INFECTIONS IN THE
IMMUNOCOMPROMISED HOST
Be na dino Roca Villanue a
Se icio de Medicina In e na, Hospi al Gene al de Cas ellón
Depa amen o de Medicina, Uni e sidad Jaume I
b [email protected]
In ec ious Diseases
Lesson 14
Objec i es, lea ning
goal and con en s
Objec i e
To unde s and he p incipal mechanisms o
in ec ion in he immunocomp omised hos
To know he clinical p esen a ion o in ec ion in
he mos common immunode iciency s a es
Lea ning goal
To de elop enough skills o ecognize and
p ope ly manage he p incipal in ec ions
ela ed o immunode iciency s a es, in he
mos p e alen clinical scena ios
Con en s
•The immunocomp omised hos : gene al concep s
•Pa hogenesis and mic obiology o in ec ion in pa ien s wi h…
•…neu openia and mucosi is
•…cell-media ed immunode iciency
•…wi h mixed de ici s ound in bone ma ow ansplan a ion
•Managemen o in ec ion in pa ien s wi h…
•…neu openia and mucosi is
•…cell-media ed immunode iciency
•In ec ions ela ed o splenec omy
•In ec ions ela ed o immunosupp essi e agen s and immune
modula o s used in in lamma o y diseases
•Key messages
•Fu he eading

The
immunocomp omised
hos : gene al concep s
Gene al causes o immunode iciency
•T ea men o leukemia, lymphoma, o solid umo s wi h:
•Chemo he apy
•Bone ma ow ansplan (including s em cell ansplan ), o
solid o gan ansplan
•Splenec omy
•T ea men wi h immunosupp essi e agen s and immune
modula o s o in lamma o y diso de s
•HIV in ec ion
•Gene ic, mainly o pedia ic in e es
Gene al causes o immunode iciency
•T ea men o leukemia, lymphoma, o solid umo s wi h:
•Chemo he apy
•Bone ma ow ansplan (including s em cell ansplan ), o
solid o gan ansplan
•Splenec omy
•T ea men wi h immunosupp essi e agen s and immune
modula o s o in lamma o y diso de s
•HIV in ec ion
•Gene ic, mainly o pedia ic in e es
Wisko -Ald ich synd ome:
•Eczema
•Th ombocy openia
•Recu en in ec ions
Pa hogenesis and
mic obiology o in ec ion
in pa ien s wi h
neu openia and mucosi is

In ec ing o ganisms
•In mos cases hose ound in:
•Skin (coagulase-nega i e s aphylococci and S. au eus)
•O al ca i y (S ep ococcus i idans and anae obes)
•Gas oin es inal ac (g am nega i e ods and anae obes)
•Some imes hose in oduced by con amina ion om
en i onmen , o example in inges ed ood
•Gene ally bac e ia and ungi
Bac e ia: g am-posi i e pa hogens
•The mos equen cause o in ec ion in neu openic pa ien s
•They usually o igina e in ascula ca he e o o he de ices
•Incidence has ↑ in ecen yea s, p obably as a consequence o
•Use o long-las ing indwelling enous ca he e s
•O e use o luo oquinolones
•Mainly:
•Coagulase-nega i e s aphylococci
•S aphylococcus au eus
•S ep ococcus i idans
•En e ococci
•Co ynebac e ium spp.
Bac e ia: g am-nega i e pa hogens
•Second in equency
•They usually o igina e om he gas oin es inal ac
•Polymic obial some imes
•Mainly
•Esche ichia coli
•Klebsiella species
•Pseudomonas ae uginosa
•Less commonly, En e obac e spp., P o eus spp., Acine obac e
spp., S eno ophomonas spp., and Ci obac e spp.
Bac e ia: anae obes
•Despi e hei p esence in la ge numbe s in he
gas oin es inal ac , anae obic g am-nega i e ods
such as Bac e oides spp. a e no equen causes o
bac e emia in neu openic pa ien s
•Occasionally seen in associa ion wi h se e e mucosi is
Fungi
•Gene ally a e 7 days o eb ile neu openia, when an ibio ics ha e
↓ bac e ial lo a, so “supe in ec ions”
•I pa ien has ecei ed an ibio ics ecen ly and ungal coloniza ion
in he gu is high, hey may p oduce in ec ion ea lie
•Some ungi a e acqui ed by inhala ion, and become symp oma ic
la e , a e hey ha e mul iplied and in aded lung pa enchyma and
blood essels, hus appea ing a supe in ec ion
•Candida spp. (albicans, opicalis, k usei, glab a a, and o he s),
occasionally Aspe gillus spp. and a ely Muco spp o o he

