ANTIBIOTICOS.

Clasificacin x Mecanismo de accin

1) i sntesis de la pared celular
4) Sntesis y replicacin del DNA

--lactmicos : Glucopeptidos:
(Vancomicina) Cicloserina Bacitracina Antimic.imidazoles Fosfomicina 5) Antimetabolitos Sulfas y Trimetoprim

Quinolonas

4) i RNA polimerasa

Rifampicina
DNA PABA THFA
Ribosomas

RNAm

DHFA

50s

30s

3) Sntesis proteica (Ribos: i 30s)

Aminoglucsidos Tetraciclnas

Acido Folico Purinas 2) Alt membrana celular Polipeptidos(polimixina B Colistina), Nistatina y Anfoteric B

3) Sntesis proteica (Ribos: i 50s)

Macrlidos -Ketlidos Cloranfenicol Lincomicinas

Penicilinas
Amidasas

1929 Alexander Fleming. Penicillium notatum Estructura quimica: Todas formado por nucleo Acido 6aminopenicilanico (6APA) unido a un anillo tiazolidinico y a otro B-lactamico, enlazados a una cadena lateral por un enlace amidico.

DE DONDE SE OBTIENE?

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 PENICILINASA v.o.: Oxa, cloxacilina, dicloxacilina. Parenteral: oxa, meticilina, flucoxac, nafcilina, temocilina.

3. AMINOPENICILINAS o P. DE AMPLIO ESPECTRO

Ampi, amoxi, bacampi, cicla y heta.

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

INHIBIDORES DE BETALACTAMASAS -Amoxi250+clavulanato65.5 (Curam) o sulbactam; -Ampi+sulbactam; -Pipera+tazobactam; Ticar+clavulanato.

MEC ACCION. ESTRUCTURA PARED BACTERIANA

GRAM NEGATIVOS

GRAM POSITIVOS

50-100 mol

1-2 mol

Presion intracelular 20-25 atmosferas

Peptidoglicano o mureina, es un heteropolimero conformado por polisacaridos, alternadamente 2 aminoazucares (N-acetil glucosamina y N-acetil muramico).

Inhiben Sintesis de pared bacteriana, especificamente la Transpeptidacion o 4ta etapa (Blactamicos, vancom). Etapas: 1. Sintesis (fosfomicina y cicloserina); 2.Transporte (bacitracina); 3. Polimerizacion 4. Transpeptidacion (=cefalosp)

(NAM) (NAG)

MECANISMO DE ACCION
Ligandose a las PBP1-8 (Proteinas Copuladoras de P presentes en m.c.) provocando la lisis y la formacion de formas alargadas o esferoplastos.
Ejm.: No ligadura = R Estafilococo aureus y Estreptococo pneumoniae a meticilina y Pen G.

Tipos de bacterias
Bacteria Gram-positiva. 1-membrana citoplasmtica, 2-peptidoglicano (pared celular) 3-fosfolpidos, 4-protenas,
PBP PBP PBP

5-cido lipoteicoico.

Bacteria Gram-negativa.

PBP PBP

1-membrana citoplasmtica (m. interna), 2-espacio periplasmico, 3-membrana exterior, 4-fosfolpidos, 5peptidoglicano, 6-lipoprotena, 7protenas, 8-lipopolisacridos, 9porinas.

Antibiticos betalactamicos

PBP

RESISTENCIA A PENICILINA mecanismos:

1. Por enzimas:
4

penicilinasas (B-lactamasas) y amidasas).

2. Disminucion de permeabilidad de pared a penic. 3. Alteraciones de las PBP (mutaciones). 4. Tolerancia al efecto del atb.

Resistencia no genetica o inducida

(NO SUCEDE XA P.)

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. RESISTENTES A PENICILINASA o ISOXAZOLICAS v.o.: Oxa, cloxacilina, dicloxacilina. Parenteral: oxa, meticilina, nafcilina, temocilina.
III. P. DE AMPLIO ESPECTRO O AMINOPENICILINAS : ampi, amoxi, bacampi, cicla y metacilina. IV. P. ANTI PSEUDOMONAS o CARBOXIP: Carbenicilina y ticarcilina V. P. ANTI PSEUDOMONAS o P. 4ta GENERACION o UREIDOPENICILINAS: azlocilina, mezlocilina, piperacilina VI. AMIDINOPENICILINAS: mecilinam y pivmecilinam. INHIBIDORES DE BETA-LACTAMASAS -Amoxi+clavulanato o sulbactam; -Ampi+sulbactam; -Pipera+tazobactam; Ticar+clavulanato.

