antibioticos 28oct 2013

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Agentes antimicrobianos,

Los antibióticos, sulfonamidas yantimicóticos



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)



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.



CONCENTRACIÓN INHIBITORIA MÍNIMA (CIM)

La concentración más baja de antibiótico queinhibe el crecimiento bacteriano.



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)



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



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



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



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)



¿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



OBJETIVOS PARA LOS FÁRMACOS ANTI-BACTERIANAS

RibosomaMacrolidos

Tetraciclinas

NucleoidFluoroquinolonas

Pared celularcefalosporinas,

Las penicilinas

vancomicina

Membrana

celularAntisepticosTriclosan

MetabolismoDrogas sulfa, antifolatos

La división

celular



¿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



FUENTES TRADICIONALES

Distribución de las medicinas derivadas de la naturaleza

Anti-protozoos Medicina humana

Antibacteriales Antifúngicos

Non-Actinomycetes

ActinomycetesFungiHigher Plants

ACTINOMICETES



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



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



ASCOMICETOS - AMIGO O ENEMIGO? algunos (actinomicetos como el israelí,

nocardia asteroides) producen enfermedades en el hombre.

Penicillium Acremonium



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



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



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



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



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



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



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



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



g

Anti-bacterials

0

10

20

30

40

50

6070

Nucleoid Cell Wall Cell

Membrane

Ribosome Metabolism

Inhibition of Global Targets by Intervention



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



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



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



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?



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



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



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



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



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



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



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



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



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



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



ANTI-MRSA CEPHALOSPORINS IN CLINICAL



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



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



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



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



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



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

antibioticos 28oct 2013

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