AIM

Antibiotics-good or bad for us?

Certificate of Authenticity
This is to certify that Parvez Hassan Ansari a student of class 12th has successfully completed the research product on the topic antibiotics-good or bad for us? under the guidance of Mrs. MEENA. This project is absolutely genuine and does not indulge in plagiarism of any kind. This reference taken in making this project has been declared at the end of this project.

Signature {subject teacher}

Signature {examiner}

Acknowledgement
I feel proud to present my investigatory project in Biology on the antibiotics-good or bad for us? This project would not have been feasible without the proper rigorous guidance of biology teacher Mrs.Neena Dhawan. Who guided me throughout this project in every possible way? An investigatory project involves various difficult lab experiments, which have to obtain the observations and conclude the reports on a meaningful note. Thereby, I would like to thanks Mrs.Neena Dhawan for guiding me on a systematic basis and ensuring that in completed all my research with ease. Rigorous hard work has put in this project to ensure that it proves to be the best. I hope that it proves to be the best. I hope that this project will prove to be a breeding ground for the next generation of students and will guide them in every possible way.

Introduction
In common usage, an antibiotic (from the Ancient Greek: anti, "against", and bios, "life") is a substance or compound that kills bacteria or inhibits their growth.[1] Antibacterial is an alternative name. Antibiotics belong to the broader group of antimicrobial compounds, used to treat infections caused by microorganisms, including fungi and protozoa. The term "antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.[2] This original definition excluded naturally occurring substances that kill bacteria but are not produced by microorganisms (such as gastric juice and hydrogen peroxide) and also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibiotics are relatively small molecules with a molecular weight less than 2000 atomic mass units.

Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. Genes can be transferred between bacteria in a horizontal fashion by conjugation, transduction, or transformation. Thus a gene for antibiotic resistance which had evolved via natural selection may be shared. Evolutionary stress such as exposure to antibiotics then selects for the antibiotic resistant trait. Many antibiotic resistance genes reside on plasmids, facilitating their transfer. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug or super bacteria. The primary cause of antibiotic resistance is antibiotic use both within medicine and veterinary medicine. The greater the duration of exposure the greater the risk of the development of resistance irrespective of the severity of the need for antibiotics.

First we have to study antibioticsAntibiotic

n common usage, an antibiotic (from the Ancient Greek: anti, "against", and bios, "life") is a substance or compound that kills bacteria or inhibits their growth. Antibacterial is an alternative name. Antibiotics belong to the broader group of antimicrobial compounds, used to treat infections caused by microorganisms, including fungi and protozoa. The term "antibiotic" was coined by Selman Waksman in 1942 to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution. This original definition excluded naturally occurring substances that kill bacteria but are not produced by microorganisms (such as gastric juice and hydrogen peroxide) and also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibiotics are relatively small molecules with a molecular weight less than 2000 atomic mass units. With advances in medicinal chemistry, most antibiotics are now semi synthetic modified chemically from original compounds found in nature, as is the case with betalactase (which include the penicillins, produced by fungi in the genus Penicillium, the cephalosporins, and the carbapenems). Some antibiotics are still produced and isolated from living organisms, such as the amino glycosides, and others have been created through purely synthetic means: the sulfonamides, the quinolones, and the oxazolidinones. In addition to this origin-based classification into natural, semi synthetic, and synthetic, antibiotics may be divided into two broad groups according to their effect on microorganisms: Those that kill bacteria are bactericidal agents, whereas those that only impair bacterial growth are known as bacteriostatic agents.

Historyofantibiotics
Many treatments for infections prior to the beginning of the twentieth century were based on medicinal folklore. Treatments for infection in many ancient cultures using concoctions with antimicrobial properties were described over 2000 years ago. Many ancient cultures, including the ancient Egyptians and ancient Greeks used molds and plants to treat infections. The discovery of the natural antibiotics produced by microorganisms stemmed from earlier work on the observation of antibiosis between micro-organisms. Louis Pasteur observed that, "if we could intervene in the antagonism
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observed d between some bac cteria, it would w offe er perhaps s the grea atest hopes s for therapeu utics". Syn nthetic antib biotic chem motherapy as s a science and the sto ory of antib biotic developm ment began n in German ny with Pau ul Ehrlich, a German medical m scie entist in the e late 1880s. Scientific endeavours s to under rstand the science be ehind wha at caused these t diseases, the deve elopment of f synthetic antibiotic chemother rapy, the isolation i of f the natural antibiotics a marked m milestones in antibiotic a de evelopment t. Original lly known as a antibiosi is, antibiotics were dru ugs which acted a again nst bacteria. . The term ant tibiosis, wh hich means "against lif fe," was int troduced by y the Frenc ch bacteriologist Vuillem min as a desc criptive nam me of the phenomenon n exhibited by these dr rugs.(Antib biosis was first described d in 1877 in n bacteria when w Louis Pasteur and a Robert Koch obse erved that an airborne ba acillus coul ld inhibit th he growth of Bacillus s anthracis s.). These drugs d were lat st in ter renamed antibiotic cs by Selm man Waksm man, an Am merican microbiologi m 1942.

