antibiotice _ mecanisme de actiune si rezistenta la
DESCRIPTION
un curs foarte util studentilor medicinistiTRANSCRIPT
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Antibiotice – mecanisme de actiune si rezistenta la antibiotice
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Remember – mecanisme de actiune antibiotice
Quinolone: ADN-giraza
Rifampina:ARN-polimeraza – ADNdependenta
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Principalele mecanisme de actiune - 1
(1) Distrugerea peretelui bacterian• Antibiotice beta-lactamice
– Peniciline, cefalosporine si cefamicine, carbapeneme si
monobactami, combinatii inhibitori de beta-lactamaza/betalactamine
• Glicopeptide– Vancomicina
• Polipeptide– Bacitracina, polimixine
• Antibiotice utilizate in tratamentul infectiilor cu micobacterii– Izoniazida, etionamida, etambutol, cicloserina
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Principalele mecanisme de actiune - 2
(2) Inhibarea sintezei proteice• Actiune pe ribozomii 30S
– Aminoglicozide– Tetracicline
• Actiune pe ribozomii 50S– Cloramfenicol– Macrolide– Clindamicina– Streptogramine– Oxazolidinone
www.microbelibrary.org
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Principalele mecanisme de actiune - 3
(3) Inhibarea sintezei de acizi nucleici
• Actiune pe replicarea ADN
• Quinolone
• Metronidazol
• Actiune pe sinteza ARN
• Rifampin (Rifampicina)
• Rifabutin
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Principalele mecanisme de actiune - 4
(4) Antimetaboliti
• Sulfonamide
• Trimetoprim
• Acid paraaminosalicilic
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Mecanismul (1):
DISTRUGEREA PERETELUI BACTERIAN
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(1)Sinteza: activitatea antibioticelor asupra peretelui celular la G+ si G-
Gram negativiGram pozitivi
Polipeptide
Beta-lactamineGlicopeptide
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BETA-LACTAMINELE
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Clasificarea beta-lactaminelor
Monobactami: AZTREONAM
Dibactami: - PENAMI (PENICILINE) - INHIBITORI BL + PENAMI - PENEMI - CARBAPENEMI - CEFEME
(CEFALOSPORINE)- CARBACEFEME
Tribactami: SANFETRINEM
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Peniciline
Carbapeneme
Cefalosporine: mai rezistente la penicilinaze, spectru antibacterian mai larg, proprietati farmacokinetice imbunatatite
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DIBACTAMI:PENICILINELE (PENAMII)Antibiotic Spectru de activitate
Peniciline naturale (Penicilina G, Penicilina V) Toti streptococii; activitate minimala fata de stafilococi; meningococi; majoritatea anaerobilor G+
Peniciline rezistente la beta-lactamaze
(Peniciline M: nafcilina, meticilina, oxacilina, cloxacilina, dicloxacilina)
Ca mai sus, dar cu activitate crescuta pe stafilococi
Peniciline cu spectru extins (Peniciline A: ampicilina, amoxicilina; Carboxipeniciline: carbenicilina, ticarcilina; Ureidopeniciline: azlocilina, mezlocilina, piperacilina)
Coci G+ si unii bacili G-
Beta-lactami cu inhibitori de beta-lactamaze
(amoxicilina/ ac.clavulanic, ampicilina
sulbactam, ticarcilina/ac. clavulanic,
piperacilina/tazobactam
Activitate ameliorata fata de bacteriile producatoare de beta-lactamaze (stafilococi si unele G-); nu inhiba toate beta-lactamazele
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DIBACTAMIPENAMI (PENICILINE)
1. PENICILINE BIOSINTETICE NATURALEA. BENZILPENICILINA – PENICILINA G f. 400.000 UI
actiune rapida 1.000.000 UI
5.000.000 UI
Spectru actiune (SA): Coci G +; Coci G -; Bacili G +Utilizare terapeutica (UT): boli provocate de germeni sensibiliFarmacologie (FC): doar parenteral → c% plasmatica eficienta
→ difuzeaza bine in tesuturi (exceptie LCR, ochi, seroase)Reactii adverse (RA): alergice → soc anafilacticAdministrare: i.m. din 6 in 6 ore; i.v. in perfuzieObservatie:
! Cu ser fiziologic sau cu H2O distilata!!! NU cu glucoza sau alte substante in siringa
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B. FENOXIMETILPENICILINA – PENICILINA V, OSPEN – cp. 400.000 UI
1.000.000 UIAsemanatoare Penicilinei G cu actiune mult mai slabaObservatie:- pe stomacul gol cu o ora inainte de masa sau doua ore
dupa masa- doze duble fata de Penicilina G;- din 6 in 6 ore.
