C. Folosirea abuziv i incorect a terapiei cu antibiotice (AB) a condus la: creterea alarmant a procentului de izolare a unor tulpini plurirezistente la antibiotice, fapt care impune obligatoriu: elaborarea unor strategii de supraveghere strict a prescrierii antibioticelor; stabilirea unei politici de control a utilizrii antibioticelor.

II. Factori sociali: A. Existena unei educaii medicale deficitare n plan populaional. B. Majoritatea populaiei dispune de venituri personale modeste, urmare a crora:- costul semnificativ al antibioticoterapiei prescrise conduce uzual la reducerea volutar (de ctre pacient ) a dozei i/sau duratei antibioticului prescris sau la nlocuirea acestuia cu altul mai ieftin, dar ineficient.

Principii de chimioterapie antimicrobian

Deci:

1. Care afeciuni trebuie tratate ?

2. Cum decidem schema de tratament antibacterian ?a) tratament de primo intenie (empiric);b) tratament bazat pe criterii stiinifice (antibiogram);

3. Monoterapie/asociere de AB ?- terapie de - escaladare !!!

4. Alegerea AB/ajustarea dozelor funcie de:- APP ale pacientului;- localizarea infeciei.- efectele secundare ale AB.

MECANISM DE ACIUNE A ANTIBIOTICELORAntibioticulMecanism de aciuneEfectBetalactamine Acioneaz asupra peretelui bacterian, inhibnd sinteza peptidoglicanului Se leag de penicilin binding proteins (PBP) ce sunt enzime din membrana citoplasmatic inhibnd transpeptidazaBactericidGlicopeptide(Vancomicina) Blocheaz secvenele de aminoacizi din structura peptidoglicanului BactericidVancomicinaPolipeptide(Colistina) Acioneaz asupra membranei citoplasmatice Modif. bariera osmotic a membranei citoplasmatice.BactericidAminoglicozide

Inhib sinteza proteinelor la nivel ribozomal Se leag la interferena dintre subunitile ribozomale 30S, 50SBactericidTetraciclinele Se leag la unitatea ribozomal 30SBacteriostaticCloramfenicol Se leag la unitatea ribozomal 50SMacrolideLincosamideBactericidRifamicinele Acioneaz asupra aparatului nuclear Inhib ARN-polimearaza ADN-dependent, blocnd sinteza ARN-mesager i secundar, sinteza protei-nelor ribozomale.BactericidChinolonele Inhib ADN-giraza, enzim,care supraspiraleaz ADN-ul, blocnd diviziunea celular.Metronidazol Efect toxic direct asupra ADN-ului.Cotrimoxazol Acioneaz competitiv cu metabolii analogi (acid folic, acid folinic).

I. Familia Betalactaminelor GRUPASUBGRUPANTIBIOTICMONO-BACTAMIAZTREONAM AztreonamDI-BACTAMIPENAMIPeniciline de biosintez Pencilina V/G Procainpenicilina (Efitard) Benzatinpenicilina (Moldamin)Penicilina M (rezistent la penicilinaz) Nafcilina, Meticilina Derivai de izoxazolil-penicilin (Cloxacilina/ Dicloxacilin, Flucloxacilin)Aminopenicilinele Ampicilina, Pivampicilina Bacampicilina, AmoxicilinaPeniciline anti-pseu-domonas Amidino-peniciline; Mecilinam Ureido-peniciline; Azlocilina, Mezlocilina, Piperacilina Carboxi-peniciline; Carboxipenicilina TicarcilinaPenami + Inhibitori de Betalactamaze Amoxicilin + Acid clavulanic (Augumentin, Amoxiklav)Ampicilin+Sulbactam (Unasyn/Ampiplus)Ticarcilin+Acid clavulanic (Timentin)Piperacilin+Tazobactam (Tazocin) Cefoperazon+Sulbactam (Sulperazona)

Familia Betalactaminelor (continuare)

DI-BACTAMIPENEMI RitipenemCARBAPENEMI Imipenem/Cilastatin (Tienam) Ertapenem(Invanz) MeropenemCEFEMECefalosporine gen. I Cefazolina (Kefzol), Cefalotina Cefaloridina, CefaleximaCefalosporine gen. II Cefaclor (Ceclor) Cefamandola (Mandol) Cefuroxima (Zinat, Zinacef) Cefoxitin, Cefotiam (Axetin) Cefotetam, Cefonicid.Cefalosporine gen. III Cefotaxima (Claforan) Cefoperazona (Cefobid) Ceftazidim (Fo rtum) Ceftriaxon (Rocephin/Cefort) Ceftibuten (Cedax) Cefditoren/CefdinirCefalosporine gen. IV Cefpiroma (Cefrom) Cefepime (Maxipim) Cefchinona,CefchidinaTRI-BACTAMI SANFETRINEM Sanfetrinem

