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The International Sepsis Forum Consensus Conference on Definitions of Infection in the Intensive Care Unit
[Crit Care Med. 2005;33(7):1538-1548. 2005 Lippincott Wi ia!" # Wi $in"%

Sepsis Forum on Definitions of Infection in Intensive Care Unit

Results
&'e "i( !o"t co!!on in)ection "ite" *ere identi)ied a" pne+!onia, - ood"trea! in)ection" (inc +din. in)ecti/e endocarditi"), intra/a"c+ ar cat'eter-re ated "ep"i", intra-a-do!ina in)ection", +ro"ep"i", and "+r.ica *o+nd in)ection".[2% 0n t'e )o o*in. "ection" *e pro/ide a -rie) rationa e and -ac$.ro+nd and t'e "+..e"ted )or!+ ation o) eac' de)inition. Pneumonia 1or t'e p+rpo"e" o) de)inin. *'et'er pne+!onia i" pre"ent or a-"ent, it i" not nece""ar2 to !a$e t'e di"tinction -et*een co!!+nit2-ac3+ired pne+!onia (C45), 'ea t' care-re ated pne+!onia, 'o"pita -ac3+ired pne+!onia, and /enti ator-a""ociated pne+!onia (645), a t'o+.' t'eir a""ociated ri"$ )actor" and pre"entation" di))er. [4-7% Contro/er"2 contin+e" a-o+t 'o* to -e"t dia.no"e 645, -+t "peci)icit2 i" i!pro/ed on 2 a)ter !icro-io o.ica c+ t+re data are o-tained, in)or!ation t'at i" "e do! a/ai a- e *'en patient" are )ir"t e/a +ated )or t'e etio o.2 o) "ep"i" "2!pto!".[7, 8, 8% &'ere)ore, t'e de)inition i" de"i.ned to !a(i!i9e t'e i$e i'ood o) t'e patient 'a/in. re"pirator2 in)ection, +"in. c inica criteria, -+t t'e initia dia.no"i" o) pne+!onia can -e !odi)ied once !icro-io o.ica data -eco!e a/ai a- e. Wit' "+c' data, pne+!onia can -e c a""i)ied, post hoc, a" )a in. into one o) t'ree cate.orie" ( &a- e 1 ): Micro-io o.ica 2 con)ir!ed or de)inite: C inica 2 pre"ent *it' a-nor!a c'e"t radio.rap' and t'e i"o ation o) a i$e 2 p+ !onar2 pat'o.en, or t'e i"o ation o) a i$e 2:po""i- e p+ !onar2 pat'o.en in 'i.' concentration )ro! a 3+antitati/e o*er re"pirator2 tract "a!p e, or po"iti/e "ero o.2. [4, 5, 7, 10% 5ro-a- e: C inica 2 pre"ent *it' a-nor!a c'e"t radio.rap' -+t *it'o+t !icro-io o.ica or "ero o.ica con)ir!ation 5o""i- e: 4-nor!a c'e"t radio.rap' o) +ncertain ca+"e, *it' o* or !oderate c inica "+"picion o) pne+!onia, -+t *it' !icro-io o.ica or "ero o.ic criteria o) de)inite or pro-a- e pne+!onia 1or enro !ent in "ep"i" tria ", it !a2 not -e po""i- e to inc +de on 2 patient" *it' !icro-io o.ica 2 con)ir!ed c inica in)ection "ince t'e +"e o) anti-iotic" (eit'er +r.ent 2 )or "ep"i", or -e)ore t'e on"et o) "ep"i") can inter)ere *it' t'e 2ie d o) !icro-io o.ica te"tin.. 1or "ep"i" tria ", *e propo"e t'at patient" *it' c inica pne+!onia -e inc +ded initia 2 and t'at t'e tria de"i.n "peci)2 *'et'er !icro-io o.ica con)ir!ation 'a" -een o-tained post hoc, "o t'at t'e reader can deter!ine t'e de.ree o) .enera i9a-i it2 to an2 ot'er patient pop+ ation. Mo"t c inica tria " in "ep"i" are de"i.ned a" intent to treat, and 'ence a patient" are inc +ded in t'e pri!ar2 data ana 2"i". ;o*e/er, post hoc in)or!ation, a t'o+.' not +"e)+ to dra* e))icac2 conc +"ion", !a2 -e +"e)+ to e(a!ine "+-"et" o) pne+!onia patient" )or '2pot'e"i" .eneration. &'e c inica dia.no"i" o) pne+!onia re3+ire" t'e pre"ence o) a radio.rap'ic in)i trate, *it' "+"picion t'at t'e in)i trate i" ca+"ed -2 in)ection. &'i" can -e deter!ined -2 !ea"+re!ent" o) )e/er, *'ite - ood ce co+nt, de.ree o) "p+t+! p+r+ ence, de.ree o) o(2.enation i!pair!ent, and t'e pre"ence o) potentia pat'o.en" in o*er re"pirator2 tract "ecretion" .[8, 11, 12% 0n C45, t'e dia.no"tic "en"iti/it2 and "peci)icit2 o) eac' o) t'e"e co!ponent" 'a/e not -een )or!a 2 in/e"ti.ated; a ne* in)i trate p +" t'e pre"ence o) )e/er, and at ea"t t*o o) p+r+ ent "p+t+!, co+.', c'an.e in e+$oc2te co+nt, and i!paired o(2.enation, *o+ d -e eno+.' )or t'e dia.no"i" o) pro-a- e pne+!onia. <apid dia.no"tic te"t" "+c' a" Legionella or pne+!ococca +rinar2 anti.en and ne*er te"t" "+c' a" "o +- e tri..erin. receptor e(pre""ed on !2e oid ce " [13% !a2 pro/ide ear 2 data a-o+t etio o.2, a t'o+.' "+c' te"t" are not a *a2" *ide 2 a/ai a- e and re3+ire )+ /a idation. =ero o.ic te"tin. )or Legionella, Mycoplasma, and Chlamydophila pneumoniae i" a/ai a- e -+t .enera 2 re3+ire" co ection o) ac+te and con/a e"cent "a!p e" to oo$ )or a )o+r-)o d ri"e in titer. > ood and p e+ra c+ t+re", i) po"iti/e, can -e dia.no"tic o) a -acteria etio o.2. 0n t'e dia.no"i" o) 645 and "e/ere C45, t'e"e "i( co!ponent" 'a/e -een co!-ined into t'e c inica p+ !onar2 in)ection "core (C50=), and a t'o+.' t'i" too 'a" not -een +"ed in ot'er t2pe" o) pne+!onia, it inc +de" a o) t'e c inica )eat+re" +"ed to dia.no"e pne+!onia. [8, 11% 1or t'e p+rpo"e o) a !ore "peci)ic (rat'er t'an "en"iti/e) de)inition o) an2 )or! o) pne+!onia, t'e patient "'o+ d 'a/e a C50= o) ?7 ( &a- e 1 ).

