Post on 30-Apr-2018
The current status of multiple-
drug-resistant bacteria in Europe
Departamento de
Microbiología II
Universidad
Complutense. Madrid
Hospital Universitario Ramón y CajalSERVICIO DE MICROBIOLOGÍA Y PARASITOLOGÍA
Dr. Rafael Cantón
24th Annual meeting of Japanese Society for Clinical Microbiolgy
Yokohama, Japan. 2nd and 3rd, February, 2013
Current status of MDR in Europe
Co-resistance and multi-drug-resistance definition
- microbiological interpretation (genetic capitalisms)
- clinical interpretation
Review microorganisms with propensity to acquire resistance
mechanisms either by mutational events or acquisition of
resistance genes (ESKAPE organisms)
- increasing prevalence of resistance in EU
- emergence of new resistance mechanism in EU
Objectives
Multi-drug- resistance: the microbiological view
Cross resistance (class resistance)
- a R mechanisms affecting antimicrobials from the same family
Multi-resistance (co-resistance)
- different R mechanisms afecting diffent families of antimicrobials
Pleiotropic resistance
- a single R mechanisms affecting antibiotics from different families
E. coli ciprofloxacinR (tooisomerase mutations)
S. aureus meticillinR (PBP2a production)
P. aeruginosa with efflux resistance mechanisms
S. pneumoniae with ribosomal alterations
Multi-drug-resistant P. aeruginosa , A. baumannii
SARM, muti-resistant S. pneumoniae
β-lactamases:
- blaKPC-2, blaVIM-19,
- blaCMY-2, blaCTX-M-15,
- blaSHV, blaTEM
Aminoglycoside modified enzymes
- aacA6;
- aadA
Other resistant genes
- sulI (sulphonamydes)
- dfrA1 (trimetoprim)
Antibiotic MIC (mg/L) Interpretation*
Ampicillin >16 R
Amox/clav >256/2 R
Pip/taz >256/4 R
Cefoxitin >256 R
Cefotaxime >32 R
Ceftazidime >256 R
Cefepime 128 R
Aztreonam >256 R
Imipenem 32 R
Meropenem 16 R
Ertapenem 64 R
Ciprofloxacin >32 R
Gentamicin 64 R
Amikacin 16 R
Trimethoprim >256 R
Tetracycline >256 R
Tigecycline 2 R
Colistin 16 R
*EUCAST
Klebsiella pneumoniae from a urinary tract
infection in a hospitalized patient in Greece
Genetic capitalism
Different antimicrobials might select the same resistant bacteria
A single antimicrobial might select different resistant bacteria
Multi-drug-resistance: the microbiological view
… the model of the blaCTX-M-9 and blaCTX-M-2 ESBL genes
Cantón & Coque. Curent Opin Microbiol 2006; 9:466-75
Valverde et al. Antimicrob Agents Chemother 2006; 50:799-802
Novais et al. Antimicrob Agents Chemother 2006; 50:2741-50
Tn21-like, associated with disemmination and manteinace of blaCTX-M
ANTIBIOTIC AND BIOCIDE RESISTANCE
Variable region, integration of
cassettes of resistance
ANTIBIOTIC RESISTANCE
Insertion sequence, mobilization and
expression of resistance genes
ANTIBIOTICSRESISTANCE
Multi-drug-resistance: the microbiological view
0
10
20
30
40
50
60
70
80
90
100
CTX-M-9 CTX-M-14 CTX-M-10 other CTX-M-
type
SHV-type TEM-type
% o
f R
str
ain
s
AMK GEN TOB KAN STR SUL
TMP TET CMP NAL CIP
Morosini, García-Castillo, Coque, Valverde, Novais, Loza,
Baquero, Cantón. Antimicrob Agent Chemother 2006; 2006; 50:2695-9.
Co-resistance in ESBL producing organisms
Multi-drug-resistance: the microbiological view
Epidemic & endemic
A
Fixation of resistant genes and resistant
bacteria in bacterial populations Allodemic
A
Mutation
Selection
A = antibiotic pressure
Lateral transfer
Spread
Well-adapted clones
Multi-drug-resistance: the consequences
ESBL - Hospital Universitario Ramón y Cajal (1988-2000)
0
5
10
15
20
25
30
88 89 90 91 92 93 94 95 96 97 98 99 0
Year
No
. o
f p
ati
en
ts
0
5
10
15
20
25
30
88 89 90 91 92 93 94 95 96 97 98 99 0
Year
No
. o
f p
ati
en
ts/c
lon
e
Baquero, Cantón, Coque. Lancet Infect Dis 2002; 2:591-2
Emergence and dissemination of resistant bacteria
Magiorakos et al. Clin Microbiol Infect 2012; 18:268-81
Term Definition Comment
Multi-drug
resistant
(MDR)
Non-susceptibility to at least
one agent in three or more
antimicrobial categories*
R to multiple antimicrobial agents (≥3), classes or subclasses.
