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Agentes antimicrobianos,
Los antibióticos, sulfonamidas yantimicóticos
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Antibioticos
defin ic ión
Son sustancias antibacterianas producidas por varias especies de microorganismos (bacterias, hongos
actinomicetos) que suprimen el crecimiento de otros microorganismos.
El uso común a menudo se extiende a los antibióticos a largo plazo para incluir a los agentes antimicrobianos
sintéticos, tales como sulfonamidas y quinolonas
El primer antibiótico de ser descubierto fue la penicilina, un producto natural de moho
Penicillium. Innumerables productos microbianos se han investigado desde entonces
Antibióticos semi-sintéticos: antibióticos naturales modificados
¿Por qué modificar? Ellos se modifican en un intento de:
aumentar los efectos beneficiosos
minimizar los efectos indeseables
aumentar la solubilidad
aumentar la estabilidad
mejorar la farmacocinética (es decir, una distribución más amplia y más larga vida media)
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BACTERIOSTÁTICAOS FRENTEMEDICAMENTOS BACTERICIDAS
Agentes bacteriostáticos inhiben la replicación celularbacteriana, pero requieren factores inmunes delhuésped para eliminar la infección, mientras que losagentes bactericidas matan las bacterias.
Si se suprime la inmunidad del huésped o la infecciónestá en un área de vigilancia inmunológica pobre, losagentes bacteriostáticos pueden no ser tan eficacescomo agentes bactericidas.
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CONCENTRACIÓN INHIBITORIA MÍNIMA (CIM)
La concentración más baja de antibiótico queinhibe el crecimiento bacteriano.
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SINERGISMO VERSUS ANTAGONISMO
Sinergismo drogas se produce cuando los medicamentospueden interactuar en formas que mejoran o magnifican uno omás efectos, o efectos secundarios de estos fármacos. Porejemplo, los b-lactámicos y aminoglucósidos
Lo contrario de la sinergia es el antagonismo, el fenómeno por elcual dos agentes en combinación tienen un efecto general quees menor que la predicha a partir de sus efectos individuales. Porejemplo, cloranfenicol (generalmente bacteriostático) antagonizalas acciones de penicilinas (bactericida)
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Basis of Choice of the Proper Antibiotic
However, in the critically ill patient in whom there is some chance that a bacterial
infection may be a contributing factor, it is prudent to administer antibioticseffective against the most likely pathogens
The decision to prescribe an antibiotic is based upon proof or strong suspicion
that the patient has a bacterial infection
Probable viral infectious or noninfectious processes should not be treated with antibiotics
Whenever possible the antibiotic selection should be based upon the isolation of
a pathogen (followed by cultivation and identification and the susceptibility to
antibiotics)
But most patients who require antibiotic therapy present with an acute problem
that mandates initial empiric therapy
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Empiric Therapy the specific antibiotic chosen is based upon:
1. knowledge of the pathogens likely to cause a specific infection and its susceptibility to particular antibiotic
2. the ability of the pathogen to inactivate the antibiotic
3. spectrum of activity of the antibiotic
4. safety of the antibiotic and its most common side effects
5. site of infection
6. patient’s history7. cost of the therapy, compared to agents of equal safety and efficacy
If more than one antibiotic is active against the likely pathogens at the site of
infection, the specific agent should be chosen on the basis of relative toxicity,
convenience of administration and cost
Basis of Choice of the Proper Antibiotic
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Clasificación de los antibióticos por el Mecanismo de acción
La inhibición de la síntesis de la paredcelular
vancomicinaLas penicilinas
Las cefalosporinas AztreonamImipenem
La inhibición de la síntesis de ácido nucleicorifampicinaLas quinolonas
metronidazol
La inhibición de la síntesis de proteínas
Los aminoglucósidosSpectinomycinLas tetraciclinasEl cloranfenicol
eritromicinaLa clindamicina
La inhibición de la síntesis de folatoSulfonamidasTrimethoprim
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Los antibióticos beta-lactámicos
bactericida Interferir con la biosíntesis de la pared celular (mediante la inhibición de la
reticulación de peptidoglicanos)
Un grupo grande incluyendo:
Las penicilinas
cefalosporinas
Carbapenems monobactámicos
La mayoría de las penicilinas (por ejemplo, ampicilina) sondestruidas por b-lactamasa
Cefalosporinas, carbapenems y monobactamas todas sonresistentes b-lactamasa
uso amplio
Las penicilinas son a menudo primera opción para combatir lasinfecciones (cefalosporinas de segunda)
La resistencia se está convirtiendo en un problema cada vez mayor(véase más adelante)
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¿POR QUÉ NECESITAMOS NUEVOS ANTIBIÓTICOS?