C. PROCAINPENICILINA – EFITARD fl 800.000 UIAsemanatoare Penicilinei G, dar de semidepoziti.m. monodoza
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D. BENZATINPENICILINA - MOLDAMIN, BENZATINPENICILINA - MOLDAMIN, RETARPENRETARPEN fl. 600.000
1.200.000 UI
Asemanatoare Penicilinei G, dar de depoziti.m. 1 doza/saptamana – 2 – 3 saptamani
(teoretic!)
Observatie:- NU dizolvata in H2O distilata- NU i.v. (pericol de embolie pulmonara)- NU la copii < 3 ani
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2. PENICILINE ANTISTAFILOCOCICE – PENICILINE “M”- METICILINA- OXACILINA- CLOXACILINA- DICLOXACILINA- NAFCILINA
OXACILINA – OXACILIN caps. 0,250; fl. 0,500SA: stafilococi meticilinosensibili producatori de BLUT: - infectii stafilococice ca monoterapie - infectii stafilococice grave (endocardite septice) in
asociere cu un AGFC: pe stomacul gol si parenteral → c% sanguine eficienteAdm: caps, fl.
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3. AMPICILINE: PENICILINE “A”3. AMPICILINE: PENICILINE “A”- AMPICILINAAMPICILINA- AMOXICILINAAMOXICILINAAMPICILINA – AMPICILINA – caps. 0,250 g fl. 0,250 g; 0,5 gSA: CG +; CG -; BG –UT: boli provocate de acesti germeniFC: oral si parenteral → c% biliara inalta = ATB biliar;
se concentreaza renalAdm: oral din 6 in 6 ore i.m. din 6 in 6 ore i.v. perfuzieAMOXICILINA – AMOXICILINA – caps 0,250 g; 0,5g;
fl. 0,250 gSA: asemanatoare AmpicilineiUT: idem Ampicilina cu eficacitate mai mare
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4. CARBOXIPENICILINELE4. CARBOXIPENICILINELE
• CARBENICILINACARBENICILINA
• TICARCILINATICARCILINA
Active indeosebi pe piocianic
TICARCILINA – TICARCILINATICARCILINA – TICARCILINA fl. 1 g, 3 g
SA: Pseudomonas aeruginosa, Proteus, Enterobacter, Serratia
UT: infectii cu germeni sensibili
Adm: i.m., i.v., i.v. perfuzie
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5. UREIDOPENICILINELEUREIDOPENICILINELE
• MEZLOCILINAMEZLOCILINA
• AZLOCILINAAZLOCILINA
• PIPERACILINAPIPERACILINA
PIPERACILINA: PIPERACILPIPERACILINA: PIPERACIL fl. 2 g, 3 g, 4 g
SA: Pseudomonas aeruginosa, Proteus, Enterobacter, Serratia, enterococi
UT: infectii severe urinare, biliare, osoase, meningiale
Adm: i.m., i.v.
