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Antibioticos.

Clasificacin x Mecanismo de accin


1) i sntesis de pared celular
--lactmicos
Cicloserina Vancomicina Bacitracina
Fosfomicina

4) Sntesis y replicacin del DNA

Quinolonas

4) i RNA polimerasa

Rifampicina
DNA

Azoles
PABA
5) Antimetabolitos
Sulfas y
Trimetoprim

THFA

DHFA

Ribosomas

50s

30s

RNAm

3) Sntesis proteica
(Ribos: i 30s)

Aminoglucsidos
Tetraciclnas

Acido Folico
Purinas

2) Membrana celular
Polimixina B
Colistina,
Nistatina y
Anfoteric B

3) Inh Sntesis proteica (Ribos:50s)


-MACRLIDOS-KETLIDOS
-LINCOSAMIDAS

Cloranfenicol y Tianfenicol

ANTIBIOTICOS MACROLIDOS

Bacteriostaticos --- bactericidas.


Eritromicina 1952.
Alternativa en pctes alergicos a penicilina.
Usos: infecciones respiratorias, de piel y tejidos
blandos. ITS (Chlamydia y chancroide), perono
activ N. gonorrhoeae, H. influenza. Px en Ruptura
prematura de membranas (250 mg c/6h x7d o
hasta parto).
PeroAbsorcion G-I erratica, vida corta,
niveles sanguineos bajos e inestabilidad en medio
acido=penicilinas.

2
G
E
N
E
R
A
C
I
O
N
E
S

1 G.

Eritromicina S. erytreus
Oleandomicina S. antibioticus
Carbamicina
Espiramicina S. ambofaciens
Josamicina
Miocamicina

2 G.

Azitromicina
Diritromicina
Claritromicina
Rokytamicina
Roxitromicina

Naturales
BACTERIOSTTICOS
dosis + bacterias en
crecimiento
BACTERICIDAS

Semisinteticos
BACTERICIDAS
Efecto postantibiico prolongado

MACROLIDOS
KETOLIDO$
Telitromicina (Ketex) y Cetromicina
Derivados semisinteticos de eritromicina

Gran actividad contra Neumococo-R a penic


y resto macrolidos.
EPA: 10 h contra Neumococo.
Usos: Neumococo de comunidad,
amigdalitis, bronquitis y otitis media. 400
mg, bid.

MACROLIDOS
Espectro Actividad Anti-microbiana

1ra Generacion =bacteriostaticos


pero dosis bactericidas. Activos xa Gram+.
Sust naturalesActinomycetos.
Pseudomonas y Enterobacterias son resistentes a Macrlidos de 1ra

2da generacion =bactericidas.


Activos Gram+ y algunos Gram- (Azitro y
Claritro). Semisinteticas.
Pseudomonas aun son resistentes a Macrlidos de 2da

Espectro de actividad

Estreptococo

Neumococo

Mycoplasma

Listeria

Cl. tetani.

Cl. perfringes.

Estafilococo ?

2da generacin (Eleccin)

H. influenzae

Chlamydia

Coryn. difteriae

Mycoplasma
pneumoniae

Campylobacter
diarrea

Legionella
Morax. catarralis

Neisseria g. ?

En con diarrea del viajero la Azitromicina es de eleccion

MACROLIDOS

Tienen EPA (Claritro 3v > Eritro)

MEC ACCION: Unen reversible a sitio P de subunidad 50s ribosomal (33


proteinas diferentes y 2 moleculas de ARN).
bloquea transpeptidacion y translocacion y detiene la elongacion de cadena
peptidica.

Antagonismo competitivo!!!

MACROLIDOS
RESISTENCIA
1. Mutacion cromosomica en R ribosomal,
x plasmidos, cruzada. Gram+, Gram-,
Legionella y otros.
2. Impermeabilidad pared bacteriana
(Enterobacteriaceas y S.
epidermidis).

3. Enzimas (esterasas y fosforilasas) q


hidrolisan a macrolidos.
Enterobacteriaceas. Cruzada.
(Ags: 3 enzimas q`acetilan, adenilan y
fosforilan) (cloranfenicol: acetiltransferasa).

MACROLIDOS
FARMACOCINETICA
Eritromicina-base se destruye en medio acido
(Tab cubierta enterica, sales de Eritro: estolato, etilsuccinato, estearato).

2da G.: +resistentes a medio acido. biodisp.

Absorcion retardada por alimentos.