Peniciline de biosintezAntibioticDoze/zi, RitmSpectru de aciunePenicilina G(P.G/Na/K)Doze/zi: - copil: 50.000 - 200.000 U/Kgc/zi(sub 8 ani : 800.000 U/zi)- adult: 2 x 1-2 mil.U.i.m./i.v.(maxim 10 mil. U/zi)Ritm:discontinuu (la 12 h interval) Coci Gram pozitiv: - aerobi: Strept. pyogenes/viridans, pneumoniae); - anaerobi:(Peptostreptococ). Coci Gram negativ: (N.meningitidis)

Bacili Gram pozitiv:- anaerobi: (Clostridium,spp., Actinomyces)- aerobi: B.crbunos, B difteric, L. monocitogenes

Borrelia

Fuzospirili

Leptospire

Spirochete Penicilina V(Ospen)Doze: - doza dubl p.o., fa de doza P.G.; - pe stomacul gol (cu 2h inainte i 2h post prandial)Ritm: discontinuu(12h interval)Procain-penicilina(Efitard)Doze: 2x 400.000 U/zi

Ritm: discontinuu, la 12hBenzatin-penicilina(Moldamin)Doze:- copil (peste 5 ani): 600.000.U/spt - adult: 1.200.000U/saptRitm: 1 fl./spt./i.m. Evitarea complicaiilor post streptococice

Difuziune tisular:

bun n: ITRS/ITRI, ficat, rinichi, muchi, placent, tegument, ureche intern;

n prezena inflamaiei n: secreii purulente, lichid pleural peritoneal, sinovial, umoare apoas

Eliminare: renal (filtrare glomerular, excreie tubular)Efecte adverse

Reacii alergice (febr, urticarie, edem Quinke, oc anafilactic, boala serului)

Reacie Herxheimer

Neurotoxicitate (convulsii, mioclonii)

Hiperkalemie (spasme musculare, com, stop cardiac)

Tulburri hematologice (anemie hemolitic, neutropenie, T )

Infiltrate pulmonare cu eozinofile

Nefrit interstiial -> IRA

Vasculite alergice

Injectite / flegmon paraterapeutic

Accidente embolice arteriale/sau venoase (dup administrare i.v.)

Difuziune tisular redus n: LCR, seroase, prostat Eliminare: renal; biliar (+/_ oxacilin, nafcilin) Recii adverse: Hepatotoxicitate: icter colesatic (la N-N, sugar, gravide trimestrul III (oxacilin), creterea ALAT (oxacilin, nafcilin) Hematologice: neutropenie, leucopenie (nafcilin) Colit pseudomembranoas cu Cl.difficile Nefrit interstiial

Peniciline M. AntibioticulDoza/zi/ritmSpectrul de aciuneOxacilinaDoze:- copil: 200mg/kgc/zi- adult: 2g-8g/zi Ritm: 8-12 ore interval, i.m, i.v., p.o Stafilococ meticilino- sensibil (MSSA) NafcilinaIzoxazolil-penicilin DicloxacilinaDoze:-adult: 500 mg-2 g /zi Ritm: la 8h intv. i.m. Cloxacilina Flucloxacilina

AminopenicilineAntibioticDoze/zi, RitmSpectru de aciuneAminopenicilineAmoxicilinDoze:-copil: 150 mg/Kgc/zi- adult: 3- 8 g/ziRitm:6-8h i.m./i.v Coci Gram pozitiv:aerobi:(Str.pyogenes/ viri-dans/pneumoniaeanaerobi: Peptostreptococ

Coci Gram negativi( N.meningitidis);

Bacili Gram neg:(H.influenzae);AmpicilinDoze:- adult: 3x 2g/ziRitm:6-8h, p.o/i.v /i.m.Amino-peniciline+Inhibitori deBetalactamazeAmoxicilin +Ac. clavulanic(Augumentin/Amoxiklav)Doze: 2,4g-4,8g/zi/i.v.Ritm:8-12 h / i.m., i.v, p.o.Ampicilin +Sulbactam (Ampiplus/ Unasyn/Doze: 3-6 g/zi Ritm: 6-8 ore interv. i.m./ i.v /p.os.Bacili Gram pozitivanaerobi: Clostridium, Bacteroides;

Difuziune tisular:

bun n: ITRS/ITRI; tract biliar, tract urinar, ORL (sinusuri, ureche intern); n prezena inflamaiei: secreii purulente, lichid pleural peritoneal, seroase, umoare apoas

Eliminare: renal (filtrare glomerular, excreie tubular) biliarEfecte adverse

Reacii alergice (erupii alergice, oc anafilactic)

Reacie Herxheimer

Tulburri digestive (diaree, greuri, vrsturi)

Colit pseudomembranoas cu C.difficile

Obs: a). Ampicilina poate fi admin. p.o, profilactic, pentru prevenirea: infeciei cu H. influentzae, Str, penumoniae la pacienii splenectomizai/ agamaglobulinemie, endocarditei infecioase ( 2 gr/ zi); b) ineficient adm.profilactic a Penicilinei la bolnavi comatoi / insuficien cardiac pentru evitarea suprainfeciilor meningococice/ITRI.