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INHIBITORII DE BETALACTAMAZE (IBL)
• ACIDUL CLAVULINIC• SULBACTAM• TAZOBACTAM
ATB minore, activitate scazuta
O N
BLBL
BACTERIABACTERIA
Leg. betalactam
NO
Leg. betalactam
ATBATB
minorminor
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Principalele prod. comerciale IBL + IBL +
BETALACTAMINEBETALACTAMINE
1. ACID CLAVULANIC + AMOXICILINA = ACID CLAVULANIC + AMOXICILINA = AUGMENTIN, AUGMENTIN,
AMOXIKLAVAMOXIKLAV susp., caps., fl., la 8
ore2. ACID CLAVULANIC + TICARCILINA = ACID CLAVULANIC + TICARCILINA = TIMENTINTIMENTIN
fl. (i.m., i.v.) la 6 ore3. SULBACTAM + AMPICILINA SULBACTAM + AMPICILINA SULTAMICILINASULTAMICILINA
== UNASYN UNASYN susp, caps, fl.(i.m.,
i.v.) la 8 ore
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PENEMIPENEMIRITIPENEMRITIPENEM fl. si caps
CARBAPENEMICARBAPENEMIIMIPENEMI – CILASTATINA : IMIPENEMI – CILASTATINA : TIENEMTIENEMSA: “ultralarg” – toate bacteriileMecanism de actiune (MA): asemanator – se
fixeaza pe PBP2 → efect bactericid rapid si intens
FC: difuzeaza bine in tesuturi, LCR (90%), urinaAdm: i.v., i.v. perfuzie
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CARBAPENEMI
Antibiotic Spectru de activitate
Carbapenemi
(imipenem, meropenem, ertapenem)
Activitate antibacteriana larga fata de majoritatea bacteriilor G+ si G- aerobe si anaerobe, cu exceptia:
SARM, SERM, E.faecium,
anumiti bacili G-
(Burkholderia, Stenotrophomonas
Pseudomonas)
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CEFEME - CefalosporineleAntibiotic Spectru de activitate
Generatia I . Spectru ingust
(cefalexin, cefazolin, cefalotin,
cefapirin)
Bacterii G+ & unele G- (E.coli, Klebsiella, Proteus)
(= P, Oxa, Ampi)
Generatia a IIa. Spectru extins
(cefaclor, cefuroxim, cefoxitin)
Bacterii G+ &
G- ameliorat (Enterobacteraciae, Citrobacter, Proteus)
Generatia a IIIa . Spectru larg
(cefotaxim, ceftriaxon, ceftazidim, cefixim)
Bacterii G+ & G- spectru larg;
(= P, Oxa, A, Genta + Pseudomonas) - CTZ
Generatia a IVa. Spectru extins
(cefepim, cefpirom)
Bacterii G+ & activitate usor crescuta fata de G- BLSE + comparativ cu CGIII
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CEFEME – CEFALOSPORINECEFEME – CEFALOSPORINE
MA: asemanator PenicilinelorSA: difera de la o generatie la alta
GENERATIA IGENERATIA I
CEFACEFAZOLINAZOLINA (KEFAZOL) CEFA (KEFAZOL) CEFAZEDONAZEDONACEFACEFALOTINALOTINA (KEFLIN) (KEFLIN) CEFACEFAPIRINAPIRINASpectru “largit” ca si spectrul Penicilinei G
Oxacilinei Ampicilinei
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GENERATIA A II-AGENERATIA A II-A
CEFUCEFUROXIMAROXIMA (ZINNAT) (ZINNAT) CEFOCEFOTIAMTIAM
CEFACEFAMANDOLMANDOL (MANDOL) (MANDOL) CEFOCEFOTEMTEM
Spectru “larg” ca si spectrul Penicilinei G
Oxacilinei
Ampicilinei
Gentamicinei
Metronidazol
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GENERATIA A III-AGENERATIA A III-A
CEFOCEFOTAXIMATAXIMA (CLAFORAN) (CLAFORAN) CEFTCEFTAZIDIMAAZIDIMACEFTCEFTRIAXONARIAXONA (ROCEPHIN) (ROCEPHIN) CEFOCEFOPERAZONAPERAZONA
(CEFOBID)(CEFOBID)Spectru “ultralarg” ce include spectrul Penicilinei G
OxacilineiAmpicilineiGentamicineiMetronidazolTicarcilina
GENERATIA A IV-AGENERATIA A IV-A
CEFPIROMACEFPIROMA CEFEPIMACEFEPIMASpectrul “foarte larg” ce include si enterococul
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“CACIULA CIOBANULUI”“CACIULA CIOBANULUI”
CEF gen. I
CEF gen. II
CEF gen. III
SPECTRUL ANTIBACTERIAN AL CELOR 3 GEN. DE CEFSPECTRUL ANTIBACTERIAN AL CELOR 3 GEN. DE CEF
ENTEROCOC
PIOCIANIC
BACTEROIDESFRAGILIS
PIOCIANIC
G
OP
A
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CARBACEFEMECARBACEFEMELORACARBEFLORACARBEF
MONOBACTAMIMONOBACTAMIAZTREONAMAZTREONAM – piocianic
