REVIEW ARTICLE
Antimicrobial prophylaxis in peripheral vascular surgery: is cephalosporin
still the gold standard?
Eduardo LichtenfelsI; M€rcio L. LucasII; Ronaldo WebsterIII; Pedro A. d’AzevedoIV
IVascular sur geon, I r m andade Sant a Casa de Miser icór dia de Por t o Alegr e ( I SCMPA) , Por t o Alegr e,
RS, Br azil. Gr aduat e st udent , Pr ogr am of Pat hology , Fundação Faculdade Feder al de Ciências Médicas de Por t o Alegr e ( FFFCMPA) , Por t o Alegr e, RS, Br azil.
I IVascular sur geon, I SCMPA, Por t o Alegr e, RS, Br azil. Gr aduat e st udent , Pr ogr am of Hepat ology ,
FFFCMPA, Por t o Alegr e, RS, Br azil.
I I IPlast ic sur geon, I SCMPA, Por t o Alegr e, RS, Br azil. Gr aduat e st udent , Pr ogr am of Pat hology ,
FFFCMPA, Por t o Alegr e, RS, Br azil.
I VAssociat e pr ofessor , Micr obiology , FFFCMPA, Por t o Alegr e, RS, Br azil. PhD. Pr ofessor , Gr aduat e
Pr ogr am in Pat hology , FFFCMPA, Por t o Alegr e, RS, Br azil.
Cor r espondence
J Vasc Br as. 2007; 6( 4) : 378- 87.
ABSTRACT
I n per ipher al v ascular sur ger y , cephalospor ins ar e now aday s r egar ded as t he fir st choice for oper at iv e ant ibiot ic pr ophy lax is. We hav e r ecent ly obser v ed changes in colonizing pat t er ns, pat hogen pr ev alence and ant ibiot ic suscept ibilit y t o ant im icr obials. Mult ir esist ant pat hogens ar e becom ing m or e fr equent in v ascular sur gical w ound infect ions, show ing r egional and local
v ar iat ions as t o pr ophy lact ic ant ibiot ic suscept ibilit y . Dat a fr om t he av ailable lit er at ur e so far hav e show n no st r ong ev idence for a change in r out ine sur gical ant ibiot ic pr ophy lax is. We m ust consider r egional and inst it ut ional pr ev alence of pat hogen r esist ance and pat t er ns of ant ibiot ic suscept ibilit y t o est ablish specific guidelines for t he use of alt er nat iv e ant ibiot ics.
Keywords:Ant ibiot ic pr ophy lax is, sur gical w ound infect ion, v ascular sur gical pr ocedur es, sur ger y .
RESUMO
m ult ir r esist ent es v êm se t or nando cada v ez m ais fr eqüent es nas infecções de fer ida cir úr gica v ascular , dem onst r ando v ar iações r egionais e locais quant o à suscet ibilidade aos ant im icr obianos pr ofilát icos ut ilizados na r ot ina cir úr gica. Os dados e a lit er at ur a disponív el at é o m om ent o
dem onst r am que não ex ist e ev idência suficient e par a um a m udança na r ot ina pr ofilát ica
per ioper at ór ia. Ent r et ant o, dev em os lev ar em consider ação os padr ões r egionais e inst it ucionais de pr ev alência de pat ógenos r esist ent es e padr ões de suscet ibilidade aos ant im icr obianos par a
est abelecer guias e or ient ações específicas par a a ut ilização de ant im icr obianos pr ofilát icos alt er nat iv os.
Pa la v r a s- ch a v e : Ant ibiot icopr ofilax ia, infecção da fer ida oper at ór ia, pr ocedim ent os cir úr gicos
v ascular es, cir ur gia.
H ist or y
Post oper at iv e sur gical infect ions, unt il t he m id- 19t h cent ur y , w er e t he gr eat obst acle t o t he pr ogr ess and dev elopm ent of sur ger y . Aft er t he discov er y of ant isept ics in 1867 by Joseph List er , sur ger y ex per ienced it s gr eat ev olut ion. Associat ed w it h ot her hist or ical figur es and new
discov er ies, infect ion r at es fell fr om 90 t o 10% unt il t he lat e 19t h cent ur y .1 - 3
Post oper at iv e sur gical w ound infect ion is consider ed t he m ain av oidable cause of m or bidit y and m or t alit y in pat ient s subm it t ed t o sur ger y ,4 account ing for 25% of all infect ions acquir ed at
hospit als.5 Despit e adv ances in ant isept ics ( st er ile m at er ial, ant isept ic solut ions, hand w ashing) in
pr eoper at iv e ant im icr obial pr ophy lax is and in per ioper at iv e car es, post oper at iv e sur gical infect ion is st ill a r eason for concer n, being r esponsible for high m or bidit y and m or t alit y r at es and significant cost s. The est im at ed cost per pat ient s w it h infect ion is US$ 2.100, gener at ing annual ex penses of US$ 4.5 billion5 in t he USA. I nt r oduct ion of ant im icr obials in pr eoper at iv e pr ophy lax is br ought hope
of r educt ion in infect ion r at es in sur gical pat ient s, especially sev er e infect ions.2 , 3 How ev er , t her e is
cur r ent ly an incr ease in cases of sev er e hospit al infect ions and a gr ow ing num ber of incidence of ant im icr obial- r esist ant pat hogens.
