AIMAntibiotics-good or bad for us?

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Certificate of AuthenticityThis is to certify that Parvez Hassan Ansari a student of classlly completed the research product on the topic antibiotics-goodder the guidance of Mrs. Neena Dhawan. This project is absolutelyes not indulge in plagiarism of any kind. This reference taken inoject has been declared at the end of this project.Signature {subject teacher}Signature {examiner}2

12th has successfuor bad for us? ungenuine and domaking this pr

Acknowledge mentI 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 forguiding me on a systematic basis and ensuring that in completed all my researchwith ease. Rigorous hard work has put in this project to ensure that it provesto 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.

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IntroductionIn common usage, an antibiotic (from the Ancient Greek: a i , "agai s", a d life") is a susa ce r cmpu d ha kills aceria r i hiis heir grwh.[1] A iacerial is a aler aive ame. A iiics el g he rader grupf a imicrial cmpu ds, used rea i feci s caused y micrrga isms,i cludi g fu gi a d prza. The erm "a iiic" was ci ed y Selma Waksmai 1942 descrie a y susa ce prduced y a micrrga ism ha is a ag isic he grwh f her micrrga isms i high dilui .[2] This rigi al defi ii excluded aurally ccurri g susa ces ha kill aceria u are prduced y micrrga isms (such as gasric juice a d hydrge perxide) a d alsexcluded sy heic a iacerial cmpu ds such as he sulf amides . Ma y a iiics are relaively small mlecules wih a mlecular weigh less ha 2000 amic mass u is.A iiic resisa ce is a ype f drug resisa ce where a micrrga ism is ale survive expsure a a iiic. Ge es ca e ra sferred ewee aceriai a hriz al fashi y c jugai , ra sduci , r ra sfrmai . Thusa ge e fr a iiic resisa ce which had evlved via aural seleci may eshared. Evlui ary sress such as expsure a iiics he selecs fr hea iiic resisa rai. Ma y a iiic resisa ce ge es reside plasmids, faciliai g heir ra sfer. If a acerium carries several resisa ce ge es,i is called muliresisa r, i frmally, a superug r super aceria. The primary cause f a iiic resisa ce is a iiic use h wihi medici e a dveeri ary medici e. The greaer he durai f expsure he greaer he risk f he develpme f resisa ce irrespecive f he severiy f he eed fr a iiics.4

Firs we have sudy a iiicsA iiiccmm usage, a a iiic (frm he A cie Greek: a i, "agai s", a d ie") is a susa ce r cmpu d ha kills aceria r i hiis heir grwh. A iacerial is a aler aive ame. A iiics el g he rader grup f aimicrial cmpu ds, used rea i feci s caused y micrrga isms, i cludi g fu gi a d prza. The erm "a iiic" was ci ed y Selma Waksma i 1942 descrie a y susa ce prduced y a micrrga ism ha is a ag isic he grwh f her micrrga isms i high dilui . This rigi al defi ii excluded aurally ccurri g susa ces ha kill aceria u are prduced y micrrga isms (such as gasric juice a d hydrge perxide) a d als excludedsy heic a iacerial cmpu ds such as he sulf amides. Ma y a iiics are relaively small mlecules wih a mlecular weigh less ha 2000 amic massu is. Wih adva ces i medici al chemisry, ms a iiics are w semi sy heic mdified chemically frm rigi al cmpu ds fu d i aure, as is he casewih ealacase (which i clude he pe icilli s, prduced y fu gi i he ge us Pe icillium, he cephalspri s, a d he carape ems). Sme a iiics are sillprduced a d islaed frm livi g rga isms, such as he ami glycsides, a d hers have ee creaed hrugh purely sy heic mea s: he sulf amides, he qui l es, a d he xazlidi es. I addii his rigi -ased classificaii aural, semi sy heic, a d sy heic, a iiics may e divided i w rad grups accrdi g heir effec micrrga isms: Thse ha kill aceria are acericidal age s, whereas hse ha ly impair acerial grwh are k w as acerisaic age s.Hisry f a iiicsMa y reame s fr i feci s prir he egi i g f he we ieh ce ury were ased medici al flklre. Treame s fr i feci i ma y a cie culures usi g c cci s wih a imicrial prperies were descried ver 2000 years ag. Ma y a cie culures, i cludi g he a cie Egypia s a d a cie Greeksused mlds a d pla s rea i feci s. The discvery f he aural a iiics prduced y micrrga isms semmed frm earlier wrk he servai fa iisis ewee micr-rga isms. Luis Paseur served ha, "if we culd ierve e i he a ag ism5

