4.2. Penicilinas

ANTIBIOTICOS. Clasificación x Mecanismo de acción

50s 30s

1) i síntesis de la pared celular 4) Síntesis y replicación del DNA

Quinolonas

2) Alt membrana celular

4) i RNA polimerasa

Rifampicina

5) Antimetabolitos3) Síntesis proteica (Ribos: i 30s)

Aminoglucósidos

Tetraciclínas

3) Síntesis proteica (Ribos: i 50s)

Macrólidos -Ketólidos

Cloranfenicol

Lincomicinas

Polipeptidos(polimixina B Colistina), Nistatina y Anfoteric B

--lactámicos : Glucopeptidos: (Vancomicina) Cicloserina Bacitracina Antimic.imidazoles Fosfomicina

Sulfas y Trimetoprim

PABA

THFA

DHFA

Acido Folico

Purinas

DNA

RNAmRibosomas

Penicilinas

Estructura quimica:

Todas formado por

nucleo Acido 6-

aminopenicilanico (6-

APA) unido a un anillo

tiazolidinico y a otro

B-lactamico,

enlazados a una

cadena lateral por un

enlace amidico.

1929

Alexander Fleming.

Penicillium notatum

Amidasas

¿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. AMIDINOPENICILINASMecilinam y pivmecilinam

INHIBIDORES DE BETA-LACTAMASAS

-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

Peptidoglicano o mureina, es un heteropolimero

conformado por polisacaridos, alternadamente 2

aminoazucares (N-acetil glucosamina y N-acetil

muramico).

Presion

intracelular

20-25

atmosferas

(NAM)

(NAG)

Inhiben Sintesis de pared bacteriana,

especificamente la Transpeptidacion o 4ta etapa (B-

lactamicos, vancom). Etapas:

1. Sintesis (fosfomicina y cicloserina);

2.Transporte (bacitracina);

3. Polimerizacion

4. Transpeptidacion (=cefalosp)

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 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

PBPPBP

PBPPBP

2

Antibióticos

betalactamicos

PBP

RESISTENCIA A PENICILINA

mecanismos:

1. Por enzimas: 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.

1

2

3

4

Resistencia no genetica o inducida(NO SUCEDE XA P.)

CLASIFICACIONI. PENICILINAS NATURALES o Bencilpenicilinas :


-Procaina,

-Clemizol,

-Benzatinica.

-Fenoximetilpenicilina o Penicilina V o P. oral

II. P. RESISTENTES A PENICILINASA o ISOXAZOLICAS


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.


-Amoxi+clavulanato o sulbactam;

-Ampi+sulbactam;


COCOS GRAM +

Streptococo

pyogenesE. agalactiae E. viridans E. Pneumonia

(excepto enterococos

Estafilococo dorado.

Sensible 90% por 1ra

vez.

I) PENICILINAS NATURALES

Espectro antibacteriano

BACILOS GRAM +

Bacillus anthracis Corynebacterium diphteriae

Clostridium perfringens

y tetani (Exc C. difficile)

Eubacterias y

Lysteria monocitogenes

• Cocos Gram-

• Espiroquetas

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)

Los niveles séricos

dependen de:

•CLASE DE

PREPARADO

•FUNCIÓN RENAL

•EDAD

•BENCILPENICILINA O PENICILINA G

•BENCILPENICILINA G PROCAÍNA

•BENCILPENICILINA CLEMIZOL

•BENCILPENICILINA BENZATÍNICA

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 U—120 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).

• Penicilina G + clemizol = depósito

• IM cada 12 h.

• Es un antihistamínico, prolonga la vida ½ de penicilina.

3.Bencilpenicilina clemizol

• IM, se obtienen niveles séricos bajos por 3 a 4 sem.

• Se usa en infecciones de estreptococo del grupo A, Pxde fiebre reumática y Tto de sífilis.

• DOSIS: 1.2 - 2.4 millones de unidades

4. Bencilpenicilinabenzatínica

PENICILINA V o FENOXIMETILPENICILINA o P.

