of S.aur S.aur e us in e us in the the hospita l hospita l a nd - - PowerPoint PPT Presentation

E pide miolog y E pide miolog y a nd a nd re sista nc e re sista nc e

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• f S.aur

e us S.aur e us in

in the the hospita l hospita l a nd a nd the the c ommunity c ommunity

M.Strue le ns UL B-Ho p ita l Era sme

T he E ve r More Re sista nt

Staphylococcus aur e us

1950 Penicillin R 1961 Oxacillin R 1969 Gentamicin R 1997 Vancomycin I 2002 Vancomycin R Plasmid Plasmid Tn4001 Plasmid Tn1546 SCCmec Mutation

mec complex ccr complex

SCCmec I SCCmec I I SCCmec I V SCCmec I I I SCCmec V

• rfX

IS431 mecA

Staphylococcal Cassette Chromosome mec

Tn554 pUB110 pT181

THE EVOLUTION OF MRSA

Enright et al. PNAS 2002;99:7687

20 40 60 80 100

Cipro Erythro Clinda Genta Tobra Mino

1995 1997 2001 2003 2005

Proportion of MRSA resistant to antimicrobials, Belgium 1995-2005

% of isolates

National surveys, MRSA reference laboratory

S.aureus ATCC 29213 VISA strain - P1V44 Vancomycin MIC 8 mg/l

T he Sha dow Muta nt: Va nc omyc in Inte rme dia te S.aur

e us / VISA

Denis JAC 2002;50:383

Electron microscopy X 60.000

Na tiona l surve ys of MRSA with de c re a se d va nc omyc in susc e ptibility

Author, year Country

• No. of Strains

Percent Hetero VI SA Percent VI SA Hiramatsu, 1997 Japan 1149 1_20 Kantzanou, 1999 Greece 56 1.8 Schmitz, 1999 Europe 302 Geisel,1999 Germany 85 8.2 Bierbaum, 1999 Germany 457 0.5 0.2 Chesneau, 2000 France 25 20 Nonhoff, 2005 Belgium 455 0.7

*screening at 4 µg/ml and MIC after subculture at increasing concentrations of vancomycin

*

MIC distribution for 511 MRSA isolates, Belgian hospital survey, 2003

Denis AAC 2006

20 40 60 80 100 0.06 0.12 0.25 0.5 1 2 4 Daptomycin Tigecycline Ceftobiprole Linezolide

MIC µg/ml % of isolates

L ine zolid Re sista nt S.aur

e us

• Rare case reports of emergence during

treatment

• Long-term treatment of CAPD MRSA

peritonitis

• Multi-copy 23S rRNA V region mutations
• No fitness cost of mutation detected

Tsiodras Lancet 2001;358:207 Pillai JID 2002;186:1603

S.aureus daptomycin resistance emergence in bacteremic patients

• RCT of daptomycin vs PRP or vancomycin +

gentamicin for bacteremia/ RS endocarditis

• 44% vs 42 % success at 42 days D vs STD
• Microbiological failure in 16 % D vs 10 %

STD therapy

• 6/19 daptomycin failure showed 8-fold MIC

increase

Fowler NEJM 2006;355:653

Methicillin resistance of S. aureus isolates from blood cultures, 2005

http://www.earss.rivm.n

Isola tion Pre c a utions for MRSA by E urope a n Re g ion,

2001

10 20 30 40 50 60 70 80 90 100

% hospitals

All Northern Western South + I sr.+ TK Southeast C.+ E.+ Balt.St.

SINGLE ROOM GLOVES GOWN

* = p<0.01

10 20 30 40 50 60 Den Neth Lux Ger Bel Gre Ire Por UK 1999 2000 2001 2002 2003 2004 2005

Trends in MRSA bacteraemia EARSS, 1999 to 2005

% of S. aureus http://www.earss.rivm.nl

Excess mortality associated with MRSA vs MSSA bacteremia

Study Design Relative risk

Cosgrove, 2003 Meta-analysis 2.03 (1.55-2.65) Blot, 2002 ICU Cohort study 1.93 (1.54-2.42) Talon, 2002 Cohort study 2.97 (1.12-3.18) Melzer, 2003 Cohort study 1.72 (0.92-3.20) Gastmeier, 2005 Multi-ICU cohort 3.84 (1.51-10.2)

Burde n of MRSA Infe c tions in E urope

• Estimate from 2002 EARSS data:
• 11,697 cases of MRSA bacteremia
• 1,277 attributable deaths
• Extra-cost of care: 117 million Euros

Source: SCORE Report, 2004(www.scoreproject.org)

MRSA incidence in Belgian hospitals 1994-2005

Hospitals w ith at least 3 participations betw een 1 9 9 4 and 2 0 0 5 Guidelines 1 9 9 3 Guidelines 2 0 0 3

N=130 N=126 +3%/y., p<0,001 +0,28/1000 adm., p<0,001

5 10 15 20 25 30 35

1 9 9 4 / 2 1 9 9 5 / 1 1 9 9 5 / 2 1 9 9 6 / 1 1 9 9 6 / 2 1 9 9 7 / 1 1 9 9 7 / 2 1 9 9 8 / 1 1 9 9 8 / 2 1 9 9 9 / 1 1 9 9 9 / 2 2 / 1 2 / 2 2 1 / 1 2 1 / 2 2 2 / 1 2 2 / 2 2 3 / 1 2 3 / 2 2 4 / 1 2 4 / 2 2 5 / 1

Study periods MRSA proportion (%) 0.5 1 1.5 2 2.5 3 3.5 4 4.5 MRSA / 1000 admissions Resistance proportion n-MRSA incidence

Source:

• B. Jans ISP

Secular trends of MRSA Clonal Distribution by PFGE-MLST-SCCmec typing

Belgium National Surveillance, Acute Care hospitals, 1992-2005

20 40 60 80 100 1992 (n=62) 1995 (n=85) 1997 (n=90) 1999 (n=31) 2001 (n=100) 2003 (n=112) 2005 (n=127)

Years

A1 ST247-I A20 ST8-IV B2 ST45-IV C3 ST5-IV G10 ST5-II L1 ST22-IV

% of institutions

Denis AAC 2004;48:3265 & AAC 2006;50:2680

I m p

• r

t e d a l i e n

• r

h

• m

e g r

• w

n e v i l d

• e

r ?

