Download Infeksjoner hos immunsupprimerte.

Infections in the
immunocompromised patient.
Inger Karin Lægreid
Avd for nyresykdommer
St.Olavs Hospital
Desember 2011
Immunocompromised patients:
• Organtransplanted – immunosuppressive
medications
• Cancerpatients – cytotoxic drugs + xray
• Systemic illnesses – ex. Vasculitis,
Lupus, RA
- immunosuppressive medications +
cytotoxic drugs
• HIV pos / AIDS
Risk factors for infections
• 1. High dosis of
immunosuppressive
medications
- Because of treatment
failure or rejection
- Repeating treatments
- Cumulative dosis
• 2.Leucopenia
- Induced by
a.medications:
- Most often cytotoxic
drugs and
- azathioprine(Imurel),
mycophenalate (Cell
Cept or Myfortic)
- or b.virus: CMV
Mecanisme of defense
• Granulocytes – ability to granulocytosis (BM), important with
numbers and function
• Cellulær immunity – remove intracellulære patogens and virusinfected cells
– Cytotoxic effector cells and spes. T cells
• Humoral immunity – remove extra-cellulare bacteria, B cells and
Ag and plasmacells – Ab
• Skin-barriere broken: wound, venflone, catheter
– entry for bacteria og virus
• Mucous membranes (mouth, GI tractus, urinary tract)
Types of agens
•
-
Virus:
Cytomegalo CMV
Epstein Barr EBV
Varicella zoster VZV
HepatitisB HBV
Hepatitis C HCV
Herpesvirus HHV 6-7
Polyomavirus
Influenza A, pandemic
• Bacteria:
• Gram neg
– Pseudomonas, E.coli,
Klebsiella, enterobacti
• Gram pos cocci
– staf.cocci, streptococci
- Legionella sp.
- Listeria sp
- Tbc
Cont. types of agens
•
•
-
Fungi:
Candida
Cryptococcus
Mucor
Aspergillus
• Protozoer:
• Pneumocystis jirovecii
• Toxoplasmose sp.A
Causes of infection, fever and
neutropenia
• Fever without known cause (drugfever)
• Clinically def. infection (- pos. culture)
• Bacteremia (pos.blodkultur)
• - Gram neg
10%
– Gram pos cocci
– Mixed
– Polymicrobial
19%
1%
6%
• Non bacteremia
–
–
–
–
Gram neg
Gram pos cocci
Mixed
Polymikrobial
39%
17%
35%
9%
2%
3%
1%
3%
Am. cancerpopulasjon
Kasuistikk
•
•
•
•
•
Mann f.1944
Ulcerøs colitt
Nyretransplantert 2002
Sarkoidose
Står på trippel immunsuppresjon:
– Sandimmun, Cellsept og Prednisolon
• Inntil det aktuelle: god almentilstand,
kreatinin 160.
Kasuistikk
• Feber, tørrhoste, slapphet frå 3.12
• Opps fastlege , får Ciproxin
• Ny kontakt pga ingen effekt/ forverring av
symptomer → innlegges.
• Ved innk 10.12: feber, hoste, tungpust,
CRP:130, kreatinin 204 (eGFR 28 ml/min)
• Rtg.thoraks: småflekka infiltrat bilat, mest
utbredt perihilært. Atypisk pneumoni??
• Starter Rocephalin (cephalosporin)
Kasuistikk
• Trass i Rocephalin – tilstanden forverres,
økende dyspnoe, stigende CRP
• Utifrå klinikk, CT thoraks og rtg.thorax funn –
atypisk pneumoni: ?? Pneumocystis Jirovecii
• Planlagt bronkoskopi med BAL – pas for dårlig.
• Starter Trim Sulfa (TMS) på mistanke, red dose
pga nyresvikt
• Forverring → Respirator
• Bronkoskopi med BAL: Pneumoc J → høg dose
TMS
Pneumocystis jirovecii pneumonia
• Typisk røntgenfunn
• Bilat hilusnære
småflekka
fortetninger
Kasuistikk
•
•
•
•
•
Uendra resp.status over fleire dager
Terapisvikt pga initial låg TMS dose?
Høg dose → økende nyresvikt + rhabdomyolyse
Red TMS, må seponeres.
04.01.11: fortsatt på respirator, betring i nyrefunksjon
(kreat 125), CRP 102, svært usikker prognose.
