ÐÏà¡±á>þÿ QSþÿÿÿ:;<=>?@ABCDEFGHIJKLMNOPÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿÿì¥Áq`ø¿º" bjbjqPqP7X::mÿ%ÿÿÿÿÿÿ¤ppppppp„¬è¬è¬è8äè,ýD „'^`:š"¼¼¼———Z \ \ \ \ \ \ $…híŠ€ apÄ)——Ä)Ä)€ pp¼¼ÛáºÍºÍºÍÄ)Ædp¼p¼Z ºÍÄ)Z ºÍºÍV‚Õ@ppFÖ¼T¤ú¨ß²Ê¬èŠŽÖ0ÂÕ.ô,÷0'ÎÕxw`¿wFÖwpFÖè—›ÞºÍyLÅ ÿ———€ € bÍX———'Ä)Ä)Ä)Ä)„„„DÊÈÎä„„„ÈÎ„„„ppppppÿÿÿÿEuropean Heart Journal doi:10.1093/eurheartj/ehp285 Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009) The Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and by the International Society of Chemotherapy (ISC) for Infection and Cancer Authors/Task Force Members: Gilbert Habib (Chairperson) (France)*, Bruno Hoen (France), Pilar Tornos (Spain), Franck Thuny (France), Bernard Prendergast (UK), Isidre Vilacosta (Spain), Philippe Moreillon (Switzerland), Manuel de Jesus Antunes (Portugal), Ulf Thilen (Sweden), John Lekakis (Greece), Maria Lengyel (Hungary), Ludwig Mu¨ ller (Austria), Christoph K. Naber (Germany), Petros Nihoyannopoulos (UK), Anton Moritz (Germany), Jose Luis Zamorano (Spain) ESC Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson) (France), Angelo Auricchio (Switzerland), Jeroen Bax (The Netherlands), Claudio Ceconi (Italy), Veronica Dean (France), Gerasimos Filippatos (Greece), Christian Funck-Brentano (France), Richard Hobbs (UK), Peter Kearney (Ireland), Theresa McDonagh (UK), Keith McGregor (France), Bogdan A. Popescu (Romania), Zeljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Panos Vardas (Greece), Petr Widimsky (Czech Republic) Document Reviewers: Alec Vahanian (CPG Review Coordinator) (France), Rio Aguilar (Spain), Maria Grazia Bongiorni (Italy), Michael Borger (Germany), Eric Butchart (UK), Nicolas Danchin (France), Francois Delahaye (France), Raimund Erbel (Germany), Damian Franzen (Germany), Kate Gould (UK), Roger Hall (UK), Christian Hassager (Denmark), Keld Kjeldsen (Denmark), Richard McManus (UK), Jose´ M. Miro´ (Spain), Ales Mokracek (Czech Republic), Raphael Rosenhek (Austria), Jose´ A. San Roma´n Calvar (Spain), Petar Seferovic (Serbia), Christine Selton-Suty (France), Miguel Sousa Uva (Portugal), Rita Trinchero (Italy), Guy van Camp (Belgium) The disclosure forms of the authors and reviewers are available on the ESC website HYPERLINK "http://www.escardio.org/guidelines" www.escardio.org/guidelines * Corresponding author. Gilbert Habib, Service de Cardiologie, CHU La Timone, Bd Jean Moulin, 13005 Marseille, France. Tel: N33 4 91 38 63 79, Email: gilbert.habib@free.fr The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of the ESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to Oxford University Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC. Disclaimer. The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Health professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’s guardian or carer. It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription. & The European Society of Cardiology 2009. All rights reserved. For permissions please email: HYPERLINK "mailto:journals.permissions@oxfordjournals.org" journals.permissions@oxfordjournals.org. C:>2>4OI85 ?@8=F8?K ?> ?@>D8;0:B8:5, 4803=>AB8:5 8 ;5G5=8N 8=D5:F8>==>3> M=4>:0@48B0 (=>20O 25@A8O 2009) Abbreviations and acronyms BCNIE 8=D5:F8>==K9 M=4>:0@48B A >B@8F0B5;L=>9 :C;LBC@>9 :@>28 CD :0@480;L=>: CAB@>9AB2> CDRIE :0@480;L=K9 2K7K20==K9-CAB@>9AB2>< 8=D5:F8>==K9 M=4>:0@48B ! 2@>645==K9 ?>@>: A5@4F0 CNS :>03C;070-=530B82=K5 AB0D8;>:>::8 " (CT) :><>3@0D8O ELISA B25@4>D07=K9 8<A>@15=B=K9 0=0;87 ! 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K7202H85 <8:@>>@30=87 staphylococci, streptococci 8 enterococci.28 a. =D5:F8>==K9 M=4>:0@48B 87-70 streptococci 8 enterococci @0;L=K5 (?@5645 2A53> viridans) streptococci >1@07CNB A<5H0==CN 3@C??C <8:@>>@30=87<>2, :>B>@0O 2:;NG05B @07=>284=>AB8, B0:85 :0: S. sanguis, S. mitis, S. salivarius, S. mutans, 8 Gemella morbillorum. 8:@>>@30=879 3@C??K ?