ANTIBIOTICOS. Clasificación x Mecanismo de acción

Presentación del tema: "ANTIBIOTICOS. Clasificación x Mecanismo de acción"— Transcripción de la presentación:

1 ANTIBIOTICOS. Clasificación x Mecanismo de acción
1) inh síntesis de la pared celular --lactámicos : Glucopeptidos: (Vancomicina) Cicloserina Bacitracina Antimic.imidazoles Fosfomicina 4) Inh Síntesis y replicación del DNA Quinolonas 4) Inh RNA polimerasa Rifampicina DNA PABA THFA Ribosomas RNAm 50s 30s 3) Síntesis proteica (Ribos: i 30s) Aminoglucósidos Tetraciclínas 5) Antimetabolitos DHFA Sulfas y Trimetoprim 3) Síntesis proteica (Ribos: i 50s) Macrólidos -Ketólidos Cloranfenicol Lincomicinas Acido Folico Purinas 2) Alt membrana celular Polipeptidos(polimixina B Colistina), Nistatina y Anfoteric B

2 Penicilinas 1929 Alexander Fleming. Penicillium notatum
Estructura química: Todas formadas x núcleo Acido 6-aminopenicilanico (6-APA) unido a un anillo tiazolidinico y a otro B-lactamico, enlazados a una cadena lateral por un enlace amidico. Amidasas

3 ¿De DONDE se OBTIENE? Penicillum Notatum Chrysogenum (Penic G)

4 CLASIFICACION 1. PENICILINAS NATURALES o Bencilpenicilinas
-Cristalina o Penicilinas G: Na y K, -Procaina, -Clemizol, -Benzatinica. -FenoxiPenicilinas: fenoximetilpenicilina o Penicilina V o P. oral y, Propicilina. 2. P. ISOXAZOLICAS o RESISTENTES a la PENICILINASA v.o.: Oxa, cloxacilina, dicloxacilina. Parenteral: oxa, meticilina, flucoxac, nafcilina, temocilina.

5 Aminopenicilinas o P. de AMPLIO ESPECTRO
Ampi, Amoxi, bacampi, cicla y meta. 4. P. ANTIPSEUDOMONAS o CARBOXIP. : Carbenicilina y ticarcilina 5. Ureidopenicilinas o P. 4ta GENERACION o P. ANTIPSEUDOMONAS : azlocilina, mezlocilina, piperacilina, 6. AMIDINOPENICILINAS Mecilinam y pivmecilinam

6 7. INHIBIDORES de BETA-LACTAMASAS -Amoxi250+clavulanato65
7. INHIBIDORES de BETA-LACTAMASAS -Amoxi250+clavulanato65.5 (Curam) o sulbactam; -Ampi+sulbactam; -Pipera+tazobactam; Ticar+clavulanato.

7 GRAM POSITIVOS GRAM NEGATIVOS MEC ACCION. ESTRUCTURA PARED BACTERIANA
mol 1-2 mol Presion intracelular atmosferas Peptidoglicano o mureina, es un heteropolimero conformado por polisacaridos, alternadamente 2 aminoazucares (N-acetil glucosamina y N-acetil muramico).

8 1. Sintesis (fosfomicina y cicloserina); 2.Transporte (bacitracina);
Inhiben Síntesis de pared bacteriana, uniéndose a las PBP. especificamente la Transpeptidacion o 4ta etapa (B-lactamicos, vancom). Etapas: 1. Sintesis (fosfomicina y cicloserina); 2.Transporte (bacitracina); 3. Polimerizacion 4. Transpeptidacion (=cefalosp) PBP en la m.c. Son enzimas (transpeptidasas, carboxipeptidasas, endopeptidasas) encargadas del ensamblaje de los peptidoglicanos. (NAM) (NAG)

9 MECANISMO DE ACCION Ligandose a las PBP1-8 (Proteinas Copuladoras de Penic presentes en la m.c.) son enzimas (transpeptidasas, carboxipeptidasas, endopeptidasas) encargadas del ensamblaje de los peptidoglicanos ----→ provocando la lisis y la formacion de formas alargadas o esferoplastos (Gram-) y protoplastos (Gram+). Ejm.: No ligadura = R Estafilococo aureus y Estreptococo pneumoniae a meticilina y Pen G.