Ph y siopa t h ology
Post oper at iv e sur gical infect ions alw ay s occur w hen t he com binat ion of m icr oor ganism num ber and v ir ulence in t he sur gical w ound is lar ge enough t o beat local defense m echanism in t he host and est ablish an inv asion of t issues.1 , 2 A st udy in t he 1960's ident ified t hat pr act ically all sur gical
w ounds hav e, at least , a sm all num ber of bact er ia, but few dev elop infect ion.6
Sur gical w ound infect ion r at es published in t he lit er at ur e ar e, r espect iv ely , 1.5- 2.9% for clean w ounds; 2.8- 7.7% for clean and cont am inat ed w ounds; 6.4- 15.2% for cont am inat ed w ounds; and 7.1- 40% for dir t y w ounds.7 , 8
The m ain fact or s inv olv ed in t he dev elopm ent of sur gical w ound infect ion ar e bact er ial, w ound and t he pat ient 's ow n fact or s. Bact er ial deposit ion and gr ow t h ar e r equir em ent s for infect ion, as w ell as t ype of pat hogen and t ox ins pr oduced by it . Many pat hogens hav e specific com ponent s t hat
epider m idis biolfim s. Sev er al st udies on sur gical w ounds dem onst r at ed t hat , in healt hy pat ient s, it is necessar y t o hav e a cont am inat ion w it h a num ber higher t han 105 bact er ia t o hav e infect ion at a
giv en fr equency . Local fact or s include sur gical m at er ial, sur gical t echnique, gr aft im plant at ion, hem at om as, dead space and w ound car e. Fact or s associat ed w it h t he pat ient ar e all sy st em ic alt er at ions t hat can influence t he sur gical w ound. Am ong t hem ar e age, r educed blood flow t o t he w ound., hy pot her m ia, ur em ia, cor t icost er oid, neoplasm s and t r aum a.1 - 3 , 8 - 1 1
Cla ssifica t ion of su r gica l w ou n ds
Classificat ion of sur gical w ounds accor ding t o r isk of infect ion:
- Clean w ound: r educed pot ent ial of infect ion; no opening of hollow v iscer a or infr act ion of asept ic t echnique; r isk of infect ion bet w een 1.5- 2.9% ( ex am ple: ar t er ial v ascular sur ger y ) .
- Clean- cont am inat ed w ound: opening of hollow v iscer a, w it h m inim al cont ent ex t r av asat ion or sm all t echnical infr act ions; r isk of infect ion bet w een 2.8- 7.7% ( ex am ple: cholecy st ect om y ) .
- Cont am inat ed w ound: opening of hollow v iscer a w it h gr oss cont ent ex t r av asat ion; acut e inflam m at ion w it hout pus, gr oss infr act ions in asept ic t echnique and t r aum at ic lesions w it h less t han 6 hour s; r isk of infect ion is bet w een 6.4- 15.2% ( ex am ple: colect om y ) .
- Dir t y / infect ed w ound: pr esence of pus, per for at ed hollow v iscer a and t r aum at ic lesions w it h m or e t han 6 hour s of ev olut ion; r isk of infect ion is bet w een 7.1- 40% ( ex am ple: abscess dr aining) .7 , 8
Pr oph y la ct ic m e t h ods
The four basic pr inciples of pr ophy lax is for sur gical w ound infect ions ar e pat ient 's pr eoper at iv e pr epar at ion, sur gical t echnique, per ioper at iv e ant im icr obial pr ophy lax is and post oper at iv e car e w it h t he sur gical w ound.5 Sur gical ant im icr obial pr ophy lax is is cur r ent ly accept ed as r out ine in sur gical pr act ice in clean- cont am inat ed sur ger ies, as w ell as in som e clean sur ger ies. I n cont am inat ed and dir t y w ounds, ant im icr obials ar e alw ay s t her apeut ic, and not pr ophy lact ic.4 Sur gical ant im icr obial
pr ophy lax is should obey t he pr inciples and indicat ions est ablished t o be successful; ot her w ise, dev elopm ent of m ult i- r esist ant pat hogens t hat ar e not suscept ible t o usual ant im icr obials w ill be t he nat ur al cour se. I ndicat ion of pr ophy lact ic ant im icr obials in sim ple and clean sur ger ies occur s only in special cases, as in sur ger ies r equir ing gr aft s and sy nt het ic m at er ial. Due t o a low r isk of infect ion, ar ound 1% , t he pot ent ial t o r educe t his low r at e does not j ust ify ex penses and collat er al effect s of t heir adm inist r at ion.1 , 1 2
An t im icr obia l pr oph y la x is: cu r r e n t st a t u s
Recent st udies hav e suggest ed t hat t he act ual incidence of post oper at iv e infect ions aft er clean sur ger ies w it hout use of gr aft s is lar ger t han t hat r epor t ed in t he lit er at ur e. I t is est im at ed t hat m or e t han 50% of com plicat ions occur aft er t he pat ient is dischar ged, w hich ar e
under diagnosed.1 3 - 1 5 Such cases do not affect hospit al inst it ut ions, but affect t he com m unit y and t he healt h sy st em . Ot her st udies show ed t hat pat ient s subm it t ed t o clean pr ocedur es using pr ophy lact ic ant im icr obials had low er post oper at iv e infect ion r at es.1 6 - 1 9
Ther e ar e m any ant im icr obials used as pr ophy lax is in sur gical infect ions, and it is im por t ant t o obser v e t he pat hogens lik ely t o cause post oper at iv e infect ion and det er m ine w het her t her e w ill be penet r at ion of par t s of t he or ganism car r y ing anaer obic bact er ia, especially int est inal ( bact er oid species) . The dr ug of choice in sur ger ies in w hich t her e is no cont act w it h cont am inat ed sit es by anaer obic bact er ia is cefazolin ( fir st- gener at ion cephalospor in) , w hich aim s at cov er ing especially st aphy lococci, t he m ain agent s causing infect ions in noncav it ar y sur ger ies.2 0 , 2 1 Som e aut hor s r epor t t hat som e second- gener at ion cephalospor ins ( cefur ox im e, for ex am ple) could be m or e effect iv e in t he t r eat m ent of m et hicillin- sensit iv e st aphy lococci, bot h in v it r o2 2 and in clinical pr act ice,2 3 but t hey hav e a significant ly higher cost .5 I n cases in w hich t her e is cont act w it h
int est inal flor a, an ant im icr obial dr ug w it h act iv it y against gr am - negat iv e and anaer obic bact er ia should be associat ed ( azt r eonam and am inogly cosides) . Gy necological and obst et r ical, biliar y and gast r oduodenal sur ger ies, w hich hav e specific flor a ( Table 1) , ar e benefit ed fr om ant im icr obials alt er nat iv e t o cefazolin, such as, for ex am ple, cefox it in, piper acillin, am picillin/ sulbact am and am ox icillin/ clav ulanat e.2 0 I n cases of aller gy t o bet a- lact am s, er y t hr om y cin, clindam y cin or
v ancom y cin can be used, and t he lat t er should be r eser v ed, w henev er possible, for t he t r eat m ent of m et hicillin- r esist ant St aphy lococcus aur eus .1
Now aday s, 1/ 3 of all pr escr ipt ions for ant im icr obials for out pat ient s ar e unnecessar y . A st udy car r ied out in Tur k ey show ed t hat in 23% of pat ient s t he ant im icr obials w er e being incor r ect ly used.2 4 A r ev iew including 44 hospit als in New Yor k , USA, show ed t hat 44 differ ent t y pes of ant im icr obials w er e used in pr eoper at iv e pr ophy lax is and, despit e being used in 81- 94% of pat ient s, 27- 54% w er e adm inist er ed at t he w r ong m om ent .5
An t im icr obia l r e sist a n ce
ant im icr obials and change in pr ofile of com m unit y and hospit al colonizing pat hogens, t he m ost im por t ant quest ion cur r ent ly is w het her t he classical ant im icr obials, used w it h sur gical pr ophy lax is, ar e st ill t he gold st andar d t o pr ev ent post oper at iv e sur gical infect ions, especially w hen com par ed t o v ancom y cin and t eicoplanin. The Am er ican Cent er for Disease Cont r ol and Pr ev ent ion ( CDC) does not indicat e r out ine use of v ancom y cin as ant im icr obial pr ophy lax is for any t y pe of sur gical
pr ocedur e.2 1 Cer t ainly t her e ar e ex cept ions, especially in cases in w hich t he hospit al or inst it ut ion
has r at es higher t han 20% of post oper at iv e infect ions caused by m et hicillin- r esist ant
St aphy lococcus aur eus ( MRSA) .2 5 I n t hese cases, sur gical ant im icr obial pr ophy lax is should be car r ied out w it h t he use of v ancom y cin or t eicoplanin.