Penicicline anti-pseudomonasAntibioticulDoza/zi/ritmSpectru de aciuneA. Amidino-peniciline MecilinamDoze:- 100 mg/kgc/zi (rar folosit) Bacili Gram negativiB. Carboxi-penicilineCarbenicilina (Pyopen) Doze: 600 mg/kgc/zi(nu se mai folosesc dat instal.rezist.bacteriene. Coci Gram poz. - aerobi/ anaerobi: -Peptostreptococ, -Clostridium);

Bacili Gram negativi: - aerobi: -Enterobacterii,- Serratia, - Yersinia enterocolitica;

- anaerobi:-Bacteroides,- Fusobacterium);

Sternotropfomonas maltofilia TicarcilinaDoze: 4 x 3-4 g/ziRitm: la 6h intervalC.Carboxipeniciline +Inhib. de BL-mazeTicarcilina +Acid clavulanic (Timentin)Doze: 3 x 3,2 g/zi;Ritm: la 8h interval.D. Ureido- peniciline MezlocilinaRar folositAzlocilinaPiperacilina (Pipril)Doze: 4 x 3,5 g/ziRitm: la 6 ore interval i.v.Piperacilin +Tazobactam (T azocinDoze: 3 x 4,5 g/zi

Ritm: la 8 ore interval. i.v.TemocilinDoz: 2x 1-2 mg/kgc /zi i.v Bacili Gram negativi MDR

Difuziune tisular bun: - osoas;- la nivelul meningelui inflamat (tazobactam)

Eliminare: biliar (concentraii biliare nalte) renal.

Efect : sinergic cu AG; aditiv cu FQ Efecte adverse

Reacii de sensibilizare ( reacii cutanate, buloase, eritem polimorf, sindrom Steven-Johnson, necroliz epidermic toxic).

Neutropenie

Hepatotoxicitate (ASAT, ALAT +/- icter colestatic)

Manifestri hemoragipare( alte-rarea funciei plachetare/ prelungirea timpului de sngerare)

Encefalopatie (convulsii)

Tulburri elecrolitice ( hipo K+, hipo Mg++, hiper Na+) Tulburri digestive (diaree, greuri, vrsturi)

Flebite

CefalosporineAntibioticulDoza/zi/ritmSpectru de aciuneCef. gen. ICefalotina, Cefaloridina,Cefazolina,CefalexinaDoze:- copil: 50-100 mg/Kgc//zi /i.v.-adult: 6-12 g/zi i.v.

Ritm:- la 6-8 ore interval Coci Gram poz.: - Str.pyogenes/viridans,agalactiae-Str. pnemoniae( PSSP/PRSP) Coci Gram neg.:N.meningitidis, N.gonorrhae)Cef. gen. IICefamandol (Mandol), Cefuroxima (Zinacef ),CefprozilCefaclor (Ceclor),Cefoxitin Coci Gram poz. / neg (idem Cef.Gen. I); Bacili Gram neg. Moraxella catarhalis Cef. gen. IIICefotaxima (Claforan),Cefoperazona (Cefobid)Cefoperazona+ Tazobactam (Sulperazona)Ceftriaxona (Rocephin/ Cefort), Ceftazidima (Fortum),Doze:- copil:100-180mg/Kgc/zi/ i.v.- adult: 2- 6 g/zi i.v.

Ritm:la 8-12h interv(except Ceftriaxona) Bacili Gram neg.: E.coli, Klebsiella, Enterobacter, Proteus, H. Influenzae; Serratia Coci Gram poz / neg- MSSA, Staf. epidermidis Anaerobi ( Bacteroides) Cefixima (Eficef)Ceftibuten (Cedax)- 2x1cp/zi- 1cp/ziCef. gen. IVCefpiroma (Cefrom)Cefepima (Maxipim)Doze:- copil: 50mg/Kgc/zi/i.v- adult: 4 g/zi i.v.Ritm: la 12h Bacili Gram negativi:-Enterobacterii(cef.III.rez;Ps.aeru-ginosa) Coci Gram poz.:- Enterococ. Ceftobiprole (Zeftera)Ceftaroline Coci Gram poz. (eficient pt. MRSA i Enterococ faecalis) Ps.aeruginosa