Menos nuevos antibióticos
0
20
40
60
80
100
120
1930 1940 1950 1960 1970 1980 1990 2000
Year
R e g i s t r a t i o n s
0
20
40
60
80
100
1930 1940 1950 1960 1970 1980 1990 2000
Year
R e s i s t a n t i s o l a t e s ( % )
Las bacterias más resistentes
Penicillin-resistant staphylococci
Methicillin-resistant staphylococci
• La disminución de los esfuerzos deinvestigación
• El aumento de los requisitosreglamentarios
• Varias clases de antibióticos potentes
Las bacterias evolucionancontinuamente
Penicillinintroduced
Methicillinintroduced
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OBJETIVOS PARA LOS FÁRMACOS ANTI-BACTERIANAS
RibosomaMacrolidos
Tetraciclinas
NucleoidFluoroquinolonas
Pared celularcefalosporinas,
Las penicilinas
vancomicina
Membrana
celularAntisepticosTriclosan
MetabolismoDrogas sulfa, antifolatos
La división
celular
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¿CÓMO ELEGIR EL MEJOR MECANISMO?
Cell Wall
Metabolism
Cell
Membrane
DNAProtein
biosynthesis
Ventas por tipo de mecanismo
Algunos targets pueden no ser accesibles a las moléculas
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FUENTES TRADICIONALES
Distribución de las medicinas derivadas de la naturaleza
Anti-protozoos Medicina humana
Antibacteriales Antifúngicos
Non-Actinomycetes
ActinomycetesFungiHigher Plants
ACTINOMICETES
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ACTINOMICETES l son un grupo heterogéneo de bacterias filamentosas parecidas superficialmente a los hongos. el
crecimiento característico es un micelio ramificado que tiende a fragmentarse en elementos bacterianos. muchos actinomicetos llevan vida
libre, particularmente en el suelo.
Enfermedad costra de patata Nocardisis, infección pulmonarProducción de antibioticos
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ANTIBIOTICOS DESDE ACTINOMICETOS
Nematocidas, insecticidas, acaricidas y acaricidas• milbemicina, nicomicina, avermectinas
Anti-protozoals
• Lasalocid, monensina, nigericina
Antimicóticos
• anfotericina
Anti-bacterianos• Macrólidos, rifamicinas, cloranfenicol,
• tetraciclinas, aminoglucósidos
Anti-virales
• ribavirina, rifamicinas, antraciclinas
Herbicidas
• bialophos
Los agentes anti-tumorales• Estreptonigrina, antraciclinas
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ASCOMICETOS - AMIGO O ENEMIGO? algunos (actinomicetos como el israelí,
nocardia asteroides) producen enfermedades en el hombre.
Penicillium Acremonium
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P TOGENI
Tiene como habitat al hombre, encontrándose en los dientes, faringe yamígdalas e muchas personas normales. Algunos factores parecen favorecer el desarrollo de la enfermedad causada porestos microorganismos, como son los traumatismos (extracción de una piezadental), las infecciones piógenas asociadas y la hipersensibilidad.Producen la activinomicosis, que es una infección granulamatosa crónicacaracterizada por el desarrollo de abscesos que se abren y originan fístulasmúltiples.
Por su localización puede ser facial, torácica y abdominal
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PRODUCTOS NATURALES DE HONGOS
Agentes inmunosupresores
• Ciclosporina AAgentes que reducen el colesterol
• Las estatinasAlcaloides del cornezuelo de centeno
LSD, psycobilin, mescalina
Los agentes anti-tumoralescitocalasinas
Antimicóticos
griseofulvina, estrobilurinasAnti-bacterianos
Penicilinas, cefalosporinas
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MYXOBACTERIA
Epothilones Anti-cancer
1953 Primer informe1980 aurachin, megovalicins1990 ambruticin, ripostatins, epotilonas, estipiamida
Myxothiazol Anti-fungal
Ambruticin Anti-fungal
Stipiamide Anti-cancer
N
S
O
OH
O
OHO O
OH
O
NH
OH
N
S
S
N
OO
NH2
O
O
OH
OHO
OH
O
PLANTAS
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PLANTAS
NH
N
O
OH
HO
O
Psychotri a ipecacuanha
Emetine
Anti-fungal Anti-protozooal
Hydrastis canadensis
O
O N
O
O
+
Berberine
Anti.bacterial Anti-fungal Anti-protozooal
N
NOH
O
H
Chinchona pubescens
Quinine
Anti-protozooal
FUENTES DE MUESTRAS DE DETECCIÓN
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FUENTES DE MUESTRAS DE DETECCIÓN
alimento mohoso
penicilina
suelo andino
estreptomicina
aguas residuales
del Mediterráneo
cefalosporina
suelo del cemente
clorotetraciclina
Los suelos forestal
eritromicina
El cloranfenicol
CLASSICAL SCREENING METHODS
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CLASSICAL SCREENING METHODS
Fleming‘s original photograph of
Penicillium growing on a plate withbacteria
From the 1990‘s microtitreplates of higher sample density have been used
for routine & high throughput screening
Introduction of the disc-testmethod in the 1940‘s
allowed more samples to
be tested
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GENOMICS – REVOLUTION?
