Carbapenem-resistance in Enterobacteriaceae - SPILF · VJarlier 2010 Carbapenem-resistance in...
Transcript of Carbapenem-resistance in Enterobacteriaceae - SPILF · VJarlier 2010 Carbapenem-resistance in...
VJarlier 2010
Carbapenem-resistance in Enterobacteriaceae :
bacteriology and infection control view points
(in a country of low prevalence)
Vincent JarlierBacteriology-Hygiene
Pitié-Salpêtrière Hospital, Paris
Central Infection control teamAssistance Publique – Hôpitaux de Paris
VJarlier 2010
1st detection of CARBAPENEMASES in EUROPE
2001
1997
2004
2004
2005
VIM-1
KPC-2KPC-3
Carbapenemasesclass A
Carbapenemases class B, metalloenzymes
G.Arlet, ann biol clin, 2006
VJarlier 2010
1st outbreak in France : winter 2003-summer 2004
VJarlier 2010
Paul Brousse hospital
(Paris) 2004 Klebsiella pneumoniae VIM-1
+ SHV-5
(index case : transfer
from
Athens)
MIC : imipenem 32 mg/l ; gentamicin 8 mg/l
Pip Tic TzAmx
Ctx Amc CazFox
Imp
Atm TccCf
Mox
Fep
Ma
Amk NetTb
Cip Ofx
G
Pi
FosTmp
Cs
K
Sul
Courtesy: N. Kassis-Chikhani
~Therapeutical dead end
VJarlier 2010
Initial control measures From December 2003 to June 2004
–
IR-Kp
carriers isolation in 1 bed rooms
–
Promotion of alcohol-based-hand rubing
–
daily staff training
–
Screening ICU patients at admission and 1/week (rectal swabs, 4 mg/l imipenem
containing agar )
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
Extended control measures in June 2004 (1)
•
ICU divided in 3 separate sections–
1 for cohorting
IR-Kp
carriers (“IR-Kp ICU”)
–
2 for the IR-Kp-free patients (“IR-Kp free ICU”)•
for expected duration >> 2days and “heavy”
ICU (“”long”)
•
for expected duration ≤2days and “ligth”
ICU (“short”)
•
Acute care divided in two sections :–
1 for IR-Kp-free patients but
transferred from ICU or
patients previously hospitalized in the ward (at risk
to be carrier : ”contact patients”)
–
1 for new
patients (not
at risk : “IR-KP free ACF”)Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
Paul Brousse
hospital (Paris) 2004 Klebsiella pneumoniae VIM-1
+ SHV-5 :
splitting the ward in distinct sectors
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
•
nurse staff exclusively dedicated to “IR-Kp ICU”
•
nurse staff exclusively dedicated to “IR-Kp free ICU”
Extended control measures in June 2004 (2)
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
•
Strict limitation of patient transfer
to other wards or other care centers :
•
Screening all contact patients till discharge and after and in case of readmission
•
Limitation of broad spectrum antibiotics•
IR-Kp
carriers informed on their status and
received specific instructions at discharge
Extended control measures in June 2004 (3)
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
Paul Brousse hospital
(Paris) 2004 Klebsiella pneumoniae VIM-1
+ SHV-5 :
screening : 277 patients (~1,000 swabs)
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
December January MarchFebruary April May June July August
1
2
3
4
7
8
6
ICU4th
floor
Medecine
unit
3rd
floor
5
First isolation of KP
Rectal swab
Blood
