ppt jurnal erni anggriani

8/18/2019 Ppt Jurnal Erni Anggriani

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JOURNAL READING

REVIVING OLD ANTIBIOTICS

PEMBIMBING :

dr. Eleazer Permana Gadroen, Sp.An, MSc

Presentan :

Erni Anggriani Sitorus

1161!"#


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REVIVING OLD

ANTIBIOTICS

$rsula %&euretz'ac&er1(, )ranc*oise +an Bam'ee-, a/ael 0anton", 0&ristiaGise2,!, 3o&an 4. Mouton6,#,

oger 5. Nation, Mical Paul7, 3o&n 8. %urnidge1 and Gunnar 9a&lmeter11,1

Journal of Antimicrobial Chemothera! A"#ance Acce$$ ubli$he" June %&


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10enter /or AntiIn/ecti;e Agents, +ienna, Austria< -P&armacologie cellulaire et m5ou;ain 8rug esearc& Institute, $ni;ersitecat&oli=ue de 5ou;ain, Brussels, Belg

de Micro'iolog>a, ?ospital $ni;ersitario amon @ 0aal and Instituto amon In;estigacion Biomedica IC0ISD, Madrid, Spain< 20linical Micro'iolog@, 5-:-

$ni;ersit@ ?ospital, Solna, Stoc&olm, Seden

am'am ?ealt& 0are 0ampus and )acult@ o/ Medicine, %ec&nion F Israel Institute o?ai/a, Israel< 1Sc&ool o/ Biological Sciences, $ni;ersit@ o/ Adelaide,Adelaide, Sou

Australia< 118epartment o/ 0linical Micro'iolog@, 0entral ?ospital, +aHo , 1-8epartment o/ Medical Sciences, 8i;ision o/ 0linical Bacteriolog@, $ppsala $

$ppsala, Seden


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IN%8$0%IN

- As 'acterial resistance to anti'iotics increases, p&@siciano/ten need to use old anti'iotics t&at ma@ still 'e acti;e some o/ t&e eHisting M8 or J8 pat&ogens

- %&ese old anti'iotics ere ne;er de;eloped using a struprocess /or drug assessment and regulator@ appro;al

- 0urrent standards and t&e re=uirements /or clinical testie;ol;ed o;er time.

- As a conse=uence, re;i;ed old anti'iotics are 'eing presusing t&e limited noledge generated !F# @ears ago

- %&is practice ma@ carr@ signiKcant riss /or patient outcoad;erse e;ents and t&e emergence o/ resistance.


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4&ic& old anti'iotics need to 'e rede;elopedL

0urrentl@ and into t&e near /uture, t&ere are /e or no treatmealternati;es /or M8 or J8 'acterial strains causing t&e in/ec

• listed 'elo

iD 0ommunit@ac=uired in/ections caused '@ ESB5producingEntero'acteriaceae

(•)Entero'acteriaceae t&at produce ESB5s are resistant toaminopenicillins and cep&alosporins, and are /re=uentl@ coreuoro=uinolones, aminogl@cosides and ot&er anti'iotics. ld t&at are increasingl@ used as re;i;ed oral treatment options /are /os/om@cin trometamol,nitro/urantoin and mecillinam.


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iiD ?ospitalac=uired in/ections caused '@ ESB5producingEntero'acteriaceae

%&e increasing pre;alence o/ ESB5producing Entero'actit& coresistance to ot&er anti'acterial drug classes &as

t&e empirical use o/ car'apenems and &as led to increasinselection pressure and car'apenem resistance


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iiiD Se;ere &ospitalac=uired in/ections caused '@ car'aperesistant Gramnegati;e 'acilli

- %&ese 'acteria are usuall@ J8 and onl@ suscepti'le topol@m@Hins colistin, pol@m@Hin BD or sometimes tigec@c/os/om@cin and or some aminogl@cosides.

- Pol@m@Hins &a;e &ad a su'stantial resurgence as a lasttreatment o;er t&e last decade


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- A set o/ e@ o'ecti;es as de;eloped in -1" to eHplore t&e /actort&e sa/e and eOecti;e use o/ pol@m@Hins, to identi/@ gaps in noleset priorities /or /uture researc&

- e;i;ing old anti'iotics as a =uic solution to t&e t&in anti'iotic disc

de;elopment pipeline re=uires agreement on t&e most promising ca/or /urt&er action.