Cefalosporine de generaia a III-a

DE EXTREM STNGDE CENTRUDE EXTREM DREAPT PNEUMOCOC P.R. BACILI GRAM NEG.( enterobacteriaceae)CEFTRIAXONCEFOTAXIM BACILI GRAM NEG.(enterobacteriaceae, inclusiv.Ps. aeruginosa, Morganella) CEFTAZIDIMCEFOPERAZONCEFEPIMA/CEFPIROMACEFTOBIPROLE ANAEROBI(peptospreptococi,bacteroides fragilis,B. burgdorferi)CEFTRIAXONCEFOTAXIM,CEFTIZOXIM

Difuziune tisular: a) bun n LCR: Cefuroxim (Cef.gen II) Cef.gen.III------------------------------------ n tratamentul M.B cu Pneumococ, H.influenzae,N.meningitidis

b) Cef.gen.IV au o stabilitate mai mare la aciunea cefalosporinazelor / ESBLEliminare: biliar (concentraii biliare nalte/ excreie pe cale biliar (Ceftriaxon i Cefoperazon) renal. Efecte adverse

Reacii de sensibilizare ( reacii cutanate, buloase, eritem polimorf, sindrom Steven-Johnson, necroliz epidermic toxic).

Neutropenie

Hepatotoxicitate (ASAT, ALAT +/- icter colestatic, litiaz biliar)

Manifestri hemoragipare ( alterarea funciei plachetare/ prelungirea timpului de sngerare)

Encefalopatie (convulsii)

Tulburri elecrolitice (hipoK+/Mg++, hiper Na+) Flebite

CarbapenemiAntibioticulDoza/zi/ritmSpectrul de aciuneIndicaii terapeutice (trat. empiric) Imipenem/Cilastatin(Tienam)Doze: 1,5 - 3g/zi, i.v.

Ritm: 6-8 ore intv.Germ.Gram poz./neg. - aerobi,- anaerobi:Clostridium; Bacteroides; B. Gram neg.prod. de ESBL;Germ MDR Ss comunitar/nosocomial; Pneumonii nosocomiale (de ventilaie); Teren neutropenic; Electiv, in infectii severe cu Entero-coc faecalis; Infecii polimicrobiene intra-ab-dominale aerob/ anaerobe (genito-ITU, pancreatit ulcero-necrotic;)Ertapenem(Invanz)Doz unic:- 1g/zi, i.m. MeropenemDoze:- 6 g/zi n infeciile S.N.C.Ritm: 6-8 ore Infecii cu b.Gram neg. prod de ESBL (genito - urinare); Infecii complicate ale pielii i esuturilor moi; Infecii severe cu Acinetobacter baumannii MDR ( Nu Ertap) Indicat n plus, n infecii SNC (concentreaz foarte bine n LCR) compar. cu Imipenem.DoripenemDoze: 3x 500 mg /zi i.v Ind. exclusiv in infec. nosocomiale cu : Ps. Aeruginosa i Acinetobacter baumannii MDR;

TIENAMPseudomonasAcinetobacterCarbapenemii: spectrul antibacterianS.aureusBacteroidesKlebsiellaINVANZE.coliProteusMRSAMEROPENEM, DORIPENEM

AminoglicozideAntibioticulDoza/zi/ritmSpectru de aciuneIndicaiiGen. IStreptomicinaKanamicinaParamomicinaSpectinomicinaDoze: 1g/zi M. tuberculosis; N. gonoreae; Brucella; F. tularensis; Yersinia pestis; TBC cu m.tuberculosis (in asociere cu alte tbc-statice); Tularemie; Bruceloz; Pest; Gonoree;NeomicinaAdmin. local Infecii cu MSSA/-MRSA;Gen. II-aGentamicinaDoza:-copil: 3-5mg/ Kgc/zi. - adult: 2x80mg/ ziRitm: discont., la 12 ore interval. Coci Gram poz. - aerobi:(MSSA/MRSA, Enterococ);

Bacili Gram neg. - aerobi. Infecii sistemice

Infecii pe teren neutropenic

E.I cu Enterococ (n asociere cu Glicopeptide);TobramicinaDoza:-adult: 2x80mg/ziRitm: discont., la 12 ore intervalGen III-aAmikacinaDoza/ritm:2x500mg/zi la 12 h sau doz unic. Infecii grave cu B. Gram neg. (R la Gentamicin/ Tobra-micin)Netilmicina

Difuziune tisular: bun n: rinichi, urechea intern, placent; satisfctoare n; secreii bronice, os, umoare apoas, LCR;

concentraia:- n bil/ lichidul sinovial < concen-traia seric.

Eliminare: renal (94%);

saliv/ alte lichide ale organismului.