10

11 Tipos de bacterias Bacteria Gram-positiva. 1-membrana citoplasmática,
2-peptidoglicano (pared celular) 3-fosfolípidos, 4-proteínas, 5-ácido lipoteicoico. Bacteria Gram-negativa. 1-membrana citoplasmática (m. interna), 2-espacio periplasmico, 3-membrana exterior, 4-fosfolípidos, 5-peptidoglicano, 6-lipoproteína, 7-proteínas, 8-lipopolisacáridos, 9-porinas. PBP PBP PBP PBP PBP

12 Antibióticos betalactamicos
Enzimas: Constitut (lipasas, proteinasas, oxidasas) RNA polimerasa. Inductivas (penicilinasa, fosfat alcalina), Granulos citoplas (almacenes) Antibióticos betalactamicos 10-25% del peso: Peptidoglicanos, Ac teitoicos y Polisacaridos. ADN y ARN PBP Plásmidos Espacio periplásmico

13 RESISTENCIA a PENICILINA mecanismos:
1. Por enzimas: penicilinasas (B-lactamasas) y amidasas). 2. ▼ de permeabilidad de pared a penic. 3. Alteraciones de las PBP (mutaciones). 4. Tolerancia al efecto del atb. 4 2 3 1

14 Resistencia no genetica o inducida (NO SUCEDE xa Pseudomona.)

15 CLASIFICACION 1. PENICILINAS NATURALES o Bencilpenicilinas :
-Cristalina o Penicilinas G: Na y K, -Procaina, -Clemizol, -Benzatinica. -Fenoximetilpenicilina o Penicilina V o P. oral 2. P. RESISTENTES A PENICILINASA o ISOXAZOLICAS v.o.: Oxa, cloxacilina, dicloxacilina. Parenteral: oxa, meticilina, nafcilina, temocilina. 3. P. de AMPLIO ESPECTRO o Aminopenicilinas : ampi, amoxi, bacampi, cicla y metacilina. 4. P. ANTI PSEUDOMONAS o CARBOXIP: Carbenicilina y ticarcilina 5. P. 4ta GENERACION o Ureidopenicilinas o P.ANTI PSEUDOMONAS: azlocilina, mezlocilina, piperacilina 6. AMIDINOPENICILINAS: mecilinam y pivmecilinam. 7. INHIBIDORES de BETA-LACTAMASAS -Ac. Clavulanico o clavulanato, -sulbactam, -tazobactam

16 1) PENICILINAS NATURALES Espectro antibacteriano
a. Cocos Gram + Streptococo pyogenes E. viridans E. Pneumoniae (excepto enterococos) E. agalactiae Estafilococo dorado. Sensible 90% por primera vez Estafilococo dorado. Sensible 90% por 1ra vez. 16

17 b. Bacilos Gram + Bacillus anthracis Corynebacterium diphteriae
Cocos gram negativos Espiroquetas Clostridium perfringens y tetani (Exc C. difficile) Eubacterias y Lysteria monocitogenes 17

18 1) PENICILINAS NATURALES Espectro antibacteriano. BACTERICIDAS
c. Cocos Gram-: Neisseria meningitidis, N. gonorroheae y veillonella. d. Bacilos Gram- : Bacteroides (excepto B. fragilis). Fusobacterium. Pasteurella multocida, Spirillum minus, Streptobacillus moniliformis. e. Otros: Espiroquetas: Treponemas: pallidum, perteneu y carateum. Leptospiras y Leptorrichia buccalis.

19 PENICILINAS NATURALES son PARENTERALES (EXCEPTO Penic. V)
CLASE DE PREPARADO FUNCIÓN RENAL EDAD Los niveles séricos dependen de: BENCILPENICILINA O PENICILINA G BENCILPENICILINA BENZATÍNICA BENCILPENICILINA G PROCAÍNA BENCILPENICILINA CLEMIZOL BENCILPENICILINA BENZATÍNICA 19

20 1. BENCILPENICILINA O PENICILINA G Na y K (perenteral)
Para casos q necesitan dosis altas (meningitis, celulitis). 4 millones c/4h, U/kg/d. Vida media de 30’ (cateter i.v.)