Broncho-pulmonary
Urine
Urine
Rectal swab-Blood-Abdominal
Rectal Swab
Rectal swab
2
No link link
MDR Mesures renforcées
Paul Brousse hospital
2004
Classical MDR measures Reinforced measures
No new case since 2005
Kassis-ChikaniEurosurveillance
2010 in press
VJarlier 2010
Practicing control of emerging MDROs
in France : VRE
Summer 2004-2007
VJarlier 2010
VRE cases per month 39 univ. hosp. Paris area (AP-HP)
2004-2007
0
10
20
30
40
50
08.0
409
.04
10.0
411
.04
12.0
401
.05
02.0
503
.05
04.0
505
.05
06.0
507
.05
08.0
509
.05
10.0
511
.05
12.0
501
.06
02.0
603
.06
04.0
605
.06
06.0
607
.06
08.0
609
.06
10.0
611
.06
12.0
601
.07
02.0
703
.07
04.0
705
.07
06.0
707
.07
08.0
709
.07
10.0
7
Date
Nom
bre
Nouveaux cas Infection
Classical MDRmeasures
Reinforced measures (2006)
Founier 2010 submitted
VJarlier 2010
VRE cases per month observed and predicted by time series analysis
39 univ. Hosp. Paris area (AP-HP) 2004-2007
-10
0
10
20
30
40
50
60
Aug
-04
Oct
-04
Dec
-04
Feb-
05
Apr
-05
Jun-
05
Aug
-05
Oct
-05
Dec
-05
Feb-
06
Apr
-06
Jun-
06
Aug
-06
Oct
-06
Dec
-06
Feb-
07
Apr
-07
Jun-
07
Aug
-07
Oct
-07
Dec
-07
Mon
thly
num
ber o
f VRE
cas
es
Observed casesPredicted values from the segmented regression modelPredicted values (with 95% CI) from the segmented regression model estimated on period 1
Period 1 (Multidrug resistant bacteria guidelines)
Period 2(Enhanced measures)
Founier 2010 submitted
95% CI
Classical MDRmeasures
Reinforced measures (2006)
VJarlier 2010
The 23 VRE outbreaks in 39 univ. hosp. Paris area (AP-HP)
2004-2007
Aug-
04Oc
t-04
Dec-0
4Fe
b-05
Apr-0
5Ju
n-05
Aug-
05Oc
t-05
Dec-0
5Fe
b-06
Apr-0
6Ju
n-06
Aug-
06Oc
t-06
Dec-0
6Fe
b-07
Apr-0
7Ju
n-07
Aug-
07Oc
t-07
Dec-0
7
(894 days - 112 cases)(310 days - 17 cases)
(62 days - 9 cases)(168 days - 4 cases)(60 days - 3 cases)(7 days - 3 cases)
(63 days - 39 cases)(31 days - 6 cases)
(568 days - 68 cases)(782 days - 37 cases)
(25 days - 3 cases)(70 days - 11 cases)
(7 days - 4 cases)(30 days - 5 cases)
(116 days - 5 cases)(29 days - 2 cases)
(109 days - 16 cases)(94 days - 2 cases)(92 days - 6 cases)(32 days - 4 cases)(34 days - 2 cases)
(49 days - 14 cases)(13 days - 8 cases)
(Duration of outbreak - No. of cases)
Start in period 1Start in period 2
*
*
**
**
*
**
*
Classical MDRmeasures
Extendedmeasures (2006)
Founier 2010 submitted
VJarlier 2010
Releasing French national guidelines for emerging
MDROs
control (e.g. Carb-R Enterobacteriaceae):
2006 (new edition 2010)
VJarlier 2010
As soon as identification of the index case
•
Isolate
the patient in a single bedroom •
Alert
hospital administrator and IC team•
Stop transfer
to other units or hospitals of (a) the index case and (b) patients of the same unit (defined as contact patients)
•
Limit admissions
in the unit as much as possible•
Screen contact patients
French MDRO control guidelines 2006, 2010
VJarlier 2010
The two days following the identification
•
Identify other contact patients: including those already transferred to another unit of the hospital at time of detection of the index case.