Pa hogenesis and
mic obiology o in ec ion in
pa ien s wi h cell-media ed
immunode iciency
Causes o cell-media ed
immunode iciency
•P e alence o in ec ions ela ed o supp ession o T
lymphocy e unc ion is p og essi ely inc easing
•Those in ec ions a ec :
•Pa ien s wi h au oimmune disease, ecei ing cy okine
an agonis s: co icos e oids →new cy okine an agonis s
•O gan ansplan ecipien s, ecei ing agen s di ec ed
agains T lymphocy es
Pos - ansplan in ec ions occu ing
du ing he i s pos ope a i e mon h - I
•The same hospi al-acqui ed pa hogens as o he hos s
•G am-nega i e bacilli such as P. ae uginosa, e c.
•G am-posi i e cocci, such as ancomycin- esis an
en e ococci and me hicillin- esis an S. au eus
•Fungi, such as Aspe gillus spp. and azole- esis an
Candida spp.
•Clos idium di icile
Pos - ansplan in ec ions occu ing
du ing he i s pos ope a i e mon h - II
•Be o e o gans a e ha es ed, adequa e he apy is
p o ided, bu bac e ia can su i e in a ascula
aneu ysm o o he p o ec ed si es
•In ec ions ansmi ed by he dono o gan: S. au eus o
pneumococci o g am-nega i e ods
•Asymp oma ic low-g ade in ec ion in he dono ha
becomes appa en only when he o gan is ansplan ed;
examples: Wes Nile i us, lymphocy ic cho iomeningi is
i us, abies, leishmaniasis, and Chagas disease
C yp ococcus neo o mans pneumonia

In asi e pulmona y
aspe gillosis: halo sign (A)
and ai -c escen sign (B) a e
eco e y o neu openia
Pos - ansplan in ec ions occu ing one o six
mon hs a e ansplan a ion: i uses - I
•Vi uses ha a e la en in he body o he ecipien
•In ec ions wi h new i uses, h ough:
•T ans usion
•T ansplan ed o gan
Pos - ansplan in ec ions occu ing one o six
mon hs a e ansplan a ion: i uses -II
•Cy omegalo i us (CMV) he mos common, eac i a ed o
acqui ed; isk o in ec ion depends on an ibody s a us:
•Recipien -, dono + →high isk
•Recipien +, dono - →in e media e isk
•Recipien -, dono - →lowes isk
•Gene al symp oms, gas e oen e i is, and e ini is
•Tes s o diagnosis and moni o esponse o he apy in CMV
in ec ion:
•An igen es , co ela es wi h ac i e eplica ion
•PCR es , can de ec la en and ac i e in ec ion (high copy
numbe indica e ac i e in asi e in ec ion)
Cy omegalo i us e ini is
Pos - ansplan in ec ions occu ing one o six
mon hs a e ansplan a ion: i uses -III
•Eps ein-Ba ac i ely eplica es in 20-30 % o ansplan
ecipien s and can cause a lymphop oli e a i e
synd ome
•O he i al in ec ions:
•He pes simplex
•He pes zos e
•Human he pes i us-6
•Hepa i is B and C i uses