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0n it" ori.ina de"cription, t'e !icro-io o.ica criteria +"ed )or t'e C50= *ere c+ t+re re"+ t" )ro! a o*er re"pirator2 tract "a!p e, -+t one recent "t+d2 ca c+ ated t'e "core +"in. a @ra! "tain o) a -ronc'oa /eo ar a/a.e or - ind protected te e"copin. cat'eter "a!p e and "cored t'e re"+ t" a" eit'er po"iti/e or ne.ati/e. A"in. t'i" approac', t'e C50= )or patient" *it' con)ir!ed 645 *a" "i.ni)icant 2 'i.'er t'an t'e /a +e )or noncon)ir!ed 645.
[12%

&'e pro-a-i it2 o) pne+!onia "'o+ d -e a""e""ed post hoc, once c+ t+re data are a/ai a- e, and t'e pre"ence o) a po"iti/e 3+antitati/e c+ t+re o) a o*er re"pirator2 tract "a!p e (at a t're"'o d o) 10 3 )or protected "peci!en -r+"', 104 )or -ronc'oa /eo ar a/a.e, and 105-107 )or endotrac'ea a"pirate) increa"e" t'e pro-a-i it2 t'at pne+!onia i" pre"ent.[14-17% Bloodstream Infections > ood"trea! in)ection" (>=0") acco+nt )or 30-40B o) a ca"e" o) "e/ere "ep"i" and "eptic "'oc$. [2% ;o*e/er, t'e incidence o) >=0 a" a ca+"e o) "e/ere "ep"i" i" pro-a- 2 +ndere"ti!ated in t'e 'o"pita "ettin., "ince - ood c+ t+re" are )re3+ent 2 dra*n )ro! patient" treated *it' -road-"pectr+! anti-iotic". Con/entiona 2, >=0" 'a/e -een di/ided into t*o cate.orie": a) pri!ar2 >=0 co!pri"in. >=0 o) +n$no*n ori.in in patient" *it'o+t an identi)ia- e )oc+" o) in)ection, and intra/a"c+ ar cat'eter-re ated >=0; and -) "econdar2 >=0 de)ined a" a >=0 ca+"ed -2 a !icroor.ani"! re ated to an in)ection at anot'er "ite. &'e proportion o) pri!ar2 >=0 reported in t'e iterat+re /arie" -road 2 -et*een "t+die", ran.in. )ro! C5B to D30B. [2, 17-21% &'i" *ide /ariation re) ect" di))erence" o) "t+d2 ai! and de"i.n (i.e., epide!io o.ic "t+die" /". "ep"i" treat!ent tria ", pro"pecti/e /". retro"pecti/e "t+die") and o) de)inition" (i.e., i!ited to >=0 o) +n$no*n ori.in in "o!e "t+die", *'i e a "o inc +din. intra/a"c+ ar acce"" de/ice-re ated >=0 in ot'er "t+die"). Land!ar$ "t+die" per)or!ed in t'e 1880" and 1880" 'a/e pro/ided /er2 'e p)+ de)inition" o) >=0 t'at 'a/e -een +"ed -2 n+!ero+" in/e"ti.ator".[17, 20% 0n recent 2ear", t'e de)inition" o) no"oco!ia in)ection" o) t'e Center" )or Ei"ea"e" Contro and 5re/ention (CEC) 'a/e -een t'e .o d "tandard +"ed in !o"t epide!io o.ic "t+die". &'e ate"t +pdate o) t'e"e de)inition" *a" p+- i"'ed in 1887, [1% in *'ic' >=0" *ere di/ided into a-orator2-con)ir!ed >=0 and c inica "ep"i". 4 -eit *ide 2 +"ed, t'ere are "e/era pro- e!" *it' t'e CEC de)inition". Ee"i.ned )or no"oco!ia in)ection", t'e"e de)inition" are not "+ited )or co!!+nit2-ac3+ired in)ection". &'e de)inition" 'a/e not -een +pdated "ince 1887 and !a$e re)erence to o-"o ete !icro-io o.ica dia.no"tic too ", "+c' a" detection o) -acteria anti.en" in - ood. &'e CEC doc+!ent doe" not pro/ide a de)inition )or "econdar2 >=0, nor doe" it addre"" t'e concept o) repeated epi"ode" o) >=0. 0ndeed, in critica 2 i 0CA patient", !+ tip e epi"ode" o) >=0 )re3+ent 2 occ+r t'at !a2 -e ca+"ed -2 t'e "a!e (i.e., per"i"tent or re ap"in. >=0) or -2 di))erent !icroor.ani"!" (i.e., rein)ection). 1ina 2, one o) t'e criteria +"ed -2 t'e CEC to de)ine >=0 re3+ire" t'at appropriate anti!icro-ia t'erap2 -e in"tit+ted -2 a p'2"ician. C ear 2, >=0 "'o+ d -e de)ined independent 2 o) t'e p'2"icianF" deci"ion to initiate or *it''o d anti!icro-ia t'erap2. 0n "+!!ar2, t'e e(i"tin. CEC de)inition" 'a/e a n+!-er o) i!itation" *'en app ied to c inica "ep"i" "t+die". =e/era "t+die" in patient" *it' "ep"i" "2ndro!e 'a/e e(a!ined *'ic' a"pect" o) t'e 'i"tor2, c inica "2!pto!" and "i.n", and a-orator2 /aria- e" !i.'t 'e p predict t'e pre"ence o) a >=0. [22-25% 0n .enera , prediction !ode " +"in. t'e"e )actor" are c'aracteri9ed -2 a re ati/e 2 'i.' "peci)icit2 -+t a /er2 o* "en"iti/it2. Mi"c a""i)ication" are )re3+ent, and t'e c inica +ti it2 o) t'e"e predicti/e !ode " re!ain" to -e de!on"trated. Ee)inition" )or t'e principa c inica entitie"-a) >=0 o) +n$no*n ori.in or pri!ar2 >=0 and -) "econdar2 >=0-are .i/en in &a- e 2 and &a- e 3 . Infective Endocarditis 0n)ecti/e endocarditi" acco+nt" )or a-o+t 1B o) a ca"e" o) "e/ere "ep"i" and i" a""ociated *it' a !orta it2 rate o) 33B.[27% Ee"pite t'eir *ide acceptance, t'e c a""ic /on <e2n criteria [23% )or dia.no"i" o) in)ecti/e endocarditi" *ere not *e "+ited )or c inica +"e. 0n 1884, E+rac$ et a . [27% propo"ed ne* dia.no"tic criteria )or in)ecti/e endocarditi", re)erred to a" t'e E+$e criteria, -a"ed on !icro-io o.ica data and ec'ocardio.rap'ic i!a.in. )indin.". 4ccordin. to t'e"e criteria, patient" are c a""i)ied into t'ree dia.no"tic cate.orie" (de)inite, po""i- e, and reGected in)ecti/e endocarditi"). &'e +"e)+ ne"" o) t'e"e criteria in a""e""in. patient" "+"pected o) in)ecti/e endocarditi" 'a" -een /a idated -2 n+!ero+" "t+die". <ecent 2, !odi)ication" o) t'e E+$e criteria 'a/e -een propo"ed to ta$e into acco+nt "e/era identi)ied "'ortco!in." o) t'e ori.ina criteria, inc +din. t'e increa"in. dia.no"tic ro e o) tran"e"op'a.ea ec'ocardio.rap'2, t'e re ati/e ri"$ o) in)ecti/e endocarditi" in >=0 d+e to Staphylococcus aureus, t'e 'i.' n+!-er o) patient" cate.ori9ed a" 'a/in. po""i- e in)ecti/e endocarditi", and a poor dia.no"tic "en"iti/it2 in "+"pected ca"e" o) H )e/er endocarditi". [28% 4dditiona !odi)ication" 'a/e -een propo"ed -+t 'a/e not -een pro"pecti/e 2 e/a +ated. &'ere)ore, t'e propo"ed de)inition" o) in)ecti/e endocarditi" are t'o"e -a"ed on t'e !odi)ied E+$e criteria propo"ed -2 Li et a ..[28%

