!"#!$#%!$&' over mensen, bacteriën en antibiotica. goedkoop is duurkoop. Jan Kluytmans. antibiotica

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1 over mensen, bacteriën en antibiotica goedkoop is duurkoop Jan Kluytmans antibiotica $'

2 Two is a company De gevolgen van resistentie!"""# $%%%# $%%$# $%%&# $%%+# $%%"# $%%!# $%%'# $%%(# $%%)# $%%*#! Behandeling wordt complexer! Duurder! Meer bijwerkingen! Minder orale mogelijkheden (hospitalisatie)! Soms zelfs onmogelijk! Ziektelast neemt toe (meer mensen worden ziek) 10 Jaarlijkse economische consequenties van Staphylococcus aureus (USA)!!""#$%&"'("$!!""#$')*("+$!!""#$*("#,("$,-./.0-12-#! -+."/""#*("$#&*&0)1*$&+$2"%)+3/"&3*%)#2$! 4""+$+&"56"$7+(&.&)(&07$77+$3"$/)#&%)+$ 11 %'

3 3-# #98685:;# 8"$9""*("$7+(&.&)(&07$6)#3"+$()"2":7*($.&;$3&"#"+$!!""*(7<$.&;$2"%)+3"$3&"#"+$ )(' *(' $+(' "!(' <1/D87.#1:1E0F-689-A2># <1/D87.#0F-689-A2># GAD81.#0F-689-A2># H0F-6#I9-.2>/5-.#-0>J#! 8"$2"=)<2"+$ Voorbeeld: MRSA!! Search and Destroy!! Strategie is effectief &'

4 !"#$%&'()*+,-.#/)01()2334) F"5"*',(5-<::=G-H=-5>5"(- 6"7,$F&;%>G#%#/F&;%H)I:)>)0) "! <::8-!123-+".+%+- "! F>>*5I1$"%(IJ"+#B,'"(G-K77::- "! F"5"*',(5G-HL:-- "! 2#"*B#"G-7:-)-<:M- "! 77:I<<:-"N#*,-5>5"(-."*-O,,*-!"#$%&%''%()*"+%+#,(#-+#,.$-,/*"/+-0!1234-&,/+"5-- (",*'6-789:::-5",#$+-- %(-#$"-;(%#"5-2#,#"+-%(-<::=-- Opkomst varkens-mrsa Amphia Ziekenhuis kosten! 5.54 / opname Opbrengsten: >15 levens / jaar!10.11 / opname SWAB. NethMap Consumption of antimicrobial agents and antimicrobial resistance among medically important bacteria in the Netherlands MRSA bij mensen die werken met varkens!!prevalentie:!! Varkenshouders 65%!! Dierenartsen!50%!! Rest van de bevolking <0.1%,'

5 LA-MRSA in dierenartsen (1 jaar) LA-MRSA in huisgenoten (1 jaar) 137 veterinarians 137 veterinarians 41 persistent MRSA carrier (30%) 42 intermittent MRSA carrier (31%) 54 no MRSA carrier (39%) 41 persistent MRSA carrier (30%) 42 intermittent MRSA carrier (31%) 54 no MRSA carrier (39%) 25 HHM! 1 MRSA (20%) 12 HHM! 1 MRSA (10%) 5 HHM! 1 MRSA (3%) Dynamiek van dragerschap!! Stammen kunnen zeer lang aanwezig blijven binnen een persoon!! Als transmissie naar gezinsleden optreedt wordt meer variabiliteit gezien Persistent Intermittent No RR (95% CI) MRSA carrier MRSA carrier MRSA carrier General Characteristics persistent vs (N = 41) (N = 41) (N = 51) no carriage Burden of disease during one year follow-up Hospital contact no. (%) 2 (4.9) 3 (7.3) 6 (11.8) 0.42 ( ) General practioner contact no. (%) 16 (39.0) 25 (61.0) 29 (56.9) 0.69 ( ) Visit the outpatient clinic no. (%) 14 (34.1) 13 (31.7) 14 (27.5) 1.24 ( ) Allergies no. (%) 14 (34.1) 8 (19.5) 10 (19.6) 1.74 ( ) Eczema no. (%) 4 (9.7) 3 (7.3) 5 (9.8) 1.00 ( ) Skin and soft tissue infections no. (%) 8 (19.5) 3 (7.3) 2 (3.9) 4.98 ( ) Common cold no. (%) 22 (53.7) 27 (65.8) 40 (78.4) 0.68 ( ) Angina no. (%) 8 (19.5) 12 (29.2) 11 (21.6) 0.91 ( ) Sinusitis no. (%) 2 (4.9) 8 (19.5) 4 (7.8) 0.62 ( ) Pneumonia no. (%) 0 (0.0) 1 (2.4) 0 (0.0) COPD no. (%) 4 (9.8) 1 (2.4) 2 (3.9) 2.49 ( ) Antibiotic use no. (%) 14 (9.8) 6 (14.6) 6 (11.8) 0.83 ( ) +'