serve d ewee sme aceria, i wuld ff er perhap s he grea es hpes frherapeu ics". Sy heic a i iic chemherapy a s a scie ce a d he s ryf a i iic develpme ega i Germa y wih Pa ul Ehrlich, a Germa medical scie is i h e lae wha 1880s. Scie ific e deavur s u der sa d he scie ce ehi d caused hese f diseases, he develpme f sy heic a iiicchemherapy, he islai he aural a iiics marked miles es i a iiic develpme . as a iisis, a iiics were dr ugs which aced agai s aceria. Origi ally k w The erm a iisis, wh ich mea s "agai s life," was irduced y he Fre ch acerilgis uillemi as a des cripive a me f hephe me exhiied y hese drugs.(A i isis was firs descried i 1877 iaceria whe Luis Paseur a d Rer Kch se rved ha a airr e acillus culd i hii he grwh f Bacillus a hracis.). These d rugs were laer reamed a iiics y Sel ma Waks ma , a America micrilgis i 1942.Bacerial a ag ism f Pe icillium spp. were firs descried iE gla d y JhTy dall i 1875.The sig ifica ce a iiic discvery was realize d u il he wrk f Eh rlich sy h eic a ii ic chemherapy, wh ich marked he irh f he a iiic revlu i . Ehrlich ed ha cerai dye s wuld id a d c lr huma , a imal, r acerial cells, while hers did . He he exe ded he idea ha i migh e pssile make ce rai dyes r chemicals ha wuld ac as a m agic ulle r seleciv e drug ha wuld i d a dkill aceria while harmi g he huma hs. Af er much experime a i , scree i g hu dreds f dyes agai s vari us rga ism s, he disc vered a me dicially useful drug, he ma -made a ii ic, Salva rsa . I 1928 Flem i g made aimp ra serva i c cer i g he a iisis y pe icilli . Flemi g psulaed h a he effec was mediaed y a ye-u ide ified a iiic-like cmpud ha culd e expl ied. Alhugh he i iially characerized sme f is a i iic prpe ries, he did purs ue is develpme . I h e mea im e, a her sy heic a iaceri al a iii c Pr sil was develped a d ma ufacured fr cmme rcial use y Dmagk i1932. Pr sil, he firs cmmercially availale a iacerial a iiic, was develped y a research eam le d y Gerhard Dmagk (wh received he 193 9 Nel Pri ze fr Med ici e fr his effrs) a he Bayer Lararies f he IG Fare c glmerae i Germa y . Pr sil had a relaively rad e ffec agai s Gram-p siive ccc i u a gai s e eraceria. The disc very a d develpme f his firs sulf amide drug pe ed he era f a iiics. I 1 939, discver y y Re e Dus f he firsaurally der ived a ii ic-like s usa ce amed gramici di frm B. revis.I was e f he firs c mmercially ma ufacured a iiics i use d uri g Wrld War II prve highly effecive i r eai g wu ds a d ulcers.

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Flrey a d Chai succeeded i purifyi g pe icilli . The purified a iiic displayed a iacerial aciviy agai s a wide ra ge f aceria. I als had lw xiciy a d culd e ake wihu causi g adverse effecs. Furhermre, is aciviy was i hiied y ilgical c siue s such as pus, u like he sy heic a iiic class availale a he ime, he sulf amides. The discvery fsuch a pwerful a iiic was u precede ed. The develpme f pe icilli led re ewed i eres i he search fr a iiic cmpu ds wih similar capailiies.Because f heir discvery f pe icilli Er s Chai , Hward Flrey a d Alexa der Flemi g shared he 1945 Nel Prize i Medici e. Flrey credied Dus wih pi eeri g he apprach f delieraely, sysemaically searchi g fr a iacerial cmpu ds. Such a mehdlgy had led he discvery f gramicidi , which revived Flreys research i pe icilli .A iiic resisa ceSEM depici g mehicilli resisa Saphylcccus aureus aceria.The emerge ce f a iiic resisa ce is a evlui ary prcess ha is ased seleci fr rga isms ha have e ha ced ailiy survive dses f a iiics ha wuld have previusly ee lehal. A iiics like Pe icilli a d Eryhrmyci , which used e e-ime miracle cures are w less effecive ecause aceria have ecme mre resisa . A iiics hemselves ac as a selecive pressure ha allws he grwh f resisa aceria wihi a ppulai a di hiis suscepile aceria. A iiic seleci f pre-exisi g a iiic resisa mua s wihi acerial ppulai s was dem sraed i 1943 y he experime . Survival f aceria fe resuls frm a i heriale resisa ce. A ya iiic resisa ce may impse a ilgical cs. Spread f a iiic-resisa aceria may e hampered y reduced fi ess assciaed wih he resisa ce,which is disadva ageus fr survival f he aceria whe a iiic is prese . Addii al muai s, hwever, may cmpe sae fr his fi ess cs a d aids he survival f hese aceria. The u derlyi g mlecular mecha isms leadi g a iiic resisa ce ca vary. I ri sic resisa ce may aurally ccur as aresul f he acerias ge eic makeup. The acerial chrmsme may fail ecde a prei ha he a iiic arges. Acquired resisa ce resuls frm a muai i he acerial chrmsme r he acquisii f exrachrmsmal DNA.A iiic-prduci g aceria have evlved resisa ce mecha isms7

ha have ee shw e similar , a d may have ee ra sferred , a iiicresisa srai s. The spread f a iiic resisa ce mecha isms ccurs hrugh verical ra smissi f i heried muai s frm previus ge erai s a d ge eic recmi ai f DNA y hriz al ge eic excha ge. A iiic resisa ce is excha ged ewee differe aceria y plasmids ha carry ge es ha e cde a iiic resisa ce ha may resul i c-resisa ce muliple a iiics. These plasmids ca carry differe ge eswih diverse resisa ce mecha isms u relaed a iiics u ecause hey arelcaed he same plasmid muliple a iiic resisa ces mre ha e aiiic is ra sferred. O he her ha d, crss-resisa ce her a iiics wihi he aceria resuls whe he same resisa ce mecha ism is resp silefr resisa ce mre ha e a iiic is seleced fr. A iiic-resisa micrrga isms, smeimes referred as "superugs", may c riue he reemerge ce f diseases which are curre ly well-c rlled. Fr example, cases fuerculsis (TB) ha are resisa radii ally effecive reame s remai a cause f grea c cer healh prfessi als. Every year, early half a milli ew cases f mulidrug-resisa uerculsis (MDR-TB) are esimaed ccur wrldwide. NDM-1 is a ewly-ide ified e zyme ha makes aceria resisa a rad ra ge f ea-lacam a iiics. U ied Ki gdm Healh Preci Age cy has saed ha "ms islaes wih NDM-1 e zyme are resisa all sadard i rave us a iiics fr reame f severe i feci s."A iiic resisa ceis a ype f drug resisa ce where amicrrga ism is ale survive expsure a a iiic. Ge es ca e ra sferred ewee aceria i a hriz al fashi y c jugai , ra sduci , r ra sfrmai . Thus a ge e fr a iiic resisa ce which had evlved via aural seleci may e shared. Evlui ary sress such as expsure a iiicshe selecs fr he a iiic resisa rai. Ma y a iiic resisa ce ge es reside plasmids, faciliai g heir ra sfer. If a acerium carries several resisa ce ge es, i is called muliresisa r, i frmally, a superug r super aceria. The primary cause f a iiic resisa ce is a iiic use hwihi medici e a d veeri ary medici e. The greaer he durai f expsure he greaer he risk f he develpme f resisa ce irrespecive f he severiyf he eed fr a iiics.8

