Recent update in the management of invasive fungal infection (1).ppt
Transcript of Recent update in the management of invasive fungal infection (1).ppt
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Recent Update In The
Management Of InvasiveCandidiasis
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Overview
Invasive Fungal Infections
Antifungal Agents
Polyenes Azoles
Glucan ynthesis Inhi!ito"s
I#A T"eatment Guidelines
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Review of our Fungal
“Players” Oppo"tunistic fungi
$o"mal %o"a Candida spp&
U!i'uitous in ou" envi"onment Aspergillus spp& Cryptococcus spp& Mucor spp&
(ndemic geog"aphically"est"icted Blastomyces sp& Coccidioides sp& Histoplasma sp&
) $e*ly eme"gingfungi
) Fusarium
) Scedosporidium) Trichosporin
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Ran+ o"de" of nosocomial !loodst"eampathogens and thei" associated mo"tality
1 Coagulase negative-staphylococci 30.9 21
2 Staphylococcus aureus 15.7 25
3 Enterococci 11.1 32
4 Candida species 9 38
5 Escherichia coli 5.7 24
Klebsiella species 5.4 27
7 Enterobacter
species 4.5 288 Pseudomonas species 4.4 33
9 Serratia species 1.4 2
10 !iri"ans streptococci 1.4 23
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Predisposing Factors to FungalInfections (IFI)
,"oad spect"um anti!iotics Immunosupp"ession Co"ticoste"oids
P"olonged hospitalization -ICU tay. TP$ -int"avascula" cathete" use. P"olonged neut"openia /emodialysis 0Acute Renal Failu"e
#ia!etes Mellitus Mechanical 1entilation Recent gast"ointestinal 0 Ca"diac su"ge"y ,u"ns Colonization
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Incidence of InvasiveFungal Infections
olid O"gan T"ansplant 2 3 456 7idney 2 8 946 /ea"t 2 8 :56 /ea"t3;ung0;ung 92 8 : 8 45 6
,one Ma""o* T"ansplant 92 3 526
Intensive Ca"e Unit 9>6
ingh? $& CI# 5@@@ :9B24232:
1incent ;& Intensive Ca"e Med 9DD= 54B 5@
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Mortality Rates
Candidemia has a mo"tality "ate of E4@6&
Invasive aspe"gillosis continues to !e ahighly lethal oppo"tunistic infectionB
:>26 inc"ease in mo"tality due to Aspergillus species f"om 9D=@ to 9DD>& Ove"all mo"tality "ate in patients *ith
invasive aspe"gillosis is "epo"ted to !e
2=6& Mo"tality continues to !e high "ega"dless
of the antifungal the"apy used&(dmond M, et al& CI# 9DDD5DB5:D344&$ational Cente" fo" /ealth tatistics -9D=@39DD>.
;in et al& CI# 5@@9:5B:2=3
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Challenges
#elaying antifungal the"apy until!lood cultu"es a"e positive isassociated *ith inc"eased mo"tality
#iagnostic limitations
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Clinical approaches to assessris
Fungal colonizing indeB the g"eate" thenum!e" of positive sites? the g"eate"the inc"eased "is+ fo" invasive infection
Com!ine colonization *ith othe" "is+facto"sB su"ge"y on admission? TP$? andsepsis
$o colonisation inde !ut include
va"ia!lesB 4 days in ICU? C1C? #M?ne* hemodialysis? TP$? and !"oad3spect"um anti!iotics
Pittet D. Ann Surg. 1994;220:751-758.