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Catheter-Related Sepsis &'e dia.no"i" o) cat'eter-re ated in)ection (C<0) i" o)ten a dia.no"i" o) e(c +"ion, at ea"t at t'e ti!e o) enro !ent, "ince t'e de)initi/e dia.no"i" *i on 2 -e po""i- e in !o"t in"tance" once c+ t+re re"+ t" are a/ai a- e (i.e., 24-48 'r" a)ter c inica "+"picion o) C<0 and enro !ent in a c inica tria ), to.et'er *it' t'e con)ir!ed a-"ence o) ot'er "o+rce". C inica )indin." are too non"peci)ic to e"ta- i"' a dia.no"i" o) cat'eter-re ated "ep"i", and !an2 !ore patient" are "+"pected o) 'a/in. a C<0 t'an 'a/e a con)ir!ed C<0. [28, 30% &'ere)ore, to decrea"e t'e pro-a-i it2 t'at patient" *it'o+t C<0 are enro ed in a c inica tria , *e 'a/e )oc+"ed on identi)2in. t'o"e patient" at t'e 'i.'e"t ri"$ o) C<0. 0dea 2, *'en -actere!ia occ+r" in a patient 'a/in. an ind*e in. cat'eter and no ot'er o-/io+" "o+rce i" identi)ied, con)ir!ation o) *'et'er -actere!ia ori.inate" )ro! t'e cat'eter (i.e., i" cat'eter-re ated) or i" "econdar2 to anot'er "o+rce !+"t -e "o+.'t. &'i" i" done -2 ta$in. appropriate c+ t+re" *'ic' !a2 or !a2 not re3+ire cat'eter re!o/a .[31% 4 c inica "+"picion o) cat'eter in)ection in t'e pre"ence o) ot'er*i"e +ne(p ained "e/ere "ep"i" or "eptic "'oc$, 'o*e/er, "'o+ d pro!pt cat'eter re!o/a [28% and appropriate c+ t+re" o) t'e cat'eter tip (i.e., 3+antitati/e or "e!i3+antitati/e cat'eter "e.!ent c+ t+re), [32, 33% - ood c+ t+re" (at ea"t one perip'era and one centra - ood c+ t+re), and e(it "ite or '+- c+ t+re" dependin. on t'e pre"entation (1i.. 1).