CausesThe widespread use f a iiics h i side a d uside f medici e is playi ga sig ifica rle i he emerge ce f resisa aceria. A iiics are feused i reari g a imals fr fd a d his use am g hers leads he creai f resisa srai s f aceria. I sme cu ries a iiics are sld verhe cu er wihu a prescripi which als leads he creai f resisa srai s. I suppsedly wellregulaed huma medici e he majr prlem f he emerge ce f resisa aceria is due misuse a d veruse f a iiics y dcrs as well as paie s. Oher pracices c riui g wards resisa ce i clude he addii f a iiics he feed f livesck. Husehld use f a iacerials i saps a d her prducs, alhugh clearly c riui g resisa ce, is als discuraged (as ei g effecive a i feci c rl). Als usu d pracices i he pharmaceuical ma ufacuri g i dusry ca c riue wards he likelihd f creai g a iiic resisa srai s. Cerai a iiicclasses are highly assciaed wih cl isai wih superugs cmpared her a iiic classes. The risk fr cl isai i creases if here is a lack fse siiviy (resisa ce) f he superugs he a iiic used a d high issuepe erai as well as rad specrum aciviy agai s "gd aceria". I hecase f MRSA, i creased raes f MRSA i feci s are see wih glycpepides, cephalspri s a d especially qui l es. I he case f cl isai wih C difficile he high risk a iiics i clude cephalspri s a d i paricular qui les a d cli damyci .I medici eThe vlume f a iiic prescried is he majr facr i i creasi g raes f acerial resisa ce raher ha cmplia ce wih a iiics. A si gle dse f aiiics leads a greaer risk f resisa rga isms ha a iiic i he pers fr up a year. I apprpriae prescrii g f a iiics has ee ariued a umer f causes i cludi g: peple wh i sis a iiics, physicia s simply prescrie hem as hey feel hey d have ime explai why hey are ecessary, physicia s wh d k w whe prescrie a iiicsr else are verly cauius fr medical legal reas s. A hird f peple fr example elieve ha a iiics are effecive fr he cmm cld a d 22% f peple d fi ish a curse f a iiics primarily due ha fac ha hey feel eer (varyi g frm 10% 44% depe di g he cu ry). Cmplia ce wih ce daily a iiics is eer ha wih wice daily a iiics. Su pimum a iiic c ce rai s i criically ill peple i crease he freque cy f a iiic resisa ce rga isms While aki g a iiics dses less ha hse recmmeded may i crease raes f resisa ce, shre i g he curse f a iiics mayacually decrease raes f resisa ce.9

Pr ha d hygie e y hspial saff has ee assciaed wih he spread f resisa rga ismsa d a i crease i ha d washi g cmplia ce resuls i decreased raes f hese rga isms.Rle f her a imalsDrugs are used i a imals ha are used as huma fd, such as cws, pigs, chicke s, fish, ec., a d hese drugs ca affec he safey f he mea, milk, a d eggs prduced frm hse a imals a d ca e he surce f superugs. Fr example,farm a imals, paricularly pigs, are elieved e ale i fec peple wih MRSA. The resisa aceria i a imals due a iiic expsure ca e ra smied huma s via hree pahways, hse ei g hrugh he c sumpi f mea,frm clse r direc c ac wih a imals, r hrugh he e vir me . The WrldHealh Orga izai c cluded ha a iiics as grwh prmers i a imal feeds shuld e prhiied (i he ase ce f risk assessme s). I 1998, EurpeaU i healh mi isers ved a fur a iiics widely used prme a imal grwh (despie heir scie ific pa els recmme dai s). Regulai a ig he use f a iiics i Eurpea feed, wih he excepi f w a iiicsi pulry feeds, ecame effecive i 2006. I Sca di avia, here is evide ce ha he a has led a lwer prevale ce f a imicrial resisa ce i ( -hazardus) a imal acerial ppulai s. I he USA federal age cies d cllec daa a iiic use i a imals u a imal huma spread f drug resisa rga isms has ee dem sraed i research sudies. A iiics are sill usedi U.S. a imal feedal g wih her i gredie s which have safey c cer s. Grwi g U.S. c sumer c cer au usi g a iiics i a imal feed has led a iche marke f "a iiic-free" a imal prducs, u his small marke is u likely cha ge e re ched i dusry-wide pracices. I 2001, he U i f C cer edScie iss esimaed ha greaer ha 70% f he a iiics used i he US are give fd a imals (e.g. chicke s, pigs a d cale) i he ase ce f disease. I 2000 he US Fd a d Drug Admi israi (FDA) a u ced heir i e i revke apprval f flurqui l e use i pulry prduci ecause f susa ial evide ce li ki g i he emerge ce f flurqui l e resisa campylacer i feci s i huma s. The fi al decisi a flurqui l es frm usei pulry prduci was made u il five years laer ecause f challe gesfrm he fd a imal a d pharmaceuical i dusries. Tday, here are w federal ills (S. 549 a d H.R. 962) aimed a phasi g u " -herapeuic" a iiicsi US fd a imal prduci10

