Annexes to Chapter 6.1: Antibacterial Drug Resistance
Priority Medicines for Europe and the World
"A Public Health Approach to Innovation"
Background Paper for Review
Annexes to
Antibacterial Drug Resistance
Per Nordberg, Dominique L. Monnet, Otto Cars
11 October 2004
6.1-1
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Table of Contents
Annex 6.1.1. Antibacterial-drug projects funded by the EU 5th Framework Programme for
Research and Technological Development, 1999-2002 ................................................................... 3
Annex 6.1.2. Antibacterial drugs in the development pipeline ..................................................... 6
Annex 6.1.3. Vaccines that could be used to prevent bacterial infections and may contribute
to combating bacterial resistance: development pipeline ............................................................... 7
6.1-2
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Annex 6.1.1. Antibacterial-drug projects funded by the EU 5th
Framework Programme for Research and Technological Development,
1999-200298
Year
of
start
2000
Project acronym
Project name
NAACAP
Development and evaluation of nucleic acid
amplification methods for the detection of
respiratory pathogens in community acquired
pneumonia
New strategies for treatment and prevention of
mycobacterial diseases
Development of integratable sensors for screening
of antibiotic resistance in Mycobacterium
Development of antimicrobial peptides as novel
anti-infective drugs
Bacterial two-component system as targets for the
development of novel antibacterials and antiinfectives
Replication initiation proteins as new targets for
bacterial growth inhibition
Molecular mechanism of macrolide antibiotic action
and resistance: application in drug development
Comparative analysis of proteome modulation in
human pathogenic bacteria for the identification of
new vaccines, diagnostics and antibacterial drug
targets
Glycosylation engineering for novel antibiotics
Metabolic engineering of glycopeptide antibiotics:
technology, optimisation and production
European resistance intervention study reducing
resistance in respiratory tract pathogens in children
Pneumococcal disease in Europe
Severe Streptococcus pyogenes disease in Europe
New generation genetic markers and techniques for
the epidemiology and control of tuberculosis
TREAT – a system for balancing antibiotic treatment
against development of drug resistance
Network
for
automated
bacterial
strain
fingerprinting in Europe
Microbiological and structural strategies for the
diagnostics and epidemiology of Pseudomonas
aeruginosa infections
Structural
and
functional
genomics
of
Mycobacterium tuberculosis
Novel drug targets specific to persistent (latent)
tuberculosis infection: crystallisation, structure
determination and functional studies
Type IV secretion systems as targets for anti-
TB prevention cluster
DISSARM
PANAD
TCS-Targets
DNA
replication
inhibitors
MOL-MECH-MAC
EBP
GENOVA
Mega-Top
EURIS
PNC-EURO
Strep-EURO
Mol. Epidemiology TB
TREAT
Gene
2001
Pseudomonas virulence
X-TB
Persistent TB
TFSS
6.1-3
EU
Contribution
(million €)
1.2
2.0
0.9
1.8
1.3
2.0
0.7
0.7
1.8
1.2
1.7
1.5
1.2
0.9
1.4
0.4
1.2
2.3
0.8
1.6
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Year
of
start
Project acronym
TNA
BAS anti-microbials
ACTAPHARM
Cyanomyces
COINS
ADRI
DYNAMICRO
SANITAS
PROSAFE
DEAR
EU-MENNET
SALM-GENE
Genus Clostridium
2002
New antimycobacterials
Upgrade Diagno MDRTB
Ribosome inhibitors
ANTISTAPH
POLYCARB
RASTUD
PulmInfect
LONG-DRUG
Upgrade Diagno MDR-
Project name
EU
Contribution
(million €)
infectious therapies
Towards new antibiotics
Development of novel anti-bacterials and antiinfectives that target programmed bacterial cell
death
Novel sources of actinomycete diversity for
detection
of
antimicrobial
agents
with
pharmaceutical applications
Combinatorial biosynthesis: generation of novel
therapeutic substances by combining genes from
Actinomyces and cyanobacteria
Discovery of a new class of bioactive compounds:
bacterial conjugation inhibitors
Novel inhibitors of adhesin/receptor interactions
involved in microbial infection at mucosal surfaces
Development of photodynamic treatment to
eradicate and control the current spread of
infectious antibiotic resistant microorganisms in
man
Screening assays for new bacterial inhibitors based
on targets active in septation
Biosafety evaluation of probiotic lactic acid bacteria
used for human consumption
Dynamics of the evolution of antimicrobial drug
resistance
Impact of meningococcal epidemiology and
population biology on public health in Europe
Strengthening international Salmonella surveillance
through strain typing and differentiation
Pathology and ecology of the genus Clostridium in