Efecte adverse

Nefrotoxicitate

Ototoxicitate/ toxicitate vestibular

Blocad neuro-muscular

Reacii alergice minore

Reacii locale (durere, flebite dup administrare)

Macrolide AntibioticDoz/ritmSpect.de aciuneIndicaii

Gen. IEritromicinaDoze: copil:30 mg/kgc/ziRitm:- 6 ore interv./p.os.Germ. aerobi: Coci gram poz.

Bacili gram poz.( b. difteric, L. monicytogenes)

B. gram neg. ( Campylobacter, B. pertussis, L. pneumophilla)

Mycoplasma spp. Chlamydii; Mycobacterii atipice ( MAC)

Germ. anaerobi(Clostridium); Inf. streptococice ( pacieni alergici la Betalactamine); Pneumonii atipice Tuse convulsiv; Difterie; Listerioz; Toxoplasmoz; Actinomicoz; Infecii ORL; Piodermite; ITU cu Ch.trahom. Infecii cu H. pylori sau Campylobacter; Lues; Infecii odontogeneRovamyocina (Spiramicina)Doze/ritm: 6-9 mil.U /zi

AzalideRoxitromicina (Rulid)Doze: 2x 150-300mg/zi, p.osClaritromicina (Klacid/Fromilid)Doze/ritm: 2x250-500mg/zi; 500mg/zi ( Kacid SR, doz unic zilnic) 500 mg/zi, i.v.Azitromicina (Sumamed)

---------------------- Azitromicina retard (Z-max)Doze/ritm: 500mg/zi (doz unic zilnic/3 zile ( (efect postantibiotic 10-14 zile)---------------------------------- 2 gr.doz unic, p.o.DiritromicinaDoze: 500 mg7zi (doz unic)p.os. post prandial

Difuziune tisular: bun n: ITRS/ITRI, tegument, tract uro genital, placent;

concentreaz bine intracelular ( n macrofage, PMN)

Eliminare: biliar (excreie urinar sec.);

lapte

Efecte adverse

Tulburri digesive

Hepatotoxicitate (hepatit colestatic)

Ototoxicitate

Reacii alergice

Interaciuni medicamentoase (interfereaz cu sistemul citocromului P 450 )

Reacii locale (durere, flebite dup administrare)

ChinoloneAntibioticDoz/ziSpectru de aciuneIndicaiiGeneraia I-aBacili Gram neg. Shigella Salmonella E. Coli Campylobacter

Germ. Gram poz. aerobi/anaerobi: Chlam. trahomatis Mycoplasma spp. Legoinella pneum. MSSA / MRSA Brucella Rickettsii

M.atipice (MAC) Infecii gastro intestinale

Infecii genito-urinare ( inclusiv cu Ch.trahomatis)

Prostatite acute/cronice

Meningite bacteriene

Endocardit infecioas cu MSSA/MRSA (+AG)

Sepsis sever (+/-AG,+/-BL);

Legioneloz;

Bruceloz;

Rickettsioz;

Infecii odontogene;

Holera (FQ)

TBC cauzat de MAC;

Pre/ post interv. pe colon.Ac.nalidixic (Negram) 4x1gr/ziGeneraia a II-a (Fluorochinolone)Norfloxacin2x400 mg/ziOfloxacin2x100 mg/ziCiprofloxacin2-3x500 mg/ziPefloxacin2x400 mg/ziLomefloxacin0,8 1,6 g/ziPreparate S.R.Levofloxacin (TAVANIC)Ofloxacin OD (ZANOCIN)Moxifloxacin (AVELOX)

500 mg/zi(doz unic)Generaia a III-aTosufloxacina0,15 0,30 g/zi(doz unic)

Sparfloxacina

Familia GlicopeptideAntibioticDoz/ritmSpectruIndicaiiVancomicina(Edecin)Doz: - 4x0,5 g/zi i.v. lent

Ritm:- la 6-12h intervalCoci gram poz - aerobi : MSSA/MRSA Enterococ Str.pneum.(PRP);- anaerobi : Clostridium dificile +/- Alergie la BL. EI (+/- AG) Sepsis nosocomial pe teren neutropenic. Colit pseudomembra-noas cu Clostr. dificileTeichoplanina(Targocid)Doz: - I zi: 2x400mg/zi i.v. - II zi: 400 mg/zi Ritm: - 1 fl la 24h interval

Coci gram poz - aerobi : MSSA/MRSA Enterococ Str.pneum.(PRP);

Infecii osteo-articulare.

Sepsis nosocomial pe teren neutropenic.Telavancin (Vibativ)Doz:10 mg/kg /zi i.v. Ritm: 1 fl la 24h interval, adm lent- 60(Cl.creat. >50 mL/min.)