>GB8 2A5340 GC2AB28B5;L=K : ?5=8F8;;8=C G. 8:@>1K S. milleri 8;8 3@C??0 S. anginosus' (S. anginosus, S. intermedius 8 S. constellatus) 4>;65= 1KBL 2K45;5=K, B0: :0: >=8 8<5NB B5=45=F8N D>@<8@>20BL 01AF5AAK 8 2K7K20BL 35<0B>35==CN 48AA5<8=8@>20==CN 8=D5:F8N, :>B>@0O G0AB> B@51C5B 1>;55 4;8B5;L=>9 0=B818>B8:>B5@0?88. "0:65, 0;8<5=B0@=K9 B8? '45D5:B=>3>' streptococci, =5402=> ?5@5:;0AA8D8F8@>20==K9 2 4@C385 B8?K (Abiotrophia 8 Granulicatella), 4>;65= 1KBL >B<5G5=, B0: :0: >=8 CAB>9G82 : ?5=8F8;;8=C [<8=8<0;L=0O 10:B5@8F84=0O :>=F5=B@0F8O (M) =0<=>3> 2KH5, G5< <8=8<0;L=0O 8=3818B>@=0O :>=F5=B@0F8O ()]. @C??C D AB@5?B>:>::>2 >1@07C5B :><<5=A0;L=K5 B8?K G5;>25G5A:>3> :8H5G=>3> B@0:B0, 8 1K; 4> =5402=53> 2@5<5=8 >1J548=5=K ?>4 =0720=85< Streptococcus bovis. =8 >1KG=> GC2AB28B5;L=K : ?5=8F8;;8=C G, :0: >@0;L=K5 AB@5?B>:>::8. !@548 M=B5@>:>::>2 E. faecalis, E. faecium 8, 2 <5=LH59 AB5?5=8, E. durans O2;ONBAO B@5B>@K5 2K7K20NB -. b. !B0D8;>:>::>2K9 8=D5:F8>==K9 M=4>:0@48B "@048F8>==>, AB0D8;>:>::>2K9 - =0B82=>3> :;0?0=0 ?@>8AE>48B 87-70 S. aureus, :>B>@K9 G0I5 2A53> 2>A?@88:A0F8;;8=C, ?> :@09=59 <5@5, ?@8 2=51>;L=8G=>< -. 0?@>B82, AB0D8;>:>::>2K9 - ?@>B578@>20==>3> :;0?0=0, :>B>@K9 1K205B G0I5 2A53> 87-70 :>03C;070-=530B82=>3> AB0D8;>:>::0 (CNS), @578AB5=B=K9 : >:A0F8;;8=C. 4=0:>, 2 =5402=5< 8AA;54>20=88 1779 A;CG052 -, >1J548<=5==KE ?@>A?5:B82=> 2 16 AB@0=0E, S. aureus 1K; A0<>9 G0AB>9 ?@8G8=>9 =5 B>;L:> -, => B0:65 8 - ?@>B578@>20==>3> :;0?0=022 0>1>@>B, CNS <>65B B0:65 2K7K20BL - =0B82=>3> :;0?0=0,29 31 >A>15==> S. lugdunensis, :>B>@K9 G0AB> 8<55B 03@5AA82=>-:;8=8G5A:>5 459AB285. 2. =D5:F8>==K9 M=4>:0@48B A >B@8F0B5;L=>9 :C;LBC@>9 :@>28 87-70 ?@54H5AB2CNI59 0=B818>B8:>B5@0?88 -B0 A8BC0F8O 2>7=8:05B C ?0F85=B>2, :>B>@K5 ?>;CG0;8 0=B818>B8:8 4;O =5>1JOA=5==>9 ;8E>@04:8 ?5@54 8AA;54>20=85< :C;LBC@K :@>28, 8 C :>B>@KE 4803=>7 - =5 @0AA<0B@820;AO; >1KG=> 4803=>7, 2 :>=F5 :>=F>2, @0AA<0B@820NB ?@8 D0:B5 ?>2B>@=>3> ;8E>@04>G=>3> M?87>40 ?>A;5 ?@5:@0I5=8O 0=B818>B8:>2. 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PCR 8AA5G5==>9 B:0=8 :;0?0=0 8;8 M<1>;8G5A:>3> <0B5@80;0 4>;6=0 1KBL 2K?>;=5=0 C ?0F85=B>2 A >B@8F0B5;L=K<8 :C;LBC@0<8 :@>28, :>B>@K5 ?>425@30NBAO :;0?0==>9 >?5@0F88 8;8 M<1>;M:B><88. 803=>AB8G5A:85 :@8B5@88 8 8E >3@0=8G5=8O @8B5@88 Duke,92 >A=>20==K5 =0 :;8=8G5A:8E, ME>:0@48>3@0D8G5A:8E 8 <8:@>18>;>38G5A:8E 40==KE >15A?5G820NB 2KA>:CN GC2AB28B5;L=>ABL 8 A?5F8D8G=>ABL (~ð80% 25745) 4;O 4803=>70 -. 5402=85 ?>?@02:8 ?@87=0NB @>;L :C-;8E>@04:8 (@0A?@>AB@0=5==K9 2> 2A5< <8@5 7>>=>7, 2K7K205AB@0=5==>AB8 AB0D8;>:>::>2>9 8=D5:F88, 8 H8@>:>5 ?@8<5=5=85 ", 8 ?>;CG5==K5 B0: =07K20548D8F8@>20==K5 :@8B5@88 Duke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s). 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"01;8F0 11 >48D8F8@>20==K5 :@8B5@88 Duke 8=D5:8>==>3> M=4>:0@48B0 (040?B8@>20==K5 87 Li A A>02B.94) >;LH85 :@8B5@88C;LBC@K :@>28 ?>;>68B5;L=K5 ?@8 -: * "8?8G=K5 <8:@>>@30=87?CBAB2CNI85 - 2 42CE >B45;L=KE :C;LBC@0E :@>28: Viridans streptococci, Streptococcus bovis, 3@C??0 HACEK, Staphylococcus aureus; 8;8 =51>;L=8G=K5 M=B5@>:>::8, 2 >BACBAB288 ?5@28G=>3> >G030; 8;8 * 8:@>>@30=87?CBAB2CNI85 - A ?>AB>O==> ?>;>68B5;L=K<8 :C;LBC@0<8 :@>28; > :@09=59 <5@5 425 ?>;>68B5;L=K5 :C;LBC@K :@>28 87 ?@>1 :@>28 ?>:07K20NB @>AB > 12 G0A>2 ?> >B45;L=>AB8; 8;8 A5 B@8 8;8 1>;LH8=AB2> 87 ³ð 4 >B45;L=KE :C;LBC@ :@>28 (2 ?5@2>9 8 ?>A;54=59 ?@>15 @>AB =5 <5=55 1 G0A0 ?> >B45;L=>AB8) 8;8 * 48=AB25==0O ?>;>68B5;L=0O :C;LBC@0 :@>28 =0 Coxiella burnetii 8;8 D070 I IgG B8B@ 0=B8B5; > 1 : 8000==K5 > 2>2;5G5=88 M=4>:0@40 * -E>:0@48>3@0D8O ?>;>68B5;L=0O 4;O - 535B0F8O 1AF5AA >20O G0AB8G=0O =5A>AB>OB5;L=>ABL ?@>B57=>3> :;0?0=0 * >20O :;0?0==0O @53C@38B0F8O0;K5 :@8B5@88@54@0A?>;>65=85: ?@54@0A?>;030NI55 A>AB>O=85 A5@4F0, 8A?>;L7>20=85 8=J5:F8>==KE ?@5?0@0B>2 8E>@04:0: B5 38°ð! !