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• 9noledge gaps• ?o to rede;elop re;i;ed anti'ioticsL

)or recentl@ appro;ed anti'iotics, t&e /ormal precand clinical de;elopment processes are &ig&l@ regand undertaen predominatel@ '@ a p&armaceutic

compan@ as an in;estment /or /uture returns.

ede;elopment o/ old anti'iotics is necessaril@ das t&ese drugs are usuall@ long out o/ patent prot


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0onse=uentl@, t&ere is no Knancial incenti;e /or t&e somenumerous generic companies in;ol;ed in t&eir manu/actudistri'ution to /und t&e necessar@ studies.

%&us, pu'lic /unding t&roug& agencies suc& as t&e Europe0ommission and t&e $S National Institutes o/ ?ealt& is o/tonl@ option a;aila'le


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- %&e most ad;anced re;i;ed anti'iotic is colistin- %&e ecac@ o/ colistin ;ersus colistincar'apenem com'

t&erap@ is currentl@ 'eing tested in a elldesigned randclinical trial in t&e E$/unded AI8A proect )P#?EA5%?.-11.-.".11QPreser;ing ld Anti'iotics /or t&e supported '@ numerous nonclinical studies.

- A similar multicentre, multicountr@ clinical trial, /unded NI? &ttps: clinicaltrials.go;ct-s&oN0%-"!67D isongoing


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• In t&e AI8A proect ot&er re;i;ed anti'iotics, suc& asnitro/urantoin, /os/om@cin trometamol, oral minoc@clinri/ampicin, are 'eing assessed, noledge gaps identine in/ormation generated as a contri'ution to a pu'lde;elopment process.

0linical stud@ issues

t&ere are common pro'lems o/ in;estigatorinitiated rancontrolled trials in academic settings, suc& as singlecestudies it& a small num'er o/ patients, incomplete datcollection, prolonged stud@ duration, slo recruitment oand premature stud@ termination


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• egulator@ and /unding issues• esponsi'le use o/ re;i;ed anti'iotics

4idespread anti'iotic resistance /ollos t&emismanagement o/anti'iotics. I/ t&e use o/ re;i;edanti'iotics is indiscriminate or in;ol;es inappropriat

regimens, t&ere ill 'e groing resistance t&at ill rimpede t&eir ecac@. 0olistin is a orr@ing eHamplerapidl@ induced pol@m@Hin resistance in centres usinleading to J8 and panresistant Gramnegati;e 'a


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Access, not eHcess• Access to &ig&=ualit@ anti'iotics is not a gi;en i

parts o/ t&e orld. In loresource countries, accsome o/ t&ese anti'iotics or e;en /uture ne ageo/ten not aOorda'le.

• Scandina;ian p&@sicians &a;e success/ull@ usedpi;mecillinam /or uncomplicated $%Is since t&e 'ut in most countries pi;mecillinam is not a;aila


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• A similar situation applies to /os/om@cin i;, &icappro;ed in German@, Austria, )rance and Spainsmall num'er o/ Asian countries, and to temocill&ic& is appro;ed in onl@ /our European countrieBelgium, 5uHem'ourg, $9 and )ranceD.

• S&aring and communicating ne noledge on drugs

Not all clinical studies on re;i;ed anti'iotics arepu'lis&ed


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0onclusions

• e;i;ed old anti'iotics &a;e use/ul acti;it@ againot&erise M8 'acteria.

• %&ese anti'iotics ere not de;eloped it& t&e tonoledge applied to modern agents.

• +ital gaps in t&e noledge needed to use t&ese

appropriatel@ re=uire ne solutions to address t&pro'lems listed in t&is article


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• Strategies are urgentl@ needed to rede;elop t&edrugs using modern standards, integrating nenoledge into regulator@ /rameors andcommunicating t&e noledge /rom t&e researcto t&e 'edside

• 4it&out a s@stematic strateg@ to rede;elop t&esdrugs and rigorousl@ test t&em according to todastandards, e ris doing &arm to patients or /urtincreasing multidrug resistance.


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• All stae&olders, /rom &ealt&care specialists, patpa@ers and manu/acturers to regulator@ agenciepolic@ maers, need to 'e in;ol;ed in creating aroadmap /or taing old anti'iotics /orard and pt&em to or again, sa/el@ and eOecti;el@

• %&e c&allenge no is to Knd muc&needed resoutime, Knances and peopleQto /asttrac t&e tasoptimizing t&e use o/ t&ese potentiall@ li/esa;inand mae t&em a;aila'le to e;er@one in need.


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