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    Hindawi Publishing Corporation International Journal of Microbiology Volume 2010 !rticle I" #$%&$& ' pages doi(10)11$$*2010*#$%&$&

    Research Article

    Clinical and Microbiological Determinants of Outcome in Staphylococcus aureus Bacteraemia

    James Price, 1 Gillian Baker, 1 Ian Heath, 1 aren !alker"Bone, 1 Marc Cubbon, # $all% Curtis, &

    Mark C' (nright, & Jodi )indsa%, * John Paul, # and Martin )le+el%n 1, #

    Medical Research Building, Brighton and Sussex Medical School, University of Sussex, Falmer BN1 9 S, U!

    "e#artment of Micro$iology and %nfection, Brighton and Sussex &os#itals N&S 'rust, (astern Road, Brighton BN) *B(, U!

    Faculty of Medicine, St Mary+s am#us, %m#erial ollege, -ondon .) 1 /, U!

    St /eorges &os#ital Medical School, ranmer 'errace, -ondon S.10 R(, U!

    Correspondence should be addressed to Martin +lewelyn m),)llewelyn-bsms)ac)u.

    /ecei ed $ o ember 200 3 !ccepted & 4ebruary 2010

    !cademic 5ditor( Michael M) 6unney

    Copyright 7 2010 James Price et al) 6his is an open access article distributed under the Creati e Commons !ttribution +icense which permits unrestricted use distribution and reproduction in any medium pro ided the original wor. is properly cited)

    Sta#hylococcus aureus bacteraemia 89!:; is commonly complicated by metastatic infection or relapse after treatment) 2$3ectives . 6hestudy aim was to determine the role of bacterial host and management factors in de elopment of complicated 9!:) Methods ) !

    prospecti ely met ourdefinition of complicated disease) 5?pressed as // and $> CI complicated disease was associated with diabetes 81)$& 1)00=2)%&;in,ecting

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    determine the relati e impact of clinical and microbiologicalfactors on ris. of de eloping complicated 9!:)

    #' Methods

    :righton and 9usse? Ani ersity Hospitals H9 6rust8:9AH; is an &20 CI( 0)&&= @@)%P = .001;) 6he presence of a central line was associatedwith a reduced ris. of complicated disease 8// = 0)# $>CI( 0)$$=0)&&P = .00@;)

    In ''> of cases a primary source of bacteraemia was

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    apparent) !lthough the presence or absence of a primarysource did not correlate with complicated disease remo alof an identified focus within '2 hours was associated with alower ris. of complicated disease than when the focus wasremo ed beyond this time or not remo ed at all 8// = 0)'1

    $> CI( 0)$'=0) 0 P = .00#;) :acteraemic patients whowere symptomatic for >%& hours before eff ecti e antibiotictherapy was started were at higher ris. of complicateddisease 8// = 2)10 $> CI( 1)22=@)#1 P = .01$;) 6here

    was no relationship between duration of e ff ecti eintra enous therapy CI( 0) = 1)'0 P = .0$';)

    In the multi ariate analysis both forward and bac.wardli.elihood ratio 8+/; approaches selected diabetes mellitus

    I"A and 6ime to /emo al of Primary 4ocus in their final

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    International Journal of Microbiology@

    6 !:+5 1( Clinical Characteristics of 100 cases of S4 aureus bacteraemia identified prospecti ely from 200# to 200')

    Clinical Characteristics6otalAncomplicatedComplicated//

    $> CIP

    n = 100n = '@n = 2'

    !ge

    Median#$)$

    #'#1

    L L )@∗

    8with I /;8%#='&;8%2='';8% ='&;

    L L

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    Male Gender $ 8>;%0

    8$%)&>;1 8'0)%>;1)2&0) %=1)$0)0 #

    Patient +ocation

    !dmission Anit2'8>;1*

    12'#> 31& *4'1> 31)$#1)0'=2)2&'55.

    ICA118>;1081@)'>;1 8@)'>;0)'&0)#2=0) &)2&0

    /enal Anit1 8>;1#821) >;@ 811)1>;0)&%0)##=1)0#)2#$

    Medical ards@08>;2$8@%)2>;$ 81&)$>;0)&20)#$=1)0@)1%&

    9urgical ards1@8>;& 810) >;$ 81&)$>;

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    1)210)'&=1) 0)@2

    Community !cDuired'8>;%8$)$>;@ 811)1>;

    1)@00)#&=2)%)@&%

    Community Knset@@8>;12

    #.'5 > 31* ,1'2 > 31'*51'5# = 1'2#'514

    Comorbidities

    "iabetes Mellitus208>;15

    1&'/> 3

    15 &/'&> 31',41'55 = #'*4'5#1

    I"A'8>;1

    1'*> 3. ##'# >;,'*#5'44 = &&'*2'551

    9mo.er 228>;1@81')&>;