>AC48ABK5 D5=><5=K: 1>;LH>9 0@B5@80;L=K9 M<1>;, A5?B8G5A:85 ;53>G=K5 8=D0@:BK, <8:>B8G5A:85 0=52@87@@0388, :>=LN=:B820;L=K5 35<>@@0388, O72>G:8 659=25O <;>38G5A:85 D5=><5=K: 3;><5@C;>=5D@8B, C75;:8 A;5@0, ?OB=0 Roth, @52<0B>84=K9 D0:B>@ 8:@>18>;>38G5A:85 40==K5: ?>;>68B5;L=0O :C;LBC@0 :@>28, => =5B 1>;LH8E :@8B5@852 8;8 A5@>;>38G5A:8E 40==KE 0:B82=>9 8=D5:F88 A <8:@>>@30=87<0<8, A>3;0ACNI8<8AO A - 803=>7 - >?@545;O5AO ?@8 =0;8G88 2 1>;LH8E :@8B5@852, 8;8 1 1>;LH>3> 8 3 <0;KE :@8B5@852, 8;8 5 <0;KE :@8B5@852 803=>7 - 2>7<>65= ?@8 =0;8G88 1 1>;LH>3> 8 1 <0;>3> :@8B5@852, 8;8 3 <0;KE :@8B5@85240?B8@>20=> 87 Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG, Jr., Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633 638. G. @>3=>AB8G5A:0O >F5=:0 ?@8 3>A?8B0;870F88 =CB@81>;L=8G=0O A<5@B=>ABL ?0F85=B>2 A - 87<5=O5BAO >B 9.6 4> 26%,14,68,96 102 => 7=0G8B5;L=> >B;8G05BAO >B ?0F85=B0 ?0F85=BC. 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"59:>?;0=8= 1K; ?@54;>65= :0: 0;LB5@=0B8203 8 B@51C5B =03@C7>G=KE 4>7 (6 <3/:3/12 G0A 2 B5G5=85 3 4=59) 8 2 40;L=59H5< 6-10 <3/:3/45=L. 03@C7:0 206=0, ?>B> ?@5?0@0B A8;L=> A2O7K205BAO A 15;:0<8 AK2>@>B:8 (³ð98%) 8 ?@>=8:05B <54;5==> 2 2535B0F88.116 4=0:>, B>;L:> >3@0=8G5==K5 @5B@>A?5:B82=K5 8AA;54>20=8O >F5=8;8 53> MDD5:B82=>ABL 4;O AB@5?B>:>::>2>3>117 8 M=B5@>:>::>2>3>118 -. 5=8F8;;8=-@578AB5=B=K5 >@0;L=K5 AB@5?B>:>::8 8 3@C??0 D AB@5?B>:>::>2 5=8F8;;8=-@578AB5=B=K5 >@0;L=K5 AB@5?B>:>::8 :;0AA8D8F8@CNBAO :0: >B=>A8B5;L=> @578AB5=B=K5 (IC 0.125 2 <3/;) 8 ?>;=>ABLN @578AB5=B=K5 (IC > 2 <3/;). 4=0:>, =5:>B>@K5 @C:>2>4OI85 ?@8=F8?K AG8B0NB IC > 0.5 <3/; :0: ?>;=>ABLN @578AB5=B=K5.3,7,110 >;O B0:8E @578AB5=B=KE AB@5?B>:>::>2 @0AB5B. 5402=OO 1>;LH0O :>;;5:F8O HB0<<>2 A>>1I8;0 > > 30% >B=>A8B5;L=> 8 ?>;=>ABLN @578AB5=B=KE S. mitis 8 S. oralis.118,119 0>1>@>B, > 99% 3@C??K D AB@5?B>:>::>2 >AB0NBAO GC2AB28B5;L=K<8 : ?5=8F8;;8=C. C:>2>4OI85 ?@8=F8?K ;5G5=8O ?5=8F8;;8=-@578AB5=B=>3> AB@5?B>:>::>2>3> - ?>;030NBAO =0 @5B@>A?5:B82=K9 @O4 8AA;54>20=89. 1J548=OO G5BK@5E 87 =8E, 47/60 (78%) ?0F85=B>2 ;5G8;8AL ?5=8F8;;8=>< G 8;8 F5DB@80:A>=>< 2 1>;LH8=AB25 :><18=8@>20==KE A 0<8=>3;8:>7840<8, 0 =5:>B>@K5 8;8 :;8=40<8F8=>< 8;8 0<8=>3;8:>7840<8 B>;L:>.120 123 >;LH8=AB2> ?5=8F8;;8=-MICs 1K;> ³ð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treptococcus pneumoniae, bð-haemolytic streptococci (3@C??K A, B, C, 8 G) - 87-70 S. pneumoniae AB0; @54:8<, =0G8=0O A ?>O2;5=8O 0=B818>B8:>2. = A2O70= A <5=8=38B>< 2 30% A;CG052,124 :>B>@K9 B@51C5B A?5F80;L=>3> @0AA<>B@5=8O 2 A;CG0OE A ?5=8F8;;8=-@578AB5=B=>ABLN. 5G5=85 ?@8 ?5=8F8;;8=-GC2AB28B5;L=KE HB0<<0E (IC £ð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milleri (S. constellatus, S. anginosus, 8 S. intermedius) - >B=>A8B5;L=> @54>:.126 @C??0 AB@5?B>:>::>2 >4=>@>4=> GC2AB28B5;L=0 : 15B0-;0:B0<0<, B>340 :0: 4@C385 A5@>3@C??K <>3CB 1KBL @578AB5=B:>::>2 3@C??K B @0=LH5 0AA>F88@>20;AO A >:>;>@>4>2K< ?5@8>4><, => B5?5@L 1K205B 8 C 4@C38E 27@>A;KE, >A>15==> C ?>68;KE. !B@5?B>:>::8 3@C?? B, C, 8 G 8 S. milleri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b 8;8 <>:A8F8;;8=d 8;8 &5DB@80:A>=512-18 <8;;8>=>2 /45=L 2/2 2 6 4>70E 100-200 <3/:3/45=L 2/2 2 4-6 4>70E 2 3/45=L 2/2 8;8 2/< 2 1 4>75 5480B@8G5A:85 4>7K:f 5=8F8;;8= G 200000 /:3/45=L @0745;5==K9 =0 4-6 4>7 <>:A8F8;;8= 300 <3/:3/45=L @0745;5==K9 =0 4-6 4>7 &5DB@80:A>= 100 <3/:3/45=L 2/2 8; 2/< 2 1 4>75 4A 4A 4AI B I B I B2CE=545;L=>5 ;5G5=85(Z)5=8F8;;8= G 8;8 <>:A8F8;;8=d 8;8 &5DB@80:A>=5 ! 5=B08F8=>< 12=18 <8;;8>=>2 /45=L 2/2 2 6 4>70E 100-200 <3/:3/45=L 2/2 2 4-6 4>70E 2 3/45=L 2/2 8;8 2/< 2 1 4>75 3 <3/:3/45=L 2/2 8;8 2/< 2 1 4>75 4-5 <3/:3/45=L 2/2 2 1 4>75 5480B@8G5A:85 4>7K:f 5=8F8;;8=, 0<>:A8F8;;8= 8 F5DB@80:A>= :0: C:070=> 2KH5. 