0
20
40
60
80
100
120
140
160
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004
Year of Publication
P u b l i s h e d B a
c t e r i a l G e n o m e s
Identification of Potential Protein Targets
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Conserved
acrossspectrum
ofinterest
Human
genesless
related
Gene
essentialby
disruptionin vitro
Gene
essentialby
disruptionin vivo
Gene
not implicatedin MOA of
knownantibiotic
•103 genes as putative
antibacterial targets•286 genes as putativeantifungal targets
Identification of Potential Protein Targets
for Anti-bacterials
Known vs Predicted Protein Targets for
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g
Anti-bacterials
0
10
20
30
40
50
6070
Nucleoid Cell Wall Cell
Membrane
Ribosome Metabolism
Inhibition of Global Targets by Intervention
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Nucleoid Ribosome Cell Membrane Cell WallDihydrofolate reductase Isoleucyl tRNA synthetase Enoyl reductase Alanine racemaseDihydropteroate synthase Threonyl tRNA synthetase 3-oxo-[ACP] synthase II D-alanyl-D-alanine synthetaseRibosylphosphate-
pyrophosphokinase
Tryptophanyl tRNA synthetase biotin carboxyl carrier protein UDP-N-Ac–D-glucosaminyl-3-
enoylpyruvyl transferasePhosphoribosyl formylglycinamidinesynthetase
adenosine tetraphosphatase hydroxymyristoyl ACP dehydratase Fructose-1-phosphate transaminase
Phosphoribosylpyrophosphateamidotransferase
aspartate aminotransferase biotin carboxylase dihydropicolinate synthetase
Adenylosuccinate lyase methionyl-tRNA formyltransferase acetyl-CoA carboxylase beta aspartate-semialdehyde DH
Adenylosuccinate synthetase tyrosyl t-RNA synthetase acetyl-CoA carboxylase alpha geranyltransferase
IMP dehydrogenase leucyl tRNA synthetase glyceraldehyde 3-phosphate DH UDP-Nac-pyruvoylglucosamine reductase
Guanosine deaminase valyl tRNA synthetase CDP-diacylglycerol synthetase UDP-NAM-alanine D-glutamate ligase
Dihydroorotase asparaginyl tRNA synthetase phosphatidylglycerophosphatesynthase
UDP-NAG - NAM transferase
Dihydroorotate dehydrogenase histidinyl tRNA synthetase 3-hydroxy-3-methylglutaryl-CoAreductase
acetylmuramoyl peptide ligase
OMP PPK prolyl tRNA synthetase 3-oxo-[ACP] synthase III UDP-NAM-Ala-glutamyl-DAP ligase
OMP decarboxylase seryl tRNA synthetase Pantothenate kinase UDP-N-acetylglucosamine 2-epimerase
UMP kinase glycyl TRNA synthetase Malonyl CoA:ACP transacylase N-acetylglucosamine-I-phosphate
uridyltransferase
UDP kinase cysteinyl tRNA synthetase UDP- N- acetylglucosamine 4- epimerase
Thymidylate synthetase alanyl tRNA synthetase UDP-murNAc peptapeptide synthetase
Ribonucleoside diphosphatereductase
aspartyl tRNA synthetase phospho-NAM pentapeptide transfer
S-adenosyl methionine hydrolase phenylalanyl tRNA synthetase lipopolysaccharide core synthesis
S-adenosyl homocysteine hydrolase anthranilatephoshoribosyltransferase
lipopolysaccharide 1,2 glucosyltransferase
Xanthine oxidase indole-3-glycerol phosphate
synthase5‘ nucleotidase queuosine biosynthesis
uracil phosphoribosyltransferase lglutamate-ammonia lyaseDNA -3-methyladenine glycosidase ppGpp synthetase
dihydrofolate synthase tRNA (5-methylaminomethyl-2-
thiouridylate)-methyltransferaseGTP cyclohydrolase queuine tRNA ribosyltransferase
Dihyroneopterin aldolase
Dihydro-6-hydoxymethylpterinpyrophosphokinase
Commercially exploitedNot (widely) exploited but used byNature
Predicted by genomics
g y
in Metabolism
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FROM GENE TO SCREEN26 bacterial genomes compared to
select 100 potential targets
Tests developed to reflect