    8@@)@>;1)@00) 0=1)&&)10

    5?cess !lcohol118>;

    812)@>;2 8')%>;0)&&0)#$=1)20

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    )'22

    HIV0

    00

    L L

    L

    Haemodialysis1'8>;1%81 )2>;@ 811)1>;0)0)#'=1)12)$$

    Central line in situ%@8>;&4 ,#>;, 14', > 35'.25',,65'44'55&

    /ecent !ntibiotics2#8>;2182&)&>;$ 81&)$>;0)&'0)# =1)11)%%2

    /ecent 9teroid128>;

    812)@>;@ 811)1>;0) '0)#&=1)@&1)000

    6herapy

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    /ecent#8>;%8$)$>;2 8')%>;1)100)#2=1) #)##0

    Immunosuppression

    Management

    Primary 4ocus /emo ed

    3, 14', > 30)'10)$'=0) 0'55.

    >'2 hours*not@#8>;

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    ##&5'1> 3

    1* ,1'4 > 31)@00) &=1)'%'5.1

    remo ed

    ot identified2@8>;1$820)$>;& 82 )#>;1)1#0)&@=1)#0)%2@

    Initiation of e ff ecti e@2 8>;14

    #*'/ > 31* ,1'2 > 32)101)22=@)#1'51

    antibiotics ≥ %& hours

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    "uration of IV##8>;%'8#%)%>;1 8'0)%>;1)0'0)&%=1)@')#%1

    treatment >2 wee.s

    Kutcome

    Mortality 8all cause at@&* '∗∗

    2%*'@ 8@2) >;1%*2$∗∗ 8$#>;

    1)20) =1)'0)0$'

    @0 days;8@ )2>;

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    ∗ < alue ad,usted for ties)

    ∗∗ two patients with complicated bacteraemia were lost to follow up at @0 days)

    model where bac.ward +/ also included time to initiation ofeff ecti e antibiotics) "iabetes mellitus and I"A weresignificant at the $> le el for both approaches with < aluesin the bac.ward +/ model of)00$ and)00% respecti ely)

    2' 0etros7ecti8e $tud%

    6he two retrospecti e case series comprised $' bacteraemiasin $' patients in 1 ; respecti ely) 6he rate ofcomplicated disease among e aluable patients in the 200%series 820*'@ 82')%>;; was comparable with that found in the

    prospecti e series and higher than that found in the 1 ;; but this did not reach statistical

    significance 8 P = .0'%;) 6here was a trend towards more

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    % International Journal of Microbiology

    6 !:+5 2( Comparison of clinical characteristics of S4 aureus bacteraemia cases identified retrospecti ely from 1 ;&1 8# )&>;)%

    Patient location

    !dmission unit&*%' 81')0>;

    1&*112 81#)1>;)$@

    ICA&*%' 81')0>;1 *112 81#) >;)$&

    /enal unit&*%' 81')0>;2#*112 82@)2>;)2#

    Medical wards

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    1'*%' 8@#)2>;@2*112 82&)#>;)22

    9urgical wards#*%' 812)&>;1'*112 81$)2>;)%$

    Community acDuired2*22 8 )1>;%*'@8$)$>;)%2

    Community onset$*22 822)'>;21*'@82&)'>;)@

    "iabetes Mellitus2*22 8 >;20*'@82')%>;)0#

    I"A0*22 80>;'*'@8 )#>;)1$

    9mo.er #*22 82')@>;1 *'@82#)0>;)$$

    Central line in situ10*22 8%$)$>;@ *'@8$@)%>;)@

    diabetes mellitus and intra enous drug use in the 200% series

    compared with the 1

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    were complicated cases) Methicillin resistance was notassociated with complicated disease 82$)'> s) 2%)%> P = .&'; but was associated with e?cess mortality 8%#)&> s)@0)2> P = .02;) M/9! bacteraemia was associated with asignificant e?cess of diabetic patients 8@0)1> s) &)@>

    P = .00$; and inappropriate initial antibiotic treatment 8%0)@> s) 10)%> P = .01;)

    4or 1$2 cases full clinical and typing data were a ailable)6hese data show no association between methicillin resis<tance or staphylococcal lineage and complicated

    bacteraemia 86able %;)

    6o?in genotyping demonstrated that @*1&& were PV+ positi e81)#>; and other gene freDuencies were( tst &@*1&& 8%%)1>;

    sea ##*1&& 8@$>; and se3 %*1&& 82)1>;) 6here were nodiff erences in the freDuency of these to?in genes between thethree time