•
Screen
them•
Re-enforce hand hygiene
(alcohol base hand-rub
solution)•
Clean daily patient environment with disinfectant
•
Identify antibiotics that could be used in case of serious infection with the strain of the index case
French MDRO control guidelines 2006, 2010
VJarlier 2010
During the entire period of the outbreak•
Cohort patients in distinct sections, each with dedicated nursing staff:
-
case patients («
case section")-
contact patients ("contact patient section
")
-
newly admitted patients ("free section
")•
Screen once weekly
all contact patients •
After 3 neg
screenings, contact patients can be transferred in other unit of hospital (continue to isolate and screen)•
Resume screening in contact patients receiving antibiotic.•
Restrict antibiotics use•
Update the list of cases and contact discharged patients, set up an information system allowing to identify them in case of re-admission
French MDRO control guidelines 2006, 2010
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae at the bench
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae :
(1)
warning
VJarlier 2010
KPC-2K.pneumoniaePetri dish 1
Courtesy Kassis-Chikani
cefotaxime
Imip
VJarlier 2010
KPC-2K.pneumoniaePetri dish 2
Ertap ImipErtap Imip
Courtesy Kassis-Chikani
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae :
(2)
phenotypic confirmation
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae :
(2)
phenotypic confirmation
Metalloenzymes
VJarlier 2010
Extended-spectrum β-lactamase (ESBL) SHV-5
IMP IMPIMP+IMP+EDTAEDTA
IMPIMP
+ EDTA+ EDTA
cefepimcefepimceftazidimeceftazidime
clavulclavul + EDTA+ EDTA
VIM-1 + SHV-5 :Synergy tests for detecting
metallo-carbapemenases and ESBL
Kassis-ChikaniJAC 2006
VIM
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae :
(2)
phenotypic confirmation
Class A enzymes
VJarlier 2010
Imip-EDTA = neg Imip-Clav = pos
~ 0.5 mg/l
Synergy tests for mclasse
A carbapemenases
:
Example of KPC-2
Courtesy Kassis-Chikani
VJarlier 2010
Céfépime
Cefotax
Clav
KPC-2K.pneumoniae
Synergy C3G –clavulanate
Narrowing the distance betweenC3G and clavulanate disks
Still a doubt
VJarlier 2010
KPC-2K.pneumoniae
Synergy C3G –clavulanate
CéfépimeCefotaxCeftaz
Idem + adding clavulanateon the disks
No more doubt
VJarlier 2010
KPC-2K.pneumoniae
Hodges testimipénème
Hodges
test (~ Gots
test)
E.coli wt
KPC‐2 Kp
VJarlier 2010
KPC-2K.pneumoniae
Hodges testertapénème
Hodges
test (~ Gots
test)
KPC‐2 Kp
E.coli wt
VJarlier 2010
Detecting carbapemenase- producing
Enterobacteriaceae :
(3)
identification of enzyme : molecular tests
required
VJarlier 2010
Controlling further outbreaks of Carb-R Enterobacteriacea
in France : applying the new
guidelines
VJarlier 2010
Early warnings concerning carbapemenase-R
Enterobacteriaceae in French hospitals
(frame: French national system for signaling abnormal nosocomial events)
- 24 events 2004-2010 -
so far all controlled
(but wait and see!!!)Vaux 2010 being submission
VJarlier 2010
Investigations and control measures of a KP-KPC2 outbreak occurring in hospitals A,B and C
Suburb South of Paris, September-December 2009
A : date of admissionD : date of duodenoscopy+ : date of 1st positive specimen Carbonne
Eurosurveillance2010 in press
• 1 source case (from Greece)• 7 secondary cases linked
with duodenoscopy• 5 secondary cases linked
with cross-transmissionthrough care
Total : 13 cases
VJarlier 2010
G
E
CA
D B
Haute-Normandie
Ile-de-France
Centre
Transfer of case
Hospitals where cross-transmission occurred