Figure ! (c ic$ i!a.e to 9oo!) Eia.no"tic "trate.2 )or "+"pected cat'eter-re ated "ep"i". CVC, centra /eno+" cat'eter. I4 !ini!+! o) t*o - ood c+ t+re "et" are re3+ired, inc +din. at ea"t one "et o) centra and perip'era - ood c+ t+re" ta$en "i!+ taneo+" 2.

4" "'o*n in 1i.+re 1, t'e c inica pro-a-i it2 o) C<0 increa"e" *'en a cat'eter 'a" -een in p ace ?7 da2", and in partic+ ar *'en a cat'eter 'a" -een on."tandin. (e..., in p ace ?21 da2") or 'a" -een p aced +"in. non"teri e tec'ni3+e. 0n addition, a t'o+.' a rare occ+rrence, '2poten"ion +pon ) +"'in. t'e cat'eter i" a "tron. "i.n t'at t'e cat'eter i" in)ected. Loca "i.n" at t'e cat'eter e(it "ite a "o increa"e t'e c inica pro-a-i it2 o) C<0. Loca "i.n" "+..e"ti/e o) C<0 inc +de, in increa"in. order o) "peci)icit2, er2t'e!a or ind+ration e(tendin. ?2 c! o) t'e cat'eter e(it "ite, ce + iti" a on. t'e "+-c+taneo+" tract o) t'e cat'eter, and p+" at t'e cat'eter entr2 "ite. W'erea" t'e pre"ence o) p+" i" /irt+a 2 dia.no"tic o) in)ection, t'e ot'er "i.n" are non"peci)ic. &'e !aGorit2 o) C<0 occ+r" in t'e a-"ence o) oca "2!pto!".

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0n de)inition" +"ed )or C<0 "+r/ei ance p+rpo"e", a -actere!ia" ori.inatin. )ro! patient" *'o 'a/e a centra /eno+" cat'eter in p ace and no ot'er identi)ia- e "o+rce o) in)ection are c a""i)ied a" cat'eter-a""ociated -actere!ia.[34% &'i" de)inition i" "en"iti/e -+t non"peci)ic. 1or t'e p+rpo"e" o) enro in. patient" *it' "ep"i" in c inica tria ", on 2 patient" *'o"e -actere!ia i" act+a 2 "econdar2 to cat'eter in)ection and intra/a"c+ ar "eedin. )ro! a co oni9ed cat'eter "'o+ d -e inc +ded. &'e !o"t c'a en.in. pro- e! t'at ari"e" *'en e/a +atin. a patient *it' po""i- e cat'eter-re ated -actere!ia i" a"cri-in. a "ep"i" "2ndro!e to cat'eter in)ection *'en -actere!ia i" d+e to a co!!on "$in co!!en"a and on 2 one po"iti/e - ood c+ t+re (centra or perip'era ) i" a/ai a- e or 'a" -een o-tained. 0n t'i" "it+ation, repeat c+ t+re", *it' c+ t+re o) t'e cat'eter tip, !+"t -e per)or!ed to con)ir! cat'eter-re ated -actere!ia. &'e i$e i'ood o) cat'eter-re ated -actere!ia *i depend on t'e !icroor.ani"!, t'e n+!-er o) -ott e" ta$en in a "et, and t'e c inica pict+re. &r+e con)ir!ation t'at t'e cat'eter i" t'e "o+rce o) in)ection re3+ire" t'at t'e "a!e or.ani"! i" .ro*n )ro! perip'era - ood and t'e cat'eter "e.!ent or t'at a centra - ood "a!p e i" read a" po"iti/e ?2 'r" ear ier t'an a perip'era - ood "a!p e inoc+ ated at t'e "a!e ti!e, or t'ere i" a di))erentia co+nt o) D5:1 in )a/or o) t'e centra "a!p e. [35% W'en "+c' in)or!ation i" not a/ai a- e )or tec'nica rea"on" ( ac$ o) c+ t+re", de)ecti/e proce""in.), t'e po"iti/e - ood c+ t+re eit'er i" a conta!inant or, i) /ie*ed a" c inica 2 "i.ni)icant and no ot'er "o+rce 'a" -een identi)ied, i" ter!ed cat'eter-a""ociated -actere!ia. Cat'eter in)ection rare 2 ca+"e" "e/ere "ep"i" in t'e a-"ence o) -actere!ia; 'o*e/er, - ood c+ t+re" !a2 not .ro* or.ani"!" in "o!e patient" recei/in. anti-iotic". &'e cat'eter tip, e(it "ite, or '+- *i o)ten .ro* or.ani"!". 4" "'o*n in 1i.