5=B0<8F8= 3 <3/:3/45=L 2/2 8;8 2/< 2 1 4>75 8;8 @0745;5==0O =0 3 @02=KE 4>7K2 2 2 2 2I B I B I B I B I B @8 0;;5@388 ?0F85=B>2 : 15B0-;0:B0<0<0=:><8F8=i30 <3/:3/45=L 2/2 2 2 4>7K 5480B@8G5A:85 4>7K:f 0=:><8F8= 40 <3/:3/45=L 2/2 2 2-3 @02=> @0745;5==KE 4>70E4AI C(B0<B=>A8B5;L=> CAB>9G82K5 : ?5=8F8;;8=C (MIC 0.125-2 <3/;)!B0=40@B=>5 ;5G5=855=8F8;;8= G 8;8 <>:A8F8;;8=d A 5=B0<8F8=>=0 /45=L 2/2 2 6 4>70E 200 <3/:3/45=L 2/2 2 4-6 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 1 4>754A 4A 2I B I B# 0;;5@38G=KE : 15B0-;0:B0<0< ?0F85=B>20=:><8F8=i A 5=B0<8F8=>70E 5480B@8G5A:85 4>7K:f 0: C:070=> 2KH5 3 <3/:3/45=L 2/2 8;8 2/< 2 1 4>754A 2I C0!<>B@8B5 B5:AB 4;O 4@C38E AB@5?B>:>::>2KE HB0<<>2. b@58 C ?0F85=B>2 > 65 ;5B 8;8 A =0@CH5==>9 DC=:F859 ?>G5:. A6-=545;L=0O B5@0?8O ?@8 PVE. d;8 07K B0:85 65 :0: C 0<>:A8F8;;8=0. 5@58 4;O 0<1C;0B>@=>9 B5@0?88. f5480B@8G5A:85 4>7K =5 4>;6=K ?@52KH0BL 4>7K 27@>A;KE. g">;L:> 5A;8 =5 >A;>6=O5BAO - =0B82=>3> :;0?0=0. h>G5G=0O DC=:F8O 8 :>=F5=B@0F8O 35=B0<8F8=0 2 AK2>@>B:5 4>;6=0 >?@545;OBLAO 1 @07 2 =545;N. >340 405BAO >48= @07 2 45=L, ?@5-4>7=0O (<8=8<0;L=0O) :>=F5=B@0F8O 4>;6=0 1KBL < 1 <3/; 8 ?>AB-4>7=0O (?8:>20O; 1 G0A ?>A;5 8=J5:F88) AK2>@>B>G=0O :>=F5=B@0F8O 4>;6=0 1KBL ~ð10-12 <3/;.112 i!K2>@>B>G=0O :>=F5=B@0F8O 20=:><8F8=0 4>AB830BL 10-15 <3/; ?@8 ?@5-4>7=>< (<8=8<0;L=><) C@>2=5 8 30-45 <3/; ?@8 ?>AB-4>7=>< C@>2=5 (?8:>2K9, 1 G0A ?>A;5 ?>;=>9 8=DC788). Staphylococcus aureus 8 :>03C;075-=530B82=K5 AB0D8;>:>::8 Staphylococcus aureus >1KG=> >B25BAB25=5= 70 >AB@K9 8 45AB@C:B82=K9 -, B>340 :0: CNS 2K7K20NB 1>;55 4;8B5;L=K5 5;0?0==K5 8=D5:F88 (:@><5 S. lugdunensis 8 =5:>B>@KE A;CG052 S. capitis).130 131 "01;8F0 14 AC<<8@C5B ;5G51=K5 @5:><5=40F88 4;O <5B8F8;;8=-GC2AB28B5;L=KE 8 <5B8F8;;8=-@578AB5=B=KE S. aureus 8 CNS ?@8 - :0: =0B82=>3> B0: 8 ?@>B57=>3> :;0?0=0. 04> 70<5B8BL, GB> ?>;L70 4>?>;=8B5;L=>3> a<8=>3;8:>7840 ?@8 - 87-70 S. aureus >D8F80;L=> =5 ?@>45<>=AB@8@>20=0.132,133 -B> O2;O5BAO 65;0B5;L=K< (=5>1O70B5;L=K<) 2 B5G5=85 ?5@2KE 3 5 4=59 B5@0?88 ?@8 NVE, 8 @5:><5=4C5BAO 2 B5G5=85 ?5@2KE 2 =545;L ?@8 PVE. @0B:>2@5<5==0O (2-=545;L=0O) 8 ?5@>@0;L=0O B5@0?8O 1K;0 ?@54;>65=0 4;O =5>A;>6=5==>3> ?@02>-AB>@>==53> - (A<. B0:65 0745; L), => MB8 @568-AB>@>==53> -. PVE 87-70 Staphylococcus aureus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vancomycin-?@><56CB>G=K5 S. aureus (VISA) (MIC 4 16 <3/;) 8 35B5@>-VISA (MIC £ð 2 <3/;, => A AC1?>?C;OF8O<8, @0ABCI8<8 ?@8 1>;55 2KA>:8E :>=F5=B@0F8OE) ?>O28;8AL 2> 2A5< <8@5, 8 0AA>F88@CNBAO A =5C40G=K< @57C;LB0B>< ;5G5=8O -.138 @><5 B>3>, =5:>B>@K5 2KA>:> 20=:><8F8=-@578AB5=B=K5 S. aureus 1K;8 2K45;5=K >B 8=D8F8@>20==KE ?0F85=B>2 2 ?>A;54=85 3>4K, B@51CO =>2KE ?>4E>4>2 : ;5G5=8N. >2K9 ;8?>?5?B84 daptomycin (6 <3/:3/45=L 2/2) 1K; =5402=> >4>1@5= 4;O 10:B5@85<88 S. aureus 8 ?@2>-AB>@>==53> -.139 01;N40B5;L=K5 8AA;54>20=8O ?@54?>;030NB, GB> daptomycin <>6=> 1C45B B0:65 @0AA<0B@820BL 4;O ;52>-AB>@>==53> - 8 4;O ?@5>4>;5=8O <5B8F8;;8=>2>9 8 20=:><8F8=>2>9 @578AB5=B=>AB8.140 4=0:>, >;@545;ONI85 8AA;54>20=8O >BACBAB2CNB. 06=>, GB> daptomycin =04> =07=0G0BLBL 2 A>>B25BAB2CNI8E 4>70E 4;O 87156@=8O 40;L=59H59 @578AB5=B=>AB8.139,141 @C3>9 2K1>@ 2:;NG05B 1>;55 =>2K5 15B0-;0:B0B=>A8B5;L=> E>@>H59 PBP2A 0DD8=>ABLN, quinupristin dalfopristin A 8;8 157 15B0-;0:B0<>2,142,143 15B0-;0:B0:A07>;848=>=K,144 8 15B0-;0:B0<8F8=.145 B0:8E A;CG0OE B@51C5BAO A>2<5AB=>5 ;5G5=85 A 8=D5:F8>=8AB><. "01;8F0 14 =B818>B8:>B5@0?8O 8=D5:F8>==>3> M=4>:0@48B0 87-70 Staphylococcus spp. =B818>B8:>70 8 ?CBL 22545=8O@>4>;68B=;L=>ABL (=545;8)#@>25=L 4>:070==>AB80B82=K5 :;0?0=K5B8F8;;8=-GC2AB28B5;L=K5 AB0D8;>:>::8:$;C:;>:A0F8;;8= 8;8 :A0F8;;8= A 5=B0<8F8=><012 3/45=L 2/2 2 4-6 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:b :A0F8;;8= 8;8 D;C:;>:A0F8;;8= 200 <3/:3/45=L 2 4-6 @02=> @0745;5==KE 4>70E. 5=B0<8F8= 3 <3/:3/45=L 2/2 8;8 2/< 2 3 @02=KE 4>70E4-6 3-5 4=59 I B0F85=BK 0;;5@38G=K5 : ?5=8F8;;8=C 8;8 <5B8F8;;8=-@578AB5=B=K5 AB0D8;8:>::8:0=:><8F8=A A 5=B0<8F8=><0 30 <3/:3/45=L 2/2 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:b 0=:><8F8= 40 <3/:3/45=L 2/2 2 2-3 @02=KE 4>70E.4-6 3-5 4=59I B@>B578@>20==K5 :;0?0=K5B8F8;;8=-GC2AB28B5;L=K5 AB0D8;>:>::8:$;C:;>:A0F8;;8= 8;8 :A0F8;;8= A 8D0<512 3/45=L 2/2 2 4-6 4>70E 1200 <3/45=L 2/2 8;8 ?5@>@0;L=> 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>7K 5480B@8G5A:85 4>7K:b :A0F8;;8= 8 $;:;>:A0F8;;8= :0: C:070=> 2KH5. 