I) PENICILINAS NATURALES Espectro antibacteriano COCOS GRAM +

Streptococo pyogenes

E. agalactiae

E. viridans

E. Pneumonia (excepto enterococos

Estafilococo dorado. Sensible 90% por 1ra vez.

BACILOS GRAM +

Bacillus anthracis

Corynebacterium diphteriae

Cocos Gram Espiroquetas

Clostridium perfringens y tetani (Exc C. difficile) Eubacterias y Lysteria monocitogenes

I) PENICILINAS NATURALES Espectro antibacteriano

4. Bacilos Gram- : Bacteroides (excepto B. fragilis). Fusobacterium. Pasteurella multocida, Spirillum minus, Streptobacillus moniliformis. 5. Otros: Treponemas: pallidum, perteneu y carateum. Leptospiras y Leptorrichia buccalis. 3. Cocos Gram-: Neisseria meningitidis, N. gonorroheae y veillonella.

PENICILINAS NATURALES SON PARENTERALES (EXCEPTO Penic. V)

CLASE DE PREPARADO FUNCIN RENAL EDAD

Los niveles sricos dependen de:

BENCILPENICILINA O PENICILINA G
BENCILPENICILINA G PROCANA

BENCILPENICILINA CLEMIZOL
BENCILPENICILINA BENZATNICA

1. BENCILPENICILINA O PENICILINA G Na y K (perenteral) Para casos q necesitan dosis altas (meningitis, celulitis). 4 millones c/4h, 50.000-300.000 U/kg/d. Vida media de 30 (cateter i.v.)

2. BENCILPENICILINA G PROCAINA c/300.000 U120 mg procaina

Accion larga (12-24 h) I.M. Neumonia neumococica no complicada (500.000 U/12 h) Gonococo no R (4,000.000 U) Reaccion a procaina: ss neurologicos, ansiedad q` desaparece en 5-15min (no confundir con reaccion
alergica a peni).

3.Bencilpenicilina clemizol

Penicilina G + clemizol = depsito IM cada 12 h. Es un antihistamnico, prolonga la vida de penicilina.

4. Bencilpenicilina benzatnica

IM, se obtienen niveles sricos bajos por 3 a 4 sem. Se usa en infecciones de estreptococo del grupo A, Px de fiebre reumtica y Tto de sfilis. DOSIS: 1.2 - 2.4 millones de unidades

PENICILINA V o FENOXIMETILPENICILINA o P. ORAL (Megacilina oral)

Resistente a la acidez gastrica.

LOS MXIMOS NIVELES SRICOS SE ALCANZAN DESPUS DE 1h con 250 mg.

INFECCIONES DE TEJIDOS BLANDOS CAUSADOS POR BACTERIAS sensibles

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.

II. P. ISOXAZOLICAS O RESISTENTES A PENICILINASAS

oral: Oxa, cloxa y dicloxa. Parent: Oxa, meti, flucoxa, nafci y temocilina
VENTAJA

RESISTENTE A PENICILINASA !!!!

Staphylococcus aureus

NO efectivas en:
Enterococos

Neisserias
Enterobacterias

Temociclina: 1-2 g c/12h

SI enterobacterias

OXACILINA CLOXACILINA: Mxima concentracin en 30 60 min.

DICLOXACILINA:
Nivel mximo 30 60 min.

OXACILINA (v.o. tambin): Mxima concentracin en 1 h. Contra S. aureus

Gram (+)
Penetra LCR Excrecin heptica

TEMOCILINA (Temopen)
Vida media de 5 h.
Ligadura plasmtica de 80% (albminas) Amplia distribucin a tejidos Escasa penetracin al SNC Meninges inflamadas, aumenta penetracin hematomenngea Gram (-) productores de betalactamasa

3. PENICILINAS DE AMPLIO ESPECTRO

Aminopenicilinas: Ampi, amoxi, bacampi,
cicla y metacilina.

