???????

1
???????µ??? t?? ?????t?ta? ap? a??e?t??? ßa?t???a
???a? ?. ??s?f?d?? ?a?d?at??? ??e?d??e??µe???
???µ????????a? G ?a?d?at???? ??????? ?pp????te??
??s???µe?? Tessa???????
2
???????µ??? sta pa?d??
??s???µe?a??
?????t?ta?

• S????t?ta
• S????te?? ßa?t???a?? ???µ??? sta pa?d??

• ?p?p?????
• ?µese? (ep??tas? f?e?µ????, ap?st?µa)
• ?p?te?e? (?ef????? ?????, ?ef???? ?p??tas?, ???)

e?a?s??s?a
sta s????? a?t?µ????ß?a??
?a ?pe????a ßa?t???a
a?t???
3
?a ?pe????a ßa?t???a
??d?? ????pa???????
Gram
S????t?ta ap?µ???s??
a???t??? (-)
Klebsiella spp. Pseudomonas aeruginosa Proteus
spp. Enterobacter spp. Morganella
morganii Citrobacter spp. Serratia spp.
????te?? s????
????te?? s????
Enterococci Staphylococcus saprophyticus
?et??? ()
4
S????? a?t?µ????ß?a??

• ?-?a?t?µe?
• ?µ????????s?de?
• S???f??aµ?de?/ ???µe??p??µ?
• ??t??f???a?t????
• (F???????????e?)

• ??t?µ????ß?a?? f?sµa
• ?e??ss?te?a ????pa?????a

• Fa?µa??????t??? fa?µa??d??aµ???
• ?p?????s? ap? t??? ?ef????
• ?????? s???e?t??se?? sta ???a

???ß??µata ?pa??? ? eµf???s? a?t????
5
?????ß?a?? a?t???

• Ge?et???
• ????d?a a?t????
• ?????µ???? µ??a??sµ??
• ?p??e?µe??? µ??a??sµ?? a?t????
• ????µas?e? e?a?s??s?a? sta a?t?µ????ß?a??
• e????ste? a?asta?t???? s???e?t??se?? (MICs)
• fa???t?p?? a?t????
• ???????
• ?e?ape?t??? ap?t??esµa

6
Ge?et??? t?? a?t????

• F?s??? ? e?d??e??? a?t???
• ?p???e? se ??a ta ste???? e??? e?d??? µ????ß???
• ???µ?s?µ?a??
• ??a?t?ta? ap? t? e?d?? t?? ßa?t?????
• ??e???t?t? ap? t? ???s? a?t?ß??t????
• E??a? p??ß????µ?!
• ?p??t?t? a?t???
• ?p???e? se µe???? ste????
• ???a? ap?t??esµa e?te a??a??? (µeta????e??) st?
  ???µ?s?µ?a?? DNA ? ?a? ap??t?s? ?e?et???? ??????
  ap? ???a ßa?t???a
• S?s?et??eta? µe t? ???s? t?? a?t?ß??t????
• ?p??ß?ept? ()

7
??d??e??? a?t??? sta ????pa?????a
  Escherichia coli Klebsiella pneumoniae Proteus mirabilis Enterobacter cloacae Pseudomonas aeruginosa Entero-coccus
??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat??
?µ??????????          
?µ??/?? ??aß          
?ef/?e? 2?? ?.          
??t??µ??a????          
??t??f???a?t????          
??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s?
?ef/?e? 3?? ?.          
?a?ßape??µe?          
?µ????????s?de?          
F???????????e?        

e?d??e??? a?t??? e?d??e??? a?t??? e?d??e??? a?t??? e?d??e??? a?t??? e?d??e??? a?t??? e?d??e??? a?t???
Leclercq R, et al, 2013
8
?p??t?t? a?t??? sta ????pa?????a
  Escherichia coli Klebsiella pneumoniae Proteus mirabilis Enterobacter cloacae Pseudomonas aeruginosa Entero-coccus
??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat?? ??t?ß??t??? ap? t?? st?µat??
?µ??????????          
?µ??/?? ??aß          
?ef/?e? 2?? ?.          
??t??µ??a????          
??t??f???a?t????          
??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s? ??t?ß??t??? ??a e?d?f??ß?a ???s?
?ef/?e? 3?? ?.          
?a?ßape??µe?          
?µ????????s?de?          
F???????????e?        