Familia LincosamideAntibioticDoz/ritmSpectruIndicaiiLincomicina ( Neloren)Doz:3x0,5 g/ziCoci gram poz aerobi: MSSA/MRSA Infecii osteo-articulare (osteomielit);

Sinuzit maxilar odontogen.

Clindamicin(Dalacin)

Doz:3 x 0,25g/zi p.o /600 mg/zi i.v.Coci gram poz aerobi: Str. A,B,C,G; Str.pneum.(PRP); MSSA/MRSA;

Germ. anaerobi: Peptostreptococ; Fusobacterii Infecii septice ale glandelor salivare;

Difterie

Infecii odontogene;

Supuraie de plaeu bucal.

Familia RifamicineAntibioticRitm/ Doza/ziSpectru de aciuneIndicaiiRifampicina(Sinerdol)Doza/ Ritm:1x 600mg/zi/3x 300mg/zi, p.o. M.tuberculosis; Brucella; Coci Gram poz:(MSSA/MRSA, Str. pneumoniae);

Coci Gram neg:(N.meningitidis). Tuberculoza Bruceloza;

Mening. bact. (BL FQ);

Infec staf. cutanate, pri moi.Rifaximin (Normix)Ritm/Doza:3x0.4 g/zisau2x0.8g/zi,p os. Bacili Gram neg (Enterobacterii);

Vibrionul holeric

Anaerobi; (Clostridium, Bacteroides, Peptostreptococ). Infecii gastro-intestinale;

Encefalopatia portal hepatic;

BDA la pacieni aflai n stad SIDA;

Colit pseudomem-branoas cu Clostr. dificile

Familia CloramfenicolAntibioticDoza/RitmSpectru de aciuneIndicaiiCloramfenicol /TiamfenicolDoza:- 30mg/kg/zi.

Ritm:- la 6 h interv. p.o/i. v. Coci Gram poz. (Str.pneumoniae);

Coci Gram neg.(N. meningitidis, H.influenzae)

Bacili Gram poz:(Bacillus, Listeria)

Bacili Gram neg:(Salmonella,Shigella)

Brucella spp.

Vibrio spp).

Bacili Gram poz;

Spirochete

Chlamydia, Mycoplasma Anaerobi; Meningite bacteriene;

Febr tifoid;

Inf. cu H.Influenzae;

Rickettsioze;

Pneumonii atipice;

Actinomicoz;

Familia SulfamideAntibioticRitm/DozaSpectru de aciuneIndicaii Cotrimoxazol(Biseptol,Septrin) Ritm/Doza :

-2x800mg/zi,p.o /- 2x 3,2g/zi/ i.v. Coci Gram poz/neg: (Str.pneumoniae, N.meningitis) ;

Bacili Gram neg: ( Enterobacterii,Shigella, Salmonella;

Pneumocistis carinii. Profilaxie i trat. pneum. cu Pn. carinii; Holer

Inf. cu Y. Enterocolitica

Infecii gastro-intest;

Meningite bacteriene (n asoc. cu BL FQ);

Bruceloza. Sulfadoxinepyrimethamine (Fansidar)Doz unic:- adult: 3cps/zi-copil -2 caps/zi Plasmodium;

Toxoplasma gondii. Malarie;

Toxoplasmoz;Clotrimazin( Sulfadiazin+ trimetoprim)Doz unic:-adult: 2cps/zi- 4-20mg/Kgc/zi Malarie;

Toxoplasmoz;

Nocardioz

Familia BenzimidazoliAntibioticDoz/RitmSpectru de aciuneIndicaiiMetronidazolDoza: 0.5g-2g/ziRitm: 6-12h intv.Gram poz./neg. - anaerobi

Trichomonas vaginalis;

Giardia intestinalis.

Entamoeba histolytica.

Helycobacter pylori. Infec. cu anaerobi;

Dizenteria amoebian ;

Giardioza;

Trichomoniaza;

Ulcer gastric.

Colit seudomembranoas

Tinidazol(Fasigyn)Doza:2g/ziRitm:doza unic.Ornidazol(Tiberal)

Doza:2x0.5g/zi/p.o

Familia TetraciclineAntibioticDoza/RitmSpectru de aciuneIndicaiiGENERAIA ICoci Gram poz. - aerobi: Strept. salivarius, Lactobacillus;

Coci Gram poz. - anaerobi:(Peptostreptococ, Clostridium/ Actinomyces);

Bacili Gram neg. - anaerobi: (Fusobacterium, Bacteroides,Prevotella, Porphyromonas);

Vibrion holeric;

Brucella spp; Chlamydia, Mycoplasma;

Legionella;

Borrelia burgdorferi;

L. monocytogenes ; Periodontite;

Borelioz;

Holer;

Rickettsioze;

Infecii genit.cu Ch. trahomatis;

