Iunga| Infecnons |n

Þu|monary and Cr|nca| Care

Med|c|ne:
ACCÞ 8oard kev|ew
AoJtew l. 5bott, Mu, Mln, lAcl, lccl
wosbloqtoo nospltol ceotet
Ceotqetowo uolv.,
wosbloqtoo, uc
D|sc|osures
AsLellas
8ayer
CublsL
loresL

Þñzer
1heravance
1rlus
ln Lhe lasL year l have served as a consulLanL Lo, researcher/lnvesugaLor
for, or spoken for:
Cb[ecnves
1o descrlbe Lhe epldemlology of fungal lnfecuons ln
pulmonary dlsease
1o revlew LreaLmenL opuons for fungal lnfecuons

Wh|ch of the fo||ow|ng organ|sms |s
p|ctured be|ow?
Wh|ch of the fo||ow|ng organ|sms |s
p|ctured be|ow?
1. Asperglllus
2. Candlda
3. 8lasLomycosls
4. PlsLolplasmosls
3. Mucormycosls
Wh|ch of the fo||ow|ng organ|sms |s
p|ctured be|ow?
Wh|ch of the fo||ow|ng organ|sms |s
p|ctured be|ow?
1. Asperglllus
2. Candlda
3. 8lasLomycosls
4. PlsLoplasmosls
3. Mucormycosls
CLINICAL SÞLC1kUM CI
ÞULMCNAk¥
ASÞLkGILLCSIS
Asperg|||us 8ackground
ublqulLous soll-dweller found ln composL, debrls,
dusL, food, roued planLs
lllamenLous fungl
Cver 200 specles
– Specles paLhogenlc Lo humans lnclude:
Aspetqlllos fomlqotos
Aspetqlllos fovos
Aspetqlllos olqet
Aspetqlllos tetteos
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

Asperg|||us 8ackground
Þrlmarlly acqulred from lnanlmaLe reservolr
– Malnly vla lnhalauon of alrborne spores
Can cause several dlsuncL pulmonary enuues
– 8arely, one enuLy may change Lo anoLher enuLy (l.e.
aspergllloma lnvaslve asperglllosls
ÞauenL rlsk facLors predlspose Lo developmenL of
speclñc enuues
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

C||n|ca| Spectrum

Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.
Invas|ve Þu|monary Asperg|||os|s (IÞA):
8ackground]Inc|dence
SLudy by Croll eL al found lncrease ln raLe of lnvaslve
mycoses on auLopsles beLween 1978-1992 from
0.4° Lo 3.1°
– lÞA lncreased from 17° of all mycoses Lo 60° by end of
sLudy
MulucenLer Luropean reglsLry found 3° lncldence of
lÞA ln pauenLs wlLh acuLe leukemla
neuLropenla mosL lmporLanL rlsk facLor
8lsk of lÞA lncreases wlLh durauon of neuLropenla
(1°/day for 1
sL
3 weeks and Lhen 4°/day)
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.
Wh|ch of the fo||ow|ng carr|es the h|ghest
r|sk for deve|op|ng IÞA?
1. 8ecenL kldney LransplanL
2. AluS (Cu4 = 30)
3. 8ecenL 8M1
4. 1aklng 40 mg prednlsone dally
3. AnC of 130 for Lhe lasL week followlng
chemoLherapy
Meerseman W, Lagrou k, eL al. lnvaslve Asperglllosls ln Lhe lnLenslve Care unlL. Clln lnfecL uls 2007, 43: 203-16.

Segal 8P. Asperglllosls. n Lngl ! Med 2009, 360: 1870-1884.
IÞA: C||n|ca| Þ|cture
Slno-pulmonary LracL prlnclpally lnvolved glven
Lyplcal rouLe of acqulsluon
– Lower resplraLory LracL almosL always prlmary focus
Common presenung sympLoms lnclude fever, cough,
spuLum producuon, and dyspnea
vascular lnvaslon can presenL as pleurluc chesL paln
(small pulmonary lnfarcuons), hemopLysls
– lÞA one of mosL common causes of hemopLysls ln
neuLropenlcs (correlaLed wlLh cavlLauon seen wlLh
neuLrophll recovery)
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

