14. Infections in the immunocompromised host

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 !!!.