Pneumonia atipice(Mycoplasma , L. pneumophilla);

Listerioza;

Actynomicoza; Tularemie

Pest

Antrax cutanat

Malarie (Plasm. falc. Rez. la Clorochin)TetraciclinaDoza 1-2g/ziRitm:6-8 h interv. GENERAIA IIDoxiciclina Doza/Ritm:- 2 x 0.1g n I-a zi - 0.1g/zi (doza unic)MinociclinaDoza/Ritm:

- adult:200mg/zi

- copil:2-4mg/kgc/zi

Familia OxazolidinoneAntibioticDoz/RitmSpectruIndicaiiLinezolidDoza:3 x 250 mg/zi ,p.o., i.v.Ritm: la 8 ore interv. MRSA PRP GRE Infecii sistemice grave (sepsis sever, endocardit infecioas), declanate de microorg.rezist. la Betalactamine;

Teren neutropenic;

Infecii sistemice nosocomiale.

Familia SinergistineAntibioticDoz/ziSpectruIndicaiiQuinupristin+Daftopristin(Sinercid)Doza:7,5mg/ Kgc/zi Coci Gram poz. i neg; Bacili Gram poz. i neg; - anaerobi; Mycoplasma ; Chlamydia; Legionella Sepsis nosocomial sever; Endocardit infecioas nosocomial; Infecii pe teren eutropenic; Infecii grave cu Enterococ. Inf. ORL,osteoarticulare

Familia KetolideAntibioticDoz/ziSpectruIndicaiiTelithromycin(Ketek)Doza unic:0.4-0.8g/zip.o.(1tab=0.4g) Coci Gram poz; Bacili Gram neg:(Legionella,B.pertusis, H.Influenza; L.monocitog;Mycoplasma,Chlamydia Infecii ORL; Pneumonii comunitare; Infecii odontogene; ICRS rezist. la Penicilin G; Persoane alergice la Beta-lactam.;

Familia PolimixineAntibioticDoz/RitmSpectruIndicaiiPolimixinaDoza: - 2-3 mg/kgc/zi, i.m., i.v., la 6 ore interv. - 15,00025,000 UI/kg/zi la 12 h interv. B. Gram neg.(electiv: MDR: - Ps. aeruginosa, +/- Acinetobacter baumannii ) Infecii sistemice grave : - sepsis sever, - teren neutropenic; - pmeumoniii deventilaie---------------------------------------- - M. bact. cu B. Gram neg. (n-n i sugar)Colimicina( Colistin)Doza::a) 2-3 mg/kgc/zi;b) 60 kg, 50,000-75,000 IU/kg/zi; p.o.( inhalatii), i.m, i.v. - i. rahidian/ i. ventricularRitm: la 8 /12 ore interv.

Alternativa de trat pt. ITU AntibioticDoz/ziSpectruIndicaiiNitrofurantoinDoza: - 50-100mg/zi x2-3 ori/zi - 100 mg/zi la 24h interv. ( ITU recidivante)B. Gram neg. +/- ESBL, - MDR

+/- VRE Cistite

ITU necomplicate

ITU cu VRE

Noi clase de antibiotice

I. TIGECICLINA: a) activitatea bactericid S. aureus meticilino-rezistent (MRSA)* S. epidermidis meticilino-rezistent (MRSE) Enterococcus vancomicino-resistent (VRE) E. faecium E. faecalis Acinetobacter baumannii Bacterii rezistente

Tigeciclina: b) metabolizare i eliminareExcreieTygacil (tigecycline) Prescribing Information. Philadelphia, PA: Wyeth Pharmaceuticals Inc. 2005. Rello J. J Chemother. 2005;17 (Suppl 1):12-22. 59%bil/fecale8%Altele33% - urin (22% - nemodificat)Semnificaia clinic a parametrilor farmacocinetici este necunoscut..Eliminare nemodificat pe cale biliar/fecale

Nu afecteaz activitatea citocromului P450 (CYP)

Are un potenial sczut pt. interaciuni medicamentoase

Tigeciclina: c) doze i mod de administrare Doza Standard Doza iniial: doza de 100 mg IV urmat de 50 mg IV la 12 ore Indicat la pacienii 18 ani

Insuficiena renal: nu este necesar ajustarea dozelor nici la pacienii hemodializai

Insuficiena hepatic: nu este necesar ajustarea dozelor la pacienii cu insuficien hepatic uoar sau moderat la pacienii cu insuficien hepatic sever (Child Pugh C), doza iniial este de 100 mg IV urmat de dozei dela 50mg la25 mg IV la 12h.

Tigeciclina: d) atenionri i precauii speciale pentru utilizare

Nu este recomandat utilizarea: A) la copii: cu vrste < 8 ani datorit decolorrii danturii; cu vrsta < 18 ani : lips studii privind sigurana i eficacitatea. B) la gravid.