IÞA: C||n|ca| Þ|cture
Can see lsolaLed Lracheobronchlus wlLh ulcerauon
(more common ln AluS and lung LransplanLs)
– Can cause upper alrway obsLrucuon/secondary aLelecLasls
Spreads hemaLogenously Lo oLher organs
– 8raln mosL commonly buL can lnvolve any oLher slLe
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

IÞA: D|agnos|s
need hlgh lndex of susplclon
ueñnlLe dlagnosls:
– presence of sepLaLe, acuLe, branchlng hyphae ln lung
ussue sample +/- culLure posluve for Asperglllus from
same slLe or posluve culLure from ussue obLalned vla
lnvaslve procedure
– WlLhouL + Cx, could be lusarlum or Scedosporlum
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

IÞA: D|agnos|s
SpuLum
– Could be colonlzauon or alrway dlsease
– Leukemla or 8M1: ÞÞv 80-90°, nÞv 70°
8lood culLures
– 8arely posluve
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

IÞA: D|agnos|s
lmaglng
– Cx8
non-speclñc ñndlngs lnclude rounded denslues, pleural-
based lnñlLraLes (pulmonary lnfarcL), cavlLauon
Þleural eñuslons uncommon
– C1 scan
1yplcal ñndlngs lnclude
– Muluple nodules
– Palo slgn: low auenuauon due Lo hemorrhage around
nodule (seen ln neuLropenlcs)
– Alr-crescenL slgn: crescenL-shape lucency ln mlddle of
nodule secondary Lo necrosls
Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

Soubanl AC, Chandrasekar ÞP. 1he Cllnlcal SpecLrum of Þulmonary Asperglllosls. ChesL 2002,121: 1988-1999.

hup://radlology.rsna[nls.org/cgl/conLenL-nw/full/246/3/697/l24
Segal 8P. Asperglllosls. n Lngl ! Med 2009, 360: 1870-1884.
IÞA: D|agnos|s
8AL
– lungal smear and culLure
SpeclñclLy 97°, sensluvlLy 3-30°
– 1ransbronchlal blopsles noL very helpful
– 8AL CalacLomannan
WheaL !L. Approach Lo Lhe ulagnosls of lnvaslve Asperglllosls and Candldlasls. Clln ChesL Med 2009, 30, 367-377.
IÞA: D|agnos|s
Serology
– noL very useful
Þoor lmmune response ln mosL pauenLs and qulck onseL wlLhouL
ume for Ab formauon
– Can check serum galacLomannan
– ÞC8 ls exLra-sensluve and leads Lo hlgh false-posluves raLe
WheaL !L. Approach Lo Lhe ulagnosls of lnvaslve Asperglllosls and Candldlasls. Clln ChesL Med 2009, 30, 367-377.

What |s the current hrst-||ne treatment
for a panent w|th IÞA?
1. lluconazole
2. AmphoLerlcln 8
3. vorlconazole
4. Þosaconazole
3. Caspofungln
IÞA: 1reatment
Walsh 1!, Analssle L!, uennlng uW, eL al. 1reaLmenL of Asperglllosls: Cllnlcal Þracuce Culdellnes of Lhe lnfecuous ulseases SocleLy of
Amerlca. Clu 2008,46: 327-360.
Vor|conazo|e vs. Amphoter|c|n
PerbrechL 8, uennlng uW, Þauerson 1l, eL al. vorlconazole versus AmphoLerlcln 8 lor Þrlmary 1herapy of lnvaslve Asperglllosls.
n Lngl ! Med 2002, 347(6):408-413.
IÞA: 1reatment
Walsh 1!, Analssle L!, uennlng uW, eL al. 1reaLmenL of Asperglllosls: Cllnlcal Þracuce Culdellnes of Lhe lnfecuous ulseases SocleLy of
Amerlca. Clu 2008,46: 327-360.

