Download - 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 :
-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.
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 :
-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.
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.