TRIBACTAMITRIBACTAMISANFETRINEMSANFETRINEM – spectru “ultralarg” G + si G -,
aerobi si anaerobi
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Mecanismul de actiune al beta-lactaminelor
Beta-lactaminele inhiba formarea puntilor peptidice, prin blocarea PLP, care in mod normal functioneaza ca enzime ce intervin in sinteza peretelui bacterian (ex. transpeptidaze)
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GLICOPEPTIDELE
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Vancomicina•Obtinuta initial din Streptomycesorientalis
•Activa numai pe bacterii G+ (molecula de dimensiune mare, nu poate depasi membrana externa a bacteriillor G -)
•Folosita pentru tratamentul infectiilor cu G + rezistenti la Oxacilina
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Vancomicina: Mecanism de actiune
Mecanism: Vancomicina inhiba formarea puntilor intre straturile de peptidoglicanVancomicina se poate lega numai la D-Ala-D-Ala, nu si la D-Ala-D-lac
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POLIPEPTIDELE
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POLIPEPTIDELE
• Bacitracina (peptide ciclice) izolata din Bacillus licheniformis– Utilizata in aplicatii topice in infectii cu bacterii G+ – Interfera cu defosforilarea si ciclizarea carrier-ului
lipidic responsabil cu mobilizarea precursorilor peptidoglicanului
• Polimixina (polipeptide ciclice) izolata din Bacillus polymyxa– Interactioneaza cu lipopolizaharidele si fosfolipidele
din membrana externa, crescand permeabilitatea – Activa mai ales pe bacili G- (bacilii G+ nu poseda
membrana externa)
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Distrugerea peretelui bacterian Antibiotice pentru M. tuberculosis
Tintele actiunii isoniazidei (INH),pirazinamidei (PZA), etambutolului(ETH) si rifampinei (RMP) asupra M tuberculosis:
INH inhiba sinteza acizilor micolici,
PZA inhiba sinteza precursorilor de acizi grasi cu lant scurt
ETH interfera cu sinteza arabinogalactanului,
RMP inhiba transcriptia prin legarea la subunitatea beta a ARN polimerazei
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Mecanismul (2)
INHIBAREA SINTEZEI PROTEICE
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Antibiotice care actioneaza asupra initierii sintezei proteice
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Antibiotice care actioneaza la nivelul fazei de elongare
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Aminoglicozidele
Structura:Sunt aminozaharuri legate intre ele prin inele glicozidice,
Origine:Streptomyces: streptomicina,neomicina, kanamicina,tobramicinaMicromonospora . gentamicina,Sisomicina
Derivati sintetici:Amikacina din kanamycinNetilmicina din sisomicina
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Aminoglicozidele (AG): mod de actiune
AG trec prin peretele celular simembrana celulara, catre citoplasma (mai ales la G-; nu patrund prin membrana celulara a streptococilor si enterococilor)
Se leaga ireversibil de subunitatea 30S a ribozomilor bacterieni si blocheaza atasarea subunitatii 50S la complexul de initiere
Rezulta producerea de proteine aberante si citirea gresita a ARN
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Mecanismul de actiune al aminoglicozidelor
Met Arg Gly Ser Pro Thr
1. Trecerea prin membrana citoplasmatica a bacteriilor G- (nu pot strabate prin membrana citoplamatica a strepto- si enterococilor)2. Legarea la subunitatea 30S 3. Citirea gresita a codonilor la nivelul ARNm4. Inhibarea sintezei proteice
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AMINOGLICOZIDE (AG)AMINOGLICOZIDE (AG)
SA: BG – aerobi, coic G +
RA: ototoxicitate; nefrotoxicitate !!!