BACILOS GRAMNEGATIVOS

SON ACTIVAS CONTRA:

BACILOS GRAMPOSITIVOS

NINGUNA ES RESISTENTE A LA PENICILINASA

INEFICIENTES PARA:

La > de estafilococos Pseudomonas Algunas bacterias entricas

AMPICILINA y AMOXICILINA
Haemophilus Influenza B Enterococcus Proteus mirabilis

ACTIVIDAD CONTRA
S. typhi
Shigella

Listeria m.

E. coli

AMPICILINA
Se administran por va:

Va Oral

Va Parenteral

Alcanza niveles teraputicos en varios tejidos como:

Odo LCR Senos paranasales Bilis

Medio

Pleura

Pulmones Articulaciones

Peritoneo Aparato genitourinario

Se excreta en un 75% por el rin.

Niveles sricos mximos se alcanzan entre 20 a 64 min despus de la adm de 500 mg.

AMOXICILINA
Tiene el mismo espectro que la AMPICILINA pero con algunas ventajas:

Mejor absorcin gastrointestinal

Mayores niveles sricos Esquema de dosis ms conveniente, cada 8 h. Su excrecin puede verse retardada con la administracin de probenecid.

Produce menos diarrea

Amoxicilina. Antibiotico v.o. de 1ra lnea (?) para el tratamiento de infecciones:

Otitis Media

Infecciones

Salmonelosis

Genitourinaria

se absorbe rpidamente por v.o, biodisponibilidad del 93%

Se liga a las protenas sricas en un 20% aprox.

Su vida es de 61,3 min

Los niveles sricos de amoxicilina pueden ser detectados hasta 8 h despus de v.o.

AMOXICILINA
Espectro = q` Ampi

Ventajas: mejor absorcion, niveles sericos, dosis c/8h. < diarrea.

En: Infecciones genito-urinarias, salmonellosis, otitis media y bronquitis. Dosis: 250-500 mg c/8h

4. CARBOXIP. o P. ANTIPSEUDOMONAS
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

5. UREIDOP. o P. de 4ta generacin (Gram-)

Azlocilina

Piperacilina
Mezlocilina
Mecilinam

Activas contra Gram-, Enterob:

Klebsiellas

Pseudomonas

E. coli

Serratia

Proteus

Enterobacter

Citrobacter

Yersinia

Activas too:

Neisserias

Enterococos

Anaerobios

4ta G, Resistentes: Staphylococos-R y H. influenzae.

Estafilococos

H. influenzae

Emergencia de cepas R. +aminoglucosidos.

6. AMIDINO-PENICILINAS. MECILINAM y PIVMECILINAM (oral)

Penicilina Semisinttica util contra Gram (-) enterobactereas

Resistencia intrnseca 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

PENICILINAS

FARMACOPATOLOGIA
Hipersensibilidad o alergia: Comun. Reacciones X entre todas y Cefalosporinas. <con orales q` parenterales.

Reacciones cutaneas no urticariales. +ampi x infeccion viral concurrente (mononucleosis

infecciosa) u otros factores no inmunologicos.

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 +.

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 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 99.5F 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 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 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.

FARMACOPATOLOGIA
REACCIONES HEMATOLOGICAS

Granulocitopenia (revierte) Inhibicion de agregacion plaquetaria (P. anti-pseudomonas)sangrado. Leucopenia (+ultima generacion) RION Nefritis intersticial (eosinofilos y eritrocitos) +meticilina.

FARMACOPATOLOGIA
HIGADO

TGO, TGP (reversible) +oxacilina y carbenicilina

SISTEMA NEUROMUSCULAR

Mioclonias y convulsiones

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).

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).

PENICILINAS

INTERACCIONES MEDICAMENTOSAS

4. Con anticoagulantes
potencian efecto de estos y riesgo de hemorragias.

5. Con probenecid
Interfiere en mec de eliminacion renal, vida plasmatica de penicilinas, conc sericas./

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 nonlactating 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.