Now aday s, w it h ex ecut ion of incr easingly m or e com plex and pr olonged pr ocedur es, t r ansplant at ion in im m unodepr essed pat ient s, sur ger ies in pat ient s w it h m ult iple com or bidit ies and sur ger ies w it h im plant at ion of pr ost het ic m at er ial, pr eoper at iv e ant im icr obial pr ophy lax is aim ing at pr ot ect ion against r esist ant pat hogens has becom e a challenge.
M a in a n t im icr obia l dr u gs u se d in pr oph y la x is
Fir st - ge n e r a t ion ce ph a lospor in s
Cefazolin is a fir st - gener at ion cephalospor in w it h shor t half- life and par ent er al adm inist r at ion t hat is par t of t he fam ily of bet a- lact am ant ibiot ics. I t pr im ar ily act s by inhibit ing one st ep in t he sy nt hesis of t he bact er ial cell w all ( t r anspept idat ion) , w hich r esult s in spont aneous bact er ial cell ly sis. The m ost im por t ant r esist ance m echanism s ar e pr oduct ion of bet a- lact am ases, w hich cause hy dr oly sis of t he bet a- lact am r ing, genet ic change in penicillin- binding pr ot eins ( PBP) , bact er ial r ecept or s for bet a- lact am dr ugs. The m ost com m on adv er se effect s ar e hy per sensit iv it y , gast r oint est inal discom for t and dev elopm ent of bact er ial r esist ance.2 6 , 2 7
The concept of per ioper at iv e pr ophy lax is w as int r oduced in t he 1960's, r ev olut ionizing t he cr it er ia of ant im icr obial t r eat m ent ex ist ing so far . Such m et hod allow ed r educt ion in phenom ena of per ioper at iv e sepsis and in t he high cost of hospit al t r eat m ent due t o infect ious com plicat ions. At t hat t im e, adv ant ages r egar ding cost- benefit r at io of using cefazolin w er e dem onst r at ed.
Pr ospect iv e clinical assessm ent show ed t hat ant im icr obial pr ophy lax is using 1 g of int r av enous cefazolin in a single dose befor e t he sur ger y w as efficacious in r educing infect ion levels in sur ger ies t hat had infect ious com plicat ions in a r at e higher t han 7% .2 8 - 3 0 Now aday s, t he pr act ice of using ant im icr obial dr ugs pr ophy lact ically is w idespr ead, being pr esent in m or e t han 90% of sur gical pr ocedur es.3 1
Ant im icr obial pr ophy lax is is indicat ed in clean and clean- cont am inat ed pr ocedur es, pr efer ent ially using only one t ype of ant im icr obial dr ug, adm inist er ing t he dr ug of choice in t he pr eoper at iv e per iod.3 2
infect ion r at e, being cheaper and bet t er t oler at ed by pat ient s.3 3 Pr ev ious findings w er e confir m ed
by ot her st udies inv olv ing m ult iple t y pes of pr ocedur es, confir m ing t hat a single dose of cefazolin befor e t he sur ger y could r educe t r eat m ent cost s and m aint ain efficacy in pr ev ent ing infect ious ev ent s.3 4
Wit h t he aim of v er ify ing t he effect of pr ophy lax is w it h cefazolin on infect ion r at e in sur gical w ound in clean w ounds accor ding t o pr eoper at iv e clinical st at us, a r andom ized, double- blind clinical t r ial w as per for m ed including 303 pat ient s. Cases w er e gr ouped accor ding t o a classificat ion by t he Am er ican Societ y of Anest hesiologist s ( ASA) . Pat ient s ASA 2 and ASA 3 benefit ed fr om
ant im icr obial pr ophy lax is, show ing t hat pat ient s w ho w er e not giv en t he ant im icr obial dr ug w er e 4.3 and 4.8 t im es, r espect iv ely , m or e lik ely t o have infect ion t han t he cont r ol gr oup ( r elat iv e r isk 0.91; confidence int er v al 0.83- 0.99; p = 0.02) .3 5
I n pr ocedur es r est r ict ed t o soft and super ficial t issues, a case cont r ol st udy w as designed t o
ident ify r isk fact or s for sur gical w ound ( SW) infect ion. The cont r ol gr oup w as com pr ised of pat ient s w ho under w ent est het ic sur ger ies and did not dev elop SW infect ion. Tw elv e pat ient s in t he cont r ol gr oup and four pat ient s w ho dev eloped SW infect ion ( by St aphy lococcus aur eus) w er e included in t he st udy . Risk fact or s associat ed w it h SW infect ion w er e m ean pr ocedur e t im e ( 5 hvs. 2 h; p = 0.02) ; gener al anest hesia ( p = 0.004) ; and placem ent of dr ains ( p = 0.004) . I n t hat sam e st udy , aft er r eint r oduct ion of ant im icr obial pr ophy lax is w it h cefazolin for pr ocedur es est im at ed t o last m or e t han 3 hour s, SW infect ion r at e w as zer o.3 6 On t he ot her hand, t her e is ev idence t hat , in cer t ain t y pes of int er v ent ion, ant im icr obial pr ophy lax is does not seem t o br ing any benefit .