Hospitals where cases were transferred (no further cross-transmission)
Investigations and control measures of the KP-KPC2 outbreak in hospitals A,B,C and D,E,F,G
September-December 2009
CarbonneEurosurveillance
2010 in press
F
Screened contacts : 341A: 87B: 208C: 25
D: no contactE: no contact
F: 3G: 18
No new case since December 2009
VJarlier 2010
ESBL and Carbapenemases :
break « the infernal
circle »
VJarlier 2010
ESBL E.coli in Europe
VJarlier 2010
EARSS : E.coli resistant
to 3rd gen. cephalosporins (%) in bacteremias
2002 2009
2% 6.5%* ~5% ESBL
VJarlier 2010
% R 3rd gener. Cephalosporins in E.coli Bacteremias
in Europe, EARSS 2006-09
Stability or small increase
VJarlier 2010
ESBL K.pneumoniaein Europe
VJarlier 2010
EARSS : K.pneumoniae resistant
to 3rd generation
cephalosporins in bacteremias
2% 19%
2002 2009
~15% ESBL
VJarlier 2010
% R 3rd gener. Cephalosporins in K.pneumoniaeBacteremias
in Europe, EARSS
2006-09
Stability or small decrease
VJarlier 2010
Relation 3rd Gen Cephalosporin-Resistance E.coli vs. K.pneumoniae
EARSS 2007 : 26 countriesTitre du graphique
y = 0,2768x + 1,8969R2 = 0,4221
0
5
10
15
20
25
30
35
40
45
0 20 40 60 80 100CTXKpneu
CTX
Ecol
i
%_CTXEcoLinéaire (%_CTXEco)
R=0.65
VJarlier 2010
ESBL at national level
VJarlier 2010
ESBL National survey (« RAISIN ») Incidence rate / 1,000 DHs per area
2004-2008 (227 hospitals 3 months/year)
0
0,1
0,2
0,3
0,4
0,5
0,6
2004 2005 2006 2007 2008
NorthParisEastWestS.EastS.WestTOTAL
0.17
0.31
Rate x 2 in 4 years
VJarlier 2010
ESBL national survey
(«
RAISIN
») Incidence rates / 1,000 DHs
per activity
227 French hospitals
(3 months/year) 2003-2007
0
0,2
0,4
0,6
0,8
1
1,2
1,4
2003 2004 2005 2006 2007
Acute
ICU
LCF
TOTAL
ICU
all acute care
VJarlier 2010
Consommation
des Blactamines
à
large spectre
à
l’AP-HP 2003-09
0
2
4
6
8
10
12
14
16
2003 2004 2005 2006 2007 2008 2009
DD
J/1
00
0 J
H
Ceftriaxone Cefotaxime
0
2
4
6
8
10
12
2003 2004 2005 2006 2007 2008 2009
DD
J/1
00
0 J
H
Ceftazidime Tazocilline
0
2
4
6
8
10
12
2003 2004 2005 2006 2007 2008 2009
DD
J/10
00 J
H IMIPENEMEERTAPENEMEMEROPENEMECarbapénèmes
CefotaximeCeftriaxone
PIP-TAZ
Carbapénèmes
Ratio2 – 1 - 1
1/100 JH !!!
VJarlier 2010
Carb-R Enterobacteriaceae
VJarlier 2010
K.pneumoniae IMP-R en GRECE
A. Vatopoulos, eurosurveillance, 2008
VJarlier 2010
K.pneumoniae IMP-R en ISRAEL (Tel Aviv)
Epidémie de souches K. pneumoniae résistantes aux carbapénèmes possédant KPC-2et KPC-3 dans un hôpital à Tel Aviv de 2004 à 2006.12 clones différents et un clone majeur Q avec des profils de sensibilité différents
A.leavitt, AAC, 2007
VJarlier 2010
% R Imipenem in K.pneumoniae Bacteremias, EARSS 2005-08
0
10
20
30
40
50
2005 2006 2007 2008year
% IM
I R a
nd #
cou
ntrie
s w
ith c
ases
Israel
Greece
Cyprus
Italy
Turkey
UK
N countrieswith casesN=6
N=15
VJarlier 2010
The MDROs control programmes in France : starting 1993
VJarlier 2010
MDR program
RegionalUniv. hospitals
Paris area(AP-HP)
1993
VJarlier 2010
MDR program
National
1999
VJarlier 2010
Alcool based
hand rub solution
campaigns
2001-02
VJarlier 2010
MRSA in Europe (% in S.aureus) EARSS 2001-2009
23%
2009
33.2%
2001
24% in 2008
VJarlier 2010
18,4
39,4
0,41
0,90
0,51
1,16
0,0
5,0
10,0
15,0
20,0
25,0
30,0
35,0
40,0
45,0
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008 année
% d
e SA
RM
par
mi l
es S
.aur
eus
0
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
inci
denc
e po
ur 1
00 a
dmis
ou
100
0 jo
urs
% de SARMincidence pour 100 admissionsincidence pour 1000 JH CS