8D0@0;L=> 2 3 @02=> @0745;5==KE 4>70E³ð 6 ³ð 6 2I B0F85=BK 0;;5@38G=K5 : ?5=8F8;;8=C 8 <5B8F8;;8=-@578AB5=B=K5 AB0D8;>:>::8:0=:><8F8=A A 8D0<530 <3/:3/45=L 2/2 2 2 4>70E 1200 <3/45=L 2/2 8;8 ?5@>@0;L=> 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:b 0: C:070=> 2KH5.³ð 6 ³ð 6 2I Ba;8=8G5A:0O ?>;L70 4>102;5=8O 35=B0<8F8=0 =5 1K;0 >D8F80;L=> ?@>45<>=AB@8@>20=0. 3> 8A?>;L7>20=85 0AA>F88@C5BAO A ?>2KH5==>9 B>:A8G=>ABLN 8 ?>MB>1O70B5;L=>. b5480B@8G5A:85 4>7K =5 4>;6=K ?@52KH0BL 27@>A;K5 4>7K. A>=F5=B@0F8O 20=:><8F8=0 2 AK2>@>B:5 4>;6=0 4>AB830BL 25-30 <3/; 2 ?@5-4>7>2KE (<8=82=OE. d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nterococcus spp. -=B5@>:>::>2K9 - ?@5645 2A53> 2K7K205BAO Enterococcus faecalis (90% A;CG052) 8, 1>;55 @54:>, Enterococcus faecium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s 2 2-4 @070 =865. ;8B5;L=K5 :C@AK 35=B0<8F8=0 B@51CNB @53C;O@=>3> :>=B@>;O C@>2=59 ?@5?0@0B0 2 AK2>@>B:5 8 ?>G5G=>9 8 25AB81C;O@=>9 DC=:F89. 4=> 8AA;54>20=85 A>>1I8;> >1 CA?5E5 :>@>B:>3> :C@A0 0<8=>3;8:>784>2 (2 3 =545;8) C 74 (81%) 87 91 M?87>40 M=B5@>:>::>2>3> -.147 "0:>5 ;5G5=85 <>65B 1KBL @0AA<>B@5=> 2 A;CG0OE, 345 4;8B5;L=>5 ;5G5=85 >3@0=8G5=> B>:A8G=>ABLN. KA>:>C@>2=520O @578AB5=B=>ABL : 35=B0<8F8=C O2;O5BAO G0AB>9 C >1>8E E. faecalis 8 E. faecium.146 MIC 0<8=>3;8:>784>2 > 500 <3/; 0AA>F88@C5BAO A ?>B5@59 10:B5@8F84=>3> A8=5@387<0 A8=3818B>@0<8 :;5B>G=>9 AB5=:8, 8 0<8=>3;8:>784K =5 4>;6=K 8A?>;L7>20BLAO 2 B0:8E CA;>28OE. !B@5?B><8F8= <>65B >AB020BLAO 0:B82=K< 2 B0:8E A;CG0OE 8 1KBL ?>;57=>9 0;LB5@=0B82>9. 5 B0: 402=> A>>1I5=> > :><18=0F88 0=0 ?@>B82 35=B0<8F8=-@578AB5=B=>3> E. faecalis,148 A8=5@387< :>B>@KE 8=3818@C5B :>;6=K 1KBL >1AC645=K 1>;55 4;8B5;L=K5 :C@AK 15B0-;0:B0<>2 8;8 20=:><8F8=. 578AB5=B=>ABL : 15B0-;0:B0<0< 8 20=:><8F8=C =01;N40NBAO, 3;02=K< >1@07><, ?@8 E. faecium. "0: :0: 42>9=0O @578AB5=B=>ABL 2AB@5G05BAO @54:>, 15B0-;0:B03CB 8A?>;L7>20BLAO ?@>B82 20=:><8F8=-@578AB5=B=KE HB0<<>2 8 =0>1>@>B. 07;8G=K5 @57C;LBK A>>1I0;8AL > quinupristin dalfopristin, linezolid, daptomycin 8 tigecycline. ?OBL-B0:8, MB8 A8BC0F88 B@51CNB M:A?5@B87K 8=D5:F8>=8AB0. "01;8F0 15 =B818>B8:>B5@0?8O 8=D5:F8>==>3> M=4>:0@48B0 87-70 Enterococcus spp. =B818>B8:>70 8 ?CBL 22545=8O@>4>;68B=;L=>ABL (=545;8)#@>25=L 4>:070==>AB85B0-;0:B0<- 8 35=B0<8F8=-GC2AB28B5;L=K5 HB0<;OB>2 A<.a,b,c)<>:A8F8;;8= A 5=B0<8F8=><5200 <3/:3/45=L 2/2 2 4-6 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:f <>:A0F8;;8= 300 <3/:3/45=L 2 4-6 @02=> @0745;5==KE 4>70E. 5=B0<8F8= 3 <3/:3/45=L 2/2 8;8 2/< 2 3 @02=> @0745;5==KE 4>70E4-6d 4-6 I B<5 200 <3/:3/45=L 2/2 2 4-6 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:f @0745;5?==KE 4>70E. 5=B0<8F8= :0: C:070=> 2KH54-6d 4-6I B0=:><8F8=g A 5=B0<8F8=><530 <3/:3/45=L 2/2 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 5480B@8G5A:85 4>7K:f 0=:><8F8= 40 <3/:3/45=L 2/2 2 2-3 @02=> @0745;5==KE 4>70E 5=B0<8F8= :0: C:070=> 2KH56 6 I !aKA>:89 C@>25=L @578AB5=B=>AB8 : 35=B0<8F8=C (MIC > 300 <3/;): 5A;8 GC2AB28B5;L=>ABL : AB@5?B><8F8=C, 70<5=8BL 35=B0<8F8= =0 AB@5?B><8F8= 15 <3/:3/45=L 2 42CE @02=> @0745;5==KE 4>70E (I, ). =0G5, 8A?>;L7>20BL 1>;55 C4;8=5==K9 :C@A 15B0-;0:B0< B5@0?88. ><18=0F8O 0=>< 1K;0 =5402=> ?@54;>65=0 4;O 35=B0<8F8=-@578AB5=B=KE E. faecalis148 (IIa, B). b5B0-;0:B0<-@578AB5=B=>ABL: (i) 5A;8 87-70 ?@>4C:F88 15B0-;0:B0<07K, 70<5=8BL 0:A8F8;;8= =0 0<>:A8F8;;8=-:;02C;0=0B (I, !); (ii) 5A;8 87-70 0;LB5@0F88 PBPS, 8A?>;L7CNBAO @56820==K5 =0 20=:><8F8=5. AC;LB8@578AB5=B=>ABL : 0<8=>3;8:>7840<, 15B0-;0:B0<0< 8 20=:><8F8=C: ?@54;030NBAO 0;LB5@=0B82K (i) linezolid 2´ð600 <3/45=L 2/2 8;8 ?5@>@0;L=> ³ð 8 =545;L (IIa, C) (:>=B@>;L 35<0B>;>38G5A:>9 B>:A8G=>AB8), (ii) quinupristin dafopristin 3´ð7.5 <3/:3/45=L ³ð 8 =545;L (IIa, !), (iii) 15B0-;0:B0<=0O :><18=0F8O, 2:;NG0NI0O 8<8?5=5< ?;NA 0= ?;NA 0<5=4C5BAO ?0F85=B0< A A8<0<8 > 3 <5AOF52 8 ?