A st udy car r ied out t o det er m ine t he usefulness of pr ophy lact ic ant im icr obial dr ugs in ar t er iov enous fist ulas for dialy sis show ed t hat t he only local post oper at iv e infect ion occur r ed in a pat ient w ho had r eceiv ed pr ophy lax is. The aut hor s concluded t hat ant im icr obial pr ophy lax is is not necessar y in ar t er iov enous fist ulas for dialy sis. Wit h or w it hout ant im icr obial dr ugs, infect ion r at e is alm ost zer o.3 7
Ther e is a concer n ov er t he dev elopm ent of bact er ial r esist ance t o cefazolin. Ther e is an est im at ed pr ev alence of 30% in pat ient s w it h St aphy lococcus aur eus, and m or e t han 96% of t hem ar e m et hicillin r esist ant .3 8 The SENTRY pr ogr am , in 1997, show ed a 16.7% incidence of m et
hicillin-r esist ant St aphy lococcus auhicillin-r eus .3 9
New er st udies ar e needed t o v er ify r at e of cefazolin r esist ance in clean and clean- cont am inat ed SW infect ions, including t hose r est r ict ed t o soft t issues and skin, using local and w or ldw ide pr ogr am s, so t hat t he cur r ent st at us of cefazolin efficacy as a pr ophy lact ic agent is est ablished and new opt ions of ant im icr obial dr ugs ar e st andar dized.4 0 - 4 3
Alt e r n a t iv e a n t im icr obia l dr u gs u se d in pr oph y la x is
Widespr ead use of som e ant im icr obial dr ugs, such as fir st- and second- gener at ion cephalospor ins, for pr ophy lax is or t her apy r esult ed in a dr am at ic incr ease in t he pr ev alence of bact er ial
r esist ance.4 4 I n t his cont ex t , t her e w as an incr ease in t he pr ev alence of m ult i- r esist ant or ganism s, such as MRSA .4 5 At env ir onm ent s or inst it ut ions t hat hav e a high pr ev alence of m et
hicillin-r esist ant bact ehicillin-r ia, alt ehicillin-r nat iv e ant im ichicillin-r obial dhicillin-r ugs, i.e., w hich do not hav e a hicillin-r out ine ohicillin-r est ablished use, such as gly copept ides, ar e t he fir st choice as pr ophy lact ic agent s.4 6 , 4 7
V a n com y cin
bact er ial r esist ance t o it has been r ar ely r epor t ed.4 4 How ev er , in t he 1980's, t her e is t he
occur r ence of v ancom y cin- r esist ant coagulase- negat iv e st aphy lococci, especially St aphy lococcus epider m idis, St aphy lococcus hom inis, St aphy lococcus w ar ner i, St aphy lococcus haem oly t icus and St aphy lococcus x y losus.4 8 , 4 9 The Am er ican CDC r ecom m ends v ancom y cin t o be used only as a pr ophy lact ic agent in cases of MRSA st r ains or coagulase- negat iv e m et hicillin- r esist ant
st aphy lococcus in SW infect ion or w hen t her e is high pr ev alence of isolat ed MRSA at t he sit e or inst it ut ion.2 1 Unfor t unat ely , CDC guidelines do not at t r ibut e any v alue t o t he pr ev alence of m et hicillin r esist ance t hat could j ust ify pr ophy lax is w it h gly copept ides. Zanet t i et al.5 0
dem onst r at ed t hat a bet t er per for m ance of cefazolin in r elat ion t o suscept ible or ganism s w ould be r equir ed, unless t he pr ev alence of m et hicillin r esist ance w as low er t han 3% . Com par ing
ant im icr obial pr ophy lax is w it h v ancom y cin and cefazolin in fem or al neck fr act ur e, Mer r er et al.5 1
obt ained a sim ilar incidence of SW infect ions in pat ient s w ho w er e giv en cefazolin ( 4% ) and v ancom y cin ( 2% ) . I n addit ion, t he sam e aut hor s obser v ed t hat t he im pact of bot h ant im icr obial agent s on occur r ence of gly copept ide- r esist ant ent er ococci and st aphy lococci st ains w as sim ilar . I t is believ ed t hat use of v ancom y cin causes t he dev elopm ent and t r ansm ission of t hat r esist ance.5 2
Mor eov er , v ancom y cin is also m or e ex pensiv e and har d t o be adm inist er ed w hen com par ed w it h cefazolin, being t he fir st choice only t o pr ev ent MRSA and coagulase- negat iv e m et hicillin- r esist ant st aphy lococci.5 2 How ev er , Zanet t i et al.5 0 dem onst r at ed t hat r out ine pr ophy lax is using v ancom y cin w as m or e effect iv e t han cefazolin in pat ient s subm it t ed t o m y ocar dial r ev ascular izat ion sur ger y , pr ev ent ing a higher num ber of SW infect ions or deat hs caused by m et hicillin- r esist ant
st aphy lococci and ent er ococci. Fur t her m or e, r out ine use of v ancom y cin w as less ex pensiv e t han cefazolin; not ev en higher pur chase and adm inist r at ion cost s, neit her absence of pr ot ect ion against gr am - negat iv e bacilli r educed t he final posit iv e balance. The aut hor s concluded t hat use of
v ancom y cin in t he USA could pr ev ent 110 deat hs and 3,184 SW infect ions w hen com par ed w it h use of cefazolin. On t he ot her hand, it is har d t o r ecom m end univ er sal use of v ancom y cin due t o insufficient dat a as t o t he possible consequences of a r out ine use of v ancom y cin and it s im pact on t he dev elopm ent of bact er ial r esist ance.
