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 a nd a nd re sista nc e re sista nc e E pide miolog y of S.aur S.aur e us in e us in the the hospita l hospita l a nd a nd of the c ommunity c ommunity the 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 Plasmid Plasmid Plasmid SCC mec Tn 4001 Tn 1546 Mutation 2002 1950 1961 1969 Vancomycin Penicillin R Oxacillin R Gentamicin R R 1997 Vancomycin I

Staphylococcal Cassette Chromosome mec mec complex ccr complex SCC mec I SCC mec I I SCC mec I I I SCC mec I V SCC mec V pT181 mecA orfX pUB110 IS 431 Tn 554

THE EVOLUTION OF MRSA Enright et al. PNAS 2002;99:7687

Proportion of MRSA resistant to antimicrobials, Belgium 1995-2005 100 1995 1997 2001 80 2003 2005 % of isolates 60 40 20 0 Cipro Erythro Clinda Genta Tobra Mino National surveys, MRSA reference laboratory

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

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 Percent Hetero VI SA VI SA Hiramatsu, 1997 Japan 1149 1_20 0 Kantzanou, 1999 Greece 56 1.8 0 Schmitz, 1999 Europe 302 0 0 * Geisel,1999 Germany 85 8.2 0 Bierbaum, 1999 Germany 457 0.5 0.2 Chesneau, 2000 France 25 20 0 Nonhoff, 2005 Belgium 455 0.7 0 *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 Daptomycin 100 Tigecycline Ceftobiprole 80 Linezolide % of isolates 60 40 20 0 0.06 0.12 0.25 0.5 1 2 4 MIC µg/ml

ine zolid Re sista nt S.aur e us L • 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 SINGLE ROOM GLOVES GOWN 100 90 * = p<0.01 80 70 % hospitals 60 50 40 30 20 10 0 All Northern Western South Southeast C.+ E.+ Balt.St. + I sr.+ TK

Trends in MRSA bacteraemia EARSS, 1999 to 2005 60 1999 50 2000 2001 % of S. aureus 40 2002 2003 30 2004 2005 20 10 0 Den Neth Lux Ger Bel Gre Ire Por UK 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 Guidelines 1 9 9 3 Guidelines 2 0 0 3 N=126 N=130 35 4.5 +3%/y., p<0,001 MRSA / 1000 admissions MRSA proportion (%) 4 30 3.5 25 3 20 2.5 2 15 1.5 10 1 +0,28/1000 adm., p<0,001 5 0.5 0 0 1 1 1 1 1 1 2 2 2 2 2 2 1 2 2 1 2 1 2 1 2 1 / / / / / / / / / / / / / / / / / / / / / / 5 6 7 8 9 1 0 2 3 4 5 4 5 6 7 8 9 0 1 2 3 4 0 9 9 9 9 9 0 0 0 0 0 0 9 9 9 9 9 9 0 0 0 0 0 9 9 9 9 9 0 0 0 0 0 0 9 9 9 9 9 9 0 0 0 0 2 1 1 1 1 1 2 2 2 2 2 2 1 1 1 1 1 1 2 2 2 2 Study periods Source: Resistance proportion n-MRSA incidence B. Jans ISP Hospitals w ith at least 3 participations betw een 1 9 9 4 and 2 0 0 5

Secular trends of MRSA Clonal Distribution by PFGE-MLST-SCC mec typing Belgium National Surveillance, Acute Care hospitals, 1992-2005 A1 ST247-I A20 ST8-IV B2 ST45-IV C3 ST5-IV G10 ST5-II L1 ST22-IV 100 % of institutions 80 60 n ? e r i l e a 40 o d d e l i t v r e o p n m w 20 I o r g e m o h 0 r o 1992 1995 1997 1999 2001 2003 2005 (n=62) (n=85) (n=90) (n=31) (n=100) (n=112) (n=127) Years Denis AAC 2004;48:3265 & AAC 2006;50:2680

• Berlin ST45-IV • Iberian ST247-I ♦ UK EMRSA-2/-6 ST8-IV ♦ European distribution of HA-MRSA ∇ ♦ ∇ Brazi./Hungarian ST8-III • • ♦ clones • • • NY/Japan ST5-II • ♦ ♦ Paediatric ST5-IV ♦ ♦ • ∇ South. German ST228-I • • ♦ • UK EMRSA-15 ST22-IV • ♦ UK EMRSA-16 ST36-II ♦ ∇ • • ∇ ∇ • • ♦ ♦ • • ♦ • ♦ ∇ • • •• • ♦ ♦ ∇ ∇ ♦ ♦ • ♦ • • ♦ • ∇ • ∇ • ♦ • • • ∇ ♦ • • • ∇ ♦ • ∇ ♦ • ∇ • ∇ • • ∇ ∇ • ∇ ♦ ∇ • ♦ • • ♦ ∇ ♦

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 Hospitals Nursing Homes (n = 326 strains) (n = 587 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-SCC mec 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 Kaplan SL et al. CID 2005 40:785 Gonzalez BE et al CID 2005 41:583 Miller LG et al. NEJM 2005 352:1445 Enayet I. et al. CID 2006 42:e57 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 European distribution of • CA-MRSA ST30-IV ◊ CA-MRSA ST36-IV CA-MRSA clones • • CA-MRSA ST8-IV • • CA-MRSA ST59-V ◊ • • • • • • • • • • • • • • • • • • • • •

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 2002 teams Improved communication among health 2003 care workers: regional IC networks Surveys in nursing homes and the 2005 community Update of national guidelines 2003 Promotion of hand hygiene 2004 Multi Center Trials of control strategies 2007

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