@8 PVE. 5>=B@>;L C@>2=59 0<8=>3;8:>784>2 2 AK2>@>B:5 8 ?>G5G=>9 DC=:F88 :0: ?>:070=> 2 "01;8F5 13. f5480B@8G5A:85 4>7K =5 4>;6=K ?@52KH0BL 27@>A;K5 4>7K. g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´ð 400 <3/45=L 2/2 8;8 1000 <3/45=L ?5@>@0;L=>) - MB> <5=55 E>@>H> 4>:070==K9 2K1>@.149,150 2. 07=>284=>AB8 Non-HACEK International Collaboration on Endocarditis (ICE) A>>1I8;> > ?@8ACBAB288 non-HACEK 3@0<->B@8F0B5;L=KE 10:B5@89 2 49/2761 (1.8%) A;CG052 -.151 5:><5=4C5?5@0F8O ?;NA 4>;3>2@5<5==0O (³ð 6 =545;L) B5@0?8O A 10:B5@8F84=>9 :><18=0F859 15B0-;0:B0<>2 8 0<8=>3;8:>784>2, 8=>340 A 4>102;5=85< G8=>;>=>2 8;8 :>B@8<>:A07>;0. >3CB 1KBL ?>;57=K<8 10:B5@8F84=K5 B5ABK in vitro 8 :>=B@>;L :>=F5=B@0F88 0=B818>B8:>2 2 AK2>@>B:5. 7-70 8E @54:>AB8 8 BO65AB8 MB8 A>AB>O=8O =C6=> >1AC640BL A 8=D5:F8>=8AB><. =D5:F8>==K9 M=4>:0@48B A >B@8F0B5;L=>9 :C;LBC@>9 :@>28 ;02=K5 ?@8G8=K BCNIE AC<<8@>20=K 2 0745;5 F.152 0@80=BK ;5G5=8O AC<<8@>20=K 2 "01;8F5 16.153 @81K @81K =081>;55 G0AB> =01;N40NBAO ?@8 PVE 8 ?@8 - 87-70 IVDAs 8 C ?0F85=B>2 A >A;01;5==K< 8<<. @5>1;040NB Candida 8 Aspergillus spp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i) ?>;CG0; ;8 ?0F85=B ?@54H5AB2CNICN 0=B818>B8:>B5@0?8N 8;8 =5B (ii) 70B@038205B ;8 8=D5:F8O =0B82=K9 :;0?0= 8;8 ?@>B57 (8, 5A;8 B0:, :>340 >?5@0F8O 1K;0 2K?>;=5=0 (@0==89 ?@>B82 ?>74=53> PVE) 8 (iii) 7=0=85 ;>:0;L=>9 M?845<8>;>388, >A>15==> 4;O 0=B818>B8:>-@578AB5=B=KE 8 >?@545;5==> ?>4;8==KE :C;LBC@>-=530B82=KE ?0B>35==KE <8:@>>@30=87<>2 ("01;8F0 16). @54;>65==K5 @56820=K 2 "01;8F5 17. 56874=53> PVE 4>;6=K ?5@5:@K20BL AB0D8;>:>::8, AB@5?B>:>::8, @07=>284=>AB8 HACEK 8 Bartonella spp. 568 PVE 4>;6=K ?5@5:@K20BL <5B8F8;;8=-@578AB5=B=K5 AB0D8;>:>::8 8, 2 8450;5 non-HACEK 3@0<->B@8F80B5;L=K5 ?0B>35==K5 <8:@>>@30=87B8:>B5@0?8O 8=D5:F8>==>3> M=4>:0@48B0 A >B@8F0B5;L=>9 :C;LBC@>9 :@>28 8:@>>@30=87<5=4C5<0O B5@0?8O0 57C;LB0B ;5G5=8OBrucella spp.>:A8F8:;8= (200 <3/24 G0A) ?;NA >B@8<>:A07>; (960 <3/12 G0A) ?;NA 8D0@0;L=>5G5=85 AG8B05BAO CA?5H=K<, 5A;8 B8B@ 0=B8B5; < 1:60Coxiella burnetii (2>71C48B5;L Q-;8E>@04:8)>:A8F8:;8= (200 <3/24 G0A) ?;NA 84@>:A8E;>@>E8= (200-600 <3/24 G0A)A ?5@>@0;L=> 8;8 >:A8F8:;8= (200 <3/24 G0A) ?;NA E8=>;>=K (D;>:A0F8=, 400 <3/24 G0A) ?5@>@0;L=> (;5G5=85 > 18 <5AOF52) 5G5=85 AG8B05BAO CA?5H=K<, 5A;8 B8B@K 0=B8-D07K I IgG < 1:200, 8 B8B@K IgA 8 IgM < 1:50.Bartonella spp.&5DB@80:A>= (2 3/24 G0A) 8;8 :A0F8;;8=) (12 3/24 G0A) 2/2 8;8 >:A8F8:;8= (200 <3/24 G0A) ?5@>@0;L=> 6 =545;L ?;NA 5=B0<8F8= (3 <3/24 G0A) 8;8 5B8;<8F8= 2/2 (3 =545;8)d#A@5H=>5 ;5G5=85 >68405BAO 2 ³ð 90%Legionella spp.-@8B@><8F8= (3 3/24 G0A) 2/2 2 =545;8, 70B5< ?5@>@0;L=> 4 =545;8, ;NA 8D0D;>:A0F8= (1,5 3/24 G0A) ?5@>@0;L=> 6 =545;L?B8<0;L=>5 ;5G5=85 =58725AB=>. %8=>;>=K, 87-70 8E 2KA>:>9 GC2AB28B5;L=>AB8, 25@>OB=> 4>;6=K 1KBL 2:;NG5=K.Mycoplasma spp.>2K5 DB>@E8=>;>=K5 (;5G5=85 > 6 <5AOF52) ?B8<0;L=>5 ;5G5=85 =58725AB=>Tropherima whippleif (2>71C48B5;L 1>;57=8 Whipple)>B@8<>:A07>; 5=8F8;;8= G (1,2 MU/24 G0A) 8 !B@5?B><8F8= (1 3/24 G0A) 2/2 2 =545;8, 70B5< >B@8<>:A07>; ?5@>@0;L=> 1 3>4 8;8 >:A8F8:;8= (200 <3/24 G0A) ?;NA 84@>:A8E;>@>E8= (200-600 <3/24 G0A)A ?5@>@0;L=> ³ð 18 <5AOF52 >;3>2@5<5==>5 ;5G5=85, >?B8<0;L=0O ?@>4>;68B5;L=>ABL =58725AB=0.40?B8@>20=> 87 Brouqui and Raoult.153 07-70 =54>AB0B:0 1>;LH8E 8AA;54>20=89 >?B8<0;L=0O ?@>4>;68B5;L=>ABL ;5G5=8O - 87-70 MB8E 2>71C48B5;59 =58725AB=0. @54AB02;5==?O ?@>4>;68B5;L=>ABL >A=>20=0 =0 A>>1I5=8OE >B45;L=KE A;CG052. b>102;5=85 AB@5?B><8F8=0 (15 <3/:3/24 G0A 2 425 4>7K) 2 B5G5=85 ?5@2KE =5A:>;L:8E =545;L 2K1>@>G=> (D0:C;LB0B82=>). A>:A8F8:;8= ?;NA 384@>:A8E;>@>E8= (A :>=B@>;5< C@>2=O 384@>:A8E;>@>E8=0 2 AK2>@>B:5) 2KH5, G5< 4>:A8F8:;8= B>;L:> 8 4>:A8F8:;8=+DB>@E8=>;>=. d5:>B>@K5 B5@0?52B8G5A:85 @568>1I0NB, 2:;NG0;8 0<8=>?5=8F8;;8=K 8 F5D0;>A?