Som et im es, sy st em ic adm inist r at ion of ant im icr obial agent s is not enough t o pr ev ent gr aft infect ion, since t he ant im icr obial concent r at ion in t he t issue sur r ounding t he gr aft is v er y low . Hir ose et al.5 3 r ecent ly dev eloped a sy st em of sust ained ant im icr obial r elease by using
capr olact one ( biodegr adable m at er ial) , w hich m aint ains an effect iv e t issue concent r at ion ar ound t he pr ost het ic gr aft . The sam e aut hor s dem onst r at ed t hat sust ained r elease of v ancom y cin r educed infect ion r at e in anim al m odel gr aft s.
Te icopla n in
The m ost fr equent m icr oor ganism s causing SW infect ion in or t hopedic and v ascular sur ger ies ar e gr am - posit iv e cocci, w it h pr ev alence of St aphylococcusspp, account ing for 70- 90% of isolat ed pat hogens. The m ain r eason for such pr ev alence is t he abilit y t hose pat hogens hav e t o adher e and m ult iply in poly m er s by pr oducing biofilm .5 4 Gly copept ides hav e been consider ed a r easonable
alt er nat iv e, especially at a t im e of high pr ev alence of m et hicillin- r esist ant st aphy lococci.5 5 Many
st udies hav e com par ed effect iv eness and t ox icit y of t eicoplanin and cephalospor ins as pr eoper at iv e ant im icr obial pr ophy lax is, but r esult s w er e not inconclusiv e. Kar dak as et al.5 5 conduct ed a m et a-analy sis com par ing efficacy and safet y of t eicoplanin and fir st- ( cefazolin) and second- gener at ion cephalospor ins in pr eoper at iv e ant im icr obial pr ophy lax is for or t hopedic and v ascular sur ger ies. We ident ified t w o st udies inv olv ing v ascular pr ocedur es and four inv olv ing or t hopedic pr ocedur es bet w een Januar y 1950 and Nov em ber 2004, in a t ot al of 510 pat ient s subm it t ed t o v ascular sur ger y and 2,376 subm it t ed t o or t hopedic sur ger y . The aut hor s did not obser v e any differ ence bet w een t eicoplanin and cephalospor ins as t o dev elopm ent of SW infect ion or in ot her sit es. I n addit ion, t her e w as no differ ence as t o adv er se effect s or m or t alit y .
ant im icr obial spect r um of t eicoplanin cov er s t he m et hicillin- r esist ant st aphy lococci, w hich is par t of t he nor m al flor a in 25% of pat ient s subm it t ed t o sur ger y w it h placem ent of t ot al ar t icular gr aft .5 7
Such pr oper t ies suppor t select ion of gly copept ides as pr eoper at iv e pr ophy lact ic agent s in or t hopedic and v ascular sur ger ies w it h use of pr ost het ic m at er ial. Ther efor e, it is not sur pr ising t hat bot h v ancom y cin and t eicoplanin ar e being used at a lar ge scale in sev er al count r ies w it h t hat pur pose. How ev er , t he findings descr ibed abov e suggest t hat t her e is no super ior it y of one
ant im icr obial agent ov er anot her in t er m s of pr ev ent ion of infect ions, dev elopm ent of adv er se effect s and t ot al m or t alit y .
Wit h r egar d t o t he gly copept ide t o be used, init ial choice for sur gical pr ophy lax is is t eicoplanin due t o it s ex cellent t issue penet r at ion, dem onst r at ed by ex cellent dist r ibut ion, low t ox icit y and
pr olonged half- life. Many clinical t r ials using t eicoplanin as pr eoper at iv e pr ophy lact ic agent in clean or t hopedic, car diac, v ascular and or al sur ger ies dem onst r at e it s efficacy .5 8
An t im icr obia l a ge n t s t h a t bin d t o pr ost h e t ic gr a ft s
As an addit ional pr ophy lact ic m easur e, in cases in w hich a v ascular gr aft w ill be specifically used, use of ant im icr obial agent s t hat bind t o t he pr ost het ic gr aft has been pr oposed in high
concent r at ions.5 9 - 6 1 Regar ding v ascular sur ger y , m any ant im icr obial agent s hav e been pr oposed as
associat ed pr ophy lax is.6 2 , 6 3 Clinical t r ials hav e used Dacr on gr aft s im pr egnat ed w it h r ifam picin w it h t he aim of pr ev ent ing t heir colonizat ion and infect ion.6 2 Ot her t y pes of gr aft im pr egnat ed w it h ant im icr obial agent s have been used only in ex per im ent al st udies.4 5 Vicar et t i et al.6 4 est ablished an
anim al m odel of infect ion by St aphy lococcus epider m idis in v ascular gr aft , suggest ing t hat an incr ease in concent r at ion of r ifam picin bound t o t he gr aft ( Dacr on) could significant ly r educe incidence of v ascular gr aft infect ion caused by r esist ant st aphy lococci. On t he ot her hand, dev elopm ent of r ifam picin r esist ance, w it h lar ge- scale use of im pr egnat ed gr aft s, could r esult in t he need of dev eloping new and com plex pr ophy lact ic m et hods.6 5
Mupir ocin pr oduced by Pseudom onas fluor escens is a t opic ant im icr obial agent used in t he t r eat m ent of super ficial sk in infect ions caused by st aphy lococci (St aphy lococcus aur eus and St r ept ococcus py ogenes) and t o er adicat e t he nasal ( colonizing) St aphy lococcus aur eus .6 6
Mupir ocin w as int r oduced in clinical pr act ice in 1985, in t he Unit ed Kingdom , but t he dev elopm ent of r esist ance w as descr ibed soon aft er it st ar t ed being used clinically .6 7 Giacom et t i et al.4 4
inv est igat ed, in anim al m odels, t he efficacy of m upir ocin t o pr ev ent v ascular gr aft infect ion by St aphy lococcus epider m idis st ains w it h differ ent r esist ance pat t er ns ( m et hicillin- suscept ible, m et hicillin- r esist ant and int er m ediat e r esist ance t o v ancom y cin) . The aut hor s dem onst r at ed t hat use of Dacr on gr aft im pr egnat ed w it h m upir ocin could r esult in a significant inhibit ion of
st aphy lococcic gr ow t h, ev en w hen t hey ar e m ult i- r esist ant . Ot her aut hor s dem onst r at ed super ior it y of m upir ocin ov er r ifam picin t o pr ev ent MRSA infect ions.6 5
Mor e r ecent ly , st udies inv olv ing use of st r ept ogr am ins ( quinupr ist in/ dalfopr ist in) have been conduct ed in anim al m odels, w it h t he aim of assessing it s abilit y t o pr ev ent infect ions by
m et hicillin- r esist ant St aphy lococcus epider m idis and w it h int er m ediat e r esist ance t o gly copept ides. I n t he st udy by Giacom et t i et al.,6 8 t her e w as a significant r educt ion in bact er ial gr ow t h in gr aft s im pr egnat ed w it h t he new dr ug, in v it r o.