+re 1, *e de)ine ca"e" )a in. into t'i" cate.or2 a" po""i- e c inica cat'eter-re ated "ep"i". &'i" dia.no"i" i" +"+a 2 !ade in retro"pect, "ince it re3+ire" a po"iti/e ("e!i-) 3+antitati/e cat'eter tip or "e.!ent c+ t+re in a patient *it' c inica "ep"i" and no ot'er apparent "o+rce t'an t'e cat'eter and t'e "ep"i" re"o /e" *it'in 48 'r" o) cat'eter re!o/a in t'e a-"ence o) ne* anti-iotic t'erap2. Ee)inite cat'eter-re ated "ep"i" *it' -acterio o.ic con)ir!ation i" de)ined in &a- e 4 a on. *it' di))erent !et'od" )or !icro-io o.ica con)ir!ation o) t'e etio o.2 o) t'e in)ection. Intra-"#dominal Infections 0ntra-a-do!ina in)ection" co!pri"e a /er2 'etero.eneo+" .ro+p o) in)ectio+" proce""e" t'at "'are an anato!ica "ite o) ori.in -et*een t'e diap'ra.! and t'e pe /i". &'eir c inica co+r"e i" dictated -2 a n+!-er o) in)ectionre ated )actor" inc +din. t'e !icro-io o.2, t'e anato!ica ocation, t'e de.ree o) oca i9ation, and t'e pre"ence o) correcta- e anato!ica deran.e!ent" in/o /in. a-do!ina /i"cera. 0!portant 2, in)ection" ari"in. *it'in t'e a-do!en can -e con"idered to -e t*o-co!part!ent in)ection"-t'e )ir"t, t'e o/ert )oc+" on in)ection, and t'e "econd re"+ tin. )ro! t'e pre"ence o) a den"e !icro-ia ) ora in t'e adGacent .a"trointe"tina tract. [37, 37% 0ntraperitonea in)ection" tend to -e a""ociated *it' a .reater de.ree o) p'2"io o.ic deran.e!ent. 0n addition, t'e +ni3+e de)en"e !ec'ani"!" o) t'e peritonea ca/it2 pro!ote t'eir oca i9ation t'ro+.' t'e )or!ation o) a-"ce""e". 4 t'o+.' retroperitonea in) a!!ation in condition" "+c' a" pancreatiti" can -e de/a"tatin. in it" con"e3+ence", retroperitonea in)ection" t2pica 2 ta$e a !ore indo ent co+r"e. =o id or.an in)ection" in/o /in. t'e i/er and "p een t2pica 2 do not ari"e "econdar2 to anato!ica deran.e!ent" and !a2 -e a!ena- e to nonoperati/e or !ini!a 2 in/a"i/e !ana.e!ent.[38-41% 5ri!ar2 peritonea in)ection" (pri!ar2 peritoniti") are t'o"e t'at ari"e in t'e a-"ence o) an identi)ia- e anato!ica deran.e!ent in t'e intra-a-do!ina /i"cera ( &a- e 5 ). =econdar2 peritonea in)ection" ("econdar2 peritoniti") are t'o"e occ+rrin. "econdar2 to an anato!ica deran.e!ent "+c' a" per)oration or o-"tr+ction o) a 'o o* /i"c+" ( &a- e 7 ). &'e in)ectin. ) ora i" t'e indi.eno+" ) ora o) t'e .a"trointe"tina tract, *it' t'e i!portant pro/i"o t'at i) t'e anato!ica de)ect i" in t'e "to!ac' or d+oden+!, anaero-ic or.ani"!" are rare, -+t Candida !a2 -e a pat'o.en. &ertiar2 peritoniti" can -e de)ined a" peritoniti" t'at per"i"t" or rec+r" ?48 'r" )o o*in. apparent 2 "+cce"")+ !ana.e!ent o) pri!ar2 or "econdar2 -acteria peritoniti" ( &a- e 7 ). 0t i" c'aracteri9ed -2 a no"oco!ia ) ora inc +din. coa.+ a"e-ne.ati/e "tap'2 ococci, Candida, Enterococci, Pseudomonas, and Enterobacter and i" a""ociated *it' o/er.ro*t' o) t'e .a"trointe"tina tract *it' t'e "a!e or.ani"!". Wit'in t'i" c a""i)ication, de/ice-re ated in)ection" "+c' a" c'ronic a!-+ ator2 peritonea dia 2"i" peritoniti" or /entric+ ar peritonea "'+nt in)ection" ( &a- e 8 ) *o+ d -e con"idered "econdar2 in)ection" ("econdar2 to a co oni9ed de/ice) or tertiar2 in)ection" *'en t'e2 rec+r or per"i"t. [42% Classification of Intra-"#dominal Infections! 0ntra-a-do!ina in)ection" can -e c a""i)ied into t'ree cate.orie": !icro-io o.ica 2 con)ir!ed, pro-a- e, and po""i- e (a" de)ined in &a- e 5 , &a- e 7 , &a- e 7 , &a- e 8 , &a- e 8 , &a- e 10 , &a- e 11 , &a- e 12 , &a- e 13 ). C+ t+re" )ro! drain "ite" are not con"idered dia.no"tic o) intra-