Bacteria al antagonis sm of Penicillium spp. were first described d in n England by b John Tyn ndall in 1875.The significance to an ntibiotic disc covery was s not realize ed until the work of Eh hrlich on synth hetic antibio otic chemot therapy, wh hich marked d the birth of o the antibi iotic revolu ution. Ehrlich noted n that certain c dyes s would bin nd to and co olor human n, animal, or r bacterial cells, c while ot thers did no ot. He then extended th he idea that t it might be b possible to make ce ertain dyes or chemicals that would act as a magic m bullet t or selectiv ve drug that would bin nd to and kill l bacteria while not harming the t human host. Afte er much experimenta e ation, screenin ng hundreds s of dyes ag gainst variou us organism ms, he disco overed a me edicinally useful drug, th he man-ma ade antibio otic, Salva arsan. In 1928 Flem ming made e an impo ortant observat tion concern ning the ant tibiosis by penicillin. p F Fleming po ostulated tha at the effect t was mediated d by a yet-unidentif fied antibiotic-like compound c that could d be explo oited. Althoug gh he initially character rized some of its antib biotic prope erties, he di id not pursu ue its developm ment. In th he meantim me, another synthetic antibacteria al antibiotic c Prontosil was develope ed and man nufactured for f commer rcial use by y Domagk in i 1932. Pro ontosil, the e first commer rcially avail lable antiba acterial antib biotic, was developed d by a research team le ed by Gerhard d Domagk (w who received the 1939 9 Nobel Pri ize for Med dicine for hi is efforts) at a the Bayer Laboratories s of the IG Farben F cong glomerate in i Germany y. Prontosil had a relati ively broad ef ffect agains st Gram-po ositive cocc ci but not against a ente erobacteria. . The disco overy and dev velopment of o this first sulfonamide drug op pened the era e of antib biotics. In 1939, 1 discover ry by Rene Dubos of the first na aturally der rived antibi iotic-like su ubstance na amed gramicid din from B. . brevis. It was w one of f the first co ommercially y manufact tured antibi iotics in use during d Wor rld War II to prove highly h effec ctive in tre eating woun nds and ul lcers.
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Florey and Chain succeeded in purifying penicillin. The purified antibiotic displayed antibacterial activity against a wide range of bacteria. It also had low toxicity and could be taken without causing adverse effects. Furthermore, its activity was not inhibited by biological constituents such as pus, unlike the synthetic antibiotic class available at the time, the sulfonamides. The discovery of such a powerful antibiotic was unprecedented. The development of penicillin led to renewed interest in the search for antibiotic compounds with similar capabilities.Because of their discovery of penicillin Ernst Chain, Howard Florey and Alexander Fleming shared the 1945 Nobel Prize in Medicine. Florey credited Dubos with pioneering the approach of deliberately, systematically searching for antibacterial compounds. Such a methodology had led to the discovery of gramicidin, which revived Florey's research in penicillin.

Antibioticresistance

SEMdepictingmethicillinresistantStaphylococcusaureusbacteria.

The emergence of antibiotic resistance is an evolutionary process that is based on selection for organisms that have enhanced ability to survive doses of antibiotics that would have previously been lethal. Antibiotics like Penicillin and Erythromycin, which used to be one-time miracle cures are now less effective because bacteria have become more resistant. Antibiotics themselves act as a selective pressure that allows the growth of resistant bacteria within a population and inhibits susceptible bacteria. Antibiotic selection of pre-existing antibiotic resistant mutants within bacterial populations was demonstrated in 1943 by the experiment. Survival of bacteria often results from an inheritable resistance. Any antibiotic resistance may impose a biological cost. Spread of antibiotic-resistant bacteria may be hampered by reduced fitness associated with the resistance, which is disadvantageous for survival of the bacteria when antibiotic is not present. Additional mutations, however, may compensate for this fitness cost and aids the survival of these bacteria. The underlying molecular mechanisms leading to antibiotic resistance can vary. Intrinsic resistance may naturally occur as a result of the bacteria's genetic makeup. The bacterial chromosome may fail to encode a protein that the antibiotic targets. Acquired resistance results from a mutation in the bacterial chromosome or the acquisition of extrachromosomal DNA. Antibiotic-producing bacteria have evolved resistance mechanisms
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that have been shown to be similar to, and may have been transferred to, antibioticresistant strains. The spread of antibiotic resistance mechanisms occurs through vertical transmission of inherited mutations from previous generations and genetic recombination of DNA by horizontal genetic exchange. Antibiotic resistance is exchanged between different bacteria by plasmids that carry genes that encode antibiotic resistance that may result in co-resistance to multiple antibiotics. These plasmids can carry different genes

with diverse resistance mechanisms to unrelated antibiotics but because they are located on the same plasmid multiple antibiotic resistances to more than one antibiotic is transferred. On the other hand, cross-resistance to other antibiotics within the bacteria results when the same resistance mechanism is responsible for resistance to more than one antibiotic is selected for. Antibiotic-resistant microorganisms, sometimes referred to as "superbugs", may contribute to the re-emergence of diseases which are currently well-controlled. For example, cases of tuberculosis (TB) that are resistant to traditionally effective treatments remain a cause of great concern to health professionals. Every year, nearly half a million new cases of multidrug-resistant tuberculosis (MDR-TB) are estimated to occur worldwide. NDM-1 is a newly-identified enzyme that makes bacteria resistant to a broad range of beta-lactam antibiotics. United Kingdom Health Protection Agency has stated that "most isolates with NDM-1 enzyme are resistant to all standard intravenous antibiotics for treatment of severe infections."