Anot her r ecent st udy ev aluat ed t he efficacy of gr aft s im pr egnat ed w it h an associat ion of
v ancom y cin, t eicoplanin and fusidic acid t o pr ev ent gr aft infect ions in an anim al m odel. The aut hor s dem onst r at ed t hat t he associat ion of fusidic acid w it h gly copept ides r esult ed in a significant ly higher inhibit ion of bact er ial gr ow t h of MRSA, ev en w hen t he m ult i- r esist ant st r ains w er e inoculat ed dir ect ly in t he gr aft .4 5
st udies hav e confir m ed in v it r o t he r esult s obt ained in v it r o. How ev er , use of gr aft s im pr egnat ed w it h ant im icr obial agent s can be an im por t ant m easur e in t he fut ur e for ant im icr obial pr ophy lax is in sur ger ies r equir ing sy nt het ic m at er ial.
Con clu sion
Alt hough cephalospor ins ar e w ell est ablished as a pr eoper at iv e ant im icr obial pr ophy lact ic agent , w e should be aw ar e for t he r ecent change in colonizat ion pat t er ns and suscept ibilit y t o ant im icr obial agent s. Now aday s, m ult i- r esist ant pat hogens hav e becom e incr easingly m or e fr equent in SW infect ions, show ing r egional and ev en local v ar iat ions r egar ding suscept ibilit y t o pr ophy lact ic ant im icr obial agent s r out inely used. We conclude t hat t her e is not enough ev idence t o j ust ify change in classical sur gical ant im icr obial pr ophy lax is. How ev er , r egional and inst it ut ional pat t er ns of pr ev alence of r esist ant pat hogens and ant im icr obial suscept ibilit y should guide indiv idual decision m ak ing t o t he use of alt er nat iv e ant im icr obial agent s in pr eoper at iv e pr ophy lax is.
Re fe r e n ce s
1. Dellinger EP. I nfecções cir úr gicas e escolha dos ant im icr obianos. I n: Tow nsend CM, edit or . Sabist on: t r at ado de cir ur gia. 6ª ed. Rio de Janeir o: Guanabar a Koogan; 2003. p. 182- 200.
2. Fr y DE, edit or . Sur gical infect ions. Bost on: Lit t le Br ow n; 1995.
3. How ar d RJ, Sim m ons RL, edit or s. Sur gical infect ious diseases. Nor w alk : Applet on- Lange; 1994.
4. de Lalla F. Sur gical pr ophy lax is in pr act ice. J Hosp I nfect . 2002; 50( supplA) : S9- 12.
5. Ak alin HE. Sur gical pr ophy lax is: t he ev olut ion of guidelines in an er a of cost cont ainm ent. J Hosp I nfect . 2002; 50( supplA) : S3- S7.
6. Bur k e JF. I dent ificat ion of t he sour ce of st aphy lococci cont am inat ing t he sur gical w ound dur ing oper at ion. Ann Sur g. 1963; 158: 898- 904.
7. Dellinger EP, Ehr enk r anz NJ. Sur gical infect ions. I n: Bennet t JV, Br achm an PS, edit or s. Hospit al infect ions. 4t h ed. Philadelphia: Lippincot t - Rav en; 1998. p. 571- 85.
8. Cr use PJ, Foor d R. The epidem iology of w ound infect ion. A pr ospect iv e st udy of 62,939 w ounds. Sur g Clin Nor t h Am . 1980; 60: 27- 40.
9. Lint on RR. The pr ophy lact ic use of t he ant ibiot ics in clean sur ger y. Sur g Gy necol Obst et . 1961; 112: 218- 20.
10. Gr eif R, Ak ça O, Hor n EP, Kur z A, Sessler DI . Supplem ent al per ioper at iv e ox y gen t o r educe t he incidence of sur gical- w ound infect ion. Out com es Resear ch Gr oup. N Engl J Med. 2000; 342: 161- 7.
11. Kur z A, Sessler DI , Lenhar dt R. Per ioper at iv e nor m ot her m ia t o r educe t he incidence of sur gical-w ound infect ion and shor t en hospit alizat ion. St udy of Wound I nfect ion and Tem per at ur e Gr oup. N Engl J Med. 1996; 334: 1209- 15.
pr ophy lax is for sur gical w ounds: Guidelines for clinical car e. Ar ch Sur g. 1993; 128: 79- 88.
13. Manian FA, Mey er L. Com pr ehensiv e sur v eillance of sur gical w ound infect ions in out pat ient and inpat ient sur ger y. I nfect Cont r ol Hosp Epidem iol. 1990; 11: 515- 20.
14. Olson MM, Lee JT Jr . Cont inuous, 10- year w ound infect ion sur v eillance. Result s, adv ant ages, and unansw er ed quest ions. Ar ch Sur g. 1990; 125: 794- 803.
15. Bailey I S, Kar r an SE, Toy n K, Br ough P, Ranaboldo C, Kar r an SJ. Com m unit y sur v eillance of com plicat ions aft er her nia r epair sur ger y. BMJ. 1992; 304: 469- 71.
16. Plat t R, Zaleznik DF, Hopk ins CC, et al. Per ioper at iv e ant ibiot ic pr ophy lax is for her nior r haphy and br east sur ger y. N Engl J Med. 1990; 322: 153- 60.