Mecha is msSchemaic represe ai f hw a iiic r esisa ce evlves via aural seleci . The p seci represe s a ppul ai f ace ria efre ex psure a a iiic. The middle se ci shws he ppulai direcly a fer expsure, he phase i which selec i k place. The las seci shws he disriu i f resisa ce i a ew ge erai f aceria. The lege d i d icaes heresisa ce levels f i dividuals.A iiic resisa c e ca e a resul f h riz al ge e ra sfer, a d als fu li ked pi m uai s i he pahgege me a d a rae f au 1 i108 per ch rmsmal replicai . The a iiic aci agai s he pahge cae se e as a e vir me al pressure; hse aceria which have a muai allw i g hem survive w ill live reprdu ce. They w ill he pas s hisrai heir ffspri g, which will resul i a fully resisa cl y. The fu r mai mecha isms y which mic rrga ism s exhii resisa ce a imicr ials are:11

1. Drug i acivai r mdificai : e.g. e zymaic deacivai f Pe icilliG i sme pe icilli resisa aceria hrugh he prduci f lacamases. 2. Alerai f arge sie: e.g. alerai f PBPhe i di g arge sie f pe icilli si MRSA a d her pe icilli resisa aceria. 3. Alerai f mealic pahway: e.g. sme sulf amide resisa aceria d require paraami e zic acid(PABA), a impra precursr fr he sy hesis f flic acid a d ucleic acids i aceria i hiied y sulf amides. I sead, like mammalia cells, hey ur uilizi g prefrmed flic acid. 4. Reduced drug accumulai : y decreasi gdrug permeailiy a d/r i creasi g acive efflux (pumpi g u) f he drugs acrss he cell surface. There are hree k w mecha isms f flurqui l e resisa ce. Sme ypes f efflux pumps ca ac decrease i racellular qui l e cce rai . I gram- egaive aceria, plasmid-mediaed resisa ce ge es prduce prei s ha ca i d DNA gyrase, preci g i frm he aci f qui les. Fi ally, muai s a key sies i DNA gyrase r Tpismerase I ca decrease heir i di g affi iy qui l es, decreasi g he drugs effecive ess. Research has shw ha he acerial prei LexA may play a key rle i he acquisii f acerial muai s givi g resisa ce qui l es a d rifampici .A iiic resisa ce ca als e i rduced arificially i a micrrga ism hrugh larary prcls, smeimes used as a selecale marker exami e he mecha isms f ge e ra sfer r ide ify i dividuals ha asred a piece f DNA ha i cluded he resisa ce ge e a d a her ge e f i eres.Resisa pahge s1. Saphylcccus aureusSaphylcccus aureus (cllquially k w as "Saph aureus" r a Saph i feci) is e f he majr resisa pahge s. Fu d he mucus memra es a d he huma ski f aru d a hird f he ppulai , i is exremely adapale aiiic pressure. I was e f he earlier aceria i which pe icilli resisa ce was fu di 1947, jus fur years afer he drug sared ei g mass-prduced. Mehicilli was he he a iiic f chice, u has si ce ee replaced yxacilli due sig ifica kid ey xiciy. MRSA (mehicilli -resisa Saphylcccus aureus) was firs deeced i Briai i 1961 a d is w "quie cmm" i hspials. MRSA was resp sile fr 37% f faal cases f sepsis i he UKi 1999, up frm 4% i 1991. Half f all S. aureus i feci s i

he US are resisa pe icilli , mehicilli , eracycli e a d eryhrmyci .12

This lef va cmyci as he ly effecive age availale a he ime. Hwever,srai s wih i ermediae (4-8 ug/ml) levels f resisa ce, ermed GISA (glycpepide i ermediae Saphylcccus aureus) r ISA (va cmyci i ermediae Saphylcccus aureus), ega appeari g i he lae 1990s. The firs ide ified casewas i Japa i 1996, a d srai s have si ce ee fu d i hspials i E gla d, Fra ce a d he US. The firs dcume ed srai wih cmplee (>16 ug/ml) resisa ce va cmyci , ermed RSA (a cmyci -resisa Saphylcccus aureus) appeared i he U ied Saes i 2002. A ew class f a iiics, xazlidi es,ecame availale i he 1990s, a d he firs cmmercially availale xazlidi e, li ezlid, is cmparale va cmyci i effecive ess agai s MRSA. Li ezlid-resisa ce i Saphylcccus aureus was repred i 2003. CA-MRSA (Cmmu iy-acquired MRSA) has w emerged as a epidemic ha is resp sile fr rapidly prgressive, faal diseases i cludi g ecrizi g p eum ia, severe sepsis a d ecrizi g fasciiis. Mehicilli -resisa Saphylcccus aureus (MRSA) is he ms freque ly ide ified a imicrial drug-resisa pahge i US hspials.The epidemilgy f i feci s caused y MRSA is rapidly cha gi g. I he pas10 years, i feci s caused y his rga ism have emerged i he cmmu iy. The2 MRSA cl es i he U ied Saes ms clsely assciaed wih cmmu iy ureaks, USA400 (MW2 srai , ST1 li eage) a d USA300, fe c ai Pa -ale i eleukcidi (PL) ge es a d, mre freque ly, have ee assciaed wih ski a dsf issue i feci s. Oureaks f cmmu iy-assciaed (CA)-MRSA i feci shave ee repred i crreci al faciliies, am g ahleic eams, am g miliary recruis, i ewr urseries, a d am g me wh have sex wih me . CA-MRSAi feci s w appear e e demic i ma y ura regi s a d cause ms CA-S.aureus i feci s.2. Srepcccus a d E ercccusSrepcccus pyge es (Grup A Srepcccus: GAS) i feci s ca usually e reaed wih ma y differe a iiics. Early reame may reduce he risk f deah frm i vasive grup A srepcccal disease. Hwever, eve he es medicalcare des preve deah i every case. Fr hse wih very severe ill ess, supprive care i a i e sive care u i may e eeded. Fr pers s wih ecrizi g fasciiis, surgery fe is eeded remve damaged issue. Srai s f S.pyge es resisa macrlide a iiics have emerged, hwever all srai s remai u ifrmly se siive pe icilli . Resisa ce f Srepcccus p eum iae pe icilli a d her ea-lacams is i creasi g wrldwide. The majr mecha ismf resisa ce i vlves he i rduci f muai s i ge es e cdi g pe icilli -i di g prei s. Selecive pressure is hugh play a impra rle, ad use f ea-lacam a iiics has ee implicaed as a risk facr fr i feci a d cl izai . Srepcccus p eum iae is resp sile fr p eum ia, aceremia, iis media, me i giis, si usiis, peri iis a d arhriis.13