what is really happening in
the cell
Robotics that
can handle
many samples
in parallel
Small volumes reduce costsand save precious samplesScreening sample libraries:
Roche
synthetic
compounds
Extracts from
antibiotic
producing
microbes
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FROM SCREEN TO DRUG
Identification Optimization Clinical candidate
Biological profiling to
confirm mechanism of
action
DNA microarrays
Protein expression
Parallel chemistry
Medicinal chemistry
Biophysical
characterization of
interaction betweencompound and target
Selection based on
drug-like properties
defined in cellular
tests, on physical
properties, on
pharmacology and ontoxicology
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IMPROVEMENT OF UNDER-EXPLOITED CLASSES CAN BE ACHIEVED
O
N
NH
O
NH
Indolmycin SKB
NH2
NH
N
O OH
O
NH2
OH
Negamycin
Versicor
NOH
NH
NH
O
O
OOH
Actinonin Roche, Versicor/Novartis, British Biotech
O
O
O O
OH
NH2
O
O
O
OH
NH
O
OH
Novobiocin Abbott, Aventis, Merck,
N
NH
O
O
O
OH
NH
O
OH
NH
O
S
NH
O
NH
N
ONH
R
O
OH
Mureidomycin GlaxoWellcome
QUO VADIS?
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Q
Glycopeptides
(oritavancin, dalbavancin, telavancin)
Streptogramins
Tetracyclines(tigecycline, BAY73-6944)
Macrolides
( Ketek )
Fluoroquinolones
( Factive, Avelox , garenoxacin)
DHFR inhibitors(Iclaprim)
b -Lactams
(BAL5788, doripenem)
Ramoplanin
Daptomycin
Oxazolidinones
( Zyvox )PDF inhibitors
VRC4887
2000 2005 2010 2015
Zyvox Ketek
Factive
Avelox
Ramoplanin
Oritavancin
Dalbavancin
Tigecycline
BAL5788
Doripenem
Iclaprim
BAY73-6944
VRC4887
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OPPORTUNITIES FOR A SMALL COMPANY?Big Pharma need big drugs -- can small Pharma survive with small drugs?
0
500
1000
1500
2000
2500
3000
A u g m
e n t i n
Z i t h r o m a x
L e v a
q u i n
C i p r o x i n
K l a c i d
R o c e
p h i n
C e f t i n
C e f z i l
Z i e n
a m
C e f z o n
F o r t u
m
C i p r o x i n
U n a s
y n
F l o m
o x
P a n s
p o r i n
F l u m
a r i n
C l a f o r a n
T a z o
c i n
L e v a
q u i n
S a l e s ( M i l l i o n S F r
Oral formulation
Injectable formulation
Hospital
salesSFr 13,000
million
Primary
care
salesSFr 26,000
million
SFr 39,000 millionNiche indications combatting multi-drug
resistance
Smaller clinical trial programmes
Higher price
Innovative drugs favoured for hospital
formularies
TETRACYCLINES
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TETRACYCLINES
OH
NH2
OOOHO
NH
NH
O
NH H
OH
N
OH
tigecycline
OH
NH2
OOOHO
N H H
OH
N
OH
minocyclineOH
NH2
OOOHO
H H
OH
N
OH
OH
doxycycline
Mechanism: inhibition of ribosome function (protein biosynthesis), bacteriostaticResistance: widespread, efflux system or ribosomal protection proteinIndication: UTI, COPD exacerbation, infected venflon site, eradication of colonization
little clinical experience with MRSA in literatureSide effects: rashes, discolouration of teeth, GI upset, hepatotoxicity,
worsening of renal failure, vertigo
Status: phase III. Severe vomiting reported in earlier trials.Overcomes established resistance in Gram-positive bacteria
OH
NH2
OOOHO
NH H
OH
N
OH
NH
BAY73-6944 (PTK 0796)
Status: pre-clinical.Overcomes established resistance in Gram-positive bacteria
NEW GLYCOPEPTIDES
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NEW GLYCOPEPTIDES
O
NH
OH
Cl
O
OO
O
NH
O
NH
O
OH
NH
O
NH
NH2
O
NH
O
O
NH
OH
OH
OH
O
NH
O
O
OOH
Nh2
O
OHOHOH
Cl
Cl
OOritavancin
Status: phase III SSTI trial completed.Long half-life (>140 h)Overcomes established resistance in Gram-positive bacteria. Active against VRSA, elevatedMICs against GISA.