% MRSA in S.aureus and MRSA incidence in acute care
Univ. hospitals of Paris area (n=39) 1993-2007
% MRSA in S.aureusRate per 100 admissionsRate per 1.000 DHS
Global decrease : 53 %
Jarlier
Arch
Int Med 2010
VJarlier 2010
Classical contact precautions used to control MRSA will not be enough
for
controlling emerging “digestive tract driven”
MDROs
such as ESBL and Carb-R
Enterobacteriaceae• Mobile resistance elements
– spread of strains…– …but also spread of mobile elements
• Bacterial (and mobile elements) excretion – ~1010 per carrier and per day (feces) – ~109 per day and per UTI
• Wastes = feces and urines environment– risk of “back trough food chain”
VJarlier 2010
ESBL in hospital
wastewater (1) Brazil
Letters in Applied Microbiology 2008
VJarlier 2010
ESBL in hospital
wastewater (2) Portugal
J Antimicrob Chemother 2009
VJarlier 2010
Antibiotic
consuption
in Europe – Community
-
ESAC 2002
ESAC Goossens et al., Lancet 2005
VJarlier 2010
HC
us e
in D
DD
/100
0 in
h abi
tant
s/da
y
FI FR HR LU PL BE GR EE SI MT DK SK HU SE NO0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
Penicillins J01C
Tetracyclines J01A
Macrolides J01F
Quinolones J01M
Sulfonamides J01E
Others*
CephalosporinsJ01D
Vander Stichele J. Antimicrob. Chemother 2006; 58:159 – 167
Antibiotic
consuption
in Europe – Hospital
-
ESAC 2002
VJarlier 2010
Antibiotic
policy campaigns
in hospitals of Paris area
(AP-HP) 2006-10
VJarlier 2010
Antibiotic
consumption
in the 39 hospitals
of Assistance Publique –
Hôpitaux de Paris
2003-09Source : AGEPS-Direction des finances
Analyse : EOH/DPM
515 514
468 465
452
529
483
400
420
440
460
480
500
520
540
2003 2004 2005 2006 2007 2008 2009
DD
J/10
00 J
H
2005-2009 : - 15% only !!!
VJarlier 2010
Absolute needs today in France•
Apply specific extended measures (quick and strong intervention as soon as 1st case) for controlling emerging MDRs (Carb-R Enterobacteriaceae, VRE…)
•
Set up a global approach to limit (slow down) the spread of ESBL including E.coli (combine community, hospital, farming, environment) : take profit of a still low incidence !!!
•
Drastic restriction of antibiotic use in the community, hospital, animal
VJarlier 2010
Antibiotic stewardship and ESBL-carbapemenase
problem
• Decrease drastically global ATB consumption(e.g. in France by a factor of 2-3 !
• Promote all possible alternatives to 3rd gen. cephalosp., fluoroquinolones and carbapenems
e.g. : betalactams- inhibitors, cephamycins, nitrofuranes, fosfomycine…
• revisit in depth national recommendations (UTIs, abdominal surgery…)
VJarlier 2010
Prevent X trans-mission
Identifycarriers at discharge
Identify risk factors for carriage at entry
Decreaseantibioticpressure
ESBL spread in community (x trans + ATB)
X transmission
in HCFs
Colonization(high contration)
Patients enterring HCFs with ESBL
(low contration)
Environment, water supply, food chain
ATB policy + prevent X transm. (school, family, elderly homes..)
Wastewater treatment
Farming, Food & water
DischargeAdmission
ATB
VJarlier 2010
•
Controlling MDROs
= saving a precious collective treasure : antibiotics
•
concern comparable to saving clean water and forests or preventing planet global warming
•
1st irruption of sustainable development in medicine
VJarlier 2010
VJarlier 2010
Stabilize (at least slow down) ESBL rates and
prevent carbapemenases
spread
•
Hospital•
Community
•
Environment
•
Cross transmission•
ATB policy
•
Food-water supply
Global and integrated approach