Pe icilli -resisa p eum ia caused y Srepcccus p eum iae (cmm ly k was p eumcccus), was firs deeced i 1967, as was pe icilli -resisa g rrhea. Resisa ce pe icilli susiues is als k w as ey d S. aureus. By 1993 Escherichia cli was resisa five flurqui l e varia s. Mycacerium uerculsis is cmm ly resisa is iazid a d rifampi a d smeimesu iversally resisa he cmm reame s. Oher pahge s shwi g sme resisa ce i clude Salm ella, Campylacer, a d Srepccci. E ercccus faecium is a her superug fu d i hspials. Pe icilli -Resisa E ercccus wassee i 1983, va cmyci -resisa e ercccus (RE) i 1987, a d Li ezlid-Resisa E ercccus (LRE) i he lae 1990s.3. Pseudm as aerugi saPseudm as aerugi sa is a highly prevale ppru isic pahge . O e f hems wrrisme characerisics f P. aerugi sa c siss i is lw a iiic suscepiiliy. This lw suscepiiliy is ariuale a c cered aci fmulidrug efflux pumps wih chrmsmally-e cded a iiic resisa ce ge es (e.g. mexAB-prM, mexXY ec.) a d he lw permeailiy f he acerial cellular evelpes. Besides i ri sic resisa ce, P. aerugi sa easily develp acquired resisa ce eiher y muai i chrmsmallye cded ge es, r y he hriz alge e ra sfer f a iiic resisa ce deermi a s. Develpme f mulidrug resisa ce y P. aerugi sa islaes requires several differe ge eic eve s ha i clude acquisii f differe muai s a d/r hriz al ra sfer f a iiic resisa ce ge es. Hypermuai favurs he seleci f muai -drive aiiic resisa ce i P. aerugi sa srai s prduci g chr ic i feci s, whereas he cluseri g f several differe a iiic resisa ce ge es i i egr sfavurs he c cered acquisii f a iiic resisa ce deermi a s. Sme rece sudies have shw ha phe ypic resisa ce assciaed ifilm frmai r he emerge ce f small-cl y-varia s may e impra i he resp se f P. aerugi sa ppulai s a iiics reame .4. Clsridium difficileClsridium difficile is a scmial pahge ha causes diarrheal disease ihspials wrld wide. Cli damyci -resisa C. difficile was repred as he causaive age f large ureaks f diarrheal disease i hspials i New Yrk, Ariz a, Flrida a d Massachuses ewee 1989 a d 1992. Gegraphically dispersed ureaks f C. difficile srai s resisa flurqui l e a iiics, such as Cipr (ciprflxaci ) a d Levaqui (levflxaci ), were als repred i Nrh America i 2005.14

5. Salm ella a d E. cliEscherichia cli a d Salm ella cme direcly frm c ami aed fd. Of he mea ha is c ami aed wih E. cli, eighy perce f he aceria are resisa e r mre drugs made; i causes ladder i feci s ha are resisa a iiics (HSUS Fac Shee). Salm ella was firs fu d i huma s i he 1970s ad i sme cases is resisa as ma y as i e differe a iiics (HSUS FacShee). Whe h acerium are spread, serius healh c dii s arise. Ma y peple are hspialized each year afer ecmi g i feced, a d sme die as a resul.6. Aci eacer auma iiO Nvemer 5, 2004, he Ce ers fr Disease C rl a d Preve i (CDC) repred a i creasi g umer f Aci eacer auma ii ldsream i feci s i paie s a miliary medical faciliies i which service memers i jured i he Iraq/Kuwai regi duri g Operai Iraqi Freedm a d i Afgha isa duri g Operai E duri g Freedm were reaed. Ms f hese shwed mulidrug resisa ce (MRAB), wih a few islaes resisa all drugs esed.Aler aivesPreve iRai al use f a iiics may reduce he cha ces f develpme f ppru isic i feci y a iiic-resisa aceria due dysacerisis. I e sudy he use f flurqui l es are clearly assciaed wih Clsridium difficilei feci , which is a leadi g cause f scmial diarrhea i he U ied Saes,a d a majr cause f deah, wrldwide. There is cli ical evide ce ha picaldermalgical preparai s c ai i g ea ree il a d hyme il may e effecive i preve i g ra smial f CA-MRSA. acci es d suffer he prlem f resisa ce ecause a vacci e e ha ces he dys aural defe ses, while a a iiic peraes separaely frm he dys rmal defe ses. Neverheless, ew srai s may evlve ha escape immu iy i duced y vacci es; fr example a updaeI flue za vacci e is eeded each year. While hereically prmisi g, a i-saphylcccal vacci es have shw limied efficacy, ecause f immu lgical variai ewee Saphylcccus species, a d he limied15

