer, for example. No one really has a good idea of the extent of antibiotic resistance, because it hasn't been monitored in a coordinated fashion. â€Å"Each hospital monitors its own resistance, but there is no good national system to test for antibiotic resistance,† says Blum. This may soon change. CDC is encouraging local health officials to track resistance data, and the World Health Organization has initiated a global computer database for physicians to report outbreaks of drug-resistant bacterial infections. Experts agree that antibiotics should be restricted to patients who can truly benefit from them–that is, people with bacterial infections. Already this is being done in the hospital setting, where the routine use of antibiotics to prevent infection in certain surgical patients is being reexamined. We have known since way back in the antibiotic era that these drugs have been used inappropriately in surgical prophylaxis [preventing infections in surgical patients]. But there is more success [in limiting antibiotic use] in hospital settings, where guidelines are established, than in the more typical outpatient settings,† says Cranston. Murray points out an example of antibiotic prophylaxis in the outpatient setting–children with recurrent ear infections given extended antibiotic prescriptions to prevent future infections. (See â€Å"Protecting Little Pitchers' Ears† in the December 1994 FDA Consumer. Another problem with antibiotic use is that patients often stop taking the drug too soon, because symptoms improve. However, this merely encourages resistant microbes to proliferate. The infection returns a few weeks later, and this time a different drug must be used to treat it. Targeting TB Stephen Weis and colleagues at the University of North Texas Health Science Center in Fort Worth reported in the April 28, 1994, New England Journal of Medicine on research they conducted in Tarrant County, Texas, that vividly illustrates how helping patients to take the full course of their medication can actually lower resistance rates. The subject–tuberculosis. TB is an infection that has experienced spectacular ups and downs. Drugs were developed to treat it, complacency set in that it was beaten, and the disease resurged because patients stopped their medication too soon and infected others. Today, one in seven new TB cases is resistant to the two drugs most commonly used to treat it (isoniazid and rifampin), and 5 percent of these patients die. In the Texas study, 407 patients from 1980 to 1986 were allowed to take their medication on their own. From 1986 until the end of 1992, 581 patients were closely followed, with nurses observing them take their pills. By the end of the study, the relapse rate–which reflects antibiotic resistance–fell from 20. 9 to 5. 5 percent. This trend is especially significant, the researchers note, because it occurred as risk factors for spreading TB–including AIDS, intravenous drug use, and homelessness–were increasing. The conclusion: Resistance can be slowed if patients take medications correctly. Narrowing the Spectrum Appropriate prescribing also means that physicians use â€Å"narrow spectrum† antibiotics–those that target only a few bacterial types–whenever possible, so that resistances can be restricted. The only national survey of antibiotic prescribing practices of office physicians, conducted by the National Center for Health Statistics, finds that the number of prescriptions has not risen appreciably from 1980 to 1992, but there has been a shift to using costlier, broader spectrum agents. This prescribing trend heightens the resistance problem, write McCaig and Hughes, because more diverse bacteria are being exposed to antibiotics. One way FDA can help physicians choose narrower spectrum antibiotics is to ensure that labeling keeps up with evolving bacterial resistances. Blum hopes that the surveillance information on emerging antibiotic resistances from CDC will enable FDA to require that product labels be updated with the most current surveillance information. Many of us have come to take antibiotics for granted. A child develops strep throat or an ear infection, and soon a bottle of â€Å"pink medicine† makes everything better. An adult suffers a sinus headache, and antibiotic pills quickly control it. But infections can and do still kill. Because of a complex combination of factors, serious infections may be on the rise. While awaiting the next â€Å"wonder drug,† we must appreciate, and use correctly, the ones that we already have. {draw:rect} Big Difference If this bacterium could be shown four times bigger, it would be the right relative size to the virus beneath it. Both are microscopic and are shown many times larger than life. ) Although bacteria are single-celled organisms, viruses are far simpler, consisting of one type of biochemical (a nucleic acid, such as DNA or RNA) wrapped in another (protein). Most biologists do not consider viruses to be living things, but instead, infectious particles. Antibiotic drugs attack bacteria, not viruses. {draw:rect} *The Greatest Fe ar–Vancomycin* Resistance When microbes began resisting penicillin, medical researchers fought back with chemical cousins, such as methicillin and oxacillin. By 1953, the antibiotic armamentarium included chloramphenicol, neomycin, terramycin, tetracycline, and cephalosporins. But today, researchers fear that we may be nearing an end to the seemingly endless flow of antimicrobial drugs. At the center of current concern is the antibiotic vancomycin, which for many infections is literally the drug of â€Å"last resort,† says Michael Blum, M. D. , medical officer in FDA's division of anti-infective drug products. Some hospital-acquired staph infections are resistant to all antibiotics except vancomycin. Now vancomycin resistance has turned up in another common hospital bug, enterococcus. And since bacteria swap resistance genes like teenagers swap T-shirts, it is only a matter of time, many microbiologists believe, until vancomycin-resistant staph infections appear. â€Å"Staph aureus may pick up vancomycin resistance from enterococci, which are found in the normal human gut,† says Madden. And the speed with which vancomycin resistance has spread through enterococci has prompted researchers to use the word â€Å"crisis† when discussing the possibility of vancomycin-resistant staph. Vancomycin-resistant enterococci were first reported in England and France in 1987, and appeared in one New York City hospital in 1989. By 1991, 38 hospitals in the United States reported the bug. By 1993, 14 percent of patients with enterococcus in intensive-care units in some hospitals had vancomycin-resistant strains, a 20-fold increase from 1987. A frightening report came in 1992, when a British researcher observed a transfer of a vancomycin-resistant gene from enterococcus to Staph aureus in the laboratory. Alarmed, the researcher immediately destroyed the bacteria. Ricki_ Lewis is a geneticist and textbook author. _ {draw:rect} FDA Consumer magazine (September 1995)