Significant changes in the epidemiology of Bloodstream Infections

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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).