17. Plat t R, Zuck er JR, Zaleznik DF, et al. Pr ophy lax is against w ound infect ion follow ing her nior r haphy or br east sur ger y. J I nfect Dis. 1992; 166: 556- 60.
18. Lew is RT, Weigand FM, Mam azza J, Lloy d- Sm it h W, Tat ar y n D. Should ant ibiot ic pr ophy lax is be used r out inely in clean sur gical pr ocedur es: a t ent at iv e y es. Sur ger y . 1995; 118: 742- 6.
19. Leaper D. Use of ant ibiot ic pr ophy lax is in clean non- im plant w ounds. J Ant im icr ob Chem ot her . 1998; 41: 501- 4.
20. de Lalla F. Ant im icr obial chem ot her apy in t he cont r ol of sur gical infect ious com plicat ions. J Chem ot her . 1999; 11: 440- 5.
21. Mangr am AJ, Hor an TC, Pear son ML, Silv er LC, Jar v is WR. Guideline for pr ev ent ion of sur gical sit e infect ion. Am J I nfect Cont r ol. 1999; 27: 97- 132.
22. Ker nodle DS, Classen DC, Bur k e JP, Kaiser AB. Failur e of cephalospor ins t o pr ev ent St aphy lococcus aur eus sur gical w ound infect ions. JAMA. 1990; 263: 961- 9.
23. Kr et er B, Woods M. Ant ibiot ic pr ophy lax is for car diot hor acic oper at ions. Met a- analy sis of t hir t y y ear s of clinical t r ials. J Thor ac Car diov asc Sur g. 1992; 104: 590- 9.
24. Pehliv an M, Hay r an M, Ak alin HE. Ant ibact er ial use at I iacet t epe Univ er sit y Hospit al:
Differ ences bet w een specialit ies on appr opr iat e use. Sy m posium on Nosocom ial I nfect ions, Tur k ey , 1994.
25. Fr aise AP. Guidelines for t he cont r ol of m et hicillin- r esist ant St aphy lococcus aur eus. J Ant im icr ob Chem ot her . 1998; 42: 287- 9.
26. Kat zung BG, Ehr lich KS. Dr ogas ut ilizadas em infecções bact er ianas, fúngicas e v ir ais. I n: Kat zung B, edit or . Far m acologia clínica. 1ª ed. Por t o Alegr e: Ar t es Médicas; 1991. p. 132- 80.
27. Tice AD. Phar m acoeconom ic consider at ions in t he am bulat or y use of par ent er al cephalospor ins. Dr ugs. 2000; 59: 29- 35.
28. Bar r ionuev o CE, Koning MB, Capasso R, Bar r ionuev o R. Eficácia do uso da cefazolina per-oper at ór ia em dose única na pr ofilax ia da infecçäo pós- per-oper at ór ia em cir ur gias näo infect adas. . Rev br as m ed ot or r inolar ingol 1995; 2: 432,434- 5.
económ ica del uso de Cefazolina v er sus Ceft r iazona en la pr ofilax is per ioper at or ia. Rev cuba. far m . 2001; 35: 187- 191.
30. Valle Panchana G, Abar ca Aguilar F, Riv er a Escalant e V, Riv er a Dr ouet R. Cefazolina y su uso com o pr ofilact ion en cir ur gia. Rev Univ Guay aquil. 1987; 2: 59- 68.
31. Baca Tinoco C. Uso de ant ibiót ico par a pr ofilax is quir úr gica en el ser v icio de cir ugía gener al del HEODRA, en el per íodo ener o a diciem br e 2003. León. 2004; s.n: 45.
32. Saab A, Suck er m an- Voldm an E, Rodr íguez AR, et al. Pr ofilax ia con ant ibiót icos en cir ugía: ex per iencia en el Ser v icio de Em er gencia de un Hospit al Univ er sit ár io. Ant ibiot infecc. 1995; 5: 13- 6.
33. Bencini PL, Signor ini M, Galim ber t i M, Cav icchini S, Caput o R. Pr eoper at iv e ant ibiot ic
pr ophy lax is in flex ur al sur ger y of difficult cont am inat ion- pr one ar eas of t he sk in: t he ut ilit y of a single dose of ant ibiot ic. J Der m at ol Tr eat . 1994; 5: 17- 9.
34. Fonseca SN, Kunzle SR, Junqueir a MJ, Nascim ent o RT, de Andr ade JI , Lev in AS. I m plem ent ing 1- dose ant ibiot ic pr ophy lax is for pr ev ent ion of sur gical sit e infect ion. Ar ch Sur g. 2006; 141: 1109-14.
35. I r ibar r en O, Ar auj o M. Effect of ant im icr obial pr ophy lax is on t he incidence of infect ions in clean sur gical w ounds in hospit als under going r enov at ion. I nfect ion cont r ol and hospit al epidem iology . I nfect Cont r ol Hosp Epidem iol. 2006; 27: 1372- 6.
36. Fat ica CA, Gor don SM, Zins JE. The r ole of pr eoper at iv e ant ibiot ic pr ophy lax is in cosm et ic sur ger y. Plast Reconst r Sur g. 2002; 109: 2570- 3.
37. Mor eir a RC, Tim i JR, Abr ão E. Est udo pr ospect iv o da ant ibiot icopr ofilax ia em oper açöes de físt ula ar t ér io- v enosa par a diálise. Rev angiol cir v asc. 1992; 1: 108- 11.
38. Del Cant o Har boe E, Ur bina CR. Est udio de por t ación nasal de st aphy lococcus aur eus en est udiant es de m edicina de la Univ er sidad de Sant iago de Chile. Clin Cienc. 2001; 1: 10- 14.
39. Robledo JÁ, López J, Sier r a P, Robledo C, Pfaller MA, Jones RN. El pr ogr am a de v igilancia ant im icr obiana SENTRY en Colom bia: hallazgos iniciales en t r es hospit ales de Medellín. I nfect io. 1999; 3: 100- 7.
40. Ter zi C, Kilic D, Unek T, Hosgor ler F, Fuzun M, Er gor G. Single- dose or al cipr oflox acin com par ed w it h single- dose int r av enous cefazolin for pr ophy lax is in inguinal her nia r epair : a cont r olled
r andom ized clinicalst udy. J Hosp I nfect . 2005; 60: 340- 7.