21 2. BENCILPENICILINA G PROCAINA por c/300.000 U hay120 mg procaina
Accion larga (12-24 h) I.M. Neumonia neumococica no complicada ( U/12 h) Gonococo no Resist (4´ U) Reacción a procaina: ss neurologicos, ansiedad q` desaparece en 5-15 min (no confundir con reacción alérgica a peni).

22 3.Bencilpenicilina clemizol 4. Bencilpenicilina benzatínica
Penicilina G + clemizol = depósito IM cada 12 h. Es un antihistamínico, prolonga la vida ½ de penicilina. 4. Bencilpenicilina benzatínica IM, se obtienen niveles séricos bajos por 3 a 4 sem. Se usa en infecciones de Streptococo del grupo A, Px de fiebre reumática y Tto de sífilis. DOSIS: millones de unidades

23 PENICILINA V o FENOXIMETILPENICILINA o P. ORAL (Megacilina oral)
Resistente a la acidez gastrica. LOS MÁXIMOS NIVELES SÉRICOS SE ALCANZAN DESPUÉS DE 1h con 250 mg. INFECCIONES DE TEJIDOS BLANDOS CAUSADOS POR BACTERIAS INFECCIONES de TEJIDOS BLANDOS CAUSADOS por BACTERIAS sensibles 23

24 CLASIFICACION I. PENICILINAS NATURALES o Bencilpenicilinas :
-Cristalina o Penicilinas G: Na y K, -Procaina, -Clemizol, -Benzatinica. -Fenoximetilpenicilina o Penicilina V o P. oral II. P. ISOXAZOLICAS o RESISTENTES A PENICILINASA v.o.: Oxa, cloxacilina, dicloxacilina. Parenteral: oxa, meticilina, nafcilina, temocilina. III. P. DE AMPLIO ESPECTRO o Aminopenicilinas : ampi, amoxi, bacampi, cicla y metacilina. IV. CARBOXIP O P. ANTI PSEUDOMONAS: Carbenicilina y ticarcilina V. P. 4ta GENERACION o Ureidopenicilinas: azlocilina, mezlocilina, piperacilina y mecilinam. INHIBIDORES DE BETA-LACTAMASAS -Amoxi+clavulanato o sulbactam; -Ampi+sulbactam; -Pipera+tazobactam; Ticar+clavulanato.

25 II. P. ISOXAZOLICAS o RESISTENTES a PENICILINASAS oral: Oxa, cloxa y dicloxa. Parent: Oxa, meti, flucoxa, nafci y temocilina VENTAJA en: RESISTENTE a PENICILINASA !!!! Staphylococcus aureus

26 P. Isoxazolicas NO efectivas en:
Enterococos Neisserias Enterobacterias Temociclina: 1-2 g c/12h SI en enterobacterias

27 Presentaciones uso oral
P. Isoxazolicas: Presentaciones uso oral OXACILINA CLOXACILINA: Máxima concentración en 30 – 60 min. DICLOXACILINA: Nivel máximo 30 – 60 min.

28 Presentaciones parenterales
P. Isoxazolicas Presentaciones parenterales OXACILINA (v.o. también): Máxima concentración en 1 h. Contra S. aureus Gram (+) Penetra LCR Excreción hepática

29 TEMOCILINA (Temopen) Vida media de 5 h.
Ligadura plasmática de 80% (albúminas) Amplia distribución a tejidos Escasa penetración al SNC Meninges inflamadas, aumenta penetración hematomeníngea Gram (-) productores de betalactamasa

30 3. PENICILINAS de AMPLIO ESPECTRO Aminopenicilinas: Ampi, amoxi, bacampi, cicla y metacilina.