Adm: parenterala
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GENERATIA IGENERATIA I
STREPTOMICINASTREPTOMICINA – activa pe BK
KANAMICINAKANAMICINA
NEOMICINANEOMICINA
SPECTINOMICINASPECTINOMICINA
GENERATIA A II-AGENERATIA A II-A
GENTAMICINAGENTAMICINA
TOBRAMICINATOBRAMICINA
GENERATIA A III-AGENERATIA A III-A
AMIKACINAAMIKACINA
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Tetraciclinele: mecanisme de actiune
• Origine– Tetraciclina, oxitetraciclina izolate din
Streptomyces– Minociclina, doxiciclina sunt sintetice
• Antibiotice bacteriostatice cu spectru larg
• Spectru antibacterian similar cu Macrolidele(dar si Clamydia, Mycoplasma, Rickettsia)
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Tetraciclinele: mecanisme de actiune
Tetraciclinele blocheaza translatia legandu-se ireversibil la subunitatea 30S si deformand-o astfel incat anticodonii corespunzatori ARNt care s-au incarcat nu se pot alinia corect cu codonii ARNm
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Oxazolidinonele
• O clasa noua de antibiotice; complet sintetica
• Spectru ingust de activitate (bacterii G+, inclusiv VRE, MRSA)
• Bacterii G-neg rezistente datorita existentei pompelor de eflux
• Mod de actiune: mecanism unic; interfera cu complexul de initiere la nivelul subunitatii 50S (domeniul V al ARNr 23S)
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Oxazolidinone: mod de actiune
Inhiba formarea complexului de initiere prin legarea la subunitatea ribozomala 50S (domeniul V al ARNr 23S), afectand fazele preliminare ale sintezei proteice
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Cloramfenicolul
• Se leaga ireversibil de peptidil-transferaza subunitatii ribozomale 50S si blocheaza elongarea peptidului, interferand cu sinteza proteinelor
• Antibiotice bacteriostatic cu spectru larg• Interfera cu sinteza proteinelor in maduva
osoasa, determinand anemie aplastica• Utilizare clinica limitata in tarile vestice, datorita
efectelor nedorite• Rezistenta asociata producerii de
acetiltransferaza, care catalizeaza acetilare radicalului –OH din pozitia 3
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Macrolidele
Eritromicina – din Streptomyces erythreusStructura de baza: inel lactona• Compusi cu 14 atomi de C: eritromicina, claritromicina,roxitromicina, telitromicina (ketolide)• Compusi cu 15 atomi de C: azitromicina• Compusi cu 16 atomi de C: spiramicina, josamicinaActivitate:• Spectru larg: bacterii G+ si unele bacterii G-, incluzand
Chlamydia, Mycoplasma, Legionella, Rickettsia, Neisseria
• Azitromicina, Claritromicina sunt active asupra unor mycobacterii
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Macrolide: structura
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Mecanismul (4)
ANTIMETABOLITI
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Antimetaboliti
PABA DHFA THFA
PABA = Acid Para-Amino-BenzoicDHFA = Acid Di – Hidro FolicTHFA = Acid Tetra-Hidro-Folic
Sulfonamide Trimetoprim
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Mecanisme de rezistenta
1. Producerea de enzime care distrugsi/sau modifica ABEx. - beta-lactamaze, - enzime care modifica aminoglicozidele2. Scaderea permeabilitatii membranei3. Eflux activ al antibioticului din celula bacteriana4. Modificarea tintelor antibioticelor
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Exemple mecanisme de rezistenta
(1) Producere de enzime care inactiveaza sau distrug antibioticul– Beta-lactamaze
• Principalul mecanism de actiune al antibioticelor beta-lactam
• S.aureus rezistent la penicilina• E.coli rezistent la ampicilina
(2) Producere de enzime care modifica antibioticul– Aminoglicozide, cloramfenicol
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Exemple mecanisme de rezistenta
Enzimele inactivatoare care degradeaza antibioticul efectiv sau il fac inactiv
Enzime blocante carea ataca lanturile laterale ale antibioticului, blocandu-l functionalEx. Unele Beta-lactamaze
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Mecanisme de rezistenta
(3) Pompe de eflux:– universale– specifice
Quinolones, tetracyclines, chloramphenicol
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Mecanisme de rezistenta
(3) Pompe de eflux:
Pompa de eflux = proteina legata de membrana celulara care “pompeaza” antibioticul in afara celulei bacteriene.
