Bloodstream Infection Study Group of the Réseau des Hygiénistes du Centre ... BSI surveillance program in the Centre region of France (2.7 M inhabitants) and ...
Significant changes in the epidemiology of Bloodstream Infections Results of a prospective, longitudinal, regionwide survey conducted between 2007 and 2013 Coralie Danet1, Houssein Gbaguidi-Haore2, Julie Ortiz1, Sandra Borges Dos Santos3, Nicole Girard1, Roland Quentin3, Nathalie van der Mee-Marquet1,3 on behalf of the Bloodstream Infection Study Group of the Réseau des Hygiénistes du Centre 1Réseau
des Hygiénistes du Centre, 3Service de Bactériologie et d’Hygiène, CHRU Tours, France 2Service d’Hygiène Hospitalière CHRU Besançon, France
BSI surveillance program in the Centre region of France (2.7 M inhabitants) and a microbiological study of S. aureus and ESBLE isolates since 2000 • • • • •
National Standardized Protocol
Data collected 3 months of each year stable cohort : 33 hospitals and clinics 6330 short-stay beds 3,258,015 patient days variable studied :
. PARIS Tours
•
• patient age and sex, • recent history of catheterization (urinary,
– one central lab – tested for antimicrobial susceptibility – genotyped (PFGE, MLST)
intravenous) and mechanical ventilation,
• portal of entry
• cutaneous
surgical site
pulmonary
urinary
intravenous devices
digestive tract
endocarditis
osteoarticular
• acquisition – –
S. aureus and ESBLE isolates collected during the 7 survey periods
Into the community-stting Healthcare-associated
study period 2007-2013 – 7274 BSI cases • 3801 CA-BSI • 3473 HA-BSI • 4157 males, 3117 females
• death within 7 days of diagnosis
•
BSI incidence determined with respect to the number of patient days (PDs)
– 1096 S. aureus (MRSA 24%) – 2334 E. coli (ESBL+ 4 %) – 126 ESBLE : 88 E. coli, 27 K.pn
/1000 PD
BSI incidence rate (/1000 PD) (all BSI, all microorganisms)
CA-BSI /1000 PD 1,6
2
R = 0,5262
1,4 1,2 2
R = 0,848
1 0,8
HCA-BSI
0,6 0,4 0,2 0 2007
2008
2009
2010
inc CA-BSI R² coefficient of determination (linear regression)
2011
2012
2013
inc HCA-BSI
de Kraker ME, Clin Microbiol Infect. 2013 Gagliotti C Euro Surveill. 2011
Incidence rate (/1000 PD)
/1000 PDof determination (linear regression) R² coefficient
CA-BSI
HCA-BSI
Patient sex 1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
/1000 PD 2
R = 0,4977
2
R = 0,4827
2007
2008
2009
2010
CA-BSI in male
2011
2012
1 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
R = 0,8387
2
R = 0,8247
2007
2013
2
/1000 PD
2008
2009
2010
HCA-BSI in male
CA-BSI in female
2011
2012
2013
HCA-BSI in female
Patient age (year) 80 78 76 74 72 70 68 66 64 62 60
year 2
R = 0,7424
R2 = 0,5011
2007
2008
2009
2010
CA-BSI in male
2011
2012
CA-BSI in female
2013
80 78 76 74 72 70 68 66 64 62 60
year
2
R = 0,0363
2
R = 0,2735 2007
2008
2009
2010
HCA-BSI in male
2011
2012
HCA-BSI in female
2013
Incidence rate (/1000 PD)
R² coefficient of determination (linear regression)
Major portal of entry 0,5
/1000 PD
2
R = 0,2719 0,4 0,3
2
R = 0,7017 0,2
CA-BSI
0,1 0 2007
2008
E. coli and S. aureus
2009
2010
urinary CA-BSI
0,5
2011
2012
2013
digestive CA-BSI
/1000 PD
R2 = 0,5168
0,4 R2 = 0,6324
0,3 0,2
HCA-BSI
R2 = 0,9048
0,1 R2 = 0,6572 0 2007
2008
post-surgical BSI
2009
2010
urinary HCA-BSI
2011 IVD-BSI
2012
2013
digestive HCA-BSI
E. coli BSI incidence rate (/1000 PD)
/1000 PD
0,7
2
R = 0,3951 0,6 0,5 0,4 0,3 0,2
2
R = 0,5468 0,1 0 2007
2008
2009
2010
E. coli CA-BSI
ATBtypes
0,5
WT ticar S
ticar R
/1000 PD 2
R = 0,204 0,4 0,3
2
R = 0,073
0,2 2
R = 0,934
0,1
2011
2012
2013
E. coli HCA-BSI
3rd Gen. Cephalosp. R AmpC ESBL
0,06
2
/1000 PD
R = 0,9086
0,05 0,04 0,03 0,02 2
R = 0,7402
0,01
0
0
2007
2008
2009 Ticar S