Antibiotic resistance

is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. Genes can be transferred between bacteria in a horizontal fashion by conjugation, transduction, or transformation. Thus a gene for antibiotic resistance which had evolved via natural selection may be shared. Evolutionary stress such as exposure to antibiotics then selects for the antibiotic resistant trait. Many antibiotic resistance genes reside on plasmids, facilitating their transfer. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug or super bacteria. The primary cause of antibiotic resistance is antibiotic use both within medicine and veterinary medicine. The greater the duration of exposure the greater the risk of the development of resistance irrespective of the severity of the need for antibiotics.

Causes
The widespread use of antibiotics both inside and outside of medicine is playing a significant role in the emergence of resistant bacteria. Antibiotics are often used in rearing animals for food and this use among others leads to the creation of resistant strains of bacteria. In some countries antibiotics are sold over the counter without a prescription which also leads to the creation of resistant strains. In supposedly wellregulated human medicine the major problem of the emergence of resistant bacteria is due to misuse and overuse of antibiotics by doctors as well as patients. Other practices contributing towards resistance include the addition of antibiotics to the feed of livestock. Household use of antibacterials in soaps and other products, although not clearly contributing to resistance, is also discouraged (as not being effective at infection control). Also unsound practices in the pharmaceutical manufacturing industry can contribute towards the likelihood of creating antibiotic resistant strains. Certain antibiotic classes are highly associated with colonisation with superbugs compared to other antibiotic classes. The risk for colonisation increases if there is a lack of sensitivity (resistance) of the superbugs to the antibiotic used and high tissue penetration as well as broad spectrum activity against "good bacteria". In the case of MRSA, increased rates of MRSA infections are seen with glycopeptides, cephalosporins and especially quinolones. In the case of colonisation with C difficile the high risk antibiotics include cephalosporins and in particular quinolones and clindamycin.

In medicine
The volume of antibiotic prescribed is the major factor in increasing rates of bacterial resistance rather than compliance with antibiotics. A single dose of antibiotics leads to a greater risk of resistant organisms to that antibiotic in the person for up to a year. Inappropriate prescribing of antibiotics has been attributed to a number of causes including: people who insist on antibiotics, physicians simply prescribe them as they feel they do not have time to explain why they are not necessary, physicians who do not know when to prescribe antibiotics or else are overly cautious for medical legal reasons. A third of people for example believe that antibiotics are effective for the common cold and 22% of people do not finish a course of antibiotics primarily due to that fact that they feel better (varying from 10% to 44% depending on the country). Compliance with once daily antibiotics is better than with twice daily antibiotics. Sub optimum antibiotic concentrations in critically ill people increase the frequency of antibiotic resistance organisms While taking antibiotics doses less than those recommended may increase rates of resistance, shortening the course of antibiotics may actually decrease rates of resistance.

Poor hand hygiene by hospital staff has been associated with the spread of resistant organismsand an increase in hand washing compliance results in decreased rates of these organisms.

Role of other animals

Drugs are used in animals that are used as human food, such as cows, pigs, chickens, fish, etc., and these drugs can affect the safety of the meat, milk, and eggs produced from those animals and can be the source of superbugs. For example, farm animals, particularly pigs, are believed to be able to infect people with MRSA. The resistant bacteria in animals due to antibiotic exposure can be transmitted to humans via three pathways, those being through the consumption of meat, from close or direct contact with animals, or through the environment. The World Health Organization concluded that antibiotics as growth promoters in animal feeds should be prohibited (in the absence of risk assessments). In 1998, European Union health ministers voted to ban four antibiotics widely used to promote animal growth (despite their scientific panel's recommendations). Regulation banning the use of antibiotics in European feed, with the exception of two antibiotics in poultry feeds, became effective in 2006. In Scandinavia, there is evidence that the ban has led to a lower prevalence of antimicrobial resistance in (non-hazardous) animal bacterial populations. In the USA federal agencies do not collect data on antibiotic use in animals but animal to human spread of drug resistant organisms has been demonstrated in research studies. Antibiotics are still used in U.S. animal feedalong with other ingredients which have safety concerns. Growing U.S. consumer concern about using antibiotics in animal feed has led to a niche market of "antibiotic-free" animal products, but this small market is unlikely to change entrenched industry-wide practices. In 2001, the Union of Concerned Scientists estimated that greater than 70% of the antibiotics used in the US are given to food animals (e.g. chickens, pigs and cattle) in the absence of disease. In 2000 the US Food and Drug Administration (FDA) announced their intention to revoke approval of fluoroquinolone use in poultry production because of substantial evidence linking it to the emergence of fluoroquinolone resistant campylobacter infections in humans. The final decision to ban fluoroquinolones from use in poultry production was not made until five years later because of challenges from the food animal and pharmaceutical industries. Today, there are two federal bills (S. 549 and H.R. 962) aimed at phasing out "non-therapeutic" antibiotics in US food animal producti

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Mech hanism ms

Schema aticrepresentationofhow wantibioticre esistanceevo olvesvianatur ralselection.Thetopsecti ion representsapopula ationofbacte eriabeforeex xposuretoan nantibiotic.Th hemiddlesec ctionshowsthe t populati iondirectlyaf fterexposure e,thephasein nwhichselec ctiontookpla ace.Thelastsection s shows sthe distribut tionofresista anceinanew wgenerationof o bacteria.Thelegendind dicatesthere esistancelevelsof in ndividuals.