• Får spontan pneumothorax – vanskelig å ventilere
• Har ARDS, lungefibrose.
• Avslutter respiratorbehandling 5.1 –pas sovner inn
samme dag
Pneumocystis jirovecii
• Incidens hos organ tranplanterte: 5 – 15%
• Reservoir: barn, symp og asympt
immunkomprimerte pasienter
• Luftsmitte via mennesker – opptrer ofte i
”cluster”
• Riskofaktorer: alder, CMV infeksjoner,
rejeksjoner, ↓ lymfocytter
• Obs. coinfection (Herpesvirus)
Listeria monocytogenes
• Listeria sepsis in adults nonpregnant:
– Most are immunocompromised or elderly
– Symptoms: fever and chills
– Septic shock
– Seeding of the brain and/or meninges
– Meningoencephalitis or cerebritis
– Diagnosis: culture of blood and cerebrospinal
fluid (CSF)
– Cerebral MRI
Listeria M
• Listeria RH autum 2007:
– Kantine serverte upasteurisert gårdsost
– 15 persons got the disease
– 5 died, 3 immunocompromised and 2 unborn
childs(twins)
• Eng. studie 10 års materiale (1999 – 2009):
– Cancerpas har 5X større risiko for Listeria M
– Hematologisk cancer mest utsatt (17x)
– I tillegg til cancer: lever, nyresykdommer, bindevevssykdommer(Lupus) og inflammatoriske sykdommer
(Crohns sykdom)
Piers Mook et al; Em Inf Dis 2011
Jan
Listeria M
• Treatment:
– Ampicillin
– Gentamycin ( in combination the first days)
• Prognosis:
– Total mortality: 25%
– Higher by menigitis and sepsis
Legionella
• Pneumonia – predominantly clinical
manifestation
• Cough – initially mild
• Chest pain
• High fever > 39
• Gastrointestinal symptoms
• Headache
Legionella
• Diagnosis:
– Xray of lungs: patchy infiltrates
– Culture of blood ( specific medium)
– BAL
– Direct immunfluorescens
– Antigen- test in urine
Legionella
•Treatment:
–Erythromycin
–In combination with ciprofloxacin or
rifampicin
•Prognosis:
•Mortality: 5 – 30%
Cryptococcus
• Disseminated fungi
infection in liver
transplanted patient
• Six cutane lesions like
this one
• Biopsi and serum
antigen test –
cryptococcus
• ”fleshy” border with
centrale umbilication.
Invasive candidaisis
• Tender,
erythematøse
nodulare lesions in
neutropen pasient
with leucemia
after induction
chemotherapy.
Aspergillus
• Neutropen patient stamcelle treatment
• Multiple necrotic
lesions
• Biopsi showed
infarctions caused by
Aspergillus
Herpes Zoster
• 1. primær infeksjon: vannkopper
• 2. Herpes Zoster – reaktivering av endogent
latente varizella zoster virus i sensoriske
ganglier
– Følger dermatomer
• 75% har prodromale smerter før utslettet
• Starter ofte med små røde flekker → blemmer
• Varizella zoster pneumonitt – alvorlig prognose
Herpes Zoster
• Important with early
diagnosis and
treatment
• Zovirax/ Valtrex
early shortens the
duration of the
disease and reduces
postherpetic pain
• ”common” by organtransplanted (35%
av BM tx)
Herpes Zoster
• HIV pos.
• Hemorrhagic vesicles
• Pustles
• = seint stadium
• Obs. sekundær
infeksjon
Herpes Zoster
• Male b.1960.Refugee from Vietnam
• Cystic kidney disease,- renal transplanted april 98
• Rejection – Solumedrole + Thymoglobuline
• Creatinine at discharge from RH july 98 : 320
• Aug -98: pain at left eye and ear.
Opthalmoscopy: Shows vesicles, diagnosed as
HZ optalmicus, gets general eyedrops.
Herpes Zoster II
• 1 week later- hospitalizes with widespread
Herpes Zoster Oftalmicus with affection of
left part of the face incl. left ear
• Zovirax (in reduced dosis because of
reduced renal function)
• Discharged from hospital after 2 weeks.
Herpes Zoster III
•
•
•
•
•
•
•
1 week later – new hosp : fever, dyspnoe og cough
Blood tests: High CRP og leucopenia
Xray lungs: diffuse infiltrate – agents?
