!"#$%&'"( *" +!,-!"#$%.$/ 01&$".

(
nuala !. Meyer Mu MS lCC
AsslsLanL rofessor of Medlclne
ulmonary, Allergy, and Crlucal Care Medlclne
unlverslLy of ennsylvanla erelman School of Medlclne

2*(%3'(45$
- 8esearch supporL by nlP and ClaxoSmlLhkllne

678$%&9$(
- ldenufy common lnfecuons LhaL compllcaLe dlerenL
forms of lmmune compromlse
- Plv
- Solld Crgan 1ransplanL
- PemaLologlc Mallgnancy/LreaLmenL (neuLropenla)
- 8ecognlze non-lnfecuous compllcauons of Plv LhaL
may presenL ln Lhe lCu
- SelecL Lhe approprlaLe LreaLmenL for febrlle pauenLs
wlLh neuLropenla
+!,: ;<*/$=*'3'>? 1"/ 01.@'>$"$(*(
- Plghly acuve anu-reLrovlral Lherapy (PAA81) has
decreased Plv hosplLallzauon and morLallLy raLe
- Muluple cenLers reporL decllnlng lCu admlsslon raLe
- 4 - 12 of hosplLallzed Plv pauenLs requlre lCu
- MorLallLy among Plv pauenLs reachlng Lhe lCu decllnlng
- 8oughly 30 ln several serles (uCSl, Mayo, LlnsLeln)
- redlcLors of MorLallLy
- need for venulauon, dlagnosls of . [lrovecl (C), low
serum albumln (< 2.6 mg/dl) = Plgh 8lsk
Morrls !" $ %&'()* +*), +-*& .&/ 2002, naraslmhan +0&', 2004, Afessa +0&', 2000
A1($ B
28 year-old man presenLs w/ a 2 week hlsLory of nonproducuve
cough and dyspnea. hyslcal exam: Lachypnea, Lachycardla,
low-grade fever, whlLe paLches on oral mucosa and pharynx,
and a few basllar rales on ausculLauon. 1he C
2
saLurauon ls
83 on room alr and Lhe LacLaLe dehydrogenase (LuP) ls 370.
Cx8 revels bllaLeral ground glass lnlLraLes. Whlch of Lhe
followlng ls Lhe mosL llkely dlagnosls?
A. Candlda pneumonla
8. C
C. neumococcal pneumonla
u. 18
L. lnuenza
0"$4='%?(&( <"$4='"*1 C0A0D %14($/ 7?
0"$4='%?(&( 8*5'9$%* <"$4='"*1 C0E0D
- Sull a common cause of resplraLory fallure ln Plv/
AluS
- 8are lf Lhe pauenL ls on 1M/Sx for prophylaxls
- SubacuLe dyspnea, fever, nonproducuve cough
- Ma[orlLy of pauenLs have severe lmmune declency,
buL 3-13 wlll have Cu4 > 200/mm
3
- Co-lnfecuon wlLh oLher bacLerla common
- llndlng CMv ln Lhe 8AL ls common, buL does noL
usually requlre anuvlral LreaLmenL
AFG *" 0A0
- Cx8 may be subLle, even normal ln 10-20, buL chesL
C1 ls sensluve for ground-glass opaclcauon (CCC)
- erlhllar CCC Lhe mosL common pauern on Cx8
- May progress Lo bllaLeral alveolar lllng c/w A8uS
wlLhouL Lherapy
- CavlLauon and nodules, less common
- SponLaneous pneumoLhorax can occur and ls a
serlous compllcauon lndlcaung poor prognosls
- leural euslon Lyplcally absenL
0A0 2*1>"'(*(
- 8AL ls >93 sensluve, lower lf pauenL has been on
prophylaxls (esp penLamldlne) or lf non-Plv
- A number of sLalns wlll ldenufy C
- Crocou's meLhanamlne sllver, Loluldlne blue, Clemsa
- lmmunouorescenL anugen LesL (ulA) mosL sensluve & speclc
- CuanuLauve C8 hlghly sensluve buL false posluves
- Serum 1,3-8eLa-u-glucan: nonspeclc buL decenL sensluvlLy 92
- 1lssue dlagnosls (blopsy) rarely needed
- lnduced spuLum for C may be helpful, buL hlghly