Antibiot tic resistanc ce can be a result r of ho orizontal gen ne transfer, , and also of unlinked point mu utations in the t pathoge en genome and a a rate of o about 1 in n 108 per ch hromosoma al replication. The ant tibiotic action against the t pathoge en can be se een as an en nvironmenta al pressure e; those bact teria which h have a mut tation allow wing them to survive will w live on to t reproduc ce. They wi ill then pass s this trait to o their offsp pring, whic ch will resul lt in a fully resistant t colony. The four r main mech hanisms by y which mic croorganism ms exhibit re esistance to o antimicrob bials are:

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1. Druginactivationormodification:e.g.enzymaticdeactivationofPenicillinGin somepenicillinresistantbacteriathroughtheproductionoflactamases. 2. Alterationoftargetsite:e.g.alterationofPBPthebindingtargetsiteof penicillinsinMRSAandotherpenicillinresistantbacteria. 3. Alterationofmetabolicpathway:e.g.somesulfonamideresistantbacteriadonot requireparaaminobenzoicacid(PABA),animportantprecursorforthesynthesis offolicacidandnucleicacidsinbacteriainhibitedbysulfonamides.Instead,like mammaliancells,theyturntoutilizingpreformedfolicacid. 4. Reduceddrugaccumulation:bydecreasingdrugpermeabilityand/orincreasing activeefflux(pumpingout)ofthedrugsacrossthecellsurface. There are three known mechanisms of fluoroquinolone resistance. Some types of efflux pumps can act to decrease intracellular quinolone concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or Topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug's effectiveness. Research has shown that the bacterial protein LexA may play a key role in the acquisition of bacterial mutations giving resistance to quinolones and rifampicin. Antibiotic resistance can also be introduced artificially into a microorganism through laboratory protocols, sometimes used as a selectable marker to examine the mechanisms of gene transfer or to identify individuals that absorbed a piece of DNA that included the resistance gene and another gene of interest.

Resistantpathogens
1. Staphylococcus aureus
Staphylococcus aureus (colloquially known as "Staph aureus" or a Staph infection) is one of the major resistant pathogens. Found on the mucous membranes and the human skin of around a third of the population, it is extremely adaptable to antibiotic pressure. It was one of the earlier bacteria in which penicillin resistance was foundin 1947, just four years after the drug started being mass-produced. Methicillin was then the antibiotic of choice, but has since been replaced by oxacillin due to significant kidney toxicity. MRSA (methicillin-resistant Staphylococcus aureus) was first detected in Britain in 1961 and is now "quite common" in hospitals. MRSA was responsible for 37% of fatal cases of sepsis in the UK in 1999, up from 4% in 1991. Half of all S. aureus infections in the US are resistant to penicillin, methicillin, tetracycline and erythromycin.
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This left vancomycin as the only effective agent available at the time. However, strains with intermediate (4-8 ug/ml) levels of resistance, termed GISA (glycopeptide intermediate Staphylococcus aureus) or VISA (vancomycin intermediate Staphylococcus aureus), began appearing in the late 1990s. The first identified case was in Japan in 1996, and strains have since been found in hospitals in England, France and the US. The first documented strain with complete (>16 ug/ml) resistance to vancomycin, termed VRSA (Vancomycin-resistant Staphylococcus aureus) appeared in the United States in 2002. A new class of antibiotics, oxazolidinones, became available in the 1990s, and the first commercially available oxazolidinone, linezolid, is comparable to vancomycin in effectiveness against MRSA. Linezolid-resistance in Staphylococcus aureus was reported in 2003. CA-MRSA (Community-acquired MRSA) has now emerged as an epidemic that is responsible for rapidly progressive, fatal diseases including necrotizing pneumonia, severe sepsis and necrotizing fasciitis. Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequently identified antimicrobial drug-resistant pathogen in US hospitals. The epidemiology of infections caused by MRSA is rapidly changing. In the past 10 years, infections caused by this organism have emerged in the community. The 2 MRSA clones in the United States most closely associated with community outbreaks, USA400 (MW2 strain, ST1 lineage) and USA300, often contain Panton-Valentine leukocidin (PVL) genes and, more frequently, have been associated with skin and soft tissue infections. Outbreaks of community-associated (CA)-MRSA infections have been reported in correctional facilities, among athletic teams, among military recruits, in newborn nurseries, and among men who have sex with men. CA-MRSA infections now appear to be endemic in many urban regions and cause most CA-S. aureus infections.

2. Streptococcus and Enterococcus

Streptococcus pyogenes (Group A Streptococcus: GAS) infections can usually be treated with many different antibiotics. Early treatment may reduce the risk of death from invasive group A streptococcal disease. However, even the best medical care does not prevent death in every case. For those with very severe illness, supportive care in an intensive care unit may be needed. For persons with necrotizing fasciitis, surgery often is needed to remove damaged tissue. Strains of S. pyogenes resistant to macrolide antibiotics have emerged, however all strains remain uniformly sensitive to penicillin. Resistance of Streptococcus pneumoniae to penicillin and other beta-lactams is increasing worldwide. The major mechanism of resistance involves the introduction of mutations in genes encoding penicillin-binding proteins. Selective pressure is thought to play an important role, and use of beta-lactam antibiotics has been implicated as a risk factor for infection and colonization. Streptococcus pneumoniae is responsible for pneumonia, bacteremia, otitis media, meningitis, sinusitis, peritonitis and arthritis.
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Penicillin-resistant pneumonia caused by Streptococcus pneumoniae (commonly known as pneumococcus), was first detected in 1967, as was penicillin-resistant gonorrhea. Resistance to penicillin substitutes is also known as beyond S. aureus. By 1993 Escherichia coli was resistant to five fluoroquinolone variants. Mycobacterium tuberculosis is commonly resistant to isoniazid and rifampin and sometimes universally resistant to the common treatments. Other pathogens showing some resistance include Salmonella, Campylobacter, and Streptococci. Enterococcus faecium is another superbug found in hospitals. Penicillin-Resistant Enterococcus was seen in 1983, vancomycin-resistant enterococcus (VRE) in 1987, and Linezolid-Resistant Enterococcus (LRE) in the late 1990s.