5
a-do!ina in)ection. 0"o ation o) intrin"ica 2 e"" /ir+ ent or.ani"!" (i.e., coa.+ a"e-ne.ati/e "tap'2 ococci, Bacillus "pecie", !icrococci, etc.) *i -e con"idered on 2 i) t'e"e or.ani"!" are i"o ated in p+re c+ t+re and in "i.ni)icant 3+antitie" (D105 c)+:!L, 2J or .reater on direct c+ t+re p atin. or !oderate to !an2 on pri!ar2 c+ t+re p atin.) )ro! intra-a-do!ina "o+rce". > ood c+ t+re" *it' !icro-ia pat'o.en" co!pati- e *it' intra-a-do!ina in)ection *i a "o -e con"idered !icro-io o.ica 2 con)ir!ed in)ection in t'e pre"ence o) c inica "i.n" and "2!pto!" indicati/e o) an intra-a-do!ina in)ection. Ee)inition" )or ot'er "peci)ic t2pe" o) intra-a-do!ina in)ection" (i.e., intra-a-do!ina a-"ce"", -i iar2 tract in)ection", pancreatic in)ection", t2p' iti" and to(ic !e.aco on) are .i/en in &a- e 8 , &a- e 10 , &a- e 11 , &a- e 12 , &a- e 13 .[40, 43, 44% Urosepsis &'ere are on 2 a )e* "peci)ic "t+die" o) +rinar2 tract in)ection (A&0) in pop+ ation" o) 0CA patient" *it' "e/ere "ep"i":"eptic "'oc$, and a t'o+.' -ot' -acteria A&0 and candid+ria are /er2 co!!on, t'eir i!portance a" t'e pri!ar2 "o+rce )or "e/ere "ep"i" and "eptic "'oc$ re!ain" +nc ear. 0n partic+ ar, o*er A&0 a!on. noncat'eteri9ed patient" i" con"idered to -e a /er2 rare ca+"e o) "e/ere "ep"i":"eptic "'oc$ and i" not con"idered )+rt'er 'ere. Cat'eter-a""ociated A&0 (C4A&0) i" t'e !o"t co!!on no"oco!ia in)ection, acco+ntin. )or +p to 40B o) a in)ection" and D1 !i ion in)ection" in A.=. 'o"pita " eac' 2ear. [45, 47% Ap to a 'a ) o) patient" re3+irin. an ind*e in. +ret'ra cat'eter )or ?5 da2" *i de/e op -acteri+ria or candid+ria. &'e dai 2 incidence o) C4A&0 i" re ati/e 2 con"tant d+rin. c o"ed draina.e, at ea"t )or t'e )ir"t 10 da2", *it' 2-17B o) patient" ac3+irin. in)ection eac' da2. 0n)ection i" near 2 +ni/er"a at 30 da2". 4ccordin. to a recent Kationa Ko"oco!ia 0n)ection" =+r/ei ance report, no"oco!ia A&0 (!o"t 2 C4A&0) rate" ran.e )ro! 5.3 to 10.5 per 1000 +rinar2 cat'eter-da2" in 0CA". 0!portant 2, "i ent cat'eter-a""ociated -acteri+ria co!pri"e" a '+.e re"er/oir o) re"i"tant or.ani"!" in t'e 'o"pita , partic+ ar 2 on critica care +nit".[47-48% 0n a noncat'eteri9ed patient, t'e de)inition o) a -acterio o.ica 2 "i.ni)icant +rinar2 tract in)ection (D10 5 c)+:!L, &a- e 14 ) i" *ide 2 accepted, -+t de)inition" )or C4A&0 are e"" c ear. ;o*e/er, =tar$ and Ma$i [50% "'o*ed t'at in a cat'eteri9ed patient, t'e i"o ation o) D103 c)+:!L or.ani"!" i" 'i.' 2 predicti/e o) in)ection, and i) anti-iotic" are not .i/en, t'e e/e *i ri"e 3+ic$ 2 to D105c)+:!L. ;o*e/er, t'e"e "i.ni)icant C4A&0" are rare 2 "2!pto!atic. [51% &'e CEC 'a" atte!pted to di"cri!inate -et*een "2!pto!atic and a"2!pto!atic A&0 and C4A&0, [52% -+t t'e"e de)inition" are not *'o 2 "+ita- e )or 0CA patient" *'o )re3+ent 2 are +na- e to report "2!pto!" 2et !a2 *e 'a/e a c inica 2 "i.ni)icant (a" oppo"ed to "i!p 2 a !icro-io o.ica 2 "i.ni)icant) in)ection. Lt'er criteria "+c' a" t'e pre"ence o) p2+ria pro/ide on 2 i!ited additiona in)or!ation. [53% &a- e 15 pro/ide" an approac' t'at atte!pt" to reconci e "o!e o) t'e"e di))ic+ tie". Mo"t c inician" reco.ni9e t'at i"o ated candid+ria (i.e., in t'e a-"ence o) e/idence o) Candida "pecie" co oni9ation or in)ection at ot'er "ite") rare 2 re3+ire" treat!ent; ne/ert'e e"", candid+ria can occa"iona 2 -e t'e on 2 acce""i- e e/idence o) deep candidia"i". Candid+ria i" rare in nor!a 'ea t'2 ad+ t", and e/en in an +n"e ected 'o"pita pop+ ation on 2 a-o+t 2B o) +rine "a!p e" recei/ed in t'e a-orator2 *i "'o* candid+ria, a t'o+.' t'i" n+!-er ri"e" to 10-12B in 'i.'-ri"$ patient" "+c' a" t'o"e on 'e!ato o.2-onco o.2 +nit". [54% ;o*e/er, Candida "pecie" are c ear 2 a""ociated *it' +rinar2 in)ection !+c' !ore )re3+ent 2 in cat'eteri9ed patient", and e"pecia 2 in cat'eteri9ed patient" in t'e 0CA. =o!e "t+die" 'a/e reported t'at +p to a 3+arter o) cat'eter-re ated A&0" are ca+"ed -2 Candida "pecie", and in "o!e "erie", Candida i" identi)ied a" one o) t'e !o"t )re3+ent !icro-ia pat'o.en" i"o ated )ro! +rine "a!p e" on a "+r.ica 0CA.[55% Kote t'i" doe" not nece""ari 2 i!p 2 t'ere i" Candida +rinar2 tract in)ection. 0t i" c ear t'at t'ere i" /er2 con"idera- e +ncertaint2 a-o+t t'e criteria to -e +"ed in interpretin. t'e )indin. o) candid+ria. &'ere are "o!e rea"ona- 2 re ia- e data on t'e interpretation o) candid+ria in noncat'eteri9ed patient". &'e ear 2 *or$ o) @o d-er. et a .[57% "+..e"tin. t'at Candida "pecie" co+nt" D104:!L repre"ent c inica 2 "i.ni)icant in)ection[57% 'a" ar.e 2 -een "+pported -2 ot'er", a t'o+.' t'ere are certain 2 report" "+..e"tin. t'at o*er co+nt" can -e a""ociated *it' "2!pto!" and indeed t'at o*er co+nt" o)ten 3+ic$ 2 increa"e to 'i.'er co+nt" i) +ntreated. Con/er"e 2, pro"pecti/e o-"er/ationa "t+die" o) patient" *it' candid+ria (75B o) *'o! *ere cat'eteri9ed) 'a/e "+..e"ted t'at !o"t patient" *it' co+nt" M10 3:!L re!ain a"2!pto!atic and re3+ire no treat!ent.[57% ;ence, in t'e c inica "ettin., and in partic+ ar on t'e 0CA, c inician" *i /er2 rare 2 re 2 on !icro-io o.2 a one to decide on t'e "i.ni)icance o) candid+ria. &'e2 *i inte.rate ot'er c inica in)or!ation, G+"t a" t'e2 *o+ d in an2 ot'er c inica "ite. Ee)inition" )or "ep"i" "t+die" *it' A&0 a" t'e "o+rce are pro/ided in &a- e 14 , &a- e 15 and &a- e 17