A8ÞA
non-lnvaslve, hypersensluvlLy dlsease
Coal of Lx: prevenL exacerbauons
Lung damage can occur even ln asympLomauc
lndlvlduals
Conslder A8ÞA ln:
– 8efracLory asLhma
– Cl
lollowlng Serlal lgL cruclal
A8ÞA
D|agnosnc Cr|ter|a
-lnñlLraLes (can be lnLermluenL or perslsLenL)
-Þerlpheral blood eoslnophllla
-AsLhma
-Þosluve preclplLaung anubodles Lo A. fumlgaLus
LlevaLed LoLal lgL
-LlevaLed speclñc lgL and lgC Lo A. fumlgaLus
-8ronchlecLasls (noL requlred buL oûen presenL)
A8ÞA: 1reatment
MUCCkM¥CCSIS
Mucormycos|s 8ackground
Mucormycosls: dlsuncL group of lnfecuons caused by
fungl belonglng Lo order mocotoles ln class
2yqomycetes
ublqulLous saphrophyuc fungl ln soll or decaylng
organlc mauer
Cenera causlng human dlsease lnclude 8hlzopus,
Absldla, and Mucor
Þrlmary rouLe of lnoculauon ls lnhalauon of alrborne
spores
8lgby 1u, SeroLa ML, 1lerney LM, Mauhay MA. Cllnlcal SpecLrum of Þulmonary Mucormycosls. ChesL 1986,89:433-439.
Mucormycos|s 8ackground
very aggresslve paLhogens wlLh lnfecuon
characLerlzed by anglolnvaslon, Lhrombosls, and
hemorrhaglc lnfarcuon
Crganlsms have broad, non-sepLaLe hyphae wlLh
rlghL-angle branchlng
8lgby 1u, SeroLa ML, 1lerney LM, Mauhay MA. Cllnlcal SpecLrum of Þulmonary Mucormycosls. ChesL 1986,89:433-439.

hup://www.momu.org/CC!8ooL/v4n2/lnfec_onc_ñg1.glf
Wh|ch of the fo||ow|ng cond|nons poses a
r|sk for deve|op|ng mucomycos|s?
1. unconLrolled uM
2. Þrolonged hlgh-dose corucosLerolds
3. Leukemla
4. Solld-organ LransplanLauon
3. All of Lhe above
C||n|ca| Þresentanon
1yplcal presenLauon ls pauenL wlLh underlylng
hemaLologlc mallgnancy wlLh prolonged, profound,
neuLropenla on lmmunosuppresslve/anumlcroblals
SympLoms lnclude cough, fever, pleurluc chesL paln
– SpuLum can range from non-exlsLenL Lo grossly bloody
8lgby 1u, SeroLa ML, 1lerney LM, Mauhay MA. Cllnlcal SpecLrum of Þulmonary Mucormycosls. ChesL 1986,89:433-439.

1reatment
very aggresslve lnfecuon, so susplclon should
prompL lnluauon of LreaLmenL whlle awalung
conñrmauon
CornersLone of LreaLmenL lnvolves comblnauon of
anufungals, surglcal resecuon/debrldemenL, and
lmmune reconsuLuuon
AmphoLerlcln 8 remalns mosL acuve anufungal,
followed by posaconazole
naggle S, ÞerfecL !8. Molds: Pyalohyphomycosls, Þhaeohyphomycosls, and Zygomycosls. Clln ChesL Med 2009, 30:337-333.

n|stop|asmos|s
ManlfesLauons: uepend on lnLenslLy of exposure and
lmmune sLaLus
– AcuLe resplraLory fallure/dlñuse lnñlLraLes
– nodules (Can be ÞL1 posluve)
– 8ronchollLhlasls
– llbroslng Medlasunlus
– Þrogresslve dlssemlnaLed hlsLoplasmosls (Lhlnk of Lhe bone
marrow!!)
1reaLmenLs
– Mlld dlsease and/or chronlc manlfesLauons - noLhlng
– ModeraLe dlsease - lLraconazole
– Severe dlsease: Ampho
8|astomycos|s
Pas lsolaLed geography (cenLral/souLheasLern uS)
very broad based mold
AcuLe, subacuLe, and chronlc manlfesLauons
MosL lllness represenLs
– AcuLe resplraLory lllness wlLh lnñlLraLes LhaL falls
convenuonal anubloucs
8arely dlssemlnaLes (CnS/Skln/8one) unless
advanced AluS presenL