2010
2011
Ticar R 3rdGC S
2012 3rdGC R
2013
2007
2008
2009 ESBL+
2010
2011
3rdGC R ESBL-
2012
2013
E. coli BSI incidence rate (/1000 PD) Portal of entry 0,4 0,3 /1000 PD
2
R = 0,5029
0,2 2
R = 0,115
0,1 0 2007
2008
2009
2010
E. coli dig CA-BSI
0,4
2011
2012
2013
E. coli dig HCA-BSI 2
R = 0,1612
/1000 PD
0,3 2
0,2
R = 0,6395
0,1 0 2007
2008
2009
2010
urin CA-BSI
2011 urin HCA-BSI
2012
2013
ESBL-producing E. coli BSI Major portal of entry 0,5
/1000 PD
R2 = 0,1127
0,4 0,3 0,2 R2 = 0,8601
0,1 0 2007
2008
2009
2010
E. coli ESBL+ Urin-BSI
0,25
2011
2012
2013
E. coli ESBL- Urin-BSI
R2 = 0,3442
/1000 PD
0,2 0,15 0,1 R2 = 0,5886
0,05 0 2007
2008
2009
2010
E. coli ESBL+ Dig-BSI
2011
2012
E. coli ESBL-Dig-BSI
2013
ESBL-producing E. coli BSI 16,0
15,1
%
14,0
11,9
12,0 10,0 8,0 5,4
6,0
6,6
5,3
4,1
2,6
4,0 2,0
5,1 4,8
3,9 3,9
5,6
1,4 1,1
0,0 2007
2008
2009
2010
Prevalence E. coli ESBL+ in male
Patient sex 0,035
2011
2012
2013
Prevalence E. coli ESBL+ in female
High genetic diversity /1000 PD
0,03 0,025
2
R = 0,7403
0,02 0,015 2
R = 0,7322
0,01 0,005 0 2007
2008
2009
2010
E. coli ESBL+ in male
2011
2012
E. coli ESBL+ in female
2013
S. aureus BSI incidence rate (/1000 PD)
0,300
/1000 PD
R2 = 0,3036
0,250 0,200 0,150 0,100
2
R = 0,3919
0,050 0,000 2007
2008
2009
2010
2011
S. aureus CA-BSI MSSA
2012
2013
S. aureus HCA-BSI
MRSA
Methicillin resistance 0,35 0,3 0,25 0,2 0,15 0,1 0,05 0
2
/1000 PD
R = 0,5589
%
30,0
28,1 26,1
MRSA prevalence (%) 23,6
25,0
19,3
22,1 18,5
20,0 2
R = 0,0147
12,5
15,0 10,0 5,0
2007
2008
2009
2010
MRSA-BSI
2011
2012
MSSA-BSI
2013
0,0 2007
2008
2009
2010
2011
2012
2013
S. aureus BSI incidence rate (/1000 PD)
R² coefficient of determination (linear regression)
Portal of entry 0,12
R2 = 0,3003
/1000 PD
0,1 0,08 R2 = 0,2837
0,06 0,04
R2 = 0,241
0,02 0 2007
2008
2009
2010
cutaneous portal of entry 0,025
2011
2012
post-surgery
2013 IVD
/1000 PD
0,02 2
R = 0,2168 0,015 0,01 0,005
R2 = 0,4817
0 2007
2008
2009
2010
osteo-articular infection
2011
2012
endocarditis
2013
MRSA BSI
CC80-MRSA 1% CC72-MRSA 1% CC15-MRSA 1% CC1-MRSA ST1-MRSA 3%
ST8-MRSA CC8-MRSA
3%
50%
%
K
ST5-MRSA CC5-MRSA
100 90 80 70 60 50 40 30 20 10 0
an To a br G a en t Te a tr a Er Li y nc o P Fo R sf o FQ R ifa Fu m s Va id nc Te o ic o SX T M U P
others-MRSA 15%
29%
CC8-MRSA
0,060
/1000 PD
0,050 2
0,040
R = 0,3306
0,030 0,020 2
0,010
2008
2009
2010
CC5-MRSA
2011 CC8-MRSA
2012
ST5
ST1
ST1 CC8-MRSA CC5-MRSA CC1-MRSA allAll-MRSA MRSA
0,000 2007
CC1-MRSA
100% 80% 60% 40% 20% 0%
ST8
R = 0,4549
CC5-MRSA
2013
cutaneous urinary
surgical site IVD
pulmonary digestiv
NK endocarditis
others osteo-articular
genital
MSSA BSI
11%
CC9, Lamamy CID 2013 0,080
/1000 PD
2
R = 0,2685
0,070
5-MSSA
30-MSSA
45-MSSA
8-MSSA
1-MSSA
398-MSSA
22-MSSA
121-MSSA
SX T M U P
ic o
nc o
Te
si d
Va
CC45-MSSA 13%
Fu
ST8-MSSA CC8-MSSA
K
CC30-MSSA 19%
ifa m
others-MSSA 10%
FQ
CC15-MSSA 7%
R
6% 6%
sf o
24%
CC1-MSSA ST1-MSSA
PR
ST5-MSSA CC5-MSSA
%
Fo
CC121-MSSA 2%
100 90 80 70 60 50 40 30 20 10 0
an a To br a G en ta Te tra Er y Li nc o
CC398-MSSA CC22-MSSA 3% 5%
15-MSSA
100% 80%
0,060 0,050
R2 = 0,3087
0,040
R = 0,3105
0,030
R2 = 0,0162
2
0,020 R2 = 0,9405
0,010
60% 40% 20% 0% 5-MSSA 30-MSSA 45-MSSA 8-MSSA 15-MSSA 1-MSSA
398MSSA
0,000 2007
2008 5-MSSA
2009 30-MSSA
2010 398-MSSA
2011 45-MSSA
2012
2013 8-MSSA
cutaneous
surgical site
pulmonary
urinary
IVD others
digestiv genital
neutrop endocarditis
NK osteo-articular
rapid changes in the epidemiology of BSI •
involving the 2 major pathogens, E. coli and S. aureus
•
increasing incidence of CA-BSI associated with a digestive portal of entry – –
E. coli of WT and ESBL-producing isolates CC398 MSSA
potential role of food?
