epidemiologia di klebsiella pneumoniae resistente ai...
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Epidemiologia di Klebsiella pneumoniae
resistente ai carbapenemi in Italia e in Europa
Gian Maria Rossolini Dip. Biotecnologie
Sezione di Microbiologia
Università di Siena UOC Microbiologia e Virologia
Azienda Osp-Univ Senese
Klebsiella pneumoniae: a versatile pathogen
Urinary tract infections (UTIs)
Most common agents of UTIs, Italy
(N=13,820 - 2008-09)
Magliano et al – Sci World J 2012
0
20
40
60
80
Preva
le
nc
e (%
)
Klebsiella pneumoniae: a versatile pathogen
Urinary tract infections (UTIs)
Pneumonia (HAP & VAP)
Hospitalized patients with pneumonia
(SENTRY surveillance system - N=31,436)
Jones et al – CID 2010
Pathogen Prevalence (%)
Global United States
Europe
Staphylococcus aureus 28.0 36.3 23.0
Pseudomonas aeruginosa 21.8 19.7 20.8
Klebsiella spp. 9.8 8.5 10.1
Escherichia coli 6.9 4.6 10.1
Acinetobacter spp. 6.8 4.8 5.6
Enterobacter spp. 6.3 6.5 6.2
Serratia spp. 3.5 4.1 3.2
Stenotroph. maltophilia 3.1 3.3 3.2
Streptococcus pneumoniae 2.9 2.5 3.6
Haemophllus influenzae 2.7 2.5 3.7
Klebsiella pneumoniae: a versatile pathogen
Urinary tract infections (UTIs)
Pneumonia (HAP & VAP)
Bloodstream infections (BSIs)
Most common agents of bacteremia, Italy
(N=12,781 - 2007-08)
Luzzaro et al – DMID 2011
0
5
10
15
20
25
Preva
le
nc
e (%
)
Klebsiella pneumoniae: a versatile pathogen
Urinary tract infections (UTIs)
Pneumonia (HAP & VAP)
Bloodstream infections (BSIs)
Intra-abdominal infections
Neonatal infections
0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010
Pro
po
rtio
n %
Year
Klebsiella pneumoniae: resistance to
3rd
gen. cephalosporins and fluoroquinolones, Italy
EARS-NET
R to 3GC (ESBL)
R to FQ
Increasing role of carbapenems
0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010
Pro
po
rtio
n %
Year
Klebsiella pneumoniae, Italy
EARS-NET
R to 3GC (ESBL)
R to FQ
R to carbapenems
Concerns with carbapenem-R Klebsiella pneumoniae
- Usually exhibit an XDR phenotype
(limited/suboptimal treatment options)
Carbapenem-R K. pneumoniae (KPC)
Giani et al – JCM 2009
Antibiotic MIC mg/L(S/I/R)
Amp/Sulb >32 R
Pip/Tazo >128 R
Ceftriaxone >64 R
Ceftazidime >64 R
Cefepime >64 R
Ertapenem >32 R
Imipenem >32 R
Meropenem >32 R
Aztreonam >64 R
Amikacin >64 R
Gentamicin 2 S
Tobramycin >16 R
Ciprofloxacin >4 R
Tigecycline 1.5 I
Colistin 0.4 S
Concerns with carbapenem-R Klebsiella pneumoniae
- Often exhibit an XDR phenotype
(limited/suboptimal treatment options)
- High morbidity and mortality (infections)
- Potential for spreading (locally and
globally)
- Prolonged / high-level carriage: risk
for infection and challenge for
infection control
0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010
Pro
po
rtio
n %
Year
Carbapenem-R Klebsiella pneumoniae in Europe
EARS-NET
Greece
Italy
0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010
Pro
po
rtio
n %
Year
Carbapenem-R Klebsiella pneumoniae in Europe
EARS-NET
Greece
Cyprus
Italy
0
5
10
15
20
25
30
35
40
45
50
2005 2006 2007 2008 2009 2010
Pro
po
rtio
n %
Year
Carbapenem-R Klebsiella pneumoniae in Europe
EARS-NET
Greece
Cyprus
Italy
Hungary
Other EU countries: proportions very low (0 - 2%)
… but carbapenem-R enterics reported in
most european countries
Canton et al – CMI 2012
Hoenigl et al – AAC 2012
Carbapenem-Resistant Enterics (CRE):
a multicenter cross-sectional nationwide survey
25 centers
May 15 - June 30, 2011
CRE detected in
most centers
87% K. pneumoniae
8% Enterobacter
2% E. coli
2% Serratia
1% others
AMCLI-CoSA – Italian national CRE surveillance 2011
Inpatients: 7154 isolates
Outpatients: 6595 isolates
CRE
3.5%
0.3%
0
5
10
15
20
25
30
35
40
45
50C
-14
C-1
7
C-0
5
C-1
6
C-0
7
C-2
5
C-0
9
C-1
3
C-1
1
C-1
0
C-0
2
C-1
9
C-0
1
C-0
3
C-2
4
C-1
2
C-0
8
C-1
5
C-2
2
C-2
0
C-0
6
C-2
1
C-2
3
C-1
8
C-0
4
Carbapenem-resistant K. pneumoniae
Centers
Pro
po
rtio
n (%
)
AMCLI-CoSA – Italian national CRE surveillance 2011
Carbapenem resistance mechanisms
in Enterobateriaceae
•Porin loss +
ESBL/AmpC
production
Higher-level R
Transferable
• Carbapenemase
production
Lower-level R
Not transferable
Class A (serine)
Class D (serine)
Class B (metallo)
Acquired carbapenemases in enterics
KPC
OXA-48
IMP
VIM
NDM
Detected in Italy
Enterics VIM+
Detected since the early 2000s:
sporadic cases / small outbreaks
by K. pneumoniae, E. coli,
Enterobacter
Luzzaro et al - AAC 2004
Perilli et al – MDR 2008
Rossolini et al - AAC 2008
Cagnacci et al - JAC 2008
Aschbacher et al – JAC 2008
Falcone et al - JCM 2009
Venturelli et al – ECCMID 2011
Rossolini et al – unpublished
Low spreading potential
K. pneumoniae KPC+
Detected in survey 2011
Reported independently
No information
Rossolini GM, unpublished
KPC-Kp endemic in Italy
AMCLI-CoSA – Italian national CRE surveillance 2011
Conclusions
Rapid diffusion of carbapenem-resistant
K. pneumoniae in Italy (now endemic)
KPC carbapenemase the most prevalent
mechanism (mostly clonal) but not unique
Issues in:
treatment (XDR and TDR phenotypes)
detection and reporting
infection control
handling of carriers
transplantation medicine