dependenL on Lechnlque/experlence, yleld varlable
Pauser $ +1)2 .)3*45)41 2011
H%4.$ 0A0 I5$1.=$".
- Plgh-dose 1M/Sx (13-20 mg/kg/day of 1M) ls Lhe
drug of cholce
- 1reaL for 21 days
- Ad[uncuve corucosLerolds decrease morLallLy ln
moderaLe Lo severe C wlLh A-a gradlenL > 33 or
aC
2
< 70 mm Pg
- 1aper prednlsone over 21 days:
- 40 mg q12h on day 1-3
- 40 mg q24h on day 6-10
- 20 mg q24h on day 11-21
CuC/luSA Culdellnes 2009
H3.$5"1&9$ 0A0 I5$1.=$".
- Severe C: lv penLamldlne for 21 days, waLch for
severe, unpredlcLable hypoglycemla, pancreauus
- rlmaqulne (po) + cllndamycln po/lv
- Mlld Lo moderaLe C: for 21 days
- 1M 13mg/kg/day + dapsone
- rlmaqulne + cllndamycln
- Mlld C: aLovaquone 730mg C 8lu x 21 days wlLh
a fauy meal Lo lncrease absorpuon
- rlmaqulne and dapsone: beware of hemolysls
- C-6-u declency
CuC/luSA Culdellnes 2009
!"/*%1&'"( #'5 0A0 05'<@?31J*(
- revlous C: wlLhouL secondary prophylaxls, Lhe
annual rlsk ls 60-70
- Cu4 counL below 200/mm
3
, wlLhouL prlmary
prophylaxls, Lhe annual rlsk ls 40-30
- CLher evldence of lmmune declency
- Cral Lhrush
- Cral halry leukoplakla
A1($ K
37 yo female wlLh Plv+ for 6 years on PAA81 presenLs wlLh
resplraLory fallure requlrlng lnLubauon and mechanlcal
venulauon ln Lhe Lu. Cx8 ls shown. Per husband reporLs
adherence wlLh PAA81 and prophylaxls (8acLrlm, dlucan).
Per mosL recenL Cu4 counL was 207, vlral load was
deLecLable buL low. She ls u.S. nauve, has had no recenL
Lravel, and no hlsLory of ln[ecuon drug use.
Whlch organlsm ls Lhe mosL llkely cause of her pneumonla?
A. neumocysus [lrovecl (C)
8. SLaphylococcus aureus
C. Leglonella
u. klebslella pneumonla
L. SLrepLococcus pneumonlae
A@1">*"> A14($( '# !AL H/=*((*'" *" +!,M
- 8esplraLory fallure ls sull common, buL only 23-30
of lCu admlsslons
- ln u.S., 8acLerlal neumonla more common Lhan C
- 18 more common ln oLher parLs of Lhe world
- Many pauenLs are sull admlued Lo Lhe lCu for sepsls,
CnS dysfuncuon
- More pauenLs are belng admlued for non-AluS
relaLed lllnesses
- lmmune reconsuLuuon dlsease and Loxlclues relaLed
Lo PAA81 may also resulL ln lCu admlsslon
N1%.$5*13 0"$4='"*1 1='"> +!,M 01&$".(
- S. neumonlae mosL common
- P. lnuenzae
- S. aureus (lncreased ln lv drug users)
- klebslella, seudomonas (lncreased ln lv drug users, Cu4
counL <30)
- uncommon causes LhaL may be seen ln Plv pauenLs
- Leglonella
- 8hodococcus equl (chronlc, may cavlLaLe and mlmlc 18)
- Moraxella caLarrhalls (chronlc, oen wlLh low Cu4)
- nocardla (chronlc, nodular, may cavlLaLe)
A1($ O
33 yo female wlLh newly dlagnosed
Plv (Cu4 0, vlral load >200,000) ls
lnLubaLed ln Lhe lCu wlLh a
perslsLenL alr leak from a large
pneumoLhorax and a dluse
ground glass abnormallLy. She
undergoes bullecLomy Lo resolve
Lhe alr leak and paLhology from
her LLL ad[acenL Lo Lhe bullae ls
shown. ln addluon Lo Lreaung her
for acuLe . [lrovecl, whaL oLher