3. Pseudomonas aeruginosa
Pseudomonas aeruginosa is a highly prevalent opportunistic pathogen. One of the most worrisome characteristics of P. aeruginosa consists in its low antibiotic susceptibility. This low susceptibility is attributable to a concerted action of multidrug efflux pumps with chromosomally-encoded antibiotic resistance genes (e.g. mexAB-oprM, mexXY etc.) and the low permeability of the bacterial cellular envelopes. Besides intrinsic resistance, P. aeruginosa easily develop acquired resistance either by mutation in chromosomallyencoded genes, or by the horizontal gene transfer of antibiotic resistance determinants. Development of multidrug resistance by P. aeruginosa isolates requires several different genetic events that include acquisition of different mutations and/or horizontal transfer of antibiotic resistance genes. Hypermutation favours the selection of mutation-driven antibiotic resistance in P. aeruginosa strains producing chronic infections, whereas the clustering of several different antibiotic resistance genes in integrons favours the concerted acquisition of antibiotic resistance determinants. Some recent studies have shown that phenotypic resistance associated to biofilm formation or to the emergence of small-colony-variants may be important in the response of P. aeruginosa populations to antibiotics treatment.

4. Clostridium difficile
Clostridium difficile is a nosocomial pathogen that causes diarrheal disease in hospitals world wide. Clindamycin-resistant C. difficile was reported as the causative agent of large outbreaks of diarrheal disease in hospitals in New York, Arizona, Florida and Massachusetts between 1989 and 1992. Geographically dispersed outbreaks of C. difficile strains resistant to fluoroquinolone antibiotics, such as Cipro (ciprofloxacin) and Levaquin (levofloxacin), were also reported in North America in 2005.

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5. Salmonella and E. coli

Escherichia coli and Salmonella come directly from contaminated food. Of the meat that is contaminated with E. coli, eighty percent of the bacteria are resistant to one or more drugs made; it causes bladder infections that are resistant to antibiotics (HSUS Fact Sheet). Salmonella was first found in humans in the 1970s and in some cases is resistant to as many as nine different antibiotics (HSUS Fact Sheet). When both bacterium are spread, serious health conditions arise. Many people are hospitalized each year after becoming infected, and some die as a result.

6. Acinetobacter baumannii
On November 5, 2004, the Centers for Disease Control and Prevention (CDC) reported an increasing number of Acinetobacter baumannii bloodstream infections in patients at military medical facilities in which service members injured in the Iraq/Kuwait region during Operation Iraqi Freedom and in Afghanistan during Operation Enduring Freedom were treated. Most of these showed multidrug resistance (MRAB), with a few isolates resistant to all drugs tested.

Alternatives
Prevention
Rational use of antibiotics may reduce the chances of development of opportunistic infection by antibiotic-resistant bacteria due to dysbacteriosis. In one study the use of fluoroquinolones are clearly associated with Clostridium difficile infection, which is a leading cause of nosocomial diarrhea in the United States, and a major cause of death, worldwide. There is clinical evidence that topical dermatological preparations containing tea tree oil and thyme oil may be effective in preventing transmittal of CA-MRSA. Vaccines do not suffer the problem of resistance because a vaccine enhances the body's natural defenses, while an antibiotic operates separately from the body's normal defenses. Nevertheless, new strains may evolve that escape immunity induced by vaccines; for example an update Influenza vaccine is needed each year. While theoretically promising, anti-staphylococcal vaccines have shown limited efficacy, because of immunological variation between Staphylococcus species, and the limited

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duration of effectiveness of the antibodies produced. Development and testing of more effective vaccines is under way. The Australian Commonwealth Scientific and Industrial Research Organization (CSIRO), realizing the need for the reduction of antibiotic use, has been working on two alternatives. One alternative is to prevent diseases by adding cytokines instead of antibiotics to animal feed. These proteins are made in the animal body "naturally" after a disease and are not antibiotics so they do not contribute to the antibiotic resistance problem. Furthermore, studies on using cytokines have shown that they also enhance the growth of animals like the antibiotics now used, but without the drawbacks of nontherapeutic antibiotic use. Cytokines have the potential to achieve the animal growth rates traditionally sought by the use of antibiotics without the contribution of antibiotic resistance associated with the widespread non-therapeutic uses of antibiotics currently utilized in the food animal production industries. Additionally, CSIRO is working on vaccines for diseases.