31 SON ACTIVAS CONTRA: NINGUNA es RESISTENTE a la PENICILINASA
BACILOS GRAMNEGATIVOS BACILOS GRAMPOSITIVOS NINGUNA es RESISTENTE a la PENICILINASA INEFICIENTES PARA: La > de estafilococos Pseudomonas Algunas bacterias entéricas

32 AMPICILINA y AMOXICILINA
Haemophilus Influenza B Enterococcus Proteus mirabilis ACTIVIDAD CONTRA S. typhi Shigella Listeria m. E. coli

33 AMPICILINA Se administran por vía: Vía Oral Vía Parenteral

34 Alcanza niveles terapéuticos en varios tejidos como:
Oído Medio LCR Senos paranasales Bilis Peritoneo Pleura Pulmones Aparato genitourinario Articulaciones

35 Se excreta en un 75% por el riñón.
Niveles séricos máximos se alcanzan entre 20 a 64 min después de la adm de 500 mg.

36 Tiene el mismo espectro que la ampicilina pero con algunas ventajas:
AMOXICILINA Tiene el mismo espectro que la ampicilina pero con algunas ventajas: Mejor absorción gastrointestinal Mayores niveles séricos Esquema de dosis más conveniente, cada 8 h (Ampi c/6). Su excreción puede verse retardada con la administración de probenecid. Produce menos diarrea

37 Amoxicilina. Antibiotico v. o. de 1ra línea (
Amoxicilina. Antibiotico v.o. de 1ra línea (?) para el tratamiento de infecciones: Otitis Media Infecciones Genitourinaria Salmonelosis

38 se absorbe rápidamente por v.o, biodisponibilidad del 93%
Se liga a las proteínas séricas en un 20% aprox. Su vida ½ es de 61,3 min Los niveles séricos de amoxicilina pueden ser detectados hasta 8 h después de v.o.

39 AMOXICILINA Espectro = q` Ampi
Ventajas: mejor absorcion, niveles sericos, dosis c/8h. < diarrea. En: Infecciones genito-urinarias, salmonellosis, otitis media y bronquitis. Dosis: mg c/8h

40 4. CARBOXIP. o P. ANTI-PSEUDOMONAS Carbenicilina y Ticarcilina
Gram-: P. aeruginosa, enterococos, enterobacteriaceas y anaerobios. No actua contra Staphyl productor de B-lactamasas. CARBENICILINA (Geopen) Existe R de Citrobacter, Kliebsiella y Pseudomona. Asociar aminoglocosido, No juntos x inactivacion farmacologica. Alto contenido en Na. TICARCILINA (Ticarpen) =a carbenicilina pero + activa contra P. aeruginosa

41 5. UREIDOP. o P. de 4ta generación (Gram-)
Azlocilina Piperacilina Mezlocilina

42 Activas contra Gram-, Enterob:
Klebsiellas Pseudomonas E. coli Serratia Proteus Enterobacter Citrobacter Yersinia

43 Activas too: Neisserias Enterococos Anaerobios

44 4ta G, Resistentes: Staphylococos-R y H. influenzae.
Estafilococos H. influenzae Emergencia de cepas R. +aminoglucosidos.

45 6. AMIDINO-PENICILINAS. MECILINAM y PIVMECILINAM (oral)
Penicilina Semisintética util contra Gram (-) enterobactereas Resistencia intrínseca de Pseudomona Para IVU (vo. 400 mg bid x 5-7 d) y fiebre tifoidea. Preferida despues de Nitrofur y fosfomicina xa el Tto de IVU no-compl Se administra: 5-10 mg/kg de peso i.v. lenta

46 PENICILINAS FARMACOPATOLOGIA
Hipersensibilidad o alergia: Común. Reacciones cruzadas entre todas y con cefalosporinas. <con orales q` parenterales. Reacciones cutaneas no urticariales. +con ampi x infeccion viral concurrente (mononucleosis infecciosa) u otros factores no inmunologicos.

47 FARMACOPATOLOGIA a) Reacciones de tipo inmediato:(0.2%). Urticaria, edema angioneurotico, anafilaxia, broncoespasmo. b) Reacciones tardias (5%): Fiebre, eosinofilia, enfermedad del suero, dermatologicas eritema-dermatitis exfoliativa, Sd St Johnson. Fenomenos autoinmunes: vasculitis y anemia hemolitica, Coombs +.