6 Livestock Density as Risk Factor for Livestock-associated Methicillin- Resistant Staphylococcus!"#!$#%!$&' aureus, the Netherlands Beth J. Feingold, Ellen K. Silbergeld, Frank C. Curriero, Brigite A.G.L. van Cleef, Max E.O.C. Heck, and Jan A.J.W. Kluytmans LA-MRSA in de bevolking!! 17 ziekenhuizen gedurende 2 jaar!! 1023 nieuwe gevallen van MRSA 26,5 14,3 59,2 22% LA-MRSA (ST-398) Analyse van gehele genoom!"# $%&%'()*%# +,%&,%'# -%'."*.# /)0)*1# )*# 2'%2.# "3#,)1,# 2*)(2/#$%*.)&4#2'%#2&#)*5'%2.%$#').6#3"'#52''4)*1#/)0%.&" "5)2&%$# (%&,)5)//)*7'%.).&2*&# Staphylococcus aureus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taphylococcus aureus!"#!$!%&&'&(")!$'*!+,-$'!.$(+&/ S01'!(+$(!)$'!)$,#1!$!2$'01!&3!+1$4(+!&,()&-1#!"'!+,/ -$'#!32&-!-"'&2!(&!4"31/(+21$(1'"'0!"'31)("&'#!&3!(+1!#5"'6! 74&&*#(21$-6!21#."2$(&28!#8#(1-6!,2"'$28!(2$)(6!$'*!#,20")$4! #"(1#!91:;!<'!"')21$#"'0!.2&.&2("&'!&3!S. aureus!"'31)("&'#! Verspreiding in de omgeving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aureus!9>?@<:!92:;!a'!bccd6!ede6bcc!>?@<!"'31)/ ("4&),#!#1M,1')1!(8."'0!9@LUNQ:6!$'*!(+"#!)4&'$4!)&-.41K! +$#!$!*1-&'#(2$(1*!$##&)"$("&'!I"(+!."0#6!)&I#6!$'*!&(+12! $'"-$4#! :6! $4(+&,0+! &(+12! )4&'$4! )&-.41K1#! +$=1! :@&,"'# 23!#/)2&)"*.[# \",*.# ]"-6)*.# ^/""(E%'1# =5,""/# "3# _@E/)5# $4#&! 711'! #+&I'! (&! 71! $##&)"$(1*! I"(+! 4"=1#(&)5! $#! I144;! ]%2/&,?#^2/&)("'%?#;2'4/2*$?#`=:#8^C\C#a%)*1"/$?#VCbC#=)/E%'1%/$?# A'!#1=12$4!F,2&.1$'!)&,'(2"1#6!"')21$#1*!2"#5#!&3!)$22"$01! aclc#l@'')%'">c#b2&)"*2/#m*.&)&@&%#3"'#_@e/)5#]%2/&,#2*$#&,%#v*0)'"*7 Livestock Density as +$=1! Risk 711'! 21.&2(1*! Factor "'!.12#&'#! for "'! )&'($)(! I"(+!."0#! $'*! (%*&?# ^)/&,"0%*?# &,%# B%&,%'/2*$.# 8^C:CdC9C# 02*# L/%%3?# ;CVCeCLC# Livestock-associated =1$4!)$4=1#6!"')4,*"'0!3$2-12#6!=1(12"'$2"$'#6!$'*!#4$,0+/ Methicillin- ]%56>c#2*$#:(-,)2#]".-)&2/?#^'%$2?#&,%#B%&,%'/2*$.c#2*$#Z`#`*)7 Resistant Staphylococcus (12+&,#1!I&2512#!913614:;!A'!(+1!H1(+124$'*#6!$-&'0!(+1#1! 0%'.)&4#;%$)52/#L%*&%'?#:(.&%'$2(?#&,%#B%&,%'/2*$.#8^C:CdC9C#02*# aureus, &)),.$("&'$4!02&,.#6!(+1!.21=$41')1!&3!@LUNQ!)$22"$01!"#! classical risk L/%%3?#\C:C\CDC#b/@4&(2*.> factors the Netherlands 2&,0+48!OBV!915:6!I+121$#!(+1!.21=$41')1!&3!$'8!#(2$"'!&3! contact with livestock Beth J. Feingold, Ellen K. Silbergeld, Frank C. Curriero, >?@<!"'!(+1!01'12$4!.&.,4$("&'!"#!WEV!916:; Brigite A.G.L. van Cleef, Max E.O.C. Heck, WeM[#,&&-[YY$AC$")C"'1YQNCRFNQY%)$QSQQCQQQSKN unknown source and Jan A.J.W. Kluytmans # V(%'1)*1#M*3%5&)"@.#W).%2.%.#X#+++C5$5C1"0Y%)$#X#Z"/C#QS?#B"C#QQ?