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Κολιστίνη Τιγεκυκλίνη -. Ελένη Γιαμαρέλλου 14 Ιουνίου 2014. E S K A P E. Enterococcus Staph aureus Klebsiella pneumoniae Acinetobacter baumannii Pseudomonas aeruginosa Enterobacter cloacae. Υψηλή θνητότητα που φτάνει το 75%. CID 2009:48:1.

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-

14 2014


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E

S

K

A

P

E

Enterococcus

Staph aureus

Klebsiella pneumoniae

Acinetobacter baumannii

Pseudomonas aeruginosa

Enterobacter cloacae

75%

CID 2009:48:1


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Pseudomonas aeruginosa: Percentage (%) of invasive isolates with resistance to carbapenems, by country, EU/EEA countries, 2012

EARS-Net 2012


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Acinetobacterspp: Percentage (%) of invasive isolates with resistance to carbapenems, by country, EU/EEA countries, 2012

EARS-Net 2012


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Klebsiella pneumoniae: Percentage (%) of invasive isolates with resistance to carbapenems, by country, EU/EEA countries, 2012

EARS-Net 2012


10 2012 950

10 2012 >950 -


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KPC

NDM

NDM:

CID 2011;53:49

CID 2011;53:60

Gupta N, et al. CID 2011;53:60


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As antibiotic discovery stagnates, a public health crisis brews

Bad Bugs Need Drugs

IDSA 2006


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- 2013

*

Whonet 2013


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- 2013

*

Whonet 2013


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- 2013

A. Vatopoulos 2013


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  • Pandrug Resistant (PDR):

  • Extensive Drug Resistant (XDR): /

  • Multidrug Resistant (MDR): 3 ()

Falagas ME, Karageorgopoulos DE. CID 2008;46:1121


Klebsiella pneumoniae

Klebsiellapneumoniae

  • ( 6) :

  • ( )

  • >5

ClinMicrobiol Infect 2012;18:439

JAC 26/8/2012


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Klebsiellapneumoniae?

  • 70 , ,

  • 3 2012

  • : PO2 45, PCO2 67

  • ,

  • :

  • /


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Klebsiellapneumoniae?

  • 3 , (=39,5C) : Klebsiellapneumoniae>105cfu/ml.

  • 1g x3 IV 500mg x2 IV

  • 4 :

    • 16g/ml (A)

    • >32g/ml (A)

    • 4g/ml (E)

    • 8g/ml (A)

    • 4g/ml (I)

    • 64g/ml (E)

?


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?

XDR Gram-


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: 1950(!)

  • in vitro :

    • Pseudomonas aeruginosa

    • Acinetobacter spp.

  • in vitro :

MDR XDR


Xdr mdr a baumannii p aeruginosa

XDR MDR A.baumanniiP.aeruginosa

  • 1999-2005: 10 331

  • : >280 , : 202 (100 VAP)

    • : 25%-71%

    • :33%-67%

    • : 29%-62%

    • : 0%-37%

70%-100%


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  • (MIC)

  • ( )


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:

47,2%

?

in vivo PK/PDs?


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!

( ) 1. iu

1mg Colistin=12.500 iu

:

3 . x3IV


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Plachouras D, et al. AAC 2009;53:3430

  • 3. IU: 14,4 2,5 .

  • (3 IU) (0,6g/ml) , 2g/ml.


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a kg

Garonzik et al, AAC 2011(modified)


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(HD)

  • CMS , colistin

Garonzik et al, AAC 2011 & ECCMID 2013


Cvvhdf

CVVHDF

Garonzik et al, AAC 2011 & ECCMID 2013


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  • 9 -10 MU

  • 24

  • : 4.5 MU q12h CrCL >70 ml/min

  • : (CrCL/10)+2 2-3

  • : 1MU q12h 1U

  • CVVHDF 5 - 6 MUq12h


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VAP


Acinetobacter

Acinetobacter

  • 83 81 (71 10 )

  • 125 000 IU (: 20 000 IU - 500 000 IU )

  • VT/ITH colistin 18.5

  • 4

  • 89%

  • 11% ( /)

Karaiskos I, et al. IJAA 2013;41:499-508


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:

?


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?

  • Pseudomonas aeruginosa Acinetobacterbaumannii

  • Klebsiellapneumoniae


Klebsiella pneumoniae1

!

Klebsiellapneumoniae ?