48 Drug Fever Ruchi A. Patel, Pharm.D.; Jason C. Gallagher, Pharm.D. Pharmacotherapy. 2010;30(1):57-69 Many antibiotics are associated with a relatively high frequency of drug fever, particularly the β-lactams.[75, 76] One group of authors conducted a review of drug fever induced by antibiotics at their institution.[75] In this study, drug fever was defined as a temperature of 99.5°F or above that lasted for more than 2 days during treatment with an antibiotic, the fever was associated with neither other clinical manifestations nor laboratory findings suggestive of an infectious etiology, the fever could not be ascribed to any other measures, and the fever subsided after cessation of a suspected antibiotic. This study evaluated 390 patients who received parenteral antibiotics for more than 7 days for the treatment of pulmonary infections. A total of 56 episodes of drug fever were noted in 51 (13%) of the 390 patients. The frequency was highest in patients who received piperacillin (17%) followed by the cephalosporins cefotaxima (15%), ceftizoxime (14%), cefapirina (10%), and cefuroxime (8%). Drug fever induced by non–β-lactam antibacterials was rarely implicated. Eosinophilia developed in 25% of patients, and rash occurred in only 5% of patients with drug fever. Of 90 evaluable patients, 26 (28.9%) developed drug fever with or without rash to β-lactam antibiotics. The frequency was highest for piperacillin (35.5%), followed by imipenem cilastatina (25%), then mezlocillin (16.7%). The mean ± SD onset to drug-induced fever was 10.1 ± 5.4 days. As a group, patients receiving penicillins had a higher frequency of drug fever than those receiving cephalosporins. This study concluded that piperacillin, mezlocillin, and imipenem cilastatina are associated with increased frequency of allergic reactions including drug fever in patients with cystic fibrosis.

49 REACCIONES HEMATOLOGICAS
FARMACOPATOLOGIA REACCIONES HEMATOLOGICAS Granulocitopenia (revierte) Inhibicion de agregacion plaquetaria (P. anti-pseudomonas)→sangrado. Leucopenia (+ultima generacion) RIÑON Nefritis intersticial (eosinofilos y eritrocitos) +meticilina.

50 SISTEMA NEUROMUSCULAR
FARMACOPATOLOGIA HIGADO ↑TGO, TGP (reversible) +oxacilina y carbenicilina SISTEMA NEUROMUSCULAR Mioclonias y convulsiones

51 FARMACOPATOLOGIA OTRAS: Orales: n-v, diarrea.
Superinfecciones (C. difficile y Candidas) Reaccion Herxheimer. Sifilis (fiebre, hipotension, dolores osteomusculares). I.M. complicaciones locales (dolor y abscesos).

52 PENICILINAS INTERACCIONES MEDICAMENTOSAS
1. Con bacteriostaticos (eritromicinas, tetraciclinas, cloranfenicol y sulfas). 2. Sinergismo de suma (misma familia) y Sinergismo de potenciacion (otras flias, aminoglucosidos). 3. Con inhibidores de B-lactamasas (IBL) (clavulanato, sulbactam y tazobactam).

53 PENICILINAS INTERACCIONES MEDICAMENTOSAS
4. Con anticoagulantes potencian efecto de éstos y riesgo de hemorragias. 5. Con probenecid Interfiere en mec de eliminacion renal, vida ½ plasmatica de penicilinas, conc sericas./