Includes XDR and PDR. Definition based on in-vitro
susceptibility data with the aim to alert clinicians when treating
patients and infection control
Extremely
drug resistant
(XDR)
Non-susceptibility to at least
one agent in all but two or
fewer antimicrobial categories*
R to all, or almost all, approved antimicrobial agents.
Pan-drug
resistance
(PDR)
Non-susceptibility to all agents
in all antimicrobial categories *
Organisms resistant to:
- almost all commercially available antimicrobials
- all antimicrobials routinely tested
- to all antimicrobial available for empirical treatment.
*therapeutic categories (i.e. aminoglycosides, fluoroquinolones, cephalosporins, carbapenems, …)
Multi-drug-resistance: the clinical view
CLSI (NCCLS) EUCAST
CLINICAL BREAKPOINTS
EPIDEMIOLOGYCAL
CUT-OFF
CLINICAL BREAKPOINTS
Susceptibility interpretation criteria
Current status of MDR in Europe
Co-resistance and multi-drug-resistance definition
- microbiological interpretation (genetic capitalisms)
- clinical interpretation
Review microorganisms with propensity to acquire resistance
mechanisms either by mutational events or acquisition of
resistance genes (ESKAPE organisms)
- increasing prevalence of resistance in EU
- emergence of new resistance mechanism in EU
Objectives
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
Rice. J Infect Dis 2008; 197:1079-81
Boucher et al. Clin Infect nfect Dis 2009; 48:1-12
Rice. J Hosp Epidemiol 2010; 31 (Suppl 1):S7-10
Sandiumenge and Rello. Curr Opin Pulm Med 2012; 18:187-93
Multi-drug- resistance: the relevant bugs
Traditionally not considered as a pathogen
Increasing relevance in nosocomial infections (bacteremia, catheter..)
Epidemiological change in the last years …
- increasing prevalence of:
- E. faecium with respect to E. faecalis
- E. faecium ampR and ampR + vancoR
- clonal dispersión (CC17) of E. faecium ampR vancoR
- emergence of new variants of vancomycin resistance genes
- emergence of new resistance mechanisms
Enterococcus spp.
Witte et al. Int J Med Microbiol 2008; 298:365-77
Top et al. FEMS Immunol Med Microbiol. 2008; 52:297-308
Werner et al. Euro Surveill. 2008; 13(47). pii:19046
Arias & Murray. Nat Rev Microbiol 2012; 10:266-78
Enterococcus spp.: bacteremia
0
10
20
30
40
50
60
70
80
90
100
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
E. faecalis E. faecium Ampi-R-E. faecium
Anual cases (Hospital Ramón y Cajal)
P. Ruiz-Garbajosa et al. Servicio de Microbiología
Hospital Ramón y Cajal. Madrid. Spain
Enterococcus faecalis (2010) Enterococcus faecium (2010)
http://www.ecdc.europa.eu/en/activities/surveillance/EARS-Net/Pages/Database.aspx
Enterococcus spp.: ampicillin resistance
Invasive isolates (EARS-net)
Enterococcus spp.: vancomycin resistance
Glycopeptyde resistance phenotypes
Regional differences and within species¡
Cercenado E. EIMC 2011; 29 (Supl 5): 59-65
Invasive isolates (EARS-net)
Enterococcus faecalis (2010) Enterococcus faecium (2010)
http://www.ecdc.europa.eu/en/activities/surveillance/EARS-Net/Pages/Database.aspx
Enterococcus spp.: vancomycin resistance
E. faecium: population estructure
Willems et al.Emerg Infect Dis 2005; 11:821-8; Leavis et al. Curr Opin Microbiol 2006; 9:454-60
Willems et al. FEMS Microbiol Rev 2011; 35:872-900; Willems et al. MBio 2012; 3:e00151-12
Population snapshot based on all unique STs of the entire
E. faecium MLST database and visualized using eBURST
Previously designated as CC17
Enterococcus spp.: emerging resistance
High level-R: PBP5 hyperproduction (E. faecium)
Low level R: β-lactamase production
- constitutive expresion
- sporadic in E. faecalis and E. faecium
- describe in EEUU, Canada, Argentina, Libano, India, …
Penicillin resistance
*Sarti M, et al. J Clin Microbiol 2012; 50:169-72
Description in 2010 in Italy*
- 8 E. faecium, different PFGE of CC17
- chromosomic operon blaZ-blaI-blaR1
- detection of β-lactamase with high
inocullum and preincubation with
methicillin
Control (-)
E. faecium
bla(+) with
and withouf
methicillin
- 16 patients (Jan-2007 – Oct-2008)
- 17 E. faecium and 5. E. faecalis with MICs of linezolid 8-16 mg/L