lnfecuon should be covered?
A. M. Luberculosls u. PSv
8. 1oxoplasma gondll L. PlsLoplasma
C. CMv
A?.'=$>13'9*54( *" +!,
- ConLroverslal slgnlcance ln Plv
- CulLure + bronchoscopy: nelLher sensluve nor speclc
- C8 deLecuon from bronchoscopy: non-speclc
- Lung paLhology demonsLraung cyLopaLhlc eecL/lncluslons:
- SLClllC buL llkely lnsensluve
- CMv as a sole cause of pneumonla rare unul
advanced Plv (Cu4 < 12)
- 1reaLmenL ls recommended when
1. SympLomauc pulmonary dlsease
2. resence of CMv ln Lhe lung
3. Absence of alLernauve LreaLable condluons or fallure Lo
respond Lo LreaLmenL for oLher lnfecuons
lncluslon 8odles
Cwl's Lye nucleus"
P'"-($<&% !AL 05$($".1&'"( '# +!,
- neoplasuc ulsease
- kaposl's Sarcoma
- Lung Cancer
- non-hodgklns Lymphoma
- CnS Space-Cccupylng leslons
- Lymphoma vs 1oxoplasma vs !C vlrus
- urug 1oxlclues
- lmmune 8econsuLuuon lnammaLory Syndrome
P$'<31(&% 2*($1($
- AluS-denlng Cancers (kS, nPL, Cervlcal cancer) are
decreaslng buL sull prevalenL
- non-AluS-denlng cancers lncreaslngly recognlzed:
- Lung Cancer 2-4 fold lncreased rlsk
- Pead/neck Cancer
- Cl Mallgnancles
- PepaLocellular carclnoma (wlLh P8v/PCv colnfecuon)
A1($ Q
26 yo M ls dlagnosed wlLh Plv durlng S1u
screenlng and decllnes follow up for
10 monLhs. Cn reconLacL, Cu4 ls 19
and he c/o dyspnea ln cllnlc. 2 weeks
laLer he ls admlued wlLh hemopLysls.
Whlch of Lhe followlng organ sysLems
ln nC1 frequenLly lnvolved by Lhls
condluon?
A. Cl LracL
8. Skln
C. Cronasopharynx
u. 8raln
L. Lungs
R1<'(*S( T15%'=1
- uecreaslng lncldence ln Lhe uS slnce PAA81
- AluS-denlng lllness
- MosL commonly aecLs
- Skln - blopsy Lo dlerenuaLe from baclllary anglomaLosls
- Lung - hemopLysls, alrway leslons, parenchymal nodules
- Cl LracL/vlscera - bleedlng
- Cral cavlLy
- 1reaLmenL for sympLomauc pulmonary kS
- lnluaLe A81, conslder chemoLherapy
- ulsconunue sLerolds lf posslble
- AccounLs for ~13 of admlsslons Lo lCu
- 1oxoplasmosls and 1
o
CnS lymphoma are Lhe mosL
common causes of space-occupylng leslons
- CrypLococcus ls Lhe mosL common cause of
menlnglus
- ML due Lo !C vlrus, CMv and PSv encephallus, and
AluS encephalopaLhy also occur
- Admlsslon Lo Lhe lCu ls usually for alrway proLecuon
or managemenL of lncreased lnLracranlal pressure
APT 2*($1($ *" +!, 01&$".(
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- aradoxlcal worsenlng of a pre-exlsung lnfecuon
followlng lnluauon of Lherapy (PAA81 +/or anubloucs)
- More rarely, new presenLauon of unrecognlzed lnfecuon
- Classlc paLhogens:18, MAC, CrypLococcus, CMv, C
- 8lsk lacLors: low lnlual Cu4, sLrong response Lo PAA81
- ulagnosls of excluslon
- 1lme course: 7-14 days lf mycobacLerlal/fungal, >30d lf vlral
- lever common (excepL CMv) buL oLherwlse proLean
presenLauon
- udx lncludes drug LoxlclLy, lnadequaLe anubloucs, reslsLance
I*=*"> '# +HHGI *" .5$1.=$".-"1V9$ IN