e?d??e??? a?t??? e?d??e??? a?t??? e?d??e??? a?t??? ep??t?t? a?t??? ep??t?t? a?t???
Leclercq R, et al, 2013
9
M??a??sµ?? a?t???? sta ????pa?????a
S????te??? t??p?? ep??t?t?? a?t???? sta
????pa?????a (pa?a???? ß-?a?taµ?s??)
10
?-?a?taµ?se? ?a? E. coli
?e????????e?
?efa??sp????e?
2?? ?e????
3?? ?e????
?a?ßape?eµ?se?
?????? f?sµat?? ß-?a?taµ?se? (ESBL)
??? pa?a???? pe?????????s??
?e?????????s? (???-1, SHV-1)
??ast???t?ta
11
In vitro a?t???-??t?ß????aµµa

• In vitro a?t??? t?? µ????ß??? e????eta?
  (fa???t?p???)
• ????d? t?? d?s??? (µ???d?? d????s?? t??
  a?t?ß??t???? st? ??a?)

?p?t??esµa ??a?s??t? S ??d??µes??
e?a?s??s?a? ? ???e?t??? R

• ????d? a?a??s?? t?? a?t?ß??t???? se ???? ? ste?e?
  ??ept??? ?????

?p?t??esµa ????? MIC

• E-test

?p?t??esµa ????ß?? MIC (p.?. MIC2mg/l)
12
Fa???t?p?? a?t???? ?a? e?µ??e?t??? d??ßasµa
a?t?ß?????µµat??

• Extended-Spectrum ß-Lactamases (ESBL)
• ??t???
• ?e????????e?, ?efa??sp????e? 1??,2??, 3??, 4??
  ?e????, a?t?e???µ?
• ??? t?? ?efaµ????e? (?ef???t???), ??? t??
  ?a?ßape??µe?
• ?p??e? ?a ?p???e? e?a?s??s?a/a?t??? st???
  a?ast??e?? t?? ß-?a?taµas?? (??aß???a????,
  ta??µpa?t?µ?, s???ßa?t?µ?)
• S?????? s???p???e? a?t???
• ?µ????????s?de?, ???????e?
• ??t??µ??a????
• S?????? p?asµ?d?a???
• ??? ???????e?a
• SHV ???????e?a
• CTX-M ???????e?a ? ep???ate? sta ste????
  ?????t?ta? (ST131)

13
? ????? t?? ?????ß?a??? a?t???? se K??????
ep?ped? ep????? t?? a?t?µ????ß?a??? a?????
???d???? µ????ß?a??? a?t???? 1) ??p???
ep?d?µ??????a t?? a?t???? st?? ?????t?ta 2)
?t?µ???? pa?????te?
14
???????µ??? t?? ?????t?ta? ap? a??e?t??? µ????ß?a
sta pa?d??

• ??s? s???? e??a? ?a ap?µ????eta? st??e??? µe
  e?d??e?? a?t??? sta s????? a?t?ß??t??? ?a? ap?
  p????? pa?????te? ep??e??eta?
• ??d?? t?? ????pa???????

15
??d?? ????pa??????? ?a a?t???
Non E. coli (15-40)
Bitsori M, et al 2013, Mantadakis E, et al 2011,
Markus et al 2005
16

• Non-E. coli (20-40)

17

• P. aeruginosa (2-10)
• ?efa?. 2 ?e????
• ??t??µ??a????

??t???

• ????pa?a???t??? a????s?
• ???? a?t?ß??t???? a????? t?? p??????µe?? µ??a
• ?p??e?µe?? ??s?? t?? ????p???t???? (??????
  pa???????? ?pe???????f?µa ?ef???)

18

• Enterococcus spp. (4-5)
• ?efa??sp????e?
• ?µ????????s?de?
• ??t??µ??a????

??t???
19
???????µ??? t?? ?????t?ta? ap? a??e?t??? µ????ß?a
sta pa?d??

• ??s? s???? e??a? ?a eµfa???eta? ep??t?t? a?t???
  st? s????te?? ????pa?????? (E. coli) ?a? ap?
  p????? pa?????te? ep??e??eta?
• ??s?st? e?a?s??s?a? ?a? fa???t?p?? a?t????
  s????te??? ????pa???????

20
?p??t?t? µ????ß?a?? a?t???
Ste???? E. coli
?a?ep. G?, ?????e?? ?e?????e?? G?, ?????e??
Bitsori M, et al 2013 Anatoliotaki M, et al 2007
21
?p??t?t? µ????ß?a?? a?t??? ??
Ste???? E. coli
Mantadakis E, et al 2011 ??s?f?d?? ?a? s??, 2006
22
?a?????te? ???d???? eµf???s?? ????pa??????? E.
coli ?a? K. pneumoniae µe ESBL (2-10) st??
?????t?ta
??e???t?? ?t?? d?µ.
?p??e?µe?? ??s?? ???.
???sfat? ??s??e?a
??µe??p??-f??a??
S????? ?p?t??p??
???sfat? ??. a?t?µ???
?p?µ???s? K.pneum.
?????a lt1?t???
N cases vs N controls

Topaloglu 2010 155 155
Dayan 2013 25 125
Kizilca 2012 146 196
Fan 2013 104 208
Bitsori 2009 27 363
v
v
v
v
v
v
v
v
v
v
v
v
v
23
??????? p???? ep????? ?e?ape?a?
???d??? a?t????