6
S$in and Soft-Tissue Infections 0n)ection" o) t'e "$in and "o)t ti""+e are co!!on and enco!pa"" a "pectr+! o) i ne"" "e/erit2, )ro! )oca ce + iti" prod+cin. on 2 !i d "2!pto!" to i)e-t'reatenin. necroti9in. in)ection" re"+ tin. in e(ten"i/e ti""+e o"" and "+-"tantia ac+te !or-idit2 and !orta it2 (.[58-70)% &'e2 !a2 ari"e "pontaneo+" 2, or )o o*in. tri/ia and +napparent tra+!a, or a" a con"e3+ence o) oca tra+!a "+c' a" a -+rn or "+r.ica proced+re. 0n)ection" ari"in. at t'e "ite o) a "+r.ica proced+re are re ati/e 2 co!!on and are ter!ed "+r.ica "ite in)ection". Loca "i.n" o) in) a!!ation are t'e 'a !ar$ o) a "o)t ti""+e in)ection. 1eat+re" o) "e/ere "ep"i" rare 2 acco!pan2 a "+per)icia "+r.ica "ite in)ection and "+..e"t conco!itant ti""+e necro"i", a deep "+r.ica "ite in)ection, or a partic+ ar 2 /ir+ ent in)ectin. or.ani"!. 1 +ct+ance "+..e"t" a "+-c+taneo+" a-"ce"". Kecroti9in. in)ection i" "+..e"ted -2 t'e pre"ence o) pain (+"+a 2 "e/ere and con"tant in t'e ca"e o) necroti9in. )a"ciiti"), di"co oration o) t'e o/er 2in. "$in, -+ o+" e"ion", or "o)t ti""+e crepit+"; t'e"e )indin.", 'o*e/er, are neit'er "en"iti/e nor "peci)ic )or t'e reco.nition o) ti""+e necro"i", and e(ten"i/e necroti9in. in)ection o) t'e "+-c+taneo+" ti""+e" !a2 -e pre"ent *it' on 2 !ini!a )indin." in t'e o/er 2in. "$in. &'e dia.no"i" o) in)ection o) t'e "$in and "o)t ti""+e" i" !o"t co!!on 2 acco!p i"'ed -2 direct e(a!ination, o-tainin. c+ t+re" to identi)2 t'e in)ectin. or.ani"!" and to aid in t'e "e ection o) an opti!a anti!icro-ia a.ent. =+per)icia "+r.ica "ite in)ection i" dia.no"ed -2 openin. a portion o) t'e "+r.ica *o+nd and drainin. p+". 4 !icro-io o.ica dia.no"i" o) ce + iti" can "o!eti!e" -e !ade -2 a"piration o) t'e in/o /ed area. >iop"2 can -e +"ed to deter!ine *'et'er ti""+e necro"i" i" pre"ent and to )aci itate 3+antitati/e c+ t+re, a tec'ni3+e t'at i" +"e)+ in t'e dia.no"i" o) -+rn *o+nd in)ection. <adio o.ic e(a!ination-partic+ ar 2 co!p+ted to!o.rap'2-i" o) /a +e to de)ine t'e e(tent o) t'e proce"" and to identi)2 deep "ite" o) in)ection. &'e ter!ino o.2 +"ed to c a""i)2 "$in and "o)t-ti""+e in)ection" i" co!p icated and con)+"in. a" it i" -a"ed on )re3+ent 2 o/er appin. c a""i)ication criteria, "+c' a" de.ree o) e(ten"ion ()oca or oca i9ed /". di))+"e), dept' o) in)ection ("+per)icia /". deep), 'i"to o.ic c'aracteri"tic" (necroti9in. /". nonnecroti9in.), and c inica pre"entation (+nco!p icated /". co!p icated). 1or t'e "a$e o) "i!p icit2, "$in and "o)t-ti""+e in)ection" can -e "+-di/ided into "+r.ica and non"+r.ica in)ection" ( &a- e 17 ). =+r.ica "ite in)ection i" an in)ection t'at ari"e" *it'in 30 da2" o) an operati/e proced+re and at t'e "ite o) "+r.ica inter/ention. Ee)inition" 'a/e -een adapted )ro! t'o"e o) t'e CEC.[1% N(c +ded )ro! t'e"e de)inition" are "titc' a-"ce""e" or in)ected epi"ioto!ie". Kon"+r.ica "$in and "o)tti""+e in)ection" co!pri"e er2"ipe a", i!peti.o, )o ic+ iti", ce + iti", p2oder!a", a-"ce"", necroti9in. ce + iti" or )a"ciiti" or !2o"iti" (t'e"e ter!" enco!pa"" "e/era di"tinct c inica and -acterio o.ic entitie": pro.re""i/e -acteria "2ner.i"tic .an.rene, idiopat'ic "crota or 1o+rnierF" .an.rene, "treptococca .an.rene, c o"tridia ce + iti":!2onecro"i" [.a" .an.rene%, nonc o"tridia !2onecro"i", po 2!icro-ia necroti9in. )a"ciiti"), and !2o"iti":p2o!2o"iti":!2onecro"i".[58-71% Ee)inition" )or t'e principa c inica entitie"-ce + iti" and necroti9in. ce + iti" or )a"ciiti"-are .i/en in &a- e 17 . Infection Classification for S$in and Soft Tissue Infections! Micro-io o.ica 2 con)ir!ed "$in and "o)t ti""+e in)ection i" de)ined -2 t'e i"o ation -2 c+ t+re or @ra! "tain o) a !icroor.ani"! )ro! a *o+nd or "$in e"ion t'at 'a" drained p+", or )ro! a "$in a"pirate or -iop"2 o) t'e "+-c+taneo+" ti""+e" o) an er2t'e!ato+" "$in e"ion or *o+nd. 5ro-a- e "$in and "o)t ti""+e in)ection i" de)ined a" co!pe in. c inica and a-orator2 e/idence ("+c' a" "preadin. c+taneo+" er2t'e!a and - anc'in., or draina.e o) p+r+ ent !ateria on openin. a "+r.ica *o+nd, *it' or *it'o+t 2!p'an.iti", in a""ociation *it' )e/er D38.0OC, or e+$oc2to"i") o) t'e pre"ence o) a "$in and "o)t ti""+e in)ection -a"ed on radio.rap'ic, c inica , and "+r.ica )indin." -+t *it'o+t !icro-io o.ica con)ir!ation. 5o""i- e "$in and "o)t ti""+e in)ection i" de)ined a" c inica ("+c' a" !i d c+taneo+" er2t'e!a a""ociated *it' )e/er D38.0OC), a-orator2 ("+c' a" e+$oc2to"i"), or radio.rap'ic )indin." "+..e"ti/e o) t'e pre"ence o) a "$in and "o)t ti""+e in)ection -+t *it' in"+))icient e/idence to con)ir! dia.no"i". 0n)ection" are )+rt'er c a""i)ied a" "+per)icia or deep, -a"ed on *'et'er t'e deep )a"cia or !+"c e a2er" are in/o /ed.