• Berlin ST45-IV
• Iberian ST247-I

♦ UK EMRSA-2/-6 ST8-IV ∇ Brazi./Hungarian ST8-III

• NY/Japan ST5-II

♦ Paediatric ST5-IV ∇ South. German ST228-I

• UK EMRSA-15 ST22-IV

♦ UK EMRSA-16 ST36-II

• ♦

♦ ♦ ♦ ♦ ♦ ♦ ♦

• ♦

♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

• ♦

♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦

∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇ ∇

European distribution of HA-MRSA clones

MLST Phylogeny of Belgian Epidemic MRSA and MSSA Strains

(N=26 strains, National survey, 2003)

Hallin et al, JAC 2007 in press

Geographical distribution by province of epidemic MRSA clones, Nursing Homes versus Hospitals, 2005 Nursing Homes (n = 587 strains) Hospitals (n = 326 strains)

CA-MRSA infections

• Skin and soft tissue infections

– Most frequent (> 90%) – Furonculosis, cellulitis, cutaneous and sub-cutaneous abscess, impetigo, … – Exposed surfaces – Favourable outcome – Major pathogen in theUSA

• Children, Texas :60% hospitalisation
• Adults, Georgia: 41% hospitalization
• Major clone USA 300 ST8-SCCmec IV

Wang CC et al. CID 2004 39:481 Lee M. et al. PIDJ 2004 23:123 Kaplan SL et al. CID 2005 40:1785 King MD et al. AIM 2006 144:313

Invasive CA-MRSA infections

• Pneumonia

– Fulminant necrotizing pneumonia

• Preceding influenza or influenza-like syndrome
• High fever, hypotension, respiratory distress (+++),

haemoptysis, pleural effusion, leucopenia

• High mortality (75%)

– Other : septic emboli, empyema, lung abscess,

• Osteomyelitis and arthritis

– Multiple, bacteraemia, pneumonia, thrombophlebitis

• Other : pyomyositis, necrotizing fasciitis, severe

sepsis, …

Hunt C. et al. MMWR 1999 48:707 Dufour P. et al. CID 2002 35:819 Gonzalez BE et al CID 2005 41:583 Enayet I. et al. CID 2006 42:e57 Kaplan SL et al. CID 2005 40:785 Miller LG et al. NEJM 2005 352:1445 Adem PV et al. NEJM 2005 353:1245

Epidemiology

• Community outbreaks

– American indians, aborigens, eskimos – Prisons, military recruits, schools – Sport teams : Wrestler, fencer, football, bodybuilder – Gay community – Familial transmission

• Nosocomial outbreaks

– Obstetric and neonatal wards – Transmission to healthcare worker: pediatrician, microbiologist…

Mode of transmission

– Direct contact

• Crowding, contact sports
• Mother to child via breastfeeding
• From animals to humans

– Contaminated items

• Towels
• Sport equipment and clothes
• Sauna
• Tatoo
• Needle

– Minor wounds or skin abrasions increase risk of infection

Van Duijkeren E et al. JCM 2005 43:6209 Gantz N et al. MMWR 2003 52:793 Bagget HC JID 2004 189:1565

• CA-MRSA ST80-IV
• CA-MRSA ST30-IV

◊ CA-MRSA ST36-IV

• CA-MRSA ST8-IV
• CA-MRSA ST59-V
• ◊
• European distribution of

CA-MRSA clones

Animals as a reservoir for MRSA

• Transmission between humans and animals

– Cats, dogs, horses, cows and pigs – Transmission of human CA-MRSA and HA-MRSA

• Emerging animal reservoir: Pigs

– Holland: familial outbreaks in pig farmers – High prevalence (5 to 23%) in veterinarians – PFGE non-typeable, PVL negative, ST398 and resistant to tetracycline, erythromycine, cotrimoxazole – Also in Horses, calves, … – Described in France, Denmark, Spain, Italy, – … and Belgium: horses, pigs, 7 human cases (> 2003)

Hanselman B. et al EID 2006;12:1933 Wulf M. et al. EId 2006;12:1939

What should we do to curb MRSA ?

To do list at SBIMC 2002 Meeting

Improved surveillance in hospitals 2007 Improved MRSA detection methods 2005 Antibiotic policy : antibiotic management teams 2002 Improved communication among health care workers: regional IC networks 2003 Surveys in nursing homes and the community 2005 Update of national guidelines 2003 Promotion of hand hygiene 2004 Multi Center Trials of control strategies 2007

• ULB
• Olivier Denis
• Ariane Deplano
• Marie Hallin
• Claire Nonhoff
• Raf De Ryck
• Ricardo De Mendonça
• Baudouin Byl
• Francis Rost
• Huguette Strale
• ISP-WIV
• Bea Jans
• Erik Hendrickx
• Carl Suetens
• BAPCOC
• GDEPIH-GOSPIZ
• All participants to the Belgian

MRSA surveillance studies

Acknowledgements