Adm i.v. lactobionato (10 mcg/ml)

PLASMA

Lactobionato IV +++
Macrlidos de 2 G ++
Eritromicina +

Alfa-glicoproteina (40-90%)
Distribuye en tejidos y fluidos

Concentra

Tejido pleural y
sinovial

Eritro desmetilada en higado


(inactiva) orina 5% v.o. y
residuos
15% de parenteral.
Claritro (metab activo y vida
6h). Azitro 40h

plasmaunion proteinas, (alfa-glicoproteina, 40-90%) tejidos y fluidos


corporales +prostata, liquido sinovial y pleural, humores. Placenta
10% y leche materna. SNC incipiente (No Ags, No Tetra, Si Clor).

Eliminacin

Eritrofiltracion
glomerular y reabsorbe
parcialmente en zona
tubular,

bilis 30% y enterohepatica.


Claritromicina es=eritro
Azitro 10% orina y resto x heces.

MACROLIDOS

FARMACOPATOLOGIA
Seguros y eficaces y > 2da generacion.
+++G-intestinal: n-v, ardor epigastrico, diarrea,
regurgitaciones acidas.

I.M. dolorosa.

I.v. tromboflebitis.

Racciones alergicas (raras) exantema,


fiebre, eosinofilia, urticaria.

Superinfecciones por Cndida o Cl. difficile

Cndida

Cl. difficile

MACROLIDOS
FARMACOPATOLOGIA

Eritro: colestasis intraH, inicia en 2-3 sem:


dolores colicos, n-v, fiebre e ictericia, x
hipersensibilidad.

En no Htoxicidad pero, estenosis


hipertrofica de piloro.

Eritro dosis i.v. = ototoxicidad (reversible)

Usos Clnicos
Eleccin en:

Legionella pneumofilica
Campylobacter jejuni
Bordetella pertussis
Corynebacterium diphtheriae
Micoplasma pneumoniae
Chlamydia trachomatis

Alternativas en alergia a
penicilina: infecciones Estrepto y
Estafilo.
-Px fiebre reumatica
-Tx de trepanomatosis.

Traveler's diarrhea: updates for pediatricians


Pediatr Ann. 2008 Dec;37(12):814-20.
Ang JY, Mathur A.
Children who travel are at risk of developing the same illnesses that affect
adult travelers. Treatment, etiology and actual risk of TD in children
are not well defined. Prevention and self-treatment of TD should be
discussed in great detail during pre-travel counseling. This includes
information and instructions on various preventive measures as well as
when to use medications and the potential adverse effects associated
with these medications.
A TD that is mild can be managed effectively by appropriate use of oral
rehydration solutions. Families should be advised to carry ORS
packets and start treatment in children as soon as the diarrhea begins.
Self treatment with antibiotics such as azithromycin may be considered
in children if diarrhea is moderate to severe.
Caregivers should contact local health authorities if there is no
improvement especially after self treatment with antibiotics.

Claritromicina en

MACROLIDOS
PRECAUCIONES
No infecciones graves (Sepsis, osteomielitis).

Contraindicado estolato de Eritro en Enf H.


No asociar alcaloides cornezuelo de centeno
ergotismo con necrosis de extremidades.

ORIGINAL ARTICLE
Azithromycin and the Risk of Cardiovascular Death
Wayne A. Ray, Ph.D., Katherine T. Murray, M.D., Kathi Hall, B.S., Patrick G. Arbogast,
Ph.D., and C. Michael Stein, M.B., Ch.B.
N Engl J Med 2012; 366:1881-1890May 17, 2012

DISCUSSION
We found that a 5-day course of azithromycin was associated with a
small absolute increase in the risk of cardiovascular death, which was
most pronounced for patients in the highest decile of the baseline risk
of cardiovascular disease. There was no increased risk of death from
noncardiovascular causes among patients who took azithromycin, but
there was an increase in the risk of death from any cause. The risk of
cardiovascular death was significantly greater with azithromycin than
with either amoxicillin or ciprofloxacin but did not differ significantly
from the risk with levofloxacin.

LINCOSAMIDAS

Quimicamente diferentes a los macrolidos pero semejantes x: mec


accion, espectro antibacteriano y farmacocinetica.

LINCOSAMIDAS
ESPECTRO ANTIBACTERIANO
Sensibles, =Eritro: Gram+.
No sensibles, Gram- aerobios (C. difficile,
Neisseria, Enterobacter y H. influenza).

Resistentes Enterococos.
+++Anaerobios:
Bacteroides, Fusobacterium, Actinomyces, C.
perfringis, Peptoestreptococos y
Campylobacter.

