antibioticos macrolidos - Farmacologia Virtual

Antibioticos. Clasificación x Mecanismo de acción
1) i síntesis de pared celular
--lactámicos
Cicloserina -
Vancomicina -
Bacitracina –
Fosfomicina
Azoles
5) Antimetabolitos
Sulfas y
Trimetoprim
PABA
THFA
DHFA
Acido Folico
Purinas
4) Síntesis y replicación del DNA
DNA
Quinolonas
Ribosomas
50s 30s
2) Membrana celular
Polimixina B
Colistina,
Nistatina y
Anfoteric B
RNAm
4) i RNA polimerasa
Rifampicina
3) Síntesis proteica
(Ribos: i 30s)
Aminoglucósidos
Tetraciclínas
3) Inh Síntesis proteica (Ribos:50s)
-MACRÓLIDOS-KETÓLIDOS
-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), pero…no
activ N. gonorrhoeae, H. influenza. Px en Ruptura
prematura de membranas (250 mg c/6h x7d o
hasta parto).
• Pero…Absorcion G-I erratica, vida ½ corta,
niveles sanguineos bajos e inestabilidad en medio
acido=penicilinas.

2
G
E
N
E
R
A
C
I
O
N
E
S
1º G.
2º G.
Eritromicina S. erytreus
Oleandomicina S. antibioticus
Carbamicina
Espiramicina S. ambofaciens
Josamicina
Miocamicina
Azitromicina
Diritromicina
Claritromicina
Rokytamicina
Roxitromicina
Naturales
BACTERIOSTÁTICOS
↑ dosis + bacterias en
crecimiento
BACTERICIDAS
Semisinteticos
BACTERICIDAS
Efecto postantibióico 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 Macrólidos de 1ra
2da generacion =bactericidas.
Activos Gram+ y algunos Gram- (Azitro y
Claritro). Semisinteticas.
Pseudomonas aun son resistentes a Macrólidos de 2da

Espectro de actividad
Neumococo
Estreptococo Cl. tetani. Cl. perfringes.
Mycoplasma Listeria Estafilococo ?

H. influenzae
2da generación (Elección)
Coryn. difteriae
Legionella
Morax. catarralis
Chlamydia Neisseria g. ?
Mycoplasma
pneumoniae
Campylobacter
diarrea
En ñ 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
Alfa-glicoproteina (40-90%)
Lactobionato IV +++
Macrólidos de 2º G ++
Eritromicina +
Distribuye en tejidos y fluidos Concentra Tejido pleural y
sinovial
Eritro desmetilada en higado
(inactiva) orina 5% v.o. y
15% de parenteral.
Claritro (metab activo y vida
½ 6h). Azitro 40h
residuos
plasma—union 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).

Eritro—filtracion
glomerular y reabsorbe
parcialmente en zona
tubular,
Eliminación
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 Cándida o Cl. difficile
Cándida
Cl. difficile

MACROLIDOS
FARMACOPATOLOGIA
• Eritro: colestasis intraH, inicia en 2-3 sem:
dolores colicos, n-v, fiebre e ictericia, x
hipersensibilidad.
• En ñ no Htoxicidad pero, estenosis
hipertrofica de piloro.
• Eritro dosis i.v. = ototoxicidad (reversible)

Elección en:
– Legionella pneumofilica
– Campylobacter jejuni
– Bordetella pertussis
Usos Clínicos
– 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.

Farmacopatología
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
sintéticos
Neumococo resistente a
Penicilina y Macrólidos

Usos Clínicos de Telitromicina y Cetromicina
Amigdalitis
Bronquitis
Neumonía

• 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).

•