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Mecanisme de rezistenta
(4) Modificarea tintelor:
• PLP modificate (SPRP = PRSP engl. = Streptococcus pneumoniae Rezistent la Penicilina)
• PLP nou sintetizate (MRSE, MRSA; transfer orizontal gena mecA)
• Modificari ale ribozomilor (S. pneumoniae rezistent la macrolide)
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Mecanisme de rezistenta
BETA-LACTAMINE
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PLP si beta-lactamazele
Serin proteaze (PLP= Proteine de Legare a Penicilinei) si Metaloenzime (grup tiol care leaga Zn) cu rol de coenzime
Peste 200 enzime diferite (ex.penicilinaze, cefalosporinaze, BLSE, AmpC)
BLSE = Beta-Lactamaze cu Spectru Extins (spectru larg de activitate); codificate plasmidic, pot fi transferate de la un organism la altul
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Mecanism de actiune penicilinaze
Situs-ul de actiune al penicilinazelor
R = lant lateral; la penicilinele naturale este:
Exemple: TEM -1 este o penicilinaza frecvent intalnita la Enterobacterii, activa asupra Penicilinei G si cefalosporinelor cu spectru ingust
Rezistenta la Ampicilina la E. coli este cauzata in majoritatea cazurilor de TEM - 1
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Spatiu periplasmic
1. Beta-lactamaze:Clasa A – serinaClasa B – zincClasa C – serinaClasa D - serina
Membrana interna
Membrana externa
OprM
Mex A
Mex B
3. Pompe de eflux pentru beta-lactamineRezistenta la Pseudomonas aeruginosa
2.Transpeptidaze rezistente la beta-lactamine
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Clasificarea beta-lactamazelor dupa Ambler (criterii moleculare)
Gena ampC cromozomala, cefalosporinaze; PLP inrudite
Enzime care hidrolizeaza oxacilina
Serinproteaze, penicilinaze,BLSE
Metaloenzime, grup tiol care leaga Zn
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PLP, PLP 2’ (sau PLP 2a)
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MECANISME DE REZISTENTA
• Glycopeptide:– Vancomicina– Teicoplanina
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Mecanisme de rezistenta la vancomicina
• Rezistenta intrinseca (pentapetidul se termina cu D-Ala-D-Lac)– Leuconostoc, Lactobacillus, Pediococcus
• Sau cu D-Ala-D-Ser– Enterococcus gallinarum, Enterococcus caselliflavus
• Rezistenta castigata– O ingrosare a stratului de PG si– Modificarea aa terminali de la D-Ala--D-Ala la D-Ala--D-Lac– Gene plasmidice (vanA, B, C, D, G, E), care pot fi transferate de
la un microorganism la altul• Importanta
– VRE - E. faecium, E.faecalis rezistent la Vancomicina– VISA - S.aureus cu sensibilitate intermediara la vancomicina– GISA - S.aureus cu sensibilitate intermediara la glicopeptide– VRSA - S.aureus rezistent la Vancomicina (MIC> 32 g/L; primul
caz clinic, SUA, 2002)
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Vancomicina: mecanisme de rezistenta
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Mecanisme de rezistenta - aminoglicozide
• Modificare enzimatica a antibioticului (mecanismul obisnuit)– Rezistenta de nivel inalt >50 enzymes identificate– Gene codante pentru rezistenta localizate plasmidic – Transfer de gene intre specii