- different pulsotypes
- 12 isolates with cross resistence with vancomycin
- G2576T mutation (absence of cfr gen)
Enterococcus spp.: emerging resistance
Staphylococcus aureus: paradigm of resistance
Year Antibiotic affected Mechanism of resistance
1940 Penicillin -lactamase
1960 Methicillin PBP2a (mecA) Tetracyclin efflux Chloramphenicol CAT enzyem Macrolides 23s RNA methilase Aminoglycosides ribosomal modification enzymatic modification
1970 Co-thrimoxazole alternative pathways Rifampicin RNA polymerase modification
1980 Quinolones parC, gyrA mutations Efflux Mupirocin target modification
1990 Vancomycin thick cell wall
2000 Linezolid mutaciones 23sRNA y proteínas mutaciones proteínas ribosomales metilación 23sRNA (gen cfr) Vancomycin vanA Daptomycin membrane potential modification Tigecycline eflujx
2010 Methicillin mecC
Adquisition of resistance
mechanisms in MRSA*
(multi-resistance)
Emergence and dispersion
of new clones (CA-MRSA)
Emergence of new
resistance mechanism
- glucopeptide
- linezolid
*MRSA: methicillin resistant S. aureus
Invasive isolates
(EARS-net Project, ECDC)
2010
2001
http://ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/database.aspx
MRSA in Europe: an endemic situation
Porcentaje de Staphylococcus aureus resistente a meticilina en infección nosocomial
EPINE 1999-2012
2219 18
25 25
29
40
36 37
45
41
4542
44
48 4851
43 43 43,1
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
.
0
10
20
30
40
50
60Tasa de resistencia (%)
Nosocomial infection in Spain (EPINE study)
Angel Asensio (personal comunication)
Percentage of methicillin resistant S. aureus
0
10
20
30
40
50
60
70
80
90
100
% o
f re
sis
tan
t is
ola
tes
Eritromicina Gentamicina Cotrimoxazol Linezolid
1994 1996 2002 2006
Cuevas et al. Enferm Infec Microbiol Clin 2008; 26: 269-77
MRSA in Spain: an endemic situation
Co-resistances
four different clones (one of them was predominat)
linezolid MIC: 16-32 mg/L
variable susceptibility to other agents:
- 100% S to vancomycin, teicoplanina, daptomycin, and tygecyclin
- 20% R to co-thrimoxazol
- >85% R to ciprofloxacin, gentamicin, erithromycin
- 100% R to clindamycin
Presence of cfr gen in the chromosome
¡Now present in CNS and enterococci! Morales et al. Clin Infect Dis 2010; 50:821-5
MRSA and glicopeptide susceptibility
VISA/GISA (decrease susceptibility to vancomycin and teicoplanin):
- Intermediate homo-resistance
- all cells display similar MIC (vancomycin: 4-8-16 mg/L)
- accurate detection in the laboratory (microdilution, Etest)
- Hetero-resistance
- not all the cells display similar MIC (vancomycin: 1-4 mg/L)
- slow growth and with decreased susceptibility
- selection during the treatment
- difficult detection in the laboratory (phenotypic instability)
Resistance mechanisms associated with
thick cell wall
Glycopeptide hetero-resistance in staphylococci
MIC (mg/L) ≤ 1 1,5 2 4- 8 ≥16
SUSCEPTIBLE RESISTANT
hVISA VISA VRSA
Increased tolerance to glycopeptides
Slightly increment of daptomycin MICs but in
the susceptible range
Increment of therapeutic failure
Well documented in MRSA but less studied
in MSSA and CNS
EUCAST criteria:
MRSA in Spain: vancomycin MIC creep (Spain)
Cuevas et al. EIMC 2008; 26: 269-77
Multicentric studies VIRA study: MRSA
MIC
Year >1 mg/L
2001 6,5%
2004 20,8%
2006 30,9%
2008 16,9%
Picazo et al. EIMC 2006; 24:617-28
Picazo et al. DMID 2009; 64: 448-51
The mortality associated with bacteremia
due to MRSA was significantly higher
when and inadequate antibiotic was used
or when vancomycin MICs > 1 µg/ml
Soriano et al. Clin Infect Dis 2008; 46:193-200
Microbiology challenges in S. aureus
Methicillin resistant Staphylococcus aureus (MRSA)
Few clones has been responsible for the dissemination
of MRSA worldwide in the hospital setting
Occasionally integration of mecA gene within methicillin-
susceptible S. aureus
Emergence of specific clones in the community:
- associated with virulence traits (i.e. USA300 PVL +)
- amplification in the animal environment and latter
invasion of human setting (i.e. ST398)
Muti-resistance pattern
MRSA: new challenges?