- lor mosL opporLunlsuc lnfecuons (Cl), lnluaung
PAA81 ls recommended wlLhln 2 weeks of sLarung
Lherapy for Lhe Cl
- CurrenL recommendauons for pulmonary 18 wlLh
low Cu4 counL are Lo sLarL PAA81 aL 2 weeks,
preferred over 8 weeks, due Lo lmproved survlval
- Powever, pauenLs are hlgh rlsk for l8lS
- lf severe l8lS occurs, may dlsconunue PAA81 +/- sLerolds
- 1reaLmenL-naive pauenLs wlLh 18 menlnglus are
recommended Lo delay PAA81 for 8 weeks
!=<'5.1". 254> I'J*%*&$( 5$W4*5*">
X*.@/51Y13 '# .@$ 6Z$"/*"> 254>
- Lacuc Acldosls (n81ls AZ1, u4L) - mlLochondrlal LoxlclLy
- Abacavlr PypersensluvlLy, assoclaLed wlLh PLA 83701
- uo noL re-challenge lf dlsconunued
- SLevens !ohnson / 1Lns: any, buL Lyplcally nv, LlZ
- Severe hepaLoLoxlclLy: n81ls, nn81ls, ls, Maravlroc
- lnLracranlal hemorrhage: 1v
- Severe MyopaLhy/8esplraLory weakness (AZ1, esp w sLerolds)
- Ascendlng paralysls: u41
- nephroLoxlclLy (1ul), 8enal SLones (lnu)
- ancreauus: ddl, ddl + u41
[2H-H<<5'9$/ H"&5$.5'9*513 254>( C#'5 5$#$5$"%$D
8everse 1ranscrlpLase lnhlblLors
- nucleoslde analogs (n81l):
- Abacavlr (Zlagen)
- AZ1 (Zldovudlne, 8eLrovlr)
- ddC (zalclLablne, Plvld)
- ddl (dldanoslne, vldex)
- d41 (sLavudlne, ZerlL)
- 31C (lamlvudlne, Lplvlr)
- l1C (emLrlclLablne, LmLrlva)
- 1enofovlr (nucleoude: vlread)
- non-nucleoslde (nn81l)
- uelavlrdlne (8escrlpLor)
- Lfavlrenz (Susuva)
- nevlraplne (vlramune)
- LLravrlne (lnLelence)
- 8llplvlrlne (LduranL)
- luslon lnhlblLors
- Lnfuvlrude (luzeon)
- LnLry lnhlblLors
- Maravlroc (SelzenLry)
roLease lnhlblLors (l)
- Amprenavlr (Agenerase)
- ALazanavlr (8eyaLaz)
- uarunavlr (rezlsLa)
- losamprenavlr (Lexlva)
- lndlnavlr (Crlxlvan)
- nelnavlr (vlracepL)
- 8lLonavlr (norvlr)
- Saqulnavlr (lorLovase, lnvlrase)
- Loplnavlr/r (kaleLra)
- 1lpranavlr (1exega)
lnLegrase lnhlblLors
- 8alLegravlr (lsenLress
Comblnauon llls
- AZ1/31C (Comblvlr)
- AZ1/31C, A8C (1rlzlvlr)
- 1ul/l1C (1ruvada)
- A8C/31C (Lpslcom)
- 1ul/l1C/Llv (ALrlpla)
- 1ul/l1C/8lL (Complera)
6.@$5 I'J*%*&$(
- CnS eecLs (LlZ)
- erlpheral neuropaLhy (u41, ddl, ddC)
- Pyperllpldemla (ls, u41, AZ1)
- lnsulln reslsLance/dlabeLes melllLus (ls)
- LlpodysLrophy (u41, AZ1, ls)
- CsLeonecrosls (ls)
- ln[ecuon slLe reacuons (luzeon)
- ls and nn81ls lnhlblL cyLochrome 430 3A4
- AlLered meLabollsm of mldazolam, oplaLes, eLc
A1($ \
33 yo M former smoker h/o uM, P1n, and LS8u 4 years s/p renal
LransplanL presenLed complalnlng of le-slded/ subsLernal C x
3 weeks. Pe had been LreaLed wlLh lv anubloucs followed by an
oral uoroqulnolone for communlLy acqulred pneumonla 1
week earller, buL felL hls sympLoms had reLurned aer lnlual
lmprovemenL. 8eporLs fever, cough, and nlghL sweaLs wlLh 13 lb
welghL loss. Pe ls hypoxlc and ls admlued Lo Lhe lCu. Meds
lnclude prednlsone 10 mg, cellcepL /mycophenylaLe moul, and
lk308 (prograf).
8ronchoalveolar lavage: many Mn,
moderaLe C8, weakly acld fasL