• ???st??? ? ?ate?????µe?? ?e?ape?a

• St?at??????
• ?µpe????? ?e?ape?a

??t?p?s?
?????a
??????? e????a
???a??? ?at??????
?p?d?as? st? ??s???t?ta
??t???, ??st??
24
?µpe????? ?e?ape?a Se????? 1

• ?????a lt 3µ???? ?
• ???f??- pa?d? µe t????? ??????? e????a
• ?aµß????µe ?p??? t?? ?pa??? a?t???? ?st? ?a?
  µ????? p??a??t?ta?
• ?d??? sta ?e???? ??a ta µ? E. coli ste????
• Sta µe?a??te?a pa?d?? ??a ep??t?t? a?t???

??????alt 3 µ???? ?µp???????? ?a?
aµ????????s?d? ? ?a???? p?s??? as?e??? ?efa??sp??
??? 3?? ?e??a? aµ????????s?d?
25
?µpe????? ?e?ape?a Se????? 2

• ???f??-pa?d? gt3µ????
• ????? t????? ??????? e????a
• ????? pa?????te? ???d????
• ?aµß????µe ?p??? t?? t?p??? ep?d?µ??????a
• ????? a?t??? se aµ?????????? ?a? aµp????????
• ????? a?t??? se ??t??µ??a????
• ?????te?? a??? ?pa??t? ? a?t??? sta ?p????pa
  a?t?µ????ß?a??

• ?S????? a?t?µ????ß?a?? ??a t?? ???????µ???
• ?efa??sp????? 2?? ?e???? (ap? t? st?µa) ? 3??
  ?e???? (e?d?f??ß?a) ? aµ??????????/??aß???a????
  (ap? t? st?µa)
• ? ?d?? ??????s?? ?a?????eta? a?????a µe t??
  e?t?p?s?/??????? e????a

26
?µpe????? ?e?ape?a Se????? 3

• ???f?? (gt3µ????) ? pa?d?
• ????? t????? e????a
• ?e pa?????te? ???d????
• ?p??e?µe?? ??s? t?? ????p???t????
• ???? ??µe??p??f??a???
• ???? a?t?µ????ß?a??? a????? t? te?e?ta?? µ??a
• ?p?t??p?????se? ???????µ??e??

??p?f??? ???s?? a?t?µ????ß?a??? p?? ?????
???s?µ?p????e? ???????a µe t? ßa??t?ta t??
???????? e????a? (eµp??et? ???????µ??? vs
??st?t?da) µp??e? ?a ??e?aste? ?a ???e?
s??d?asµ?? ß-?a?taµ???? µe aµ????????s?d? t??
p??te? ?µ??e?
27
?ate?????µe?? ?e?ape?a

• ???p?p???s? t?? a????? a?????a µe t?
  a?t?ß????aµµa
• ? ???e?t???/????a??e?t??? µ????ß?a

?e?a?t??? a??pt??? a?t????
??ast??? a?t?µ????ß?a??
28
???t?st? a?t?µ????ß?a?? a???? se p???a??e?t???
????pa?????a (ESBL)

• ??epa??? ded?µ??a
• EUCAST ??te??ßa?t????e?d?

• Sta pa?d?? e????sta ded?µ??a
• ?e??te? as?e???-µa?t????

Leclercq R, et al, 2013
29
?e t? ???st?p???s? t?? a?t???? (4-5 ?µ??e?) 92
pe??pt?se?? t??p?p??????e ? a????
??at?????? eµpe????? a????
30
??at?????? a???? se ??? t? ?e?ape?a
St?? ?at?????a non-carbapenem 83 ??aße
ß-?a?taµ??? p?? ?ta? e?a?s??t? st? a?t?ß????aµµa
(?ef?ta??µ?, p?pe?/ta??µp)
31
??ßas? ESBL? ? ??s???t?ta
32
??t? ep??????
7 t?? pa?d??? se ?a?d. Sta?µ??? st? Ga???a ?ta?
ap????sµ??a µe a??e?t??? ste???? E. coli (ESBL
?a? a?t??? st?? ???????e?) ap? t?? ?d?? ?????.
33
???a??st? ??a t?? p??s??? sa?!