MRSA in Denmark – pigs and farm workers
SARM: - 20% in pig farm workers
- 40% in pig samples from slaughter house
Association with ST398 (still infrequent in man)
- origin from SASM from pigs
- polymorphisms of SSCmec (more than one integration)
- associated with avoparcin discontinuation, tetracycline use
- ST398 also in Germany, Belgium, Spain, Italy …
- PVL (-) in MRSA from pigs, occasionally (+) in humans
humanos
Wulf & Voss. Clin Microbiol Infect 2008; 46:62-8
Otter & French. Lancet Infect Dis. 2010;10:227-39
van Loo et al. Emerg Infect Dis. 2007; 13:1834-9
New mec variants
SCCmec type XI,
- mecC (mecA LGA251)
Initially susceptible to non β-lactam antibiotics
Clonal complexes: CC130, CC1943, CC705, CC425 (bovine)
Detection in:
- UK, Denmark, Ireland, Germany (rural environment)
Zoonotic reservoir with transmission to humans
Problems in the detection in the laboratory
Shore AC, et al; AAC 2011; 55:3765
García-Alvarez L, et al; Lancet Infect. Dis. 2011; 11:595
Cuny C, et al. PLoS ONE 2011; 6:e24360
Stegger M, et al. Clin Microbiol Infect 2012; 18:395
Petersen et al. Clin Microbiol Infect. 2013;19:E16-22
MRSA: new challenges?
Greece, 4 MRSA isolates with
increased values of ceftaroline
(4 mg/L)
- Reduced afinity for PBP2a
- Mutations in non-PBP domine
and transpepetidase
Jones et al. J Antimicrob Chemother 2011 66 (Suppl 3=:iii69-80
CMI (mg/L)
Nº
de a
isla
do
s
MRSA: new challenges?
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
Rice. J Infect Dis 2008; 197:1079-81
Boucher et al. Clin Infect nfect Dis 2009; 48:1-12
Rice. J Hosp Epidemiol 2010; 31 (Suppl 1):S7-10
Sandiumenge and Rello. Curr Opin Pulm Med 2012; 18:187-93
Multi-drug- resistance: the relevant bugs
ESBLs
Carbapenemasases
Enzymes able to hydrolyzed 3rd / 4rd gen. cephalosporins and
monobactams but not cephamycins or carbapenems
Inhibited by clavulanic acid (sulbactam y tazobactam)
Genetic determinants generally associated with plasmids
Associated co-resistance (aminoglyclosides, quinolones, …)
Health public concern
- high prevalence in E. coli in the community (≈8%)
- variable prevalence in K. pneumoniae (5-50%) (higher in hospitals)
- scarce prevalence in P. aeruginosa
Easy detection in the laboratory
Therapeutic options
- carbapenems
- β-lactams + β-lactamase inhbitors
- tygecycline, colistin
- fosfomycin, nitrofurantoin, ….