54

55

56 Treatment of breast infection
J Michael Dixon, professor of surgery and consultant surgeon et al: March 2010 Which micro-organisms are implicated? An up to date retrospective case series shows that during lactation the most common organism responsible is Staphylococcus aureus, including strains of meticillin resistant S aureus (MRSA), particularly if the infection was acquired in hospital. Other organisms responsible include streptococci and Staphylococcus epidermidis. Organisms responsible for non-lactating breast infections include bacteria commonly associated with skin infections but also include Enterococcus and anaerobic bacteria such as Bacteroides spp and anaerobic streptococci.8 Patients with recurrent breast abscesses have a higher incidence of mixed flora (20.5% in those with recurrence v 8.9% with a single episode), including anaerobic organisms (4.5% v 0%). How to treat mastitis Guidelines from the WHOand numerous reviews of the condition recommend treating lactating women with mastitis by prescribing appropriate oral antibiotics and encouraging milk flow from the engorged segment (by continuation of breast feeding or use of a breast pump). Such measures reduce the rate of abscess formation and thereby relieve symptoms. A Cochrane review found only one reported randomised trial of antibiotic treatment versus breast emptying alone conducted among women with lactational mastitis that showed faster clearance (mean 2.1 v 4.2 days) of symptoms in women using antibiotics. Oral antibiotics are usually sufficient, and only rarely do patients with sepsis require hospital admission and intravenous antibiotics. Lactating infection can be treated by flucloxacillin, co-amoxiclav, or a macrolide such as erythromycin or clarithromycin (in patients who are allergic to penicillin), given for at least 10 days. Tetracycline, ciprofloxacin, and chloramphenicol should not be used to treat lactating breast infection because these drugs can enter breast milk and harm the baby. If the pus is very thick and cannot be aspirated through a 21 gauge needle, then having waited for local anaesthetic to be effective, a larger gauge needle may be advanced through the skin and breast tissue into the cavity. The pus is diluted with local anaesthetic and adrenaline, after which this is aspirated. We find that using a combination of lidocaine and adrenaline in solution reduces pain and minimizes bleeding and subsequent bruising. Irrigation is continued until all the pus is aspirated and the fluid used to irrigate comes back clear. The net effect of this procedure is to control pain by a combination of providing local anaesthesia and reducing the pressure within the abscess cavity by aspirating all the pus. We send a sample of pus to the microbiology department for culture and continue appropriate oral antibiotics and analgesia until the abscess resolves. We review the patient every two to three days and repeat aspiration under ultrasound guidance if fluid is present in the abscess cavity. We continue with this approach until no further fluid is visible in the abscess cavity or the fluid aspirated does not contain pus. Few abscesses require more than two to three aspirations, although very large collections may require more. Characteristically, the fluid aspirated changes from pus to serous fluid and then to milk over a few days. Most abscesses in lactating breasts can be managed successfully in this manner. Breast feeding after breast infection Although women are encouraged to continue breast feeding after treatment of mastitis or an abscess, it may be difficult to do so from the affected side. If the infant cannot relieve breast fullness during nursing, the woman may use hand expression or a breast pump to encourage and maintain milk flow until breast feeding can resume. Although most women are able to continue breast feeding even if they have excoriation of the nipple and pain, a few experience continuous and disabling pain. If after discussion a woman chooses to stop breast feeding so that the breast infection can be controlled and the breast can heal, lactation can be suppressed using cabergoline. Which antibiotic is best? We recommend treating non-lactating and skin associated breast infections with amoxicillin and clavulanic acid or, if the patient is allergic to penicillin, a combination of erythromycin and metronidazole. Managing abscesses Non-lactating abscesses are managed in a similar way to lactating breast abscesses by aspiration or mini-incision and drainage combined with appropriate oral antibiotics. Recurrence is common after resolution of central or subareolar non-lactating abscesses because the underlying pathology in the central ducts often persists. Patients with recurrent disease require definitive surgery in the form of total duct excision to remove the diseased ducts and stop the cycle of recurrent infection. Conclusion The management of breast infection has changed and doctors in primary and secondary care should be aware of current protocols and management pathways. Breast infection is common and most cases resolve with antibiotics. Urgently refer any patient whose infection does not settle rapidly after one course of appropriate antibiotics to minimize the associated morbidity. Delay in referral or instituting inappropriate antibiotic treatment can have serious consequences, with loss of large volumes of breast tissue and substantial asymmetry (fig 8⇓). Such a result has potential medicolegal consequences in modern medicine.

57 PENICILINAS DE AMPLIO ESPECTRO b. Mecilinam (Selecidim)
Util contra Enterobacteriaceas Resistencia intrinsica de Pseudomonas Preferida en IVU y F. tifoidea 5-10 mg/Kg, I.V.

58 