Phage therapy
Phage therapy, an approach that has been extensively researched and utilized as a therapeutic agent for over 60 years, especially in the Soviet Union, is an alternative that might help with the problem of resistance. Phage therapy was widely used in the United States until the discovery of antibiotics, in the early 1940s. Bacteriophages or "phages" are viruses that invade bacterial cells and, in the case of lytic phages, disrupt bacterial metabolism and cause the bacterium to lyse. Phage therapy is the therapeutic use of lytic bacteriophages to treat pathogenic bacterial infections. Bacteriophage therapy is an important alternative to antibiotics in the current era of multidrug resistant pathogens. A review of studies that dealt with the therapeutic use of phages from 19661996 and few latest ongoing phage therapy projects via internet showed: phages were used topically, orally or systemically in Polish and Soviet studies. The success rate found in these studies was 8095% with few gastrointestinal or allergic side effects. British studies also demonstrated significant efficacy of phages against Escherichia coli, Acinetobacter spp., Pseudomonas spp and Staphylococcus aureus. US studies dealt with improving the bioavailability of phage. Phage therapy may prove as an important alternative to antibiotics for treating multidrug resistant pathogens.

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Research
New medications
Until recently, research and development (R&D) efforts have provided new drugs in time to treat bacteria that became resistant to older antibiotics. That is no longer the case.[citation needed] The potential crisis at hand is the result of a marked decrease in industry R&D, and the increasing prevalence of resistant bacteria. Infectious disease physicians are alarmed by the prospect that effective antibiotics may not be available to treat seriously ill patients in the near future. The pipeline of new antibiotics is drying up. Major pharmaceutical companies are losing interest in the antibiotics market because these drugs may not be as profitable as drugs that treat chronic (long-term) conditions and lifestyle issues. The resistance problem demands that a renewed effort be made to seek antibacterial agents effective against pathogenic bacteria resistant to current antibiotics. One of the possible strategies towards this objective is the rational localization of bioactive phytochemicals. Plants have an almost limitless ability to synthesize aromatic substances, most of which are phenols or their oxygen-substituted derivatives such as tannins. Most are secondary metabolites, of which at least 12,000 have been isolated, a number estimated to be less than 10% of the total .In many cases, these substances serve as plant defense mechanisms against predation by microorganisms, insects, and herbivores. Many of the herbs and spices used by humans to season food yield useful medicinal compounds including those having antibacterial activity. Traditional healers have long used plants to prevent or cure infectious conditions. Many of these plants have been investigated scientifically for antimicrobial activity and a large number of plant products have been shown to inhibit growth of pathogenic bacteria.A number of these agents appear to have structures and modes of action that are distinct from those of the antibiotics in current use, suggesting that cross-resistance with agents already in use may be minimal. For example the combination of 5'-methoxyhydnocarpine and berberine in herbs like Hydrastis canadensis and Berberis vulgaris can block the MDR-pumps that cause multidrug resistance. This has been shown for Staphylococcus aureus. Archaeocins is the name given to a new class of potentially useful antibiotics that are derived from the Archaea group of organisms. Eight archaeocins have been partially or fully characterized, but hundreds of archaeocins are believed to exist, especially within the haloarchaea. The prevalence of archaeocins is unknown simply because no one has looked for them. The discovery of new archaeocins hinges on recovery and cultivation of archaeal organisms from the environment. For example, samples from a novel hypersaline field site, Wilson Hot Springs, recovered 350 halophilic organisms; preliminary analysis of 75 isolates showed that 48 were archaeal and 27 were bacterial. In research published on October 17, 2008 in Cell, a team of scientists pinpointed the place on bacteria where the antibiotic myxopyronin launches its attack, and why that attack is successful. The myxopyronin binds to and inhibits the crucial bacterial enzyme, RNA polymerase. The
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myxopyronin changes the structure of the switch-2 segment of the enzyme, inhibiting its function of reading and transmitting DNA code. This prevents RNA polymerase from delivering genetic information to the ribosomes, causing the bacteria to die. One of the major causes of antibiotic resistance is the decrease of effective drug concentrations at their target place, due to the increased action of ABC transporters. Since ABC transporter blockers can be used in combination with current drugs to increase their effective intracellular concentration, the possible impact of ABC transporter inhibitors is of great clinical interest. ABC transporter blockers that may be useful to increase the efficacy of current drugs have entered clinical trials and are available to be used in therapeutic regimes.

Applications
Antibiotic resistance is an important tool for genetic engineering. By constructing a plasmid which contains an antibiotic resistance gene as well as the gene being engineered or expressed, a researcher can ensure that when bacteria replicate, only the copies which carry along the plasmid survive. This ensures that the gene being manipulated passes along when the bacteria replicates. The most commonly used antibiotics in genetic engineering are generally "older" antibiotics which have largely fallen out of use in clinical practice. These include:

ampicillin kanamycin tetracycline chloramphenicol

Industrially the use of antibiotic resistance is disfavored since maintaining bacterial cultures would require feeding them large quantities of antibiotics. Instead, the use of auxotrophic bacterial strains (and function-replacement plasmids) is preferred.

What

are superbugs?

These are normal bacteria which have crossed the limits of treatment by antibiotics. These cause pneumonia, Urinary infections and infections in other parts of the body.

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SuperbugNDM1Bacteria|Symptoms,Effects,Experiments, PreventionandExpertsSuggestions

The Superbug NDM1which stands for New Delhi metallo-beta-lactamase is started to spread in the world. The researchers found a new Bacteria called New Delhi metallobeta-lactamase (NDM-1) Bacteria, in patients of Asia and Britain. According to an international team of scientists People who traveled to India and Pakistan to get medical treatment risk picking up and spreading a new Superbug Bacteria.

