Recent update in the management of invasive fungal infection (1).ppt

8/19/2019 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

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Recent update in the management of invasive fungal infection (1).ppt