8|astomycos|s
1he classlc case on Lhe boards ls:
– Mlddle aged male reLurns from hunung Lrlp ln Arkansas
wlLh resplraLory lllness and lnñlLraLes non-responslve Lo
anubloucs. Pls dog may be acuLely lll Loo.
– 8emember: 8road based, buddlng, bubba 8LAS1C
Cocc|d|o|domycos|s
AnoLher soll dwelllng fungl
– San !oaquln valley, AZ, nM
60° of lnfecuons asympLomauc
lf lll acuLely, resembles CAÞ
lacLors ln presenLauons suggesung noL CAÞ
– Pllar LAu
– Loslnophlla
– Skln ñndlngs (eg L. nodosum)
ulagnosls
– Anubody Lesung (LLlSA, lmmunodlfusslon, eLc)
– lsolauon of classlc spherules from culLure maLerlal
Cocc|d|omycos|s
MosL lllness acuLely self-llmlLed
– 1hus may acLually accounL for 1/3
rd
of all cases ln endemlc
reglons dlagnosed as ºCAÞ"
1reaLmenL
– lmmunocompeLenL: noLhlng
lf sxs perslsL for more Lhan 6 weeks conslder Lx
– lmmunosuppressed
lluconazole
Ampho
CANDIDIASIS
Cand|da 8ackground
Cver 163 recognlzed specles
– lew are human paLhogens
vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.
Lp|dem|o|ogy
lncldence of candldemla caused by non-alblcans
specles has lncreased markedly over lasL 10 years
lncreased lncldence of ßuconazole reslsLance
– c. qlobtoto lsolaLes: 10-23° reslsLanL
– c. ktosel: lnLrlnslc reslsLance
8oughly 12° of all hosplLal-acqulred 8Sls are due
caused by Candlda
vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.

Wh|ch of the fo||ow|ng |s a r|sk factor for
deve|opment of cand|dem|a?
1. ÞarenLeral nuLrluon
2. AcuLe renal fallure
3. M8SA colonlzauon
4. 8ecenL recelpL of lluconazole for vulvovaglnlus
3. All of Lhe above
C||n|ca| Spectrum
MosL cases ln lCu: candldemla wlLh acuLe
dlssemlnauon
– 30° of candldemla sepuc shock
– SlLes: kldney, llver, spleen, eyes, endovascular sLrucLures
ÞerlLonlus: can follow guL wall ln[ury
Menlnglus: can compllcaLe neurosurglcal
lnLervenuons
Candlda lsolaLed from urlnary and resplraLory LracLs
usually represenL co|on|zanon
vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.

D|ssem|nated Cand|d|as|s
vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.

D|agnos|s
40-60° of pauenLs wlLh dlssemlnaLed candldlasls wlll
have negauve blood culLures
– Þosluve culLures may Lake days
Þepude nuclelc acld (ÞnA) llSP: alblcans vs. non-
alblcans
need hlgh lndex of susplclon
– pauenLs wlLh muluple slLes of colonlzauon (urlne, spuLum)
aL hlgher rlsk
vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.

Non-Cu|ture Methods of D|agnos|s
1-3 µ-u glucan
– Serum assay ls luA approved
– µ-u glucan: ma[or cell wall componenL ln a wlde varleLy of
fungl
– SensluvlLy: 73-100°, SpeclñclLy 88-100°
– lL ls broad specLrum and deLecLs:
Apetqlllos, cooJlJo, losotlom, Actemoolom, and oLher
fungl

vasquez !A. lnvaslve lungal lnfecuons ln Lhe lnLenslve Care unlL. Semln 8esplr CrlL Care Med 2010, 31: 79-86.

1reatment Gu|de||nes
Þappas ÞC, kauñman CA, Andes u, eL al. Cllnlcal Þracuce Culdellnes for Lhe ManagemenL of Candldlasls: 2009 updaLe by Lhe
lnfecuous ulseases SocleLy of Amerlca. Clu 2009,48:303-33.
Conc|us|ons
lungal lnfecuons cause range of dlsease
MusL have hlgh lndex of susplclon
MosL dlagnosuc Lechnlques llmlLed
Muluple Lherapeuuc opuons
– 8evlew Lhe recenL A1S guldellnes