• Reducerea permeabilitatii peretelui celular– Rezistenta la anaerobi (transportul prin membrana
celulara depinde de respiratia aeroba)
• Situsuri de legare ribozomale modificate (rar)– Rezistenta de nivel jos
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Tetraciclinele: mecanisme de rezistenta
• Rezistenta foarte raspandita
• Pompa de eflux dependenta de energie (cel mai frecvent)
• Modificarea tintei ribozomale (protectie ribozomala)
• Modificari enzimatice
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Rezistenta la oxazolidinone
• Mutatie la nivelul ARNr 23S
• Rezistenta rara; rezistenta incrucisata improbabila
• Deoarece ARNr 23S este codificat de mai multe gene
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Macrolide: mecanisme de rezistenta
• Rezistenta intrinseca – macrolidele hidrofobe patrund greu prin membrana externa (bacili G-)
• Rezistenta castigata– Modificare ribozomala– Pompa de eflux– Inactivare enzimatica
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Lincosamide
• Initial izolate din Streptomyces lincolnensis
• Mod de actiune: se leaga de subunitatea ribozomala 50S si blocheaza elongarea
• Rezistenta: metilarea ARNr 23S
• Active pe stafilococi si bacili G- anaerobi
• Nu au activitate pe bacteriile G- aerobe
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Streptogramine
• Clasa de peptide ciclice produse de Streptomyces spp.
• Doua componente care inhiba sinergic sinteza proteinelor (Quinpristindalfopristin)
• Dalfopristina inhiba elongarea lantului peptidic• Quinpristina initiaza eliberarea prematura a
peptidului • Activa pe stafilococi, streptococi si E.faecalis.
Antibiotic de rezerva pentru tratamentul VRE
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Mecanisme genetice de rezistenta
1. Transductie (bacteriofag dependenta)
2. Conjugare (Factor F)
3. Transformare (acizi nucleici liberi)
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Microorganisme rezistente – prescurtari frecvent utilizate
• ERV = VRE engl. = enterococi rezistenti la vancomicina– 70% din E. faecium in SUA (la noi o tulpina importata 2003)
• SAIG = GISA engl. = S. aureus intermediar sensibil la glicopeptide (si la noi, 2002)
• SAIV = VISA engl. = S. aureus intermediar sensibil la vancomicina
• SARV, SERV = VRSA & VRSE = S. aureus si S. epidermidis rezistent la Vancomicina– (MIC> 32 g/L; primul caz clinic descris in 2002 in SUA)
• K. pneumoniae producatoare de BLSE = ESBL producing K.pneumoniae engl. = Klebsiella pneumoniae producatoare de beta-lactamaze cu spectru extins
• SPRP = PRSP engl. = S. pneumoniae rezistent la penicilina
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Microorganisme rezistente la Peniciline – antibiotice de rezerva
• S.aureus rezistent la Penicilina (>95%) - Peniciline sintetice rezistente la beta-lactamaze (Peniciline M: Oxacilina, Cloxacilina etc.)
• K.pneumoniae producatoare de BLSE - Cefalosporine de generatia a IVa, carbapeneme (Problema!!!: KPC, NDM-1 etc.)
• E. coli rezistent la Ampicilina - Cefalosporine• S.pneumoniae rezistent la Penicilina (PLP
modificate) – doze mai mari de Penicilina• SARM, SERM (Noi PLP) - Vancomicina