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

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5

10

15

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25

Preva

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nc

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Klebsiella pneumoniae: a versatile pathogen

Urinary tract infections (UTIs)

Pneumonia (HAP & VAP)

Bloodstream infections (BSIs)

Intra-abdominal infections

Neonatal infections

0

5

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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

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20

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35

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45

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2005 2006 2007 2008 2009 2010

Pro

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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

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25

30

35

40

45

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2005 2006 2007 2008 2009 2010

Pro

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n %

Year

Carbapenem-R Klebsiella pneumoniae in Europe

EARS-NET

Greece

Italy

0

5

10

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20

25

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35

40

45

50

2005 2006 2007 2008 2009 2010

Pro

po

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n %

Year

Carbapenem-R Klebsiella pneumoniae in Europe

EARS-NET

Greece

Cyprus

Italy

0

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45

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2005 2006 2007 2008 2009 2010

Pro

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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

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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