WhaL ls Lhe preferred anuoblouc Lo LreaL hls lnfecuon?
A. enlclllln C
8. uoxycycllne
C. MeLronldazole
u. 1M/SMx and amlkacln
L. lperaclllln/LazobacLam
P'%15/*1 T<$%*$(
- lmmunocompromlsed pauenLs wlLh cell-medlaLed lmmune
dysfuncuon
- Solld organ LransplanL, hemaLologlc SC1, glucocorucolds, Plv
- ulmonary, Skln, CnS
- lnlual 1reaLmenL wlLh aL leasL 2 agenLs for severe dlsease
- 1M/SMx and amlkacln
- 1M/SMx and lmlpenem lf CnS lnvolvemenL
- lmlpenem and amlkacln
- Llnezolld also eecuve
- 3-6 weeks lv Lherapy, followed by ~12 monLhs of oral
- 1M/SMx, mlnocycllne, or Amplclllln/clavulonaLe pendlng sensluvlues
A'=='" !"#$%&'"( *" T'3*/ 65>1" G$%*<*$".(:
B
(.
]'".@
8eslsLanL 8acLerla/lungl
- M8SA, v8L
- Candlda
- C. dlmclle

nosocomlal
- Asplrauon
- CaLheLer-relaLed
- Wound lnfecuon
- AnasLomouc leak lssues

llshman n Lngl ! Med 2007, 337
uonor-derlved (8A8L)
- PSv, Plv, Wnv, rables
- 1rypanosoma cruzl

8eclplenL colonlzauon
- seudomonas, M8SA
- Asperglllus

A'=='" !"#$%&'"( *" T'3*/ 65>1" G$%*<*$".(:
]'".@( B - ^
WlLh C/CMv rophylaxls
- PCv
- olyomavlrus 8k (renal)
- C. ulmclle
- Adenovlrus, lnuenza
- CypLococcus neoformans
- M. 1uberculosls

llshman n Lngl ! Med 2007, 337
no rophylaxls
- C
- Perpesvlrus famlly PSv
CMv, L8v, vZv
- LlsLerla, nocardla,
Loxoplasma, sLrongyloldes