MRSA and ESBLE in food products emergence of livestock associated S. aureus : CC398, CC9, CC97 Poultry consumption as a risk factor for CA-MRSA colonization
•
Increasing incidence of HCA-BSI associated with urinary, surgical site and IVD – – –
increasing ability to colonize human flora ability to escape human host (CC398) increasing virulence ? • •
E. coli : increasing incidence for intestinal invasive infection S. aureus CC398 : increasing incidence for endocarditis and osteao-articular infection
subpopulations of isolates with great ability to colonize and infect human • •
host jumps in livestock environments ? horizontal transfer of genetic elements associated with human adaptation in livestock environment ?
=> alert about the need to consider these changes for the adaptation of infection control strategy especially before invasive procedure
?
CC398
MRSA in pig: livestock, human contacts and food products (Armand-Lefevre, 2005; Witte, 2007; van Belkum, 2008) a recent evolution MSSA in human, BSI, in animal-free environment (Price, 2012; Valentin-Domelier, 2011; Jimenez, 2011; Stegger, 2010; Uhleman, 2012) Enhanced adhesion to human keratinocytes and keratin, high transmissibility (Uhleman, 2012) Acquisition of a MR11-like prophage (genome accession number KC595279) » » » »
inserted into smpB superantigen similar to enterotoxin B putative RM system helper phage => during stress and lysogeny, expression of prophage-encoded chp and scn virulence genes carried by the human specific φ3-prophage => resistance against uptake of foreign DNA of the MR11-like-prophage Enhanced pathogenicity in human
(van der Mee-Marquet et al., Inf Gen Evol 2013)
Abdelbary 2014 Agnoletti 2014 Tavakol 2012
Significant changes in the epidemiology of Bloodstream Infections Results of a prospective, longitudinal, region-wide survey conducted between 2007 and 2013 Pr R Quentin, Service Bactériologie et Hygiène, CHRU Tours France The members of the Bloodstream infection study Group of the Réseau des Hygiénistes du Centre are AMIRAULT P (Vierzon), ARCHAMBAULT M (Pithiviers), BACHELIER MN (Bourges), BLOC D (Tours), BOUCHER M (Chateaudun), CATTIER B (Amboise), CHANDESRIS C (Amilly Montargis), CHEVEREAU V (La Chaussée St Victor), COUROUBLE G (Chateauroux), COURTIN M.-C (Amboise), DECREUX C (Chateauroux), DE GIALLULY C (Tours), DENIS C (Loches), DEPERROIS F (Chinon), FIEVRE C (Le Blanc), FOLOPPE P (Loches), FONGAUFFIER F (Chateaudun), FOURNIER-HOOCK R (Amilly Montargis), GIRARD N (Tours), GOURDET T (La Chaussée St Victor), GRAVERON JL (Fleury Les Aubrais), GROBOST F (La Ferté Bernard), GUILLON MF (Chateauroux), GUINARD F (Bourges), HARRIAU P (St Amand Montrond), HOMBROUCK-ALET C (Blois, Vendome, Romorantin), IMBAULT D (Vendome), JEHANNO D (Fleury Les Aubrais), KOURTA MJ (Chateaudun), LAURENT O (St Doulchard), LEHIANI O (Vierzon, Bourges, St Amand Montrond), LEPINEUX DA ROCHA A (St Amand Montrond), LESIMPLE AL (Vendome), LOUVIER X (Gien), MICHEL V (Le Blanc), MORANGE V (Tours), MOREL-DESJARDINS E (Bourges), MORIN E (Orléans), NAUDION C (Romorantin), NARBEY D (Blois), NEVEU C (Dreux), PABA O (Vendome), PERIGOIS F (Le Blanc), PETIT LE GOUAS G (Nogent Le Rotrou), POITVIN D (Chinon), PREVOST-OUSSAR M (Pithiviers), RATOVOHERY D (Chateauroux), ROUSSEAU B (Gien), ROUSSIN A (Orléans), SECHER A (Dreux). WATT S (Chinon).