humans, animals, and foodstuffs: identification,
epidemiology and prophylaxis
Inhibitors of the non-mevalonate pathway of
isoprenoid
biosynthesis
as
drugs
against
tuberculosis
Improved diagnosis, drug resistance detection, and
control of tuberculosis in Latin America
New antimicrobials targeting translation in bacteria
and fungi
Novel non-antibiotic treatment of staphylococcal
diseases
Treatment and prevention of bacterial infections by
anti-adhesion compounds
Rapid antibiotic susceptibility testing using
dielectrophoresis
Differential diagnosis of infectious lung diseases
Characterisation of Mycobacterium tuberculosis
populations during infection: a longitudinal study
on drug resistance development
Improved diagnosis, drug resistance detection and
6.1-4
1.4
2.0
2.1
1.7
0.5
1.9
0.7
1.5
1.3
1.3
1.9
1.2
0.4
1.5
1.0
2.2
2.3
1.8
0.8
0.9
1.1
1.0
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Year
of
start
Project acronym
Project name
TB
ARPAC
control of tuberculosis in Latin America
Development of strategies for control and
prevention of antibiotic resistance in European
hospitals
Towards controlling antimicrobial use and
resistance in low-income countries – an intervention
study in Latin America
Antibiotic resistance surveillance and control in the
Mediterranean region
Antimicrobial resistance transfer from and between
gram-positive bacteria of the digestive tract and
consequences for virulence
Antibiotic resistance in bacteria of animal origin - II
Resist on resistance: mobilising the research efforts
for combating multi-resistance against antibiotics
ANTRES
ARMed
ARTRADI
ARBAO-II
ROR (SCORE)
EU
Contribution
(million €)
6.1-5
0.7
1.1
0.7
1.5
0.4
0.3
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Annex 6.1.2. Antibacterial drugs in the development pipelinea 4,79,109,112-121
Development phase
Phase III
Phase II
Compound
Garenoxacin
Tigecycline
Doripenem
Faropenem daloxate
Ramoplanin
Cethromycin
Oritavancin
Dalvabancin
Iclaprim (AR-100)
BAL-5788 (pro-drug of BAL-9141)
CS-023 (R-115685)
Telavancin (TD-6424)
XRP-2868
AVE-6971
Phase I
Pre-clinical or not
disclosedb
ABT-492
Cefmatilen (S-1090)
Rifalazil
Not disclosed
R-1558
Tebipenem (L-084, pro-drug of
LJC-11036/L-036)
CAB-175
MC-02479 (RWJ-54428)
TAK-599
Sitafloxacin
Olamufloxacin (HSR-903)
DX-619
BAY 73-7388 (PTK-0796)
A-72310 & A-692345
CBR-703
MC-207110
E-1010
DZ-2640
CP-5609
BK-218
KP-736
CP-6679
Fandofloxacin (DW-116)
ECO-00501
LMB-415
aExcluding antibacterials for topical use.
bThis list may not be exhaustive.
6.1-6
Class
Quinolone
Glycylcycline (close to tetracycline)
Carbapenem
Carbapenem
Glycolipopeptide
Ketolide (close to macrolide)
Glycopeptide
Glycopeptide
Dihydrofolate reductase inhibitor (new
class)
Cephalosporin
Carbapenem
Glycopeptide
Streptogramin (close to macrolide)
Topoisomerase IV inhibitor
(same mechanism as quinolone)
Quinolone
Cephalosporin
Rifamycin (against Chlamydia)
Deformylase inhibitor (new class)
Beta-lactam
Carbapenem
Cephalosporin
Cephalosporin
Cephalosporin
Quinolone
Quinolone
Quinolone
Aminomethylcycline
(close
to
tetracycline)
Ribosome inhibitor (new class)
RNA polymerase inhibitor (new class)
Efflux pump inhibitor (new class)
Carbapenem
Carbapenem
Carbapenem
Cephalosporin
Cephalosporin
Cephalosporin
Quinolone
Unknown or not disclosed
Unknown or not disclosed
Annexes to Chapter 6.1: Antibacterial Drug Resistance
Annex 6.1.3. Vaccines that could be used to prevent bacterial infections
and may contribute to combating bacterial resistance: development
pipelinea 87,122-131
Development phase
Phase III
Vaccine
Bivalent Staphylococcus aureus
glycoconjugate vaccine
Pseudomonas aeruginosa vaccine
Phase II
Vaginal mucosal vaccine (mixture
of 10 heat-killed bacteria) for
urinary tract infections
Multivalent
group
A
streptococcal vaccine
Pre-clinical
Enterococcus faecium/E. faecalis
conjugate vaccine
Recombinant FimCH vaccine for
urinary tract infections due to
Escherichia coli
Escherichia coli PapG P fimbriae
adhesion vaccine for urinary tract
infections
Intranasal vaccine for urinary
tract infections due to Proteus
mirabilis
Trivalent Staphylococcus aureus
glycoconjugate vaccine
aThis list may not be exhaustive.
6.1-7
Indication
Prevention of S. aureus bacteremia in
high-risk patients
Prevention of P. aeruginosa infection in
cystic fibrosis patients
Prevention of recurrent urinary tract
infections in women
Prevention of diseases caused by group A
Streptococcus
Prevention and/or treatment of systemic
enterococcal infections
Prevention of recurrent urinary tract
infections in at-risk patients
Prevention of recurrent urinary tract
infections in at-risk patients
Prevention of urinary tract infections due
to P. mirabilis in patients with indwelling
catheters
Prevention of S. aureus infections in highrisk patients