How NDM-1 effects Human Body

Multi drugresistant bacteria are already a growing problem in hospitals across the world, marked by the rise of superbug infections like methicillinresistant Staphyloccusaureus(MRSA). NDM1 makes bacteria highly resistant to almost all antibiotics, including the mostpowerfulclasscalledcarbapenems. Most worryingly, NDM1producing bacteria are resistant to many antibiotics includingcarbapenems. Thescientistssaid,aclassofthedrugsgenerallyreservedforemergencyuseand totreatcausedbyothermultiresistantbacteriasuchasMRSAandCDifficile.

Johann Pitout from the University of Calgary in Canada expressed: If this emerging public health threat is ignored, sooner or later the medical community could be confronted with carbapenem-resistant (bacteria) that cause common infections, resulting in treatment failures with substantial increases in health-care costs

Symptoms of Super bug NDM-1 Bacteria, Klebsiella Pneumoniae and E. Coli Symptoms

KlebsiellabacteriacontainsthesuperbugNDM1. Klebsiella pneumoniae symptoms include sudden Onset, of High Fever and Hemoptysis. Klebsiellapneumoniaeisacommongramnegativebacteriaseenworldwide. It is also causing Urinary Tract Infections, Nosocomial Pneumonia, and Intra abdominalinfections.

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NDM1 which is found in the E. Coli bacteria may be the cause of Urinary Tract Infections. E.Coliistheleadingcauseofurinarytractinfectionsoutsideofhospitals. E.ColiisAntibioticresistant. E.ColiisalsoresponsibleforcasesofFatalPneumoniaandotherinfections.

Countries where Superbug NDM1 Bacteria is spreading

InastudypublishedinTheLancetInfectiousDiseasesjournal,theresearchersfoundthatNDM1is becomingmorecommoninBangladesh,India,andPakistanandisstartingtobeimportedbackto Britaininpatientsreturningfromthesecountries.

Experiments with Superbug NDM-1 Bacteria

Walshandhisinternationalteamcollectedbacteriasamplesfromhospitalpatientsintwoplacesin India,ChennaiandHaryana,andfrompatientsreferredtoBritainsnationalreferencelaboratory between2007and2009.Theyfound44NDM1positivebacteriainChennai,26inHaryana,37inBritain, and73inothersitesinBangladesh,India,andPakistan.

Preventing the Spread of Superbug NDM-1 Bacteria

TopreventspreadofSuperbugNDM1Bacteria,Doctorsadvisetoprovideadequatecleaningand sanitizingofallareasisthebestmeansofpreventingfurtherspreadofthesuperbugbacteria.Hospitals anddoctorsareunderadvisetostayontopofthecleanlinessissue.

Experts commenting on Walshs findings said it was important to be alert to the new bug and start screening for it early. It seems to be more dangerous than Swine flu, since it is working on Resistance of Human body.

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Articles on superbug in news papers Delhi superbug threatening world, claim UK scientists
Sanchita Sharma, Hindustan Times New Delhi, August 12, 2010 First Published: 00:54 IST(12/8/2010) Last Updated: 01:38 IST(12/8/2010)

A new hospital-acquired superbug that cannot be treated using existing drugs is spreading from India to the rest of the world, claim British scientists. Indian surgeons rubbish the claim saying its just another attempt to stop thousands of pounds from leaving the floundering British economy to

related stories

Linking India to superbug unfair and wrong, says India Govt condemns naming of superbug, refutes its linkage Some interpretations made without my knowledge: Superbug author

According to CII estimates, 1.1 million foreigners travel to India each year for cheaper treatments and surgeries. A heart bypass surgery costs $6,500 (R 3,03,550) in a corporate hospital in India, as compared to $30,000 (R 14,01,000)to $50,000 (R 23,35,000) in the US. So convinced are British scientists about the superbug infection being fuelled by Indias Rs 1,200-crore medical tourism industry that they have chosen to provocatively name the newly-identified gene that causes the drug resistance as the New Delhi metallo-betalactamase (NDM-1). A study published in The Lancet Infectious Diseases, British scientists report NDM-1 is becoming more common in Bangladesh, India, and Pakistan and is being imported back to Britain through patients returning after treatment. Healthcare experts in India say the British are just worried because they are losing patients to hospitals here. Its a false alarm, I track infection and have not seen a single case in my hospital. Hospital-acquired infections are far more common in Britain and the West than

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in India, said Dr Yatin Mehta, chairman, institute of critical care and anaesthesia, Medanta The Medicity. We offer better surgical outcomes at one-fifth the cost, he added. Dr Ashok Seth, chairman and chief interventionist, Escorts Heart Institute and Research Centre said, Most hospitals in India, including Escorts, have national and international accreditations... who send auditors to track quality including infections four times a year. The audits show that corporate hospitals here are safer than the West. Theyre definitely safer than Britains National Health Service. For the study, author Timothy Walsh from Cardiff University and his team collected bacteria samples from patients admitted in hospitals in Tamil Nadu and Haryana, and from patients referred to Britains national reference laboratory between 2007 and 2009. They found 44 NDM-1-positive bacteria in Chennai, 26 in Haryana, 37 in Britain, and 73 in other sites in Bangladesh, India, and Pakistan. Several not all British NDM-1 positive patients had recently traveled to India or Pakistan for hospital treatment, including cosmetic surgery. Whats particularly worrying, writes Walsh, is that the bacteria is resistant to all antibiotics, including carbapenem, a class of the drugs reserved to treat infections caused by other multi-resistant bugs like MRSA and C-Difficile.