MEC ACCION
Bacteriostaticas. Unen sitio A de 50s ribosomal=i sintesis
proteica. = cloranf y macrolidos.

Antagonismo competitivo!!!

Mecanismos de resistencia

-x plasmidos = macrolidos, R cruzada.


-5% Estafilococos y 0-10% de B. fragilis son R a clindamicina.

LINCOSAMIDAS
FARMACOCINETICA
CLINDA.
Oral 75% pasa a sangre y es independiente
de alimentos. Palmitato (v.o, 1h 2.8mcg/ml)
y fosfato (i.v. 5mcg/ml).
LINCO, 75% en ayunas y 25% con alimentos.

Atraviesan la placenta
No llegan LCR

LINCOSAMIDAS
FCOPATOLOGIA
Clinda y Linco, 10% diarrea y >colitis
pseudomembranosa (diarrea mucosanguinolenta, dolor abdominal, n-v) C.
difficile (toxina).
i.m.=dolor e i.v.=tromboflebitis.
Rapida=colapso cardio-vascular (K).
Clinda, no Htoxica, pero transaminasas.

Farmacopatologa

Colitis pseudomembranosa

Agrava miastenia gravis

bloqueo neuromuscular de
Aminoglucosidos e i placa
neuromotriz (no juntas)

LINCOSAMIDAS
FARMACOPATOLOGIA

Reacciones alergicas (raras)


erupciones cutaneas, fiebre, urticaria. Eritema
multiforme, anafilaxia, Sd Stevens Johnson.

USOS CLINICOS
Tx germenes
ANAEROBIOS.
+Ags en abscesos, e
infecciones abdominales
severas, peritonitis, EPI.

Alternativa (penicilina) en
osteomielitis x Estaf aureus.
Gardnerella vaginalis
(vaginosis bact)

LINCOSAMIDAS
USOS CLINICOS

Px quirurgica abdominal
Px infecciones estreptococicas
clinda+pirimetamina=encefalitis
x T.gondii (SIDA)
clinda+quinina = Malaria-R /

TELITROMICINA Y CETROMICINA
Derivados
sintticos

Neumococo resistente a
Penicilina y Macrlidos

Usos Clnicos de Telitromicina y Cetromicina


Neumona

Amigdalitis

Bronquitis

Nature Reviews Drug Discovery 9, 260 (April 2010) |


Trial watch: Phase III success for novel Clostridium difficile
antibiotic
Abstract
The results of the second of two Phase III trials evaluating the
macrocyclic antibiotic fidaxomicin (OPT-80, PAR-101), developed by
Optimer Pharmaceuticals, confirm that it is as efficacious as
vancomycin for treating patients with Clostridium difficile infection
(CDI). It is also associated with a lower incidence of recurrence of
CDI.

C difficile organism (National Institutes


of Health)

February 4, 2011 Compared with vancomycin, fidaxomicin (Optimer Pharmaceuticals, Inc)


produces noninferior rates of clinical cure in adults with Clostridium difficile infection. In addition, for
some strains, fidaxomicin is associated with a significantly lower rate of recurrence, according to the
findings of a randomized trial.
Thomas J. Louie, MD, with the University of Calgary, in Calgary, Alberta, Canada, reported the study
findings of the randomized phase 3 trial in the February 3 issue of theNew England Journal of
Medicine.
According to the researchers, fidaxomicin is a macrocyclic antibiotic that is more active in vitro
than vancomycin in clinical isolates of C difficile, including the NAP1/BI/027 strain.
"This activity, in combination with minimal systemic absorption, high fecal concentrations, and limited
activity in vitro and in vivo against components of the normal gut flora, makes fidaxomicin a
promising candidate that may provide highly active but more selective therapy for C.
difficile infection," the study authors write.
The current study included 629 adults with acute symptoms of C difficile infection, with a positive
result on a stool toxin test. Patients were randomly assigned to receive fidaxomicin at a dose of 200
mg twice daily or vancomycin at a dose of 125 mg 4 times daily. Both medicines were taken orally
for 10 days.
Of the patients, 548 (87.1%) could be evaluated for the per-protocol analysis. The rates of clinical
cure with fidaxomicin were noninferior to those observed with vancomycin in both the modified
intent-to-treat analysis (88.2% vs 85.8% with fidaxomicin vs vancomycin, respectively) and the perprotocol analysis (92.1% and 89.8%, respectively).