Klebsiella pneumoniae2

Klebsiella pneumoniae

(%)

N=64

N=29

N=56

> 1

1

Modified from: Tzouvelekis L S et al. Clin. Microbiol. Rev. 2012;25:682-707


Klebsiella pneumoniae3

Klebsiella pneumoniae

> 1

1

Daikos GL (unpublished data)


Klebsiella pneumoniae4

Klebsiellapneumoniae

  • 34

  • 298

  • 161 KPC(+)

  • 140 MBL(+)

  • 244

  • 32 VAP

Tzouvelekis LS, et al. ClinMicrobiol Rev 2012;25:682


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294 * Klebsiellapneumoniae

  • A: 2 in vitro MIC 4g/ml:8.3%**

  • B: 2 in vitro :29%

  • C: :24%

  • D: (MIC 4g/ml):25%

  • E: :35.7%

  • F: :47.2%

  • G: :54%

(%)

*70% , 20% VAP+HAP

A vs B p=0.02

A vs E p=0.03

A vs F p<0.0001

A vs G p<0.0001

B vs G p=0.014

C vs G p=0.04

D vs G p=0.03

**

Tzouvelekis LS, et al. ClinMicrobiol Rev 2012;25:682


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Tumbarello M et al. Clin Infect Dis. 2012;55:943-950


Klebsiella pneumoniae5

Klebsiellapneumoniae :

  • KlebsiellapneumoniaeVIM(+) KPC(+) MIC 8g/ml (2gx3 x4) 3 in vitro , .. .

  • MIC >8g/ml . in vitro .


Klebsiella pneumoniae6

Klebsiella pneumoniae*

**

8 g/ml

>8 g/ml

+

+

+

+

+

*

**

Daikos GL, et al. Expert Rev Anti Infect Ther 2012;10:1393-404


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15% - 58%

(0%!)


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:

  • (, )

  • ( 24 8)

!

Rev Assoc Med Pract 2010;56:752-8


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:

>15

Plachouras D, Kontopidou F, Giamarellou H. CMI 2011;17:E9


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Prevalence of use of polymyxins and/or tigecycline (percentage of hospitalised patients receiving any of these antibacterials), ECDC PPS 2011- 2012

Klebsiellapneumoniae:

Colistin

Resistance rate

in Greece

25%-35%


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-

  • ( ) XDRGram- :

    • XDR

    • VAP


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?

  • :

Morel et al. Crit Care 2010;14:R225


143 vap

143 VAP

No influence in relapse rates

Giantsou E. et al Intensive Care Med 2007;33:1533


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1

  • 62 , . 2g x2 500mg iv/ 24.

  • 7 39.5C PO2 ( FiO2 60%, PO2 80mmgHg) . .


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1

  • 2 , . , ?

    • 2g x3 ( 3 ) + 3. X3

    • + (100 x2)

    • +

    • +

  • , ( ) Klebsiellapneumoniae (MIC):

    • 8g/ml ()

    • 8g/ml ()

    • 16g/ml ()

    • 2g/ml ()

?


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:

?

14 2014


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in vitro :

:

in vitro:

Escherichia coli

Klebsiellaspp

Klebsiellaspp

Enterobacterspp

Acinetobacterspp

Staphylococcus spp

Enterococcusspp

Streptococcus pneumoniae

Bacteroidesfragilis

  • ESBL (+) E. coli Klebsiellaspp

  • Acinetobacter

  • Klebsiella pneumoniae

  • MRSA: .

  • VRE:

Tygacil , H. Giamarellou et al. AAC, 2006


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: -

  • in vitro Acinetobacter Klebsiellapneumoniae

  • Pseudomonas aeruginosa


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:

?


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, (1/9/2006 30/3/2010)


137 1025

: 137 1025

74,8%

Chemotherapy 2012; 58: 282


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: 1025

To Tygacil

Chemotherapy 2012; 58: 282


Tygacil

: Tygacil

  • 1415 3

  • 20%

  • 14%

  • 5%

  • 3

Tygacil


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:

  • P450.

  • INR per os

  • , ,

  • Child Pugh III. .

  • !

1. Tygacil , 2. Pieringeret al(2010). Annals of hematology, 89(10), 10634.


In vitro klebsiella pneumoniae

In vitro Klebsiellapneumoniae

Papaparaskevas J, et al. DiagnMicrobiol Infect 2010


77 klebsiella pneumoniae

77 Klebsiellapneumoniae *

* 35

Tzouvelekis LS, et al. ClinMicrobiol Rev 2012;25:682


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,

Klebsiellapneumoniae


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  • X : 50mg/12 ( 100mg)

  • Acinetobacter Acinetobacterbaumannii

  • : 200mg 150mg/12 ( 200mg/12!) MIC 0,5g/ml


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2

  • 36 6 (39,5C) .

  • 3 8 ( 8) ( 3) . 12.500mm

  • 5 . , Foley 10. , .


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2

  • U/S : 12 . . .

  • ?

    • 1 + 5

    • 2 + 5

    • 3 + 4


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:

  • -

Klebsiella pneumoniae :

?


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!


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