Broncoskopi with BAL: stafylococcus aureus + CMV
Sepsis- multiorgan failure – respirator – dialysis
Sep 2 of 3 immunosuppressive medications
Survives with a rel.good outcome
• status nov 2007:
-- creat 130, chronic pain in left part of face, got perforation
of tympanic membrane in -98, relapsing otitis later,
planned operative treatment (myringoplastic surgery)
Herpes Zoster ophtalmicus
• Rammer Trigeminus
dermatom
• Kan føre til corneal
affeksjon og føre til
synstap
Cytomegalovirus CMV
• Member of B-herpes family
• big ds DNA virus
. Transmitted by :
-contact (sexually, nursing)
- blood / organ (CMV pos til CMV neg)
- mother to child (in utero, perinatal, lactation)
• Asymptomatic primary infection, followed by lifelong latency, can be
reactivated
• Age related increase in seroprevalence:
- by age 20: - 40%
-by age 30: - 50%
-by age 50: - 65%
-by age 80: - 90%
CMV
• The most common viral infection in organ-transplanted
• Lungs>heart>liver>pancreas>kidney
”CMV- syndrome” (viremi):
- fever, malaise, ( ”influenza-symptoms”), leucopenia,
trombocytopenia, hepatic aminotransferase elevations
Tissue – invasive CMV:
- GI – duodenitis, gastritis, colitis, ulcus
- Lungs – pneumonitis
- Transplantat – nephritis, hepatitis, pneumonitis
- Eye - retinitis
CMV retinitis
• CMV infenction in
patient with AIDS
• Retinitis with
hemorhagies og
papille-oedema
• In the periphery– can
be difficult to localise
with ophtalmoscopi
Epstein Barr virus EBV
• 20-30% of organtransplanted has active
replication of EBV
• 80% of these have got antilymfocytt- antibodies
(because of serious rejection).
• Cyclosporine A (Sandimmun), tacrolimus
(Prograf) + Antilymfocytt-antibodies reactivate
latent EBV infection
• EBV can give mononucleosis
• Important: the role of EBV in the pathogenesis
of development of post-tx lymfoproliferative
disease.
EBV II
• B celle lymfoproliferativ process – can change
from benign polyclonale process to a highly
malignant monoclonal lymphoma which is
resistante to treatment.
• Post-tx disease – extranodale – brain,
bonemarrow, organtransplant, GI-tractus and
liver
• Important to reduce or take away
immunsuppressive medications
• Most important that the patient survives, on the
behalf of the transplanted organ.
Epstein Barr virus
Primary infection to chronic infection
• EBV infect resting
Bcells or epitelial cells
• EBV-infected cells are
kept in check by
killercells and
cytotoxic T-cells
• Latente infected
memory B cells
(EBNA) can be
reactivated and give
chronic EBV infection
EBV lymfoproliferativ sjukdom
• A. Cerebral MRImultiple tumornodules
• B. Biopsi from
perirenal tissue:
immunoblastic
lymfoma
• C. EBV nuclear
antigen - EBNA
Polyoma virus PV
• Ds DNA virus, two types ass. with humane disease:
• BK virus
• JK virus
• 60-80% av immuncompetente adults are seropos for PV
• Renal transplanted:
--PV-BK can give acute tubulo-intestitiell nephritis, ureter
stenosis, hemorragic cystitis, serious transplantat
dysfunction
--PV-JK reactivation can give progressive multifokal
leukoencephalopati
Polyomavirus
• Diagnosis:
---cells who contains virale inclutionsbodies
(”decoy cells”) in urine or biopsi of the
transplant
• Treatment:
---- reduction in immunsuppression
--- cidofovir – seldom in use, highly
nephrotoksic
Polyoma-virus
• Infecting many types of
cells, including kidney,
brain, liver, retina, lungs,
blood, lymfatic, heart,
muskulature og vasculare
endoteliale cells
• Virale particles binds to a
spesific celle-surface
reseptor and prod T
antigen early in the
infection cykel.
Genetic relationship among Human
and Swine influenza viruses 1918 2009
The Two Mechanisms whereby
Pandemic Influenza Originates.
1918 – H1N1 virus closely related to avian virus
adapted to replicate in humans
1957 and1968, reassortment events led to new viruses
that resulted in pandemic influenza.
1957 – Asian influenza
1968 – Hong Kong influenza
Future pandemic strains could arise through either
mechanism.