durai f effecive ess f he a idies prduced. Develpme a d esi g fmre effecive vacci es is u der way. The Ausralia Cmm wealh Scie ific ad I dusrial Research Orga izai ( CSIRO), realizi g he eed fr he reducif a iiic use, has ee wrki g w aler aives. O e aler aive is preve diseases y addi g cyki es i sead f a iiics a imal feed. These prei s are made i he a imal dy " aurally" afer a disease a d are a iiics s hey d c riue he a iiic resisa ce prlem. Furhermre, sudies usi g cyki es have shw ha hey als e ha ce he grwhf a imals like he a iiics w used, u wihu he drawacks f herapeuic a iiic use. Cyki es have he pe ial achieve he a imal grwhraes radii ally sugh y he use f a iiics wihu he c riui f a iiic resisa ce assciaed wih he widespread -herapeuic uses f aiiics curre ly uilized i he fd a imal prduci i dusries. Addiially, CSIRO is wrki g vacci es fr diseases.Phage herapyPhage herapy, a apprach ha has ee exe sively researched a d uilized asa herapeuic age fr ver 60 years, especially i he Svie U i , is a aler aive ha migh help wih he prlem f resisa ce. Phage herapy was widely used i he U ied Saes u il he discvery f a iiics, i he early 1940s. Baceriphages r "phages" are viruses ha i vade acerial cells a d, i he case f lyic phages, disrup acerial mealism a d cause he acerium lyse. Phage herapy is he herapeuic use f lyic aceriphages rea pahge ic acerial i feci s. Baceriphage herapy is a impra aler aive a iiics i he curre era f mulidrug resisa pahge s. A review fsudies ha deal wih he herapeuic use f phages frm 19661996 a d few laes gi g phage herapy prjecs via i er e shwed: phages were used pically, rally r sysemically i Plish a d Svie sudies. The success rae fu d ihese sudies was 8095% wih few gasri esi al r allergic side effecs. Briish sudies als dem sraed sig ifica efficacy f phages agai s Escherichiacli, Aci eacer spp., Pseudm as spp a d Saphylcccus aureus. US sudiesdeal wih imprvi g he iavailailiy f phage. Phage herapy may prve as aimpra aler aive a iiics fr reai g mulidrug resisa pahges.16

ResearchNew medicai sU il rece ly, research a d develpme (R&D) effrs have prvided ew drugs iime rea aceria ha ecame resisa lder a iiics. Tha is l ger he case.[ciai eeded] The pe ial crisis a ha d is he resul fa marked decrease i i dusry R&D, a d he i creasi g prevale ce f resisa aceria. I fecius disease physicia s are alarmed y he prspec ha effecivea iiics may e availale rea seriusly ill paie s i he ear fuure. The pipeli e f ew a iiics is dryi g up. Majr pharmaceuical cmpa ies are lsi g i eres i he a iiics marke ecause hese drugs may eas prfiale as drugs ha rea chr ic (l g-erm) c dii s a d lifesyle issues. The resisa ce prlem dema ds ha a re ewed effr e made seek a iacerial age s effecive agai s pahge ic aceria resisa curre a iiics. O e f he pssile sraegies wards his jecive is he rai al lcalizai f iacive phychemicals. Pla s have a alms limiless ailiy sy hesize armaic susa ces, ms f which are phe ls r heir xyge -susiued derivaives such as a i s. Ms are sec dary mealies, f whicha leas 12,000 have ee islaed, a umer esimaed e less ha 10% f he al .I ma y cases, hese susa ces serve as pla defe se mecha isms agais predai y micrrga isms, i secs, a d herivres. Ma y f he hers a d spices used y huma s seas fd yield useful medici al cmpu ds i cludi g hse havi g a iacerial aciviy. Tradii al healers have l g used pla s preve r cure i fecius c dii s. Ma y f hese pla s have ee i vesigaed scie ifically fr a imicrial aciviy a d a large umer f pla prducs have ee shw i hii grwh f pahge ic aceria.A umer f hese age s appear have srucures a d mdes f aci ha are disi c frm hsef he a iiics i curre use, suggesi g ha crss-resisa ce wih age salready i use may e mi imal. Fr example he cmi ai f 5-mehxyhyd carpi e a d ereri e i hers like Hydrasis ca ade sis a d Bereris vulgaris calck he MDR-pumps ha cause mulidrug resisa ce. This has ee shw fr Saphylcccus aureus. Archaeci s is he ame give a ew class f pe iallyuseful a iiics ha are derived frm he Archaea grup f rga isms. Eigh archaeci s have ee parially r fully characerized, u hu dreds f archaecis are elieved exis, especially wihi he halarchaea. The prevale ce f archaeci s is u k w simply ecause e has lked fr hem. The discvery f ew archaeci s hi ges recvery a d culivai f archaeal rga isms frmhe e vir me . Fr example, samples frm a vel hypersali e field sie, WilsH Spri gs, recvered 350 halphilic rga isms; prelimi ary a alysis f 75 islaes shwed ha 48 were archaeal a d 27 were acerial. I research pulished Ocer 17, 2008 i Cell, a eam f scie iss pi pi ed he place aceria where he a iiic myxpyr i lau ches is aack, a d why ha aack issuccessful. The myxpyr i i ds a d i hiis he crucial acerial e zyme,RNA plymerase. The17

myxpyr i cha ges he srucure f he swich-2 segme f he e zyme, i hiii g is fu ci f readi g a d ra smii g DNA cde. This preve s RNA plymerase frm deliveri g ge eic i frmai he rismes, causi g he aceria die. O e f he majr causes f a iiic resisa ce is he decrease f effecive drug c ce rai s a heir arge place, due he i creased aci f ABC ra sprers. Si ce ABC ra sprer lckers ca e used i cmi ai wihcurre drugs i crease heir effecive i racellular c ce rai , he pssile impac f ABC ra sprer i hiirs is f grea cli ical i eres. ABC rasprer lckers ha may e useful i crease he efficacy f curre drugs have e ered cli ical rials a d are availale e used i herapeuic regimes.Applicai sA iiic resisa ce is a impra l fr ge eic e gi eeri g. By c sruci g a plasmid which c ai s a a iiic resisa ce ge e as well as he ge e ei g e gi eered r expressed, a researcher ca e sure ha whe aceria replicae, ly he cpies which carry al g he plasmid survive. This e sures ha hege e ei g ma ipulaed passes al g whe he aceria replicaes. The ms cmm ly used a iiics i ge eic e gi eeri g are ge erally "lder" a iiics which have largely falle u f use i cli ical pracice. These i clude: ampicillin kanamycin tetracycline chloramphenicolIndustrially 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 ofthe body.