>@8=K 2 :><18=0F88 A 0<8=>3;8:>7840<8, 4>:A8F8:;8=><, 20=:><8F8=><, 8 E8=>;>=0<8. >78@>20=85 B0:>5 65, :0: 4;O AB@5?B>:>::>2>3> 8 M=B5@>:>::>2>3> - ("01;8FK 13 8 15).383,384 5>;55 =>2K5 DB>@E8=>;>=K O2;ONBAO 1>;55 <>I=K<8, G5< F8?@>D;>:A0F8=, ?@>B82 2=CB@8:;5B>G=KE 2>71C48B5;59, B0:8E :0: Mycoplasma spp., Legionella spp. Chlamydia spp. f5G5=85 - Whipple >AB05BAO AC3C1> M>1I5=8O >1 CA?5H=>9 4>;3>2@5<5==>9 (> 1 3>40) B5@0?88 :>B@8<>:A07>;><, gð-8=B5@D5@>= 83@05B 70I8B=CN @>;L ?@8 2=CB@8:;5B>G=KE 8=D5:F8OE 8 1K;0 ?@54;>65=0 :0: 04LN20=B=0O B5@0?8O ?@8 1>;57=8 Whipple.385,386 "01;8F0 17 @54;0305B8G5A:85 @5683> M3> ;5G5=8O 8=D5:F8>==>3> M=4>:0@48B0. (4> 8;8 157 845=B8D8:0F88 2>71C48B5;O) =B818>B8: >78@>20=85 8 ?CBL 22545=8O @>4>;68-B5;L=>ABL (=545;8) #@>25=L 4>:070=-=>AB8 ><-<5=B0@88 0B82=K5 :;0?0=K:A8F8;;8=-;02C=0B, A 5=B0<8F8=><012 3/45=L 2/2 2 4 4>70E 12 3/45=L 2/2 2 4 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E4-6 4-6 4-6IIb C IIb C0F85=BK A - A >B@8F0B5;L-=>9 :C;LBC@>9 :@>28 4>;6=K :>=AC;LB8-@>20BLAO 8=D5:F8>-=8AB><0=:><8F8=b A 5=B0<8F8=><0 A &8?@>D;>:A0-F8=><30 <3/:3/45=L 2/2 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 1000 <3/45=L ?5@>@0;L=> 2 2 4>70E 8;8 800 <3/45=L 2/2 2 2 4>70E 4-6 4-6 4-6IIb C ;O ?0F85=B>2, =5 ?5@5=>AO-I8E 15B0-;0:B0D;>-:A0F8= =5 2A5340 >48=0:>2> 459AB2C5B =0 Bartonella spp. K1>@>< O2;O5BAO 4>102;5=85 4>:A8F8:-;8=0 (A<. "01;8FC 16), 5A;8 Bartonella. spp. 25@>OB=0@>B57=K5 :;0?0=K (@0==89, < 12 <5AOF52 ?>A;5 >?5@0F88)0=:><8F8=b A 5=B0<8F8=><0 A 8D0<30 <3/:3/45=L 2/2 2 2 4>70E 3 <3/:3/45=L 2/2 8;8 2/< 2 2 8;8 3 4>70E 1200 <3/45=L ?5@>@0;L=> 2 2 4>70E 6 2IIb CA;8 =5B :;8=8G5A:>-3> >B25B0, 4>;6=0 1KBL >1AC645=0 >?5@0F8O 8, <>65B 1KBL, @0AH8@5=8O A?5:B@0 0=B818>B8-:>2 =0 3@0<->B@8F0B5;L-=K5 2>71C48B5;8 @>B57=K5 :;0?0=0 (?>74=89, > 12 <5AOF52 ?>A;5 >?5@0F88)"0: 65, :0:0: 4;O =0B82=KE :;0?0=>2a,b>=B@>;L 4>78@>20=8O 35=B0<8F8=0 8 20=:><8F8=0 B0:, :0: 2 "01;8F5 13 8 "01;8F514. <1C;0B>@=0O ?0@5=B5@0;L=0O 0=B818>B5@0?8O 8=D5:F8>==>3> M=4>:0@48B0 <1C;0B>@=0O ?0@5=B5@0;L=0O 0=B818>B8:>B5@0?8O (AT) 8A?>;L7C5BAO C > 250 000 ?0F85=B>2/;5B 2 !(.158 @8 - >=0 4>;6=0 8A?>;L7>20BLAO 4;O :>=A>;848@>20==>9 0=B810:B5@80;L=>9 B5@0?88 4> ?>O2;5=8O :@8B8G5A:8E 8=D5:F8>==KE >A;>6=5=89 (=0?@8<5@, >:>;>:;0?0==K5 01AF5AAK, >AB@0O A5@45G=0O =54>AB0B>G=>ABL, A5?B8G5A:89 M<1>;, 8 8=AC;LB). 25 @07;8G=KE D07K <>3CB 1KBL 2K45;5=K 2 B5G5=85 :C@A0 0=B818>B8:>B5@0?88 ?5@20O :@8B8G5A:0O D070 (?5@2K5 2 =545;8 B5@0?88), 2> 2@5B>@>9 AT 8<55B >3@0=8G5==K5 ?>:070=8O, 8 2B>@0O ?@>4>;60NI0OAO D070 (?>A;5 2 =545;L B5@0?88), :>340 " <>65B ?@8<5=OBLAO. "01;8F0 18 AC<<8@C5B ACI5AB25==K5 2>?@>AK ?> " 4;O -.159 @>1;5-B5E=8G5A:>3> >15A?5G5=8O 206=K 8 B@51CNB >B ?0F85=B0 8 >1A;C6820NI53> ?5@A>=0;0 :>=>AB8, :>=B@>;O MDD5:B82=>AB8 8 =530B82=KE 2>7459AB289, ?0@0<548F8=A:>9 8 A>F80;L=>9 ?>445@6:8 8 =570B@C4=5==>3> 4>ABC?0 : 2@0G51=>9 :>=AC;LB0F88. A;8 ?@>1;57=8:0NB, ?0F85=B 4>;65= 1KBL =0?@02;5= : 8=D>@<8@>20==>=0;C, 7=0:><> A;CG05<, 8 =5 2 ;N1>5 >B45;5=85 =5>B;>6=>9 ?><>I8. @8 B0:8E CA;>28OE " 2K?>;=O5BAO >48=0:>2> E>@>H> =57028A8<> >B 2>71C48B5;O 8 :;8=8G5A:>3> :>=B5:AB0.160,161 "01;8F0 18 @8B5@88, :>B>@K5 >?@545;ONB ?@83>4=>ABL 0<1C;0B>@=>9 ?0@5=B5@0;L=>9 0=B818>B8:>B5@0?88 (") 4;O 8=D5:F8>==>3> M=4>:0@48B0 $070 ;5G5=8O C:>2>4OI85 ?@8=F8?K 8A?>;L7>20=8O @8B8G5A:0O D070 (0 2 =545;8)A;>6=5=8O, 2AB@5G0NI85AO 2 MB>9 D075. MB>9 D075 >B405BAO ?@54?>GB5=85 AB0F8>=0@=>@0;L=K5 AB@5?B>:>::8, ?0F85=B AB018;L=K9, =5B >A;>6=5=89.@>4>;60NI0OAO D070 (?>A;5 2-9 =545;8)1AC48BL ": 5A;8 A>AB>O=85 AB018;L=>5. 5 >1AC640BL ": 5A;8 A5@45G=0O =54>AB0B>G=>ABL, 87<5=5==0O M;5:B@>:0@48>3@0<<0, =52@>;>38G5A:85 A8G5G=0O =54>AB0B>G=>ABL!CI5AB25==> 4;O "4CG5=85 ?0F85=B0 8 ?5@A>=0;0. 53C;O@=0O >F5=:0 ?>A;5 2K?8A:8 (<54A5AB@K 1/45=L, >A<>B@ 2@0G0 1-2/=545;O). @58 2@0G51=>-=0?@02;ONI0O ?@>3@0<<0, =5 4><0H=5-8=DC78>==0O <>45;L. 40?B8@>20=> 87 Andrews and von Reyn.159 I. 