ORAL (Megacilina oral)

LOS MÁXIMOS

NIVELES SÉRICOS SE

ALCANZAN DESPUÉS

DE 1h con 250 mg.

INFECCIONES

DE TEJIDOS

BLANDOS

CAUSADOS

POR

BACTERIAS

sensibles

Resistente a la acidez gastrica.

CLASIFICACIONI. PENICILINAS NATURALES o Bencilpenicilinas :


-Procaina,

-Clemizol,

-Benzatinica.

-Fenoximetilpenicilina o Penicilina V o P. oral

II. P. ISOXAZOLICAS o RESISTENTES A PENICILINASA


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.


-Amoxi+clavulanato o sulbactam;

-Ampi+sulbactam;


VENTAJA

Staphylococcus aureus

RESISTENTE A

PENICILINASA !!!!

II. P. ISOXAZOLICAS O

RESISTENTES A PENICILINASASoral: Oxa, cloxa y dicloxa.

Parent: Oxa, meti, flucoxa, nafci y temocilina

NO efectivas en:

• Enterococos

• Neisserias

• Enterobacterias

Temociclina: 1-2 g c/12h

SI enterobacterias

OXACILINA

CLOXACILINA:

• Máxima concentración

en 30 – 60 min.

DICLOXACILINA:

•Nivel máximo 30 – 60 min.

OXACILINA (v.o. también):

• Máxima concentración en 1 h.

•Contra S. aureus

•Gram (+)

•Penetra LCR

•Excreción hepática

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

3. PENICILINAS DE AMPLIO

ESPECTRO

Aminopenicilinas: Ampi, amoxi, bacampi,

cicla y metacilina.

SON

ACTIVAS

CONTRA:

BACILOS

GRAMNEGATIVOS

BACILOS

GRAMPOSITIVOS

INEFICIENTES

PARA:

La > de estafilococos

Pseudomonas

Algunas bacterias entéricas

NINGUNA ES

RESISTENTE A

LA PENICILINASA

AMPICILINA y AMOXICILINA

ACTIVIDAD

CONTRA

Proteus mirabilis

Haemophilus Influenza B

Enterococcus

Listeria m.

S. typhi Shigella

E. coli

AMPICILINA

Se administran

por vía:

Vía ParenteralVía Oral

Alcanza niveles terapéuticos en varios

tejidos como:

LCR

Senos paranasales

Bilis

Peritoneo

Aparato

genitourinarioArticulaciones

PulmonesPleura

Oído

Medio

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.

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.

Su excreción puede verse retardada con la

administración de probenecid.

Produce menos diarrea

Amoxicilina. Antibiotico v.o.

de 1ra línea (?) para el

tratamiento de infecciones:

Salmonelosis

Otitis Media

Infecciones

Genitourinaria

Su vida ½

es de 61,3

min

Se liga a las

proteínas

séricas en un

20% aprox.

Los niveles séricos de amoxicilina

pueden ser detectados hasta 8 h después

de v.o.

se absorbe rápidamente por

v.o, biodisponibilidad del 93%

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. ANTI-

PSEUDOMONASCarbenicilina 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

generación (Gram-)

Azlocilina

Mezlocilina

Mecilinam

Piperacilina

Klebsiellas Pseudomonas E. coli Serratia

Proteus Enterobacter Citrobacter Yersinia

Activas contra Gram-, Enterob:

Enterococos

Anaerobios

Neisserias

•Activas too:

Estafilococos

H. influenzae

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

Emergencia de cepas R. +aminoglucosidos.

6. AMIDINO-PENICILINAS.

MECILINAM y PIVMECILINAM (oral)

Penicilina Semisintética

util contra

Gram (-) enterobactereas

Resistencia

intrínseca

de Pseudomona

Se administra:

5-10 mg/kg de peso

i.v. lenta

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

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 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.

FARMACOPATOLOGIA

REACCIONES HEMATOLOGICAS

• Granulocitopenia (revierte)

• Inhibicion de agregacion plaquetaria (P. anti-pseudomonas)—sangrado.

• Leucopenia (+ultima generacion)

RIÑON

• 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

½ 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 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.

4.2. Penicilinas

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