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Superbug NDM1 Bacteria | Symptoms, Effects, Experiments, Prevention and ExpertsSuggestionsThe Superbug NDM1which stands for New Delhi metallo-beta-lactamase is started tospread 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 Pakistanto get medical treatment risk picking up and spreading a new Superbug Bacteria.How NDM-1 effects Human Body0 Multi drugresisa aceria are already a grwi g prlem i hspials acrss he wrld, marked y he rise f superug i feci s like mehicilli resisa Saphylccus aureus (MRSA). 0 NDM1 makes aceria highly resisa alms all a iiics, i cludi g he ms pwerful class called carape ems. 0 Ms wrryi gly, NDM1prduci g aceria are resisa ma y a iiics i cludi g carape ems. 0 The scie iss said, a class f he drugs ge erally reserved fr emerge cy use a d rea caused y her muliresisa aceria such as MRSA a d CDifficile.Jha Piu frm he U iversiy f Calgary i Ca ada expressed: If his emergig pulic healh hrea is ig red, s er r laer he medical cmmu iy culde c fr ed wih carape em-resisa (aceria) ha cause cmm i feci s,resuli g i reame failures wih susa ial i creases i healh-care cssSympms f Super ug NDM-1 Baceria, Klesiella P eum iae a d E. Cli Sympms0 Klesiella aceria c ai s he superug NDM1. 0 Klesiella p eum iae sympmsi clude sudde O se, f High Fever a d Hempysis . 0 Klesiella p eum iae is acmm gram egaive aceria see wrldwide. 0 I is als causi g Uri ary Trac Ifeci s, Nscmial P eum ia, a d I ra admi al i feci s.

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0 NDM1 which is fu dfeci s. 0 E. Cli isspials. 0 E. Cli isf Faal P eum ia a d

i he E. Cli aceria may e he cause f Uri ary Trac Ihe leadi g cause f uri ary rac i feci s uside f hA iiicresisa . 0 E. Cli is als resp sile fr casesher i feci s.

Cu ries where Superug NDM1 Baceria is spreadi gI a sudy pulished i The La ce I fecius Diseases jur al, he researchersfu d ha NDM1 is ecmi g mre cmm i Ba gladesh, I dia, a d Pakisa a d issari g e impred ack Briai i paie s reur i g frm hese cu ries.Experime s wih Superug NDM-1 BaceriaWalsh a d his i er ai al eam clleced aceria samples frm hspial paies i w places i I dia, Che ai a d Harya a, a d frm paie s referred Briai s ai al refere ce larary ewee 2007 a d 2009.They fu d 44 NDM1 psiive aceria i Che ai, 26 i Harya a, 37 i Briai , a d 73 i her sies iBa gladesh, I dia, a d Pakisa .Preve i g he Spread f Superug NDM-1 BaceriaT preve spread f Superug NDM1 Baceria, Dcrs advise prvide adequae clea i g a d sa iizi g f all areas is he es mea s f preve i g furher spread f he superug aceria. Hspials a d dcrs are u der advise say p f he clea li ess issue.Expers cmme i g Walshs fi di gs said i was impra e aler he ew ug a d sar scree i g fr i early. I seems e mre da gerus ha Swi eflu, si ce i is wrki g Resisa ce f Huma dy.

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Aricles superug i ews papers Delhi superug hreae i g wrld, claim UK scie issSa chia Sharma, Hi dusa Times New Delhi, Augus 12, 2010 Firs Pulished: 00:54 IST(12/8/2010) Las Updaed: 01:38 IST(12/8/2010)A ew hspial-acquired superug ha ca e reaed usi g exisi g drugs isspreadi g frm I dia he res f he wrld, claim Briish scie iss. I diasurge s ruish he claim sayi g is jus a her aemp sp husa ds f pu ds frm leavi g he flu deri g Briish ec my relaed sries0 Li ki g I dia superug u fair a d wr g, says I dia 0 Gv c dem s ami g fsuperug, refues is li kage 0 Sme i erpreai s made wihu my k wledge:Superug auhr Accrdi g CII esimaes, 1.1 milli freig ers ravel I dia each year fr cheaper reame s a d surgeries. A hear ypass surgery css$6,500 (R 3,03,550) i a crprae hspial i I dia, as cmpared $30,000 (R14,01,000) $50,000 (R 23,35,000) i he US. S c vi ced are Briish scie iss au he superug i feci ei g fuelled y I dias Rs 1,200-crre medical urism i dusry ha hey have chse prvcaively ame he ewly-ide ified ge e ha causes he drug resisa ce as he New Delhi meall-ealacamase (NDM1). A sudy pulished i The La ce I fecius Diseases, Briish scie iss repr NDM-1 is ecmi g mre cmm i Ba gladesh, I dia, a d Pakisa a d is ei gimpred ack Briai hrugh paie s reur i g afer reame .Healhcare expers i I dia say he Briish are jus wrried ecause hey are lsi g paie s hspials here. Is a false alarm, I rack i feci a d have see a si gle case i my hspial. Hspial-acquired i feci s are far mre cmm i Briai a d he Wes ha21