41. Thom as R, Alv ino P, Cor t ino G R, et al. Long- act ing v er sus shor t - act ing cephalospor ins for pr eoper at iv e pr ophy lax is in br east sur ger y : a r andom ized double- blind t r ial inv olv ing 1,766. Chem ot her apy . 1999; 45: 217- 23.
42. Mar r oni M, Cao P, Fior io M, et al. Pr ospect iv e, r andom ized, double- blind t r ial com par ing t eicoplanin and cefazolin as ant ibiot ic pr ophy lax is in pr ost het ic v ascular sur ger y. Eur J Clin Micr obiol I nfect Dis. 1999; 18: 175- 8.
43. Allababidi S, Shah JC. Efficacy and phar m acok inet ics of sit e- specific cefazolin deliv er y using biodegr adable im plant s in t he pr ev ent ion of post- oper at iv e w ound infect ions Phar m Res.
44. Giacometti A, Cirioni O, Ghiselli R, et al. Mupirocin prophylaxis against methicillin-susceptible, methicillin-resistant, or vancomycin-intermediate St aphy lococcus epider m idis vascular-graft infection. Antimicrob Agents Chemother 2000; 44:2842–4.
45. Yasim A, Gul M, Atahan E, Ciragil P, Aral M, Ergun Y. Efficacy of vancomycin, teicoplanin and fusidic acid as prophylactic agents in prevention of vascular graft infection: an experimental study in rat. Eur J Vasc Endovasc Surg. 2006;31:274–9.
46. Earnshaw JJ. Methicillin-resistant St aphy lococcus aur eus: vascular surgeons should fight back. Eur J Vasc Endovasc Surg. 2002;24:283–6.
47. Murphy GJ, Pararajasingam R, Nasim A, Dennis MJ, Sayers RD. Methicillin-resistant
St aphy lococcus aur eusinfection in vascular surgical patients. Ann R Coll Surg Engl. 2001;83:158-63.
48. McManus AT, Goodwin CW, Pruitt BA Jr. Observations on the risk of resistance with the extended use of vancomycin. Arch Surg. 1998;133:1207–11.
49. Schwalbe RS, Stapleton JT, Gilligan PH. Emergence of vancomycin resistance in coagulase-negative staphylococci. N Engl J Med. 1987;316:927–31.
50. Zanetti G, Goldie SJ, Platt R. Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis: example of coronary artery bypass surgery. Emerg Infect Dis.
2001;7:820-7.
51. Merrer J, Desbouchages L, Serazin V, Razafimamonjy J, Pauthier F, Leneveu M. Comparison of routine prophylaxis with vancomycin or cefazolin for femoral neck fracture surgery: microbiological and clinical outcomes. Infect Control Hosp Epidemiol. 2006;27:1366-71.
52. Martone WJ. Spread of vancomycin-resistant enterococci: why did it happen in the United States?Infect Control Hosp Epidemiol. 1998;19:539-45.
53. Hirose K, Marui A, Arai Y, et al. Sustained-release vancomycin sheet may help to prevent prosthetic graft methicillin-resistant Staphylococcus aureus infection. J Vasc Surg. 2006;44:377-82.
54. de Lalla F. Antibiotic prophylaxis in orthopedic prosthetic surgery. J Chemother. 2001;1:48–53.
55. Vardakas KZ, Soteriades ES, Chrysanthopoulou1 A, Papagelopoulos PJ, Falagas ME.
Perioperative anti-infective prophylaxis with teicoplanin compared to cephalosporins in orthopaedic and vascular surgery involving prosthetic material. Clin Microbiol Infect. 2005;11:775–7.
56. de Lalla F, Novelli A, Pellizzer G, et al. Regional and systemic prophylaxis with teicoplanin in monolateral and bilateral total knee replacement procedures: study of pharmacokinetics and tissue penetration. Antimicrob Agents Chemother. 1993;37:2693–8.
57. Nehrer S, Thalhammer F, Schwameis E, Breyer S, Kotz R. Teicoplanin in the prevention of infection in total hip replacement. Arch Orthop Trauma Surg. 1998;118:32–6.
58. Mini E, Nobili S, Periti P. Does surgical prophylaxis with teicoplanin constitute a therapeutic advance?J Chemother. 2000;12:40-55.
of prostheses bonded with a rifampin/collagen release system. J Vasc Surg. 1991;14:521–4.
60. Harvey RA, Alcid DV, Greco RS. Antibiotic bonding to polytetrafluoroethylene with tridodecylmethylammonium chloride. Surgery. 1982;92:504–12.
61. Osada T, Yamamura K, Fujimoto K, et al. Prophylaxis of local vascular graft infection with levofloxacin incorporated into albumin-sealed Dacron graft. Microbiol Immunol. 1999;43:317–21.
62. Bandyk D F, Novotney ML, Back MR, Johnson BL, Schmacht DC. Expanded application of in situ replacement for prosthetic graft infection. J Vasc Surg. 2001;34:411–20.
63. Goeau-Brissonniere O, Leport C, Bacourt F, Lebrault C, Comte R, Pechere JC. Prevention of vascular graft infection by rifampin bonding to a gelatin-sealed Dacron graft. Ann Vasc Surg. 1991;5:408–12.
64. Vicaretti M, Hawthorne WJ, Ao PY, Fletcher JP. An increased concentration of rifampicin bonded to gelatin-sealed Dacron reduced the incidence of subsequent graft infections following a
staphylococcal challenge. Cardiovasc Surg. 1998;6:268–73.
65. Ghiselli R, Giacometti A, Goffi L, et al. Prophylaxis against Staphylococcus aureus vascular graft infection with mupirocin-soaked, collagen-sealed Dacron. J Surg Res. 2001;99:316–20.
66. Sutherland R, Boon RJ, Griffin KE, Masters PJ, Slocombe B, White AR. Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother. 1985;27:495–8.
67. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemother. 1998;41:11-8.
68. Giacometti A, Cirioni O, Ghiselli R, et al. Efficacy of quinupristin-dalfopristin in preventing vascular graft infection due to Staphylococcus epidermidis with intermediate resistance to glycopeptides. Antimicrob Agents Chemother. 2002;46:2885–8.
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