Drugresistant'superbug'tracedtoIndia
TheTimesofIndia
CHENNAI:Scientistshavetrackeddownadrugresistantsuperbugthatinfectspatientsand causesmultipleorganfailuretoIndianhospitalsbutdoctorshereseeinitthegermofamove todamagethecountry'sboomingmedicaltourismindustry. The'superbug'resistanttoalmostallknownantibioticshasbeenfoundinUKpatientstreated inIndianhospitals.NamedaftertheIndiancapital,itisagenecarriedbybacteriathatcauses gastricproblems,entersthebloodstreamandmaycausemultipleorganfailureleadingto death. "IndiaalsoprovidescosmeticsurgeryforEuropeansandAmericans,anditislikelythebacteria willspreadworldwide,"scientistsreportedinTheLancetInfectiousDiseasesJournalon Wednesday.Whilethestudyhasthemedicalworldturningitsfocusoninfectioncontrol policiesinIndianhospitals,theIndianCouncilofMedicalResearchhasallegedabiasinthe
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reportandsaiditisanattempttohurtmedicaltourisminthecountrythatistakingawayhuge customfromhospitalsintheWest."Suchinfectionscanflowinfromanypartoftheworld.It's unfairtosayitoriginatedfromIndia,"saidICMRdirectorDrVMKatoch. Katochhasreasonstofume,asthesuperbugNDM1(NewDelhimetallobetalactamase)is namedafterthenationalcapital,whereaSwedishpatientwasreportedlyinfectedafter undergoingasurgeryin2008.SincethentherehavebeenseveralcasesreportedintheUKand in2009,thehealthprotectionagencyintheUKissuedanalertonthe'gramnegative'bacterial infectionthatisresistanttoeventhemostpowerfulandreservedclassantibioticscalled carbapenems. InajointstudyledbyChennaibasedKarthikeyanKumarasamy,pursuinghisPhDatUniversity ofMadrasandUKbasedTimothyWalshfromdepartmentofimmunity,infectionand biochemistry,departmentofmedicine,CardiffUniversityresearcherssoughttoexamine whetherNDM1producingbacteriawasprevalentinSouthAsiaandBritain. "WesawtheminmostofthehospitalsinChennaiandHaryana.Weestimatethatthe prevalenceofthisinfectionwouldbeashighas1.5%,"KumarasamytoldTOI."Wefoundthe superbugin44patientsinChennai,and26inHaryana,besides37intheUKand73inother placesacrossIndia,PakistanandBangaladesh,"hesaid. Whatmakesthesuperbugmoredangerousisitsabilitytojumpacrossdifferentbacterial species.Sofar,ithasbeenfoundintwocommonlyseenbacteria,EcoliandKpneumoniae. "Wehavefoundthatthesuperbughasthepotentialtogetcopiedandtransferredbetween bacteria,allowingittospreadrapidly.Ifitspreadstoanalreadyhardtotreatbacterial infection,itcanbeturnmoredangerous,"Kumarasamysaid. SeniordoctorsworkingininfectioncontrolsaidIndialackspoliciesonantibiotics,infection controlandregistriesforhospitalacquiredinfections.BytheICMRdirector'sownadmission, Indiacannotscientificallyfightbackallegationsofbeingthesourceofsuchsuperbugs,asthe countrydoesnothavearegistryofsuchhospitalacquiredinfections. "Twoineveryfivepatientsadmittedtohospitalsacquireinfections.Thisextendsthepatient's stayinthehospital,increasestheexpensesandcausessideeffects,"saidDrDilipMathai,head ofthedepartmentofinternalmedicine,ChristianMedicalCollege,Vellore. Foralongtime,IndiahasbeenseeingExtendedSpectrumBetaLactamase(ESBL),whichare enzymesthathavedevelopedaresistancetoantibioticslikepenicillin.ESBLenzymesaremost commonlyproducedbytwobacteriaEcoliandKpneumoniae,thetwobacteriainwhichthe newsuperbughasbeenfound."Theseweretreatedbyareservedclassofantibioticscalled carbapenems.Wehaveseenatleast3%ofpeopleinfectedwiththisdonotreacttothese reserveddrugs,"hesaid. Publichealthexpertssayglobalisationhasallowedbacteriatospreadrapidlyacrosstheworld
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andIndia,asamedicalhub,shouldbegearedforthechallenge.Katoch,whoisalsothe secretary,departmentofmedicalresearch,agrees."Atpresent,wedon'thaveanysystemin place.Thereareneitherrulesforhospitalsnoraregistrytorecordhospitalacquiredinfections. Wearenowintheprocessofformingacellthatwillactivatearegistryandissueguidelinesfor anintegratedsurveillancesystem,"hesaid. An different thing is also observe thatGeneresponsiblefordrugresistantsuperbug

found

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ConclusionOn the basis of above information we can say that antibiotics has to be take in low amount otherwise it effect is worst than its advantage. Therefore antibiotics are good but within limited value.

Result9 Antibiotics are good but within limited value. 9 Its disadvantage dominates to is advantage. 9 Deaths of people increases with time due to

antibiotic resitance.

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Bibliographywww.wikipedia.com www.google.com www.newsnet.com www.technopedia.com newpapers-The Times of India -Hindustan times -navbharat times

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