i I dia, said Dr Yai Meha, chairma , i siue f criical care a d a aeshesia, Meda a The Mediciy. We ffer eer surgical ucmes a e-fifh he cs, he added. Dr Ashk Seh, chairma a d chief i erve i is, Escrs Hear I siue a d Research Ce re said, Ms hspials i I dia, i cludi g Escrs, haveai al a d i er ai al accrediai s... wh se d audirs rack qualiy i cludi g i feci s fur imes a year. The audis shw ha crprae hspialshere are safer ha he Wes. Theyre defi iely safer ha Briai s Nai al Healh Service. Fr he sudy, auhr Timhy Walsh frm Cardiff U iversiy a d his eam clleced aceria samples frm paie s admied i hspials i Tamil Nadua d Harya a, a d frm paie s referred Briai s ai al refere ce larary ewee 2007 a d 2009. They fu d 44 NDM-1-psiive aceria i Che ai, 26 iHarya a, 37 i Briai , a d 73 i her sies i Ba gladesh, I dia, a d Pakisa. Several all Briish NDM-1 psiive paie s had rece ly raveled I dia r Pakisa fr hspial reame , i cludi g csmeic surgery. Whas paricularly wrryi g, wries Walsh, is ha he aceria is resisa all a iiics, i cludi g carape em, a class f he drugs reserved rea i feci s causedy her muli-resisa ugs like MRSA a d C-Difficile.Drugresisa superug raced I diaThe Times f I diaCHENNAI: Scie iss have racked dw a drugresisa superug ha i fecs paies a d causes muliple rga failure I dia hspials u dcrs here see ii he germ f a mve damage he cu rys mi g medical urism i dusry. The superug resisa alms all k w a iiics has ee fu d i UKpaie s reaed i I dia hspials. Named afer he I dia capial, i is a gee carried y aceria ha causes gasric prlems, e ers he ld sream a dmay cause muliple rga failure leadi g deah. " I dia als prvides csmeic surgery fr Eurpea s a d America s, a d i is likely he aceria will spread wrldwide," scie iss repred i The La ce I fecius Diseases Jur al Wed esday. While he sudy has he medical wrld ur i g is fcus i feci c rl plicies i I dia hspials, he I dia Cu cil f Medical Research hasalleged a ias i he

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repr a d said i is a aemp hur medical urism i he cu ry ha isaki g away huge cusm frm hspials i he Wes. "Such i feci s ca flw ifrm a y par f he wrld. Is u fair say i rigi aed frm I dia," saidICMR direcr Dr M Kach. Kach has reas s fume, as he superug NDM1 ( New Delhi meall ealacamase) is amed afer he ai al capial, where a Swedish paie was repredly i feced afer u dergi g a surgery i 2008. Si ce hehere have ee several cases repred i he UK a d i 2009, he healh preci age cy i he UK issued a aler he gram egaive acerial i feciha is resisa eve he ms pwerful a d reserved class a iiics called carape ems. I a ji sudy led y Che aiased Karhikeya Kumarasamy, pursui g his PhD a U iversiy f Madras a d UKased Timhy Walsh frm deparme fimmu iy, i feci a d ichemisry, deparme f medici e, Cardiff U iversiy researchers sugh exami e wheher NDM 1 prduci g aceria was prevale iSuh Asia a d Briai . "We saw hem i ms f he hspials i Che ai a d Harya a. We esimae ha he prevale ce f his i feci wuld e as high as 1.5%," Kumarasamy ld TOI. "We fu d he superug i 44 paie s i Che ai, a d 26 i Harya a, esides 37 i he UK a d 73 i her places acrss I dia, Pakisaa d Ba galadesh," he said. Wha makes he superug mre da gerus is is ailiy jump acrss differe acerial species. S far, i has ee fu d i w cmm ly see aceria, E cli a d K p eum iae. "We have fu d ha he superughas he pe ial ge cpied a d ra sferred ewee aceria, allwi g i spread rapidly. If i spreads a already hard rea acerial i feci , ica e ur mre da gerus," Kumarasamy said. Se ir dcrs wrki g i i feci c rl said I dia lacks plicies a iiics, i feci c rl a d regisries fr hspialacquired i feci s. By he ICMR direcrs w admissi , I dia ca scie ifically figh ack allegai s f ei g he surce f such superugs, as he cu ry des have a regisry f such hspialacquired i feci s. "Tw i every five paie s admied hspials acquire i feci s. This exe ds he paie s say i he hspial, i creases he expe ses a d causes sideeffecs," said Dr Dilip Mahai, head f he deparme f i er al medici e, Chrisia Medical Cllege, ellre. Fr a l g ime, I dia has ee seei g Exe ded Specrum Bea Lacamase (ESBL), which are e zymes ha have develped a resisa ce a iiics like pe icilli . ESBL e zymes are ms cmm ly prduced y waceria E cli a d K p eum iae, he w aceria i which he ew

superug has ee fu d. "These were reaed y a reserved class f a iiicscalled carape ems. We have see a leas 3% f peple i feced wih his d reac hese reserved drugs," he said. Pulic healh expers say glalisaihas allwed aceria spread rapidly acrss he wrld23

a d I dia, as a medical hu, shuld e geared fr he challe ge. Kach, wh isals he secreary, deparme f medical research, agrees. "A prese , we d have a y sysem i place. There are eiher rules fr hspials r a regisry recrd hspialacquired i feci s. We are w i he prcess f frmi g a cell ha will acivae a regisry a d issue guideli es fr a i egraed surveilla ce sysem," he said. A differe hi g is als serve ha Ge e resp silefr drugresisa superug fu d24

C clusi O he asis f ave i frmai we ca say ha a iiics has e ake i lw amu herwise i effec is wrs ha is adva age. Therefrea iiics are gd u wihi limied value.Resul09A iiics are gd u wihi limied value. 09Is disadva age dmi aes is adva age. 09Deahs f peple i creases wih ime due a iiic resia ce.25

Biligraphy www.wikipedia.cm www.ggle.cm www. ews e.cm www.ech pedia.cm ewpapers-The Times f I dia -Hi dusa imes - avhara imes26

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