Extended spectum β-lactamases
ESBL producing Enterobacteriaceae in Europe
Resistance to 3rd gen cephalosporins (invasive isolates, 2010)
http://www.ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/map_reports.aspx
Escherichia coli Klebsiella pneumoniae
Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Cantón R,
Baquero F. Antimicrob Agents Chemother 2010; 54:3043-6
%
Intraabdominal infection (SMART study 2008)
ESBL – Klebsiella pneumoniae in Europe
Hoban et al. Diagnostic Microbiology Infectr Dis 2012; 74:62-7
%
Urinary tract isolates (SMART study 2009-2010)
CTX-M 65.5%
SHV 31.0%
TEM 1.7%
ESBL producing Enterobacteriaceae in Europe
Hawkey et al. JAC 2009; 64
World wide dissemination of CTX-M-15 enzymes
ESBL producing Enterobacteriaceae worlwide
Enzymes able to hydrolyzed carbapenems and with some
exceptions all β-lactams
Different families (KPC, MBL, OXA)
Genetic determinants generally associated with plasmids
Associated co-resistance (aminoglyclosides, quinolones, …)
Health public concern
- high prevalence in K. pneumoniae
- variable prevalence in different countries
- scarce prevalence in P. aeruginosa
Easy difficult detection in the laboratory
Few therapeutic options
- carbapenems (?)
- tygecycline, colistin
- fosfomycin, nitrofurantoin, ….
Acquired carbapenemases
Carbapenemase producing Enterobacteriaceae
Carbapenem resistance (invasive isolates, 2010)
http://www.ecdc.europa.eu/en/activities/surveillance/EARS-Net/database/Pages/map_reports.aspx
Escherichia coli Klebsiella pneumoniae
Simplified general classification, expression and organisms
MOLECULAR
CLASS ENZYMES
INHIBITION
(in vitro)
CARBAPENEM
RESISTANCE
(expression)
AZTREONAM MICROORGANISMS
A (Ser)
KPC
GES/IBC
Others
CLAV Heterogeneous R
Enterobacterias
(K. pneumoniae)
P. aeruginosa
B (Zn++)
METALO
VIM
IMP
NDM
EDTA
Heterogeneous
S P. aeruginosa
Enterobacteriaceae
D (Ser) OXA CLAV Low S A. baumannii
Enterobacteriaceae
Acquired carbapenemases
Microbiology challenges in ESKAPE infections
Endemic
Interregional spread
Regional spread
Independent hospital outbreaks
Single hospital outbreaks
Sporadic occurrence
Not reported / no data
KPC
VIM
NDM
OXA-48
Other countries:
Israel
Luxembourg
Spread of carbapenemases in Europe (update Feb-2012)
Canton et al. Clin Microbiol Infect 2012 (in press)
Modified from Nordmann et al. Emerging Infect Dis 2011; 17:1791-8
World wide dissemination of KPC-Enterobacteriaceae
?
Dissemination of KPC-Enterobacteriaceae in Europe
Modified from Nordmann et al. Emerging Infect Dis 2011; 17:1791-8
Cross border dissemination from initially endemic areas? Magiorakos et al. Risk assesment on the spread of carbapenemase
producing Enterobacteriaceae. ECDC. 2011
Cantón et al. Clin Microbiol Infect 2012; 18:413-31
? USA
Israel
?
Woodford N, et al. FEMS Microbiol Rev 2011;35 :736-55
Microbiology challenges in ESKAPE infections
K. pneumoniae population structure (eBurst analysis)
KPC
Rolain et al. Clin Microbiol Infect 2010;16:1699-701
Struelens et al. Eurosurveillance 2010; 15 18 nov
NDM-1
Carbapenemase producing Enterobacteriaceae
OXA-48 First identified in K. pneumoniae in Istanbul (Turkey) in 2003
Extensively reported as a source of K. pneumoniae nosocomial outbreaks
Well disseminated in the Mediterranean area and in western EU countries
(cross-border dissemination)
Nordmann et al. Emerging Infect Dis 2011; 17:1791- 8
Cantón et al. Clin Microbiol Infect 2012; 18:413-31
Clonal and polyclonal
spread
Difficult detection unless in
isolates:
- coproducing an ESBL
- with porin deficiency
Carbapenemase producing Enterobacteriaceae in Europe
Acelerated increased in some countries: Belgium, France, …
Cantón et al. Clin Microbiol Infect 2012; 18:413-31