Dalbavancin O
NH
OH
O
OO
O
NH
O
NH
O
OH
NH
O
NH
NH2
O
NH
O
O
NH
OH
OH
OH
ONH
O
O
O
OHOHOH
Cl
Cl
O
NH
HO3
PO
NH
Status: phase III.Overcomes established resistance in Gram-positive bacteria. Active against VRSA andGISA(MIC90 2 mg/L).
TelavancinStatus: phase III.Overcomes established resistance in Gram-positive bacteria. Active against VRSA and GISA(MIC90 2 mg/L). O
O
OO
O
NH
O
NH
O
OH
NHNH
O
O
NH
OH
OH
OH
ONH
NH
O
OH
OHOOH
Cl
Cl
NH
O
NH2
OH
OH
OH
OH
OH
OH
N
FLUOROQUINOLONES
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FLUOROQUINOLONES
NH N N
O
OH
O
O
F
H
H
N
N
N
O
OH
O
O
F
Moxifloxacin Levofloxacin
Mechanism: inhibition of DNA gyrase (and topoisomerase IV) A subunit,
bactericidalResistance: by point mutations in target genes, efflux may contribute to
intermediate level resistance. Many MRSA isolates already haveelevated MICs
Indications: adults (>18 years of age) with mild, moderate, and severe infectionscaused by susceptible microorganisms in acute sinusitis, bacterial
exacerbation of chronic bronchitis, community-acquired pneumonia,uncomplicated skin and skin structure infectionsSide effects: nausea, diarrhea, dizziness, palpitation, tachycardia, hypertension,
peripheral edema, QT interval prolonged, vaginitis, flatulence,pruritus
NEW QUINOLONES
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NEW QUINOLONES
NH
N
O
O
O
O
F F
Garenoxacin
Status: phase III.Overcomes established resistance inpneumococci, elevated MICs against MRSA.
N
O
O
O
O
NH2
F
N
DX-619
Status: preclinical.Overcomes established resistance inpneumococci and MRSA.
N N
O
O
O
F
OH
WCK 771
Status: preclinical.Overcomes established resistance in MRSA.
STREPTOGRAMINS
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N
N
NH
N
NH
OO
OO
N
N OS
O
O
NH
O
N
O
OH
H
H
NO
N
NH
O
O
O
S
O
O
N
OH
H
Synercid Quinupristin + Dalfopristin
Mechanism: inhibition of ribosome function (protein biosynthesis), bacteriostaticResistance: quinupristin – MLSB determinants (cross resistance with macrolides etc)
dalfopristin – efflux, inactivation by Vat acetylasesIndication: SSTI, nosocomial pneumonia, E. faecium infections. Treatment of
MRSA in patients where vancomycin is ineffective or not tolerated.Side effects: pain, oedema and thrombophlebitis at infusion site. Reversible
arthritis/myalgia
DHFR INHIBITORS
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N
N
NH2
NH2
O
O
O
O
N
N
NH2
NH2
O
O
Mechanism: inhibition of folic acid biosynthesis,
bacteriostaticResistance: widespread, point mutation in target
gene, or bypass mechanismIndication: UTI, COPD exacerbation, infected
venflon site, eradication ofcolonization
Side effects: nausea, vomiting, rashes, GI upset,fever, headache, jaundice,haemolytic anaemia.
Little used because of concerns over side effects
Trimethoprim
Iclaprim
Status: phase II completed.Elevated MICs against TMPR isolates.
OXAZOLIDINONES
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N
O
N
OO
NH
OF
Zyvox Linezolid
Mechanism: inhibition of ribosome function (protein biosynthesis), bacteriostatic
Resistance: point mutation in 23S rRNA.