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TTE >1KG=> ?>72>;O5B >F5=8BL B@8:CA?840;L=>5 2>2;5G5=85 87-70 ?5@54=59 ;>:0;870F88 MB>3> :;0?0=0 8 >1KG=KE 1>;LH8E 2535B0F89.329 331 4=0:>, " 1>;55 GC2AB28B5;L=0 2 >1=0@C65=88 ;53>G=KE 2535B0F89332 8 01AF5AA>2 (>A>15==> A<56=KE A <5<1@0=>7=>9 ?5@53>@>4:>9), 8 0AA>F88@>20==>3> ;52>AB>@>==53> 2>2;5G5=8O. @>3=>7 8 ;5G5=85 @>3=>7 ?@02>AB>@>==53> NVE >B=>A8B5;L=> E>@>H89, A 2=CB@81>;L=8G=>9 A<5@B=>ABLN < 10%.333 335 535B0F88 4;8=>9 > 20 << 8 3@81:>20O MB8>;>38O 1K;8 3;02=K<8 ?@548:B>@0<8 A<5@B8 2 =5402=5< 1>;LH>< @5B@>A?5:B82=>< :>3>@B=>< 8AA;54>20=88 ?@02>AB>@>==53> - ?@8 IVDAs.335 # 8=D8F8@>20==KE ' ?0F85=B>2 CD4 ?>4AG5B < 200 :;5B>:/<; 8<55B 2KA>:CN ?@>3=>AB8G5A:CN F5==>ABL.320,322 1. =B810:B5@80;L=0O B5@0?8O @8 3>A?8B0;870F88 2K1>@ =0G0;L=>9 M9 0=B810:B5@80;L=>9 B5@0?88 7028A8B >B ?>4>7@5205<>3> <8:@>>@30=87<0, B8?0 ?@5?0@0B0 8 @0AB2>@8B5;O, 8A?>;L7C5<>3> =0@:><0=>< 8 ;>:0;870F859 A5@45G=>3> 2>2;5G5=8O.333,334 @8 ?@02>AB>@>==5< NVE S. aureus 4>;65= 1KBL 2A5340 >E20G5=, >A>15==> ?@8 IVDAs 8;8 8=D5:F88, A2O70==>9 A 25=>7=K< :0B5B5@><. 5G5=85 4>;6=> 2:;NG0BL ;N1>9 ?5=8F8448=070-CAB>9G82K9 ?5=8F8;;8= 8;8 20=:><8F8= 2 7028A8<>AB8 >B ;>:0;L=>9 @0A?@>AB@0=5==>AB8 MRSA.336,337 A;8 ?0F85=B ?5=B07>F8=>2K9 =0@:><0=, 4>;65= 1KBL 4>102;5= 0=B8?A524><>=04=K9 ?@5?0@0B.338 A;8 IVDA 8A?>;L7C5B :>@8G=52K9 35@>8=, @0AB2>@5==K9 2 ;8<>==>< A>:5, 4>;6=0 1KBL @0AA<>B@5=0 Candida spp. (=5 C. albicans), 8 4>102;5=> ?@>B82>3@81:>2>5 ;5G5=85.339 >;55 >1KG=>, ?@8 IVDAs A >A=>2=K<8 :;0?0==K<8 ?>2@5645=8O<8 8/8;8 ;52>AB>@>==8< 2>2;5G5=85<, 0=B818>B8G5A:>5 ;5G5=85 4>;6=> 2:;NG0BL >E20B ?@>B82 AB@5?B>:>::>2 8 M=B5@>:>::>2.333,334 A;8 1>;57=5B2>@=K5 >@30=87;8@>20=K, B5@0?8O 4>;6=0 1KBL 87<5=5=0. @8 IVDAs O2;O5BAO A>>B25BAB2CNI59 AB0=40@B=0O B5@0?8O 4;O - 87-70 MSSA, A G5B:8<8 40==K<8, 45<>=AB@8@CNI8<8, GB> @5689G82>3> ?5=8F8;;8=0 ?@52>AE>4OB 3;8:>?5?B84>-A>45@60I85 @568B82>@5G82K5 40==K5, ?>:07K20NI85, GB> 2-=545;L=>5 ;5G5=85 <>65B 1KBL 4>AB0B>G=K<341 343 8, GB> 4>?>;=5=85 0<8=>3;8:>7840 <>65B 1KBL =5=C6=K<.341 2CE=545;L=>5 ;5G5=85 >:A0F8;;8=>< (8;8 cloxacillin) A 8;8 157 35=B0<8F8=0 2>7<>6=>, 5A;8 2A5 A;54CNI85 :@8B5@88 2K?>;=5=K: üð MeB8F8;;8=-GC2AB28B5;L=K5 S. aureus 8 üð %>@>H89 >B25B =0 ;5G5=85 8 üð BACBAB285 <5B0AB0B8G5A:8E >G03>2 8=D5:F88 8;8 MA;>6=5=89 8 üð BACBAB285 0AA>F88@>20==>9 ?@>B57=>:;0?0==>9 8;8 ;52>AB>@>=5:;0?0==>9 8=D5:F88 8 üð 535B0F88 < 20 << 8 üðBACBAB285 BO65;>9 8<45?@5AA88 ( < 200 CD4 :;5B>:/<<3) A 8;8 157 !0. 7-70 >3@0=8G5==>9 10:B5@8F84=>9 45OB5;L=>AB8, ?;>E>3> ?@>=8:=>25=8O 2 2535B0F88 8 C25;8G5==K9 :;8@5=A ?@5?0@0B0 ?@8 IVDAs 3;8:>?5?B84K =5 4>;6=K 8A?>;L7>20BLAO ?@8 2-=545;L=>< ;5G5=88. !B0=40@B=K9 4 6 =545;L=K9 @568< 4>;65= 8A?>;L7>20BLAO 2 A;54CNI8E A8BC0F8OE: (a) 70<54;5==K9 :;8=8G5A:89 8;8 <8:@>18>;>38G5A:89 >B25B (> 96 G) =0 0=B818>B8:>B5@0?8N;343,344 (b) ?@02>AB>@>==89 -, >A;>6=5==K9 ?@02>9 !, 2535B0F88 > 20 <<, >AB@0O 4KE0B5;L=0O =54>AB0B>G=>ABL, A5?B8G5A:85 <5B0AB0B8G5A:85 >G038 2=5 ;53:8E (2:;NG0O MA;>6=5=8O, =0?@8<5@, >AB@0O ?>G5G=0O =54>AB0B>G=>ABL;344,345 (c) 0=B818>B8:>B5@0?8O 4@C3O, G5< ?5=8F8;;8=070-CAB>9G82KE ?5=8F8;;8=>2;342,343,346,347 (d) IVDA A BO65;>9 8<45?@5AA859 (CD4 ?>4AG5B < 200 :;5B>:/<;) A 8;8 157 !0;348,349 (e) 0AA>F88@>20==K9 ;52>AB>@>==89 -. @02>AB>@>==89 S. aureus - ?@8 IVDAs <>6=> B0:65 CA?5H=> ;5G8BL ?5@>>@0;L=K< F8?@>D;>:A0F8=>< (750 <3 2 @070 2 45=L) ?;NA @8D0288, GB> HB0< ?>;=>ABLN GC2AB28B545= : >1>8< ?@5?0@0B0< 8 A>1;N45=85 C:070=89 ?0F85=B>< BI0B5;L=> :>=B@>;8@C5BAO.350 ;O 2>71C48B5;59 :@><5 MSSA, B5@0?8O ?@8 IVDAs =5 >B;8G05BAO >B B0:>2>9 C =5=0@:><0=>2.344,351 2. ?5@0F8O %8@C@38G5A:>3> ;5G5=8O =C6=> 2 F5;>< 871530BL ?@8 ?@02>AB>@>==5< =0B82=>< -, => =04> @0AA<>B@5BL 2 A;54CNI8E A8BC0F8OE ("01;8F0 25): (a) ?@020O !, 2B>@8G=0O : BO65;>9 B@8:CA?840;L=>9 @53C@38B0F88 A ?;>E8< >B25B>< =0 48C@5B8G5A:CN B5@0?8N; 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