II. DAPTOMICINA ( CUBICIN) : - primul antibiotic din clasa lipopeptidelor ciclice naturale ; - produs de fermentaie, izolat din Streptomyces roseosporus ; - nu prezint rezisten ncruciat cu alte clase; - nu i se cunoate un mecanism de rezisten;

Daptomicina: a) spectru de aciune:

A) Majoritatea bacteriilor Gram-pozitive, precum:S. aureus, coagulase-negative staphylococci (CoNS), Enterococcus spp. (nu este aprobat pentru infectii enterococice)Streptococci-haemolytic ,S. pneumoniae, S. viridansPeptostreptococcus spp., Corynebacterium spp., Listeria monocytogenesClostridium difficile, Clostridium perfringensPropionilbacterium spp.

B) Tulpinilor Gram-pozitive MDR, precum:1,2MRSA (Meticilino-Rezistent Staphylococcus Aureus )MRSE (Meticilino-Rezistent Staphylococcus Epidermidis)VRSA (Vancomicino-Rezistent Staphylococcus Aureus )VRE* (Vancomicino-Rezistent Enteroccocus)

Daptomicin: b) doz /zi, siguran i toleran:

bine tolerat, este administrat in doz de 500mg/zi (n perfuzie i.v. de 30 min, pe o durat de 14 zile);

Nu :- au aprut reacii adverse importante care sa oblige la ntrerupere a tratamentului;- s-au raportat creteri ale CPK peste nivelul normal (204U/l);- s-au evideniat efecte adverse (nervoase, cardiace sau musculare ) la dozele optime folosite.

*****Slide 19.In addition to common pathogens, tigecycline exhibits in vitro activity against other pathogens, including the following resistant bacteria1:

Methicillin-resistant S. aureusMethicillin-resistant S. epidermidisVancomycin-resistant EnterococcusE. faeciumE. faecalisAcinetobacter baumannii Tigecycline is not affected by gram-negative bacteria that produce ESLs

ReferenceTygacil (tigecycline) Prescribing Information, Philadelphia, PA: Wyeth Pharmaceuticals Inc. 2005.**Slide 26.The primary route of tigecycline elimination is unchanged biliary excretion (59%). Secondary routes of elimination include renal excretion (22% unchanged tigecycline through urine) and glucuronidation. Tigecycline does not affect the cytochrome P450 (CYP450) enzyme family (including CYP1A2, CYP2C8, CYP2C19, CYP2D6, and CYP3A4). Based on in vitro studies, tigecycline is not expected to alter metabolism of drugs metabolized by CYP450 enzymes. Tigecycline has a low potential for drug interactions and is not metabolized by CYP450 and does not inhibit or induce CYP450.1,2In addition, when tigecycline was co-administered with digoxin or warfarin to healthy subjects in drug interaction studies, no clinically relevant drug interactions were noted. While no dosage adjustment is necessary, prothrombin time or other suitable anticoagulation test should be monitored if tigecycline is administered with warfarin.1,2Also, renal impairment does not alter the pharmacokinetic profile of tigecycline, and tigecycline is not eliminated by hemodialysis.1,2

References1. Tygacil (tigecycline) Prescribing Information. Philadelphia, PA: Wyeth Pharmaceuticals Inc. 2005. 2. Rello J. Pharmacokinetics, pharmacodynamics, safety and tolerability of tigecycline. J Chemother. 2005;17(Suppl 1):12-22. **Slide 32.Tigecycline is indicated for patients 18 years of age or older. The pharmacokinetics of tigecycline in patients younger than 18 years of age have not yet been determined. In adults, the pharmacokinetic profile of tigecycline has not been shown to be affected by age, sex, or race. The standard dosage regimen for tigecycline is an initial dose of 100 mg administered intravenously (IV), followed by 50 mg IV every 12 hours. No dosage adjustment is required in patients with renal dysfunction or in patients with mild to moderate hepatic dysfunction. However, the dosing regimen is different in patients with severe hepatic impairment. In cases of severe hepatic impairment (Child-Pugh C), the initial dose of tigecycline 100 mg IV should be followed by tigecycline 25 mg IV every 12 hours.

ReferenceTygacil (tigecycline) Prescribing Information. Wyeth Pharmaceuticals Inc.

*

Broad-spectrum antibacterial activity (in vitro)Cubicin is active in vitro against a broad spectrum of clinically relevant susceptible Gram-positive bacteria, including resistant strains such as MRSA and VRENote: Cubicin is not licensed in enterococcal infections

References1. Pfaller MA, et al. Diagn Microbiol Infect Dis 2007;57:459465 2. Sader HS, et al. BMC Infect Dis 2007;7:29*