A'=='" !"#$%&'"( *" T'3*/ 65>1" G$%*<*$".(:
H_$5 ^ ]'".@(
8acLerlal and lungal
neumonla (CA)
u1l
lungal / Mold lnfecuons
Asperglllus
Mucor
nocardla / 8hodococcus
llshman n Lngl ! Med 2007, 337
LaLe vlral lnfecuons
CMv (collus, reunlus)
Pepauus (P8v, PCv)
PSv encephallus
WesL nlle vlrus
encephallus
SA8S
!C polyomavlrus (ML)

A1($ ^
A 43 year old female S/ allogenelc SC1 for AML 3 monLhs
ago has been on prednlsone for CvPu wlLh cuLaneous and
Cl LracL lnvolvemenL. Per neuLrophll counLs are normal,
buL she develops fever. Cx8 shows a nodular leslon and
C1 demonsLraLes Lhls leslon ls surrounded by a halo" of
ground glass opaclcauon. 1he mosL llkely dlagnosls ls

A. 1uberculosls
8. SLrepLococcus pneumonla
C. Asperglllus fumlgaLus
u. enlcllllum marneel
L. 8lasLomycosls
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- lever ln a hlgh-rlsk neuLropenlc pauenL (> 7 days
neuLropenla) ls consldered a medlcal emergency
- Assume sepuc unul proven oLherwlse
- LMl8lC anubloucs Lo cover 1) suspecLed source lf
presenL and 2) mosL deadly organlsms (Cn8)
- Ceplme / lmlpenem / Meropenem/ lperlclllln-LazobacLam
- Cover 8eslsLanL Cram+ (vanco /uapLomycln /
Llnezolld)
- ll hemodynamlcally unsLable (le, MlCu)
- ll suspecL pneumonla, skln/so ussue, or caLheLer-relaLed
- ll blood culLures + for Cram + bacLerla, awalung sensluvlues
P$4.5'<$"*% T$<(*(: G*(` T.51&a%1&'"
- Low 8lsk for Serlous Compllcauons
- LxpecLed durauon of neuLropenla (AnC < 300 cells/mcl)
llmlLed Lo 7 days or fewer
- no slgnlcanL comorbldlLy (renal, hepauc lmpalrmenL)
- May noL need hosplLallzauon
- Plgh 8lsk: expecLed durauon of neuLropenla > 7 days
- 8one marrow LransplanL pre-engramenL, leukemla
- Pemodynamlc lnsLablllLy
- Severe mucoslus, new CnS sympLoms, new pulmonary sx
- lnpauenL prlor Lo fever, unconLrolled cancer, hepauc lnsu
P$4.5'<$"*% T$<(*(:
H//*&'"13 A'"(*/$51&'"(
- erslsLenL lever ln a sLable, low rlsk pauenL: no
change
- erslsLenL lever > 4 days ln hlgh rlsk pauenL
- Conslder addlng anufungal, esp lf mucoslus
- lungal agenL depends on scenarlo: anuyeasL vs anumold
- Low Lhreshold for Lreaung C. dl whlle assay pendlng
- ulsconunue vanco lf no + culLures aer 2 days, sLable
- Conslder caLheLer removal lf cx + > 3days or lf:
- M8SA, seudomonas, Candlda/fungl, mycobacLerlae
lsolaLed
- Sepuc shock, endocardlus, sepuc Lhrombophleblus
T4==15?
- lmmunocompromlsed hosLs may presenL wlLh elLher
common bacLerlal paLhogens or wlLh opporLunlsuc
lnfecuons
- SeverlLy of lmmunocompromlse ls a ma[or
deLermlnanL of Lhe llkely lnfecuon
- ln Plv + pauenLs on PAA81, conslder non-lnfecuous
processes (drug LoxlclLy) and non-Cl compllcauons
- neuLropenlc sepsls requlres emplrlc anubloucs and
ad[usLmenL as sympLoms and LesL resulLs evolve