#B"0%(E%'#FNQF# QSGQ Recente ontwikkeling! LA-MRSA ook bij pluimvee! MRSA in 15% van consumptievlees! LA-MRSA bij 22% van de mensen met MRSA zonder risicofactoren! Verspreiding in de bevolking! Vleesconsumptie (kip) is geassocieerd met risico op MRSA dragerschap!"# $%&%'()*%# +,%&,%'# -%'."*.# /)0)*1# )*# 2'%2.# "3#,)1,# ("&'#!&)),221*!"'!F,2&.1$'!G'"&'!-1-712!#($(1#!.4,#!A)1/ 2*)(2/#$%*.)&4#2'%#2&#)*5'%2.%$#').6#3"'#52''4)*1#/)0%.&"567 4$'*!$'*!H&2I$86!21#,4("'0!"'!E6CJC6CCC!1K(2$!*$8#!#.1'(! 2.."5)2&%$# (%&,)5)//)*7'%.).&2*&# Staphylococcus aureus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S bacteremia in France, 01'!(+$(!)$'!)$,#1!$!2$'01!&3!+1$4(+!&,()&-1#!"'!+,/ (8.1!"(!78!,#"'0!#($'*$2*!-1(+&*#!&3!.,4#1*/ merger of ST398, ST9!14*!014!141)/ -$'#!32&-!-"'&2!(&!4"31/(+21$(1'"'0!"'31)("&'#!&3!(+1!#5"'6! (2&.+&21#"#!98:;!A(!I$#!!2#(!*1(1)(1*!"'!(+1!H1(+124$'*#!"'! and a prophage) 74&&*#(21$-6!21#."2$(&28!#8#(1-6!,2"'$28!(2$)(6!$'*!#,20")$4! BCCU!99:!$'*6!$#!&3!BCEC6!$))&,'(#!3&2!POCV!&3!(+1!>?@<! #"(1#!91:;!<'!"')21$#"'0!.2&.&2("&'!&3!S. aureus!"'31)("&'#! )$#1#!"'!(+$(!)&,'(28!910:;!S</>?@<!+$#!'&I!711'!"*1'("/ "'=&4=1! *2,0/21#"#($'(! #(2$"'#6! "')4,*"'0! -1(+")"44"'/21#"#/!1*!4$20148!$#!$!#"'041!)4&'$4!)&-.41K!&'!(+1!7$#"#!&3!-,4/ ($'(!S. aureus!9>?@<:!92:;!a'!bccd6!ede6bcc!>?@<!"'31)/ ("4&),#!#1M,1')1!(8."'0!9@LUNQ:6!$'*!(+"#!)4&'$4!)&-.41K! +$#!$!*1-&'#(2$(1*!$##&)"$("&'!I"(+!."0#6!)&I#6!$'*!&(+12! $'"-$4#! :6! $4(+&,0+! &(+12! )4&'$4! )&-.41K1#! +$=1! :@&,"'# 23!#/)2&)"*.[# \",*.# ]"-6)*.# ^/""(E%'1# =5,""/# "3# _@E/)5# $4#&! 711'! #+&I'! (&! 71! $##&)"$(1*! I"(+! 4"=1#(&)5! $#! I144;! ]%2/&,?#^2/&)("'%?#;2'4/2*$?#`=:#8^C\C#a%)*1"/$?#VCbC#=)/E%'1%/$?# A'!#1=12$4!F,2&.1$'!)&,'(2"1#6!"')21$#1*!2"#5#!&3!)$22"$01! aclc#l@'')%'">c#b2&)"*2/#m*.&)&@&%#3"'#_@e/)5#]%2/&,#2*$#&,%#v*0)'"*7 +$=1! 711'! 21.&2(1*! "'!.12#&'#! "'! )&'($)(! I"(+!."0#! $'*! (%*&?# ^)/&,"0%*?# &,%# B%&,%'/2*$.# 8^C:CdC9C# 02*# L/%%3?# ;CVCeCLC# =1$4!)$4=1#6!"')4,*"'0!3$2-12#6!=1(12"'$2"$'#6!$'*!#4$,0+/ ]%56>c#2*$#:(-,)2#]".-)&2/?#^'%$2?#&,%#B%&,%'/2*$.c#2*$#Z`#`*)7 (12+&,#1!I&2512#!913614:;!A'!(+1!H1(+124$'*#6!$-&'0!(+1#1! 0%'.)&4#;%$)52/#L%*&%'?#:(.&%'$2(?#&,%#B%&,%'/2*$.#8^C:CdC9C#02*# &)),.$("&'$4!02&,.#6!(+1!.21=$41')1!&3!@LUNQ!)$22"$01!"#! L/%%3?#\C:C\CDC#b/@4&(2*.> 2&,0+48!OBV!915:6!I+121$#!(+1!.21=$41')1!&3!$'8!#(2$"'!&3! WeM[#,&&-[YY$AC$")C"'1YQNCRFNQY%)$QSQQCQQQSKN >?@<!"'!(+1!01'12$4!.&.,4$("&'!"#!WEV!916:; # V(%'1)*1#M*3%5&)"@.#W).%2.%.#X#+++C5$5C1"0Y%)$#X#Z"/C#QS?#B"C#QQ?#B"0%(E%'#FNQF# QSGQ December 5, 2011 )'