Glupczynski et al. Int J Antimicrob Agents 2012; 39:168-72
Mainly in E.cloacae and
in K. pneumoniae
coproducing ESBLs
- CTX-M-9, -15
- SHV-11, SHV-76
OXA-48 producing Enterobacteriaceae in Europe
Current situation of carbapenemase producing
Enterobacteriaceae at the Ramón y Cajal University Hospital
Endemic
Interregional spread
Regional spread
Independent hospital outbreaks
Single hospital outbreaks
Sporadic occurrence
Not reported / no data
KPC
VIM
NDM
OXA-48
Other countries:
Israel
Luxembourg
Non-endemic country
- 608.810 habitants (10% of the population in Madrid)
- 1058 beds with 6 ICU (including 4 surgical ICU)
- reference hospital of Barajas airport in Madrid
Complex epidemiology
Carbapenemase producing Enterobacteriaceae
0
2
4
6
8
10
12
14
16
MBL KPC OXA-48
Epidemiology situation at Hospital Ramón y Cajal, Madrid (Spain)
New cases per month
Data from Servicio de Micirobiología. Hospital Ramón y Cajal. May 2005- August 2012
KPC
VIM
OXA-48
Carbapenemase producing Enterobacteriaceae
Epidemiology situation at Hospital Ramón y Cajal, Madrid (Spain)
Clonal and polyclonal endemic situation of VIM-1 producers
since 2005 associated with IncI1, IncN and IncHI2 plasmids
- different species, mainly K. pneumoniae and E. cloacae
- dominance of ST39-K. pneumoniae, but also ST1, ST253, ST463, ST502
- presence of ST131 E. coli coproducing VIM-1 and CTX-M-15
Tato et al. Clin Infect Dis 2007; 45:1171-8; Gijón et al. J Clin Microbiol 2012; 50:1558-63
Ongoing polyclonal outbreak of KPC producers:
- KPC-3-K. pneumoniae clones different of the high-risk clone ST258
- different KPC-2 Enterobacteriaceae (K. pneumoniae, E. coli, and E. cloacae)
Curiao et al. J Antimicrob Chemother 2010; 65:1608-14. Ruiz-Garbajosa et al. (unpublished)
Recent out-burst of OXA-48 producing K. pneumoniae and
E. cloacae epidemics
Enterococcus faecium
Staphylococcus aureus
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
Enterobacter spp.
Rice. J Infect Dis 2008; 197:1079-81
Boucher et al. Clin Infect nfect Dis 2009; 48:1-12
Rice. J Hosp Epidemiol 2010; 31 (Suppl 1):S7-10
Sandiumenge and Rello. Curr Opin Pulm Med 2012; 18:187-93
Multi-drug- resistance: the relevant bugs
Increasing prevalence of MDR (ESKAPE) organisms in Europe
- co-selection proceses
- complex epidemiology (allodemia)
Emergence of new resistance mechanisms in Europe both in
Gram-positive and -negative organisms
- zoonotic origin (i.e. mecC variants in S. aureus)
- cross border transfer (i.e. carbapenemase-Enterobacteriaceae)
Dispersion of multi-drug resistance clones (high-risk clones)
within Europe
Concluding remarks
Multi-drug resistant organisms in Europe
Fernando Baquero
Rafael Cantón
Teresa M. Coque
Tania Curiao
Juan Carlos Galán
Desirèe Gijón
María Isabel Morosini
Ana Moreno
Patricia Ruiz Garbajosa
Marta Tato
Arancha Valverde
Comunidad de Madrid: CAM 2000-0049
Fondo de Investigaciones Sanitarias:
FIS PI 2043-2002; FIS 01/412
FIS 040162; REIPI C03/14, CIBER-ESP
Ministerio de Ciencia y Tecnología
SAF 2003-09285
European Commission
LSHM-CT-2003-503335; -CT-2008-223031
Fundación para la Investigación Biomédica
de Hospital Ramón y Cajal (FIBIO)
Fundación de Ciencias Microbianas (FCM)
Antonio Oliver,
Luisa Peixe, Angela Novais
Patrice Nordmann / Laurent Poirel
Johan Pitout
Ackwoledgements
RESISTANCE IN GRAM-NEGATIVE ORGANISMS:
STUDYING INTERVENTION STRATEGIES
The current status of multiple-
drug-resistant bacteria in Europe
Departamento de
Microbiología II
Universidad
Complutense. Madrid
Hospital Universitario Ramón y CajalSERVICIO DE MICROBIOLOGÍA Y PARASITOLOGÍA
Dr. Rafael Cantón
24th Annual meeting of Japanese Society for Clinical Microbiolgy
Yokohama, Japan. 2nd and 3rd, February, 2013