Pos - ansplan in ec ions occu ing one o six
mon hs a e ansplan a ion: o he pa hogens
•Pneumocys is ji o eci, pneumonia, ha should be
p e en ed wi h ime hop im-sul ame hoxazole du ing
he pe iod o peak immunosupp ession
•Toxoplasmosis, b ain abscesses and encephali is
•Dissemina ed s ongyloidiasis, o en a al, pa ien s wi h
unexplained eosinophilia should unde go s ool sampling
o exclude S ongyloides s e co alis be o e ansplan
Pa hogenesis and
mic obiology o in ec ion in
pa ien s wi h mixed de ici s
ound in bone ma ow
ansplan a ion
Phases o immunosupp ession - I
•I (days 0–30 pos - ansplan ), neu openic
•II (days 30-100 pos - ansplan ), p ima ily comp omised
cell-media ed immuni y, in ec ion wi h CMV
pa icula ly common; acu e g a - e sus-hos disease
also equen
Phases o immunosupp ession - II
•III (beyond day 100 pos - ansplan ), de ec s in cell-media ed
immuni y, plus dep essed humo al immuni y om:
•Func ional hyposplenism a e o al body i adia ion
•Ch onic GVHD * → dys unc ional B lymphocy es →
•→↓ p oduc ion o IgG2
•→ ↓ p oduc ion o speci ic pneumococcal an ibodies
* GVHD = g a -
e sus-hos disease
** In ec ions wi h encapsula ed bac e ia:
-Haemophilus in luenzae
-S ep ococcus pneumoniae
**
Choosing an ibio ics - I
•Mono he apy and dual he apy compa able esul s
•Vancomycin:
•Should no be ou inely adminis e ed as empi ic he apy
•Should be added i :
•In a ascula de ice in ec ion is suspec ed
•Coloniza ion wi h me hicillin- esis an S. au eus
•Blood cul u es g ow g am-posi i e cocci be o e inal iden i ica ion and
sensi i i y es ing
•I he pa ien is hypo ensi e o has o he e idence o ca dio ascula
comp omise

Choosing an ibio ics - II
•Linezolid equi alen o ancomycin in he neu openic
pa ien , howe e , wi h selec i e se o onin- eup ake
inhibi o s →se e e myelosupp ession in bone ma ow
ansplan pa ien s
•Blood cul u es may guide adjus men s in ea men
•B oad-spec um co e age should be gene ally main ained
a leas 7 days o un il he neu ophil > 500/mm3, o
p e en b eak h ough bac e emia
Choosing an ibio ics - III
•I e e pe sis s a e 3-5 days, ee alua ion is needed:
•Comple e physical examina ion epea ed
•Addi ional imaging, such as compu ed omog aphy o he ches
•B onchoscopy i lung in il a es
•Cul u es should be epea ed
•I e e pe sis s o mo e han 5 days, and…
•… he pa ien is imp o ing his condi ion and neu ophil coun
is expec ed o eco e quickly →con inue he same an ibio ics
•…sepsis pe sis s o wo sens →an ibio ic changed and
an i ungal added
Du a ion o an ibio ic ea men - I
•A eb ile pa ien a e 3–5 days o he apy, and neu ophil
coun has been > 500/mm3 o 2 days →discon inued
a e he pa ien has been a eb ile o 48 hou s
•A eb ile o 5 o 7 days, neu ophil coun < 500/mm3,
ini ially low isk and no cu en ly sep ic → can be
discon inued
•A eb ile, ini ially a high isk, neu ophil coun < 100/mm3,
o he pa ien has mucosi is o is clinically uns able →
con inued
Du a ion o an ibio ic ea men - I
•Pe sis en ly eb ile and neu ophil coun is > 500/mm3 o
4-5 days → can be discon inued bu pa ien should be
eassessed
•Pe sis en ly eb ile and neu ophil coun < 500/mm3, →
con inued o 2 weeks, wi h eassessmen a ha ime;
hen, i no in ec ion is e iden and he pa ien is clinically
s able → discon inued
P e en ion
•An i i al he apy is no indica ed in neu openic pa ien s
unless a speci ic i al in ec ion is documen ed
•Fluo oquinolone p ophylaxis indica ed in high- isk pa ien s
who a e expec ed o ha e a p olonged du a ion o
p o ound neu openia, < 100 cells/mm3 o > 7 days,
despi e he conce n o de elopmen o widesp ead
an ibio ic esis ance