7 Conclusies! Gestage uitbreiding van LA-MRSA! Aanwezigheid in voedselketen is zorgelijk! Genetische verandering richting aanpassing aan de mens > meer ziekmakende eigenschappen ESBL neemt overal toe ESBL: Nederland !! Snelle toename sinds 2005!! Vooral infecties die ontstaan buiten het ziekenhuis!! Bij opname 5% dragerschap!! Zelden overdracht in ziekenhuis!! Bron buiten ziekenhuis Vlees als bron van ESBL survey Percentage ESBL positive 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 86,5% 40,9% 17,6% 17,5% 11,1% Chicken Beef Pork Meat loaf Other "'

8 Y Nader onderzoek!! Micro-array (Checkpoints)!! TEM, SHV en CTX-M.!! DNA-sequentie analyse sequencing Vergelijking van de stammen 131 E. coli !58% van de stammen van menselijke dragers clusteren met kippenvlees Chicken meat Other meat types Rectal swabs Blood cultures!57% van de stammen uit clusteren met kippenvlees Conclusies!! De stammen van mensen en kippenvlees lijken sterk op elkaar!! Kippenvlees is een bron van ESBL voor de mens!! Onderzoek is elders herhaald en de bevindingen worden bevestigd!! Nader onderzoek: "!>100 genetische eigenschappen Rescaled Distance Cluster Combine Page 2 Dendrogram using Average Linkage (Between Groups) P2<B49360'54'32Q'.2/6'R6K5>4'I/053050S'R6'LG500S' -'

9 C1=52'1L'M30/0'F36'=/0>G/9/6364'K<6>:16'3632B0/0'954'>G100#F32/=3:5'F36' G50/0456:5;5656T'L2309/=56T'F/G<256:5';5656T'LAB21;565:0>A5';G15L56'56'CUDV' more food for thought Vegetariër worden? Is dit wel een risico voor de mens? Resistentie in de bodem *'

10 ESBL in de bodem Conclusies Bye bye beta-lactams!! De wereldwijde opkomst van ESBL vormt een bedreiging voor de volksgezondheid!! Het triple-b-tijdperk is nabij Laatste nieuws E6:M/1:>3Q'' A54'5/6=5'F36'556':N=L5GOW'! X50/0456:5'/6'=5'1L56'M5F12O/6;'65594'J55G'045GO'415'! Y545G/63/G';5MG</O'0L5524'556'M5236;G/NO5'G12'! C33G'11O'M/N'956056'H1G=4'F552'45'2/>A4J/66/;'954'=5J5' V156395'F36'G50/0456:5'/0'556'5G60:;5'M5=G5/;/6;'F11G' =5'F12O0;5J16=A5/='56'F5GA11;4'=5'O10456'F36'=5'J1G;''! R645G63:16325'430O'K1G>5'/6;50452=' $!'

11 V15O1904' Take home message! E6:M/1:>3';5MG</O'M/N'=/5G'56'9560'9154' =G30:0>A'H1G=56'/6;5L5GO4'! Z5J16=5'956056'56'=/5G56'915456';556' 36:M/1:>3'OG/N;56'! [/5<H5'36:M/1:>3'J/N6'61=/;'! E6=5G5'LG5F56:5'56'><G3:5F5'04G345;/5\6' '164H/OO52='H1G=56' $$'