Indications: Vancomycin-Resistant E. faecium infections, Nosocomial pneumoniacaused by S. aureus (inc. MRSA)), or Streptococcus pneumoniae (notPenR). Complicated SSTI caused by Staphylococcus aureus (inc.MRSA), Streptococcus pyogenes, or Streptococcus agalactiae.Community-acquired pneumonia caused by S. pneumoniae (not PenR)or S. aureus (not MRSA).
Side effects: diarrhoea, headache, nausea. Neuropathy (peripheral, optic) andthrombocytopenia, especially in patients with longer courses of therapy
RAMOPLANIN
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O
O
O
O
O
NH
OH
O
NH
NH
O
NH
NH
ONH
ONH
O
NH2
NH
NH
O
NH
O
O
NH2
O
OH
NH
O
NH
O
OH
O
OH
OH
NH
O
OH
ONH
NH
O
NH
O
NH2
OH
OH
OH
OOH
O
OH
OH
OH
OH
OH
Cl
NH2
O
O
Mechanism: inhibition of cell wallbiosynthesis, bactericidal
Resistance: not known
Status: phase III for eradication ofvancomycin-resistantenterococci from thegastro-intestinal tract;phase II trial for thetreatment of Clostridium
difficile-associateddiarrhea
Side effects: not known
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ANTI-MRSA CEPHALOSPORINS IN CLINICAL
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DEVELOPMENT
O
O
N
N
NS
N
N
SNH
O
H
O
N OH
NH2
COO- O
O
OO
N
S
N
NS
N
N
S
S
NH
O
H
O
N O
NH
COO-
P-O
O
OH
+
BAL5788Phase III completed
PPI 0903
Phase III starting
DHFR INHIBITORS
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N
N
NH2
NH2
O
O
O
O
N
N
NH2
NH2
O
O
Mechanism: inhibition of folic acid biosynthesis,
bacteriostaticResistance: widespread, point mutation in target
gene, or bypass mechanismIndication: UTI, COPD exacerbation, infected
venflon site, eradication ofcolonization
Side effects: nausea, vomiting, rashes, GI upset,fever, headache, jaundice,haemolytic anaemia.
Little used because of concerns over side effects
Trimethoprim
Iclaprim
Status: phase II completed.Elevated MICs against TMPR isolates.
OXAZOLIDINONES
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N
O
N
OO
NH
OF
Zyvox Linezolid
Mechanism: inhibition of ribosome function (protein biosynthesis), bacteriostatic
Resistance: point mutation in 23S rRNA.
Indications: Vancomycin-Resistant E. faecium infections, Nosocomial pneumoniacaused by S. aureus (inc. MRSA)), or Streptococcus pneumoniae (notPenR). Complicated SSTI caused by Staphylococcus aureus (inc.MRSA), Streptococcus pyogenes, or Streptococcus agalactiae.Community-acquired pneumonia caused by S. pneumoniae (not PenR)or S. aureus (not MRSA).
Side effects: diarrhoea, headache, nausea. Neuropathy (peripheral, optic) andthrombocytopenia, especially in patients with longer courses of therapy
RAMOPLANIN
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O
O
O
O
O
NH
OH
O
NH
NH
O
NH
NH
ONH
ONH
O
NH2
NH
NH
O
NH
O
O
NH2
O
OH
NH
O
NH
O
OH
O
OH
OH
NH
O
OH
ONH
N
H
O
NH
O
NH2
OH
OH
OH
OOH
O
OH
OH
OH
OH
OH
Cl
NH2
O
O
Mechanism: inhibition of cell wallbiosynthesis, bactericidal
Resistance: not known
Status: phase III for eradication ofvancomycin-resistantenterococci from thegastro-intestinal tract;phase II trial for thetreatment of Clostridium
difficile-associateddiarrhea
Side effects: not known
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UNIVERSITY NETWORK
Close working relationships with Universities gives access to
additional technology and expertise:
Basel (Biozentrum), Strasbourg, Bern
Birmingham (UK), British Columbia (Canada),
Case Western Cleveland (USA), EMBL Grenoble(France), Michigan (USA), Tübingen (Germany)
Networks supported by EU, NIH, WHO also allow us to
contribute to combating diseases outside the practical
limitations of Basilea:
filariasis, malaria, tuberculosis
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CONCLUSIONS
Anti-infectives• High unmet medical needs• Gap for innovative medicines
• Good opportunities for a small company
Institutional & governmental support
• Promote mutually beneficial collaborations between Industry &academia
• Drive projects of global importance beyond the scope of small
companies
Basilea commitment• New medicines against resistant organisms