Conclusions
&'e increa"in. "op'i"tication o) c inica tria de"i.n )or t'e in/e"ti.ation o) ne* t'erape+tic entitie" in "ep"i" !ean" t'at *e need to pa2 !ore attention to i""+e" "+c' a" acc+rate de)inition o) in)ection. 0n t'e pa"t, decidin. *'et'er a patient did or did not 'a/e an in)ection *a" ar.e 2 e)t to t'e di"cretion o) t'e in/e"ti.ator, and t'ere i"

7
itt e do+-t t'at t'i" contri-+ted to "i.ni)icant 'etero.eneit2 in t'e patient pop+ ation enro ed in c inica tria ". 4" ne* dr+." and treat!ent" )or "ep"i" -eco!e !ore "peci)ic in re"pect o) partic+ ar "+-pop+ ation" in *'o! t'e2 are indicated, *e *i need too " to attain .reater preci"ion in de)inin. t'o"e pop+ ation". We -e ie/e t'e"e de)inition" !a2 'e p in de/e opin. t'o"e too ". 4 )+rt'er -ene)it *o+ d -e t'e potentia to pro/ide a )ra!e*or$ )or .+idin. dia.no"tic or e/en t'erape+tic deci"ion !a$in. in t'e 0CA. &'e !erit o) t'e"e de)inition", -e t'e2 +"ed )or enro !ent in c inica tria " or indeed )or ot'er p+rpo"e", *i re3+ire )or!a te"tin. and /a idation, -+t in t'e !eanti!e *e -e ie/e t'at t'e2 are an i!portant "tep )or*ard in t'e proce"" o) i!pro/in. t'e 3+a it2 o) c inica tria " in patient" *it' "ep"i". "c$no%ledgements 0nternationa =ep"i" 1or+! Con"en"+" Con)erence -2 a p'a-etica order (c'apter contri-+tion): 4-ra'a! NI, >ernard @, >r+n->+i""on C. (Cat'eter-re ated "ep"i"), Ca andra &I. (> ood"trea! in)ection" and in)ecti/e endocarditi", =$in and "o)t-ti""+e in)ection"), Co'en PI. (Aro"ep"i"), Ee in.er 5I, E'aina+t P1I, N i""eo+ M, 1in)er =, ;are.e*oin 4, L2nn M, Mar"'a PI. (0ntra-a-do!ina in)ection", =$in and "o)t-ti""+e in)ection"), McMena!in Q, Kieder!an M. (5ne+!onia), Lpa =I. (0ntra-a-do!ina in)ection"), 5ar$in P, 5ittet E. (Aro"ep"i"), <ando p' 4. (Cat'eter-re ated "ep"i"), <e er >, <o-in"on L. (> ood"trea! in)ection" and in)ecti/e endocarditi"), =o o!$in P. (=$in and "o)t-ti""+e in)ection"), =pr+n. CI, &o!a2$o P, &orre" 4, &ri.." @, Apper!an P. (=$in and "o)t-ti""+e in)ection"), 6incent PLI, Witte$ 4. IMe!-er o) t'e 0=1. Funding Information
&a- e" )or:

The International Sepsis Forum Consensus Conference on Definitions of Infection in the Intensive Care Unit
[Crit Care Med. 2005;33(7):1538-1548. 2005 Lippincott Wi ia!" # Wi $in"%

Ta#le ! Pneumonia

Ta#le &! Bloodstream Infection 'BSI( of Un$no%n )rigin 'I!E!* Primar+ BSI(

Ta#le ,! Secondar+ Bloodstream Infection 'BSI( ')ther Than Catheter-Related BSI(

Ta#le -! Catheter-Related Sepsis .ith Bacteriologic Confirmation

Ta#le /! Primar+ Peritonitis

Ta#le 0! Secondar+ Peritonitis

Ta#le 1! Tertiar+ Peritonitis

Ta#le 2! Peritoneal Dial+sis-Related Peritonitis

Ta#le 3! Intra-"#dominal "#scess

Ta#le 4! Biliar+ Tract Infection

Ta#le

! Pancreatic Infection

10 Table 12. Typhlitis

Ta#le ,! To5ic 6egacolon

Ta#le -! Urosepsis in 7oncatheteri8ed Patients

11 Ta#le /! Urosepsis in Catheteri8ed Patients 'Urinar+ Catheter is Present or has Been Removed .ithin the Past 0 Da+s(

Ta#le 0! Candiduria

12
Ta#le 1! S$in and Soft Tissue Infections