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    International Journal of Microbiology$

    6 !:+5 @( +ineages of 1 0 S4 aureus bacteraemia isolates from 1

    >

    > >

    >

    >CC222')%

    2

    1@)@%

    &)$1$$0)010

    %')#1@&CC@0'2$)@

    20)01021)@11@#)#&

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    @&)12'$%CC%$#22)2@

    20)0112@)%000000

    CC11@)'

    1

    #)'#

    12)&0

    000%

    &

    CC&1@)'

    00$

    10)#2#)'

    0000

    CC$@11)100%

    &)$2#)'

    00

    00

    Kther ' ∗

    2$)#†

    %0)0' ¶

    1%)00

    @∗∗ 1%)@0

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    0

    6otal2'1001$

    100%'100@010021

    100$0100

    ∗ comprising M+96s # 128?2; 1$ 12@8?2; and 1&&

    †comprising M+96s 12 1$ 20 ' 101 and 12@

    ¶not M+96ed)

    ∗∗ comprising M+9612 8?@;)

    CC = clonal comple?)

    6 !:+5 %( +ineages of 1$2 S4 aureus isolates from episodes of uncomplicated and complicated bacteraemia)

    Clonal comple?6otalAncomplicatedComplicated//

    $> CIP

    n = 1$2n = 11# 8'#)@>;n = @# 82@)'>;

    CC@0$@

    %2 8' )2>;11 820)&>;0) %0)' =1)1@0)#&

    CC22@2 8'%)%>;10 82$)#>;1)0%0)&%=1)2&0)&2&

    CC%$

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    1$11 8'@)@>;% 82#)'>;1)0$0)'#=1)%%0)'$$

    CC111

    ' 8#@)#;% 8@#)%>;1)220)''=1) 20)2 1

    CC&'# 8&$)'>;1 81%)@>;0)&&0)#$=1)211)00

    CC$'# 8&$)'>;1 81%)@>;0)&&0)#$=1)211)00

    Kther 201$ 8'$>;$ 82$>;1)020)'&=1)@%

    1)00

    6 !:+5 $( 6he distribution of to?in genes within the # dominant S4 aureus lineages)

    Clonal Comple?

    6o?in Gene

    PV+ n = @tst51 n = &@

    se3 n = % sea n = ##CC@00

    '1)1>0

    #@)#>CC22@@)@>

    )#>0

    1)$>

    CC%$

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    0

    2)%>0

    1)$>CC10

    1)2>0

    )1>CC&01)2>0

    )1>CC$0

    @)#>100>#)1>Kther ##)#>10)&>0

    )1>

    clinical presentation were identified) In this study persistence of M/9! bacteraemia after treatment wasassociated with seg and negati ely associated with PV+)Ganga et al) found a relationship between 9CCmec typeand outcome in a study of 2$@ episodes of 9!: with9CCmec II being an independent predictor of mortality and9CCmec IVa of metastatic infection B1' )

    6he population structure of human S4 aureus comprises 10ma,or lineages or clonal comple?es which ha e e ol edindependently B' ) 5?change of genetic material betweenlineages occurs infreDuently probably because of restrictionmodification systems B1& ) ConseDuently if strain di ff erencesare important in determining whether bacteraemia is com<

    plicated by secondary sites of infection or relapse then this is

    li.ely to be apparent as an association with lineage) Howe erin our study of 1$2 cases of 9!: we ha e found no e idenceof a relationship between lineage and the de elopment ofcomplicated disease) or did we find any association betweencomplicated disease and the presence of PV+ tst sea or se3 to?in genes) 6he presence of tst gene was strongly related toCC@0 85M/9! in CC%$ we ha e found se3

    only in CC$ B1 ) Kur results uphold their hypothesis thatsuperantigen genes ha e a strong association to clonalcomple? and the most li.ely e?planation for the lineage<specific di ff erences relates to geographical ariation)

    #

    In contrast with 4owler s study B& we ha e found norelationship between complicated disease and methicillinresistance) :ut in .eeping with pre ious studies recentlysub

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    patients were not sub,ect to a standardised approach ofdiagnosis and treatment) 4or e?ample only %@> of sub,ectshad an echocardiogram and since follow

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    International Journal of Microbiology'

    H) /ingberg !) 6horen and :) +il,a EMetastatic complica

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    +) 5) ilson ") +) 6homas J) !stembors.i 6) +) 4reedman and") Vlaho EProspecti e study of infecti e endocarditis amongin,ection drug users F 6ournal of %nfectious "iseases ol) 1&$ no)12 pp) 1'#1=1'## 2002)

    J) M) Mylotte and !) 6ayara E Sta#hylococcus aureus bac