Managemen o in ec ions
in pa ien s wi h cell-
media ed
immunode iciency
Pa ien e alua ion - I
•Lis o o ganisms ha can cause in ec ion is so la ge ha
empi ic he apy is no ecommended unless…
•…a speci ic si e o in ec ion is iden i ied
•…a speci ic pa hogen is he mos likely cause
•Celluli is may ha e a nonbac e ial o igin
•Empi ic he apy may be gi en o cen al ca he e o u ina y
ac in ec ions, because he usual o ganisms con inue o
cause hese in ec ions
•Comple e clinical and social his o y equi ed o assess
communi y-acqui ed in ec ions
Pa ien e alua ion - II
•Li ing in ce ain geog aphic a eas p edisposes o speci ic
in ec ions ( eac i a ion o new in ec ion), such as
•His oplasmosis and coccidioidomycosis in he US
•Visce al leishmaniasis in Spain
•Ce ain si es o in ec ion do equi e u gen ac ion:
•Headache o o he cen al ne ous sys em complain →lumba
punc u e i no con aindica ed, as c yp ococcal o lis e ial
meningi is a e possible and equi e immedia e ea men
•Blood, u ine, and any suspicious si es should be cul u ed
Pa ien e alua ion - III
•Ce ain si es o in ec ion do equi e u gen ac ion (con d.):
•In lamed cen al line → ea men o g am-posi i e cocci
•Ches adiog aph abno mal o pa ien p oducing spu um →
g am, acid- as , sil e s aining and cul u e o spu um; i no
spu um p oduced, b onchoscopy e c. may be needed
In ec ions ela ed o
immunosupp essi e agen s
and immune modula o s
used in in lamma o y
diseases

Co icos e oids
•Dec easing unc ion and/o numbe s o :
•Neu ophils
•Lymphocy es, bo h B cells and T cells
•Monocy es and mac ophages
•Ana omical ba ie unc ion o he skin
•Risk o in ec ion ela ed o dose and he du a ion o he apy
•Mos common pa hogens:
•Pyogenic bac e ia
•In acellula pa hogens such as Lis e ia spp., ungi, and he pes
i uses
Biologic he apy
•Inc easingly used o ea many sys emic in lamma o y
condi ions
•An ibodies o o he pep ides ha :
•Inhibi in lamma o y cy okine signaling
•Inhibi T-cell ac i a ion
•Deple e B-cells
•Inc eased isk o :
•Respi a o y, in es inal and o he common in ec ions
•A ypical and oppo unis ic in ec ions by Mycobac e ium
ube culosis, he pes zos e i us, Legionella spp., and Lis e ia spp.
Key messages
To emembe …
In he immunode icien pa ien , high-g ade li e- h ea ening
in ec ion is common, he e o e apid e alua ion and empi ic
an ibio ics a e equen ly equi ed in his popula ion
Clinical p esen a ions o hese in ec ions is p o ean, so a
high index o suspicion mus be kep when a ending he
immunode icien pa ien
Fu he eading

Used e e ences
Sou hwick F. In ec ious disease. A clinical sho cou se.
3 d Edi ion. New Yo k: McG aw-Hill, 2014. Chap e 15.
Tolan RT J , MD e al. In ec ions in he
Immunocomp omised Hos . A ailable a :
h p://emedicine.medscape.com/a icle/973120-
o e iew#aw2aab6b3.
P epa ing he exam
•Sou hwick F. In ec ious disease. A clinical sho
cou se. 3 d Edi ion. New Yo k: McG aw-Hill, 2014.
Chap e 15.
•These slides !!!.