Paphitou NI. Me M!"o#. 2005;4$:2$5-24$
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Colonization in ICU patients
P"evalence of colonization in ICU is high-2@6 to >@6 o" mo"e. compa"ed *ith"elatively lo* "ate of infection? so
p"edictive value of colonization is poo"
/o*eve" colonisation *ith uneplainedfeve"? leu+ocytosis? and hypotension
may indicate invasive candidiasis
%&tro&'!-(ei"hner ). *rit *are Me. 200+;$4:857-8+$
,ggiann P. )an"et Ine"t Di&. 200$;$:+85-702
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!hich antifungal to
choose" Candida speciation may ta+e up to 2
days
and %uconazole suscepti!ility testingmay ta+e an additional 2 days
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#argeted anti$fungaltherapy
#he “challenging” wisdo% Hithhold Antifungal the"apy unless positive
diagnostic test
Advantages #i"ected the"apy? less cost? less anti3fungal
toicity
#isadvantages 1a"ia!le sensitivity and speciJcity diagnostic
tests Unp"oven !eneJt in "educing mo"tality? costs
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Treatment options of invasive fungal infections in a
Swiss Med Wly. !""# $ul !!%&'#(!)*'"+,--*#'
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Spell/erg B$ et al. Clin 0nfect 1is. !""# $an &2%-!(!+,!-Spell/erg B$ et al. Clin 0nfect 1is. !""# $an &2%-!(!+,!-
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&iagnostic &ile%%a
Clinical ettingB *ith othe" "is+ facto"s
RadiologyB applica!le mo"e fo"
Aspe"gillus Cultu"esB ;o* yield and longe" time
tainingB GM and Calco%uo" *hite
PCR AssayB not *idely availa!le
93: ,eta Glucan AssayB
Galactomannan AssayB Fo" Aspe"gillus
P$A FI/B
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PNA FISH: Clinical BenefitsSummary
Rapid and accu"ate identiJcation of !loodst"eam pathogens di"ect f"ompositive !lood cultu"es
imple to implement and easy to use
Maintains species mo"phology
Actiona!le P$A FI/ "esults fo" D26 of ,CK
#evelopment of ne* the"apeutic guidelines Imp"oved patient safety
(a"ly app"op"iate and eLective anti!iotic the"apy
Reduction in mo"tality Reduction in unnecessa"y antimic"o!ial and antifungal use
Reduction in hospital length of stay -;O.
igniJcant cost savings
5:Ma"ch 52? 5@9<
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Antifungal choice
Organism (proven, suspected) Site of disease Host factors (eg age, neutropenia,
mucositis) History of antifungal therapy
and/or prophylaxis
Tolerability/ side eects rug!rug interactions "osts
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ANTI FUNGAL AGNTS
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1950s1950s 190s190s 1970s1970s 1980s1980s 1990s1990s
GriseofulvinGriseofulvin
AM/ AM/
5* 5*
i"onao#e top3i"onao#e top3
"#otriao#e top3"#otriao#e top3
eta"onao#eeta"onao#e,"onao#e,"onao#e
i"onao#eI63i"onao#eI63
#u"onao#e#u"onao#e
Itra"onao#eItra"onao#e
erinaineerinaine
AM/ #ipi AM/ #ipi
oru#ation&oru#ation&
Itra"onao#eItra"onao#e
2000s2000s
Itra (IV)Itra (IV)
CaspofungCaspofung
VoriconVoricon
Mi"aung Mi"aung
Aniu#oung Aniu#oung
Po&a"onPo&a"onau"onau"on
#nti$ungal %rug %evelop&ent#nti$ungal %rug %evelop&ent
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Antifungal agents
#olyenes (cell membrane) "onventional $mphotericin %
&ipid formulations
$mbisome, $belcet, Amp B Colloidal Dispersion
Tria'oles (sterol synthesis) Fluconazole? It"aconazole? 1o"iconazole? Posaconazole
3avucona4ole
chinocandins (cell all) Caspofungin
Anidulofungin5 Micafungin
$llyamines (sterol synthesis)
Te"!inaJne
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A""angement of the !iomolecula" components of the cell *allaccounts fo" the individual identity of the o"ganism& Although?each o"ganism has a diLe"ent !iochemical composition? thei"g"oss cell *all st"uctu"e is simila"&
Antifungal agents ta"geted to*a"dsB
*nhibition of fungal cell all synthesis 8 caspofungin is aβ3glucan synthesis inhi!ito" seve"al mo"e compounds a"eunde" investigation
*nhibition of fungal cell membrane synthesis 8 e"goste"olis the ta"get -cell mem!"anes of fungi and mammals containdiLe"ent ste"ols.B polyenes? azoles? t"iazoles? al+ylamines
*nhibition of cell division 8 mic"otu!ule eLectsB g"iseofulvin#$AB %ucytosine&
%iochemical Targets for$ntifungal "hemotherapy
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$ntifungal $gents! Sites ofaction
chinocandinInhi!it fungal cell *
!iosynthesis
+riseofulvinInhi!its mitotic
spindle fo"mation
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("goste"ol
ymoste"ol94 Me3fecoste"ol
;anoste"ol
'ualene
%!,- +lucan
%!,. +lucan
Cell Hall Phospholipid ,ilaye"
%!,. +lucan Synthase"aspofungin
$'oles$'oles
$%
Terbina0n
e