Influenza- virus
Infl.A H1N1 (svineinfluensa)
• Forekomst – alder og kjønn.
Influenza A (H1N1= svineflu)
• Status pr. 21.12.2009 in Norway:
– 900 000 deceased persons
– 1310 hospitalized
– 170 intensive care
• 71% < 30 years
– 29 dead
• 23 had other chronic diseases.
Vaccination – immunocomprimised
patients
• The use of immunosuppresive medication gives
reduced effect of vaccination.
• These patients is recommanded 2 vaccination
with 4 weeks interval.
• In periods with very high dosis of
immunosuppresive medication (i.e just after
renal tx, vaccination not recommanded, wait till
3-6 months after tx)
• Family members are recommanded vaccination
Treatment Influenza A
• Oseltamivir (Tamiflu) – capsules,recommended
to all age groups.
Reduced dosis at eGFR < 30,
Not to dialysis patients (eGFR< 10).
• Zanavimir (Relenza) –aerosol, recommended to
age groups > 5 years.
No reduction in dosis with renal failure.
Not recommended with serious lung disease.
Status A(H1N1) des-10/jan-11:
• Alv. utbrudd i England høst 2010
– Medio sept – medio des: 10 døde
– Unge personer, fleste i risikogruppe
– Medio des: 16 innl, fleste i intensivavd.
• Sverige: gutt 7 år døde, risikogr.
• Norge: 2 innl.; lite barn + mann i 60 åra
– Høg vaksinasjonsfrekvens i 2009/2010
– Mange hadde mild sjukdom, gir immunitet
– Antar få m alv sjukdom i Norge denne vinter.
Diagnosis – infection in
immunocomprimised patients?:
• Anamnese: progress of the disease? fever?
medication? Spesific symptoms? Pain? Cough?
Abdominalia? Rash?
• Clinical examination: all organs, spec. skin –
wounds? incl. mouth,
• Blood tests: Hb, trombocytes,leukocytes with
cellcounting or only granulocytes, CRP, or SR
renal function, liver function,
Cont. diagnosis
• Urine stix + culture
• Larynx
•
•
•
•
•
•
•
Virus-serologi
Bloodculture
CBF - cerebrospinal fluid microscopy and culture
Bronkoskopi – med lavage (BAL)
Secrete from wounds
Biopsi of affected organ.
OBS! catheter –
• Radiologic – chest, sinus, US, CT , MR
• OBS: sikre diagnostiske prøver før start av antibiotika!!
Principles for antimicrobielle
therapy
• Treatment of established clinically disease
• Prophylaxis – treat the entire patient-population
prophylactic, fex all renal-transplant pat. get
TMS as prophylaxis against Pneumocystis carini
in 6 months post-tx
• Preemptive therapy – treat subpopulations fex
renaltx with pos CMV test,before clinically
symptoms.
• Obs. Studier må vise stor gevinst for å vege opp
for risiko for resistensutvikling.
Anti-microbielle treatment
Fever and neutropenia ( neutrophile < 0.5
x10 9 cells /L):
(ex: nadirperiode etter tøffe cytostatika-kurer)
• Big risk for lifethreathening infections,
spec. gram.neg bacteria
• Start with: benzylpenicillin + gentamicin
• With clear abdominal symptoms:
piperacillin/ tazobactam (Tazocin)
• Dont hesitate – important with early start!!
Antifungal treatment
• After 3-5 days with neutropenia and fever
–the risk for invasive mycosis is 25-30%
• The most common: candidasis
• Treatment: fluconazol (Diflucan)
• Suspicious for aspergillus and notflucanozol- sensitive candidasis:
voriconazol (VFEND)
Antiviral treatment
• Herpes simplex – valgancyclovir(Valcyte)
-- acyclovir (Zovirax)
-- valacyclovir (Valtrex)
• CMV –gancyclovir ( Cymvene)
– valgancyclovir
• Herpes Zoster – acyclovir (Zovirax)
• Diagnostikk: PCR- test in blood
IF (immunofluorescens)
Biopsi = gold standard
Conclusions
• Immunocompromised pasients:
– More vulnerable for infections
– More often atypical infections, remember: virus,
fungi, tbc
– Can reacte different upon infections:
• Less fever
• Later signs on x-ray
– Obs neutropenia
– Obs medications
• EARLY DIAGNOSIS and SPESIFIC
TREATMENT is important for a good outcome!