Transcript Nocardia _Actinomycosis.ppt

Infect topic
Nocardia &
Actinomycosis
Nattaya Mangkalapiwat
28 April 2008
Nocardia :History
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Edmond Nocard,
1888
Aerobic actinomycete
from cattle with
bovine farcy
Nocardia
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Genus : aerobic actinomycetes
G+ branching filamentous bacteria
Subgroup: aerobic nocardiform actinomycetes
-Mycobacterium
-Corynebacterium
-Nocardia
-Rhodococcus
-Gordona
-Tsukamurella
Nocardia
At least 13 species : cause human infection
 7most important
 1. Nocardia asteroides complex
:80% of noncutaneous dz.
:most systemic & CNS nocardiosis ***
2. Nocardia farcinica :less common,more virulent
:more antibiotic-resistant member
3.Nocardia nova
4.Nocardia brasiliensis:
skin,cutaneous,lymphocutaneous
5.Nocardia pseudobrasiliensis:systemic infections, CNS
6.Nocardia otitidiscaviarum
7.Nocardia transvalensis
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Nocardia :ECOLOGY& EPIDEMIOLOGY
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Ubiquitous environmental saphrophyte
Soil, organic matter,water
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Tropical and subtropical regions
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:Mexico, Central and South America,Africa and India
Nocardia :ECOLOGY& EPIDEMIOLOGY
Nearly all cases :sporadic
 Human-to-human
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Animal-to-human not documented
 Outbreaks : Contamination of the
hospital environment, solutions,drug
injection equipment.
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Nocardia :ECOLOGY& EPIDEMIOLOGY
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Transmission
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The risk of pulmonary or
disseminated disease
*deficient cell-mediated *
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Inhalation
Skin
-Alcoholism
-Diabetes
-Lymphoma
-Transplantation
-Glucocorticoid therapy
-AIDS CD4+ < 250
Nocardia : PATHOLOGY
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Acute pyogenic inflammatory reaction.
Branching, beaded, filamentous bacteria
G/S from a nocardial lung abscess
G/S from nocardial pneumonia
Nocardia :PATHOGENESIS
Neutralization of oxidants
 Prevention of phagosome-lysosome fusion
 Prevention of phagosome acidification.
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Mycolic acid polymers:ass.with virulence
CLINICAL MANIFESTATIONS
: 4 main form
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Lymphocutaneous syndrome
Pulmonary :Pneumonia
CNS : Brain abscess
Disseminated disease
CNS
Eyes (particularly the retinaKeratitis),
Skin& subcutaneous
Kidneys,
Joints, bone
Heart
Lymphocutaneous syndrome
-Cellulitis
-Lymphocutaneous syndrome
-Actinomycetoma
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Ubiquitous in soil inoculation injuries,
Insect and animal bites contaminated abrasions
N. brasiliensis : most common
N. asteroides : self-limited
Because initial response Rx as staphylococcus
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underdiagnosed Mycetoma
Days to months ,typical:distal limb
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Nocardial actinomycetoma swelling, multiple sinus tracts,
Pulmonary disease
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Pneumonia
Subacute(more acute in immunosuppressed)
Cough**
Small amounts of thick, purulent sputum
Fever, anorexia, weight loss, malaise
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Endobronchial inflammatory mass
Lung abscess
Cavitary disease
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Inadequate therapy Progressive fibrotic diseaseฆ
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Cerebral imaging,should be performed in all
cases of pulmonary and disseminated
nocardiosis
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Nocardial pneumonia. Discrete nodular in midlung on both sides
CT scan (A),CXR (B) from : multiple abscesses : Nocardia farcinica
CNS : Brain abscess
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Insidious presentations : mistaken for neoplasia !!!
Granulomatous , abscesses
Cerebral cortex, basal ganglia and midbrain***
Less commonly: spinal cord or meninges.
Brain tissue diagnosis in pulmonary nocardiosis
: not necessary
However,
cerebral biopsy:considered early in immunocompromised
brain abscess ; Nocardia farcinica
Nocardial abscess :rt. occipital lobe
LABORATORY DIAGNOSIS
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Gram-positive, beaded, branching filaments
usually weak acid fast+ve .
Standard blood culture :48 hrs to several wks, but
typical = 3 to 5 days
Colonization of sputum
:underlying pulmonary dz +
not receiving steroid therapy no specific therapy
Susceptibility testing
-Deep-seated /disseminated dz. fail initial therapy
-Relapse after therapy
-Alternatives to sulfonamides are being considered
MANAGEMENT
:Medication
Sulfonamides : the mainstay of therapy
treatment of choice :N. brasiliensis
N. asteroides complex
N. transvalensis.
 severely ill patients, CNS /disseminated/
immunosuppressed patients =/> 2 drugs
 Amikacin and Carbapenem or
3rd generation cephalosporin.
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MANAGEMENT
:Medication
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TMP-SMX :currently preferred
:drugs in serum:CSF = 1:20
:high MICs good therapeutic responses
-General:5-10 mg/kgTMP & 25-50 mg/kgSMX divide2- 4times
-Cerebral abscesses,severe,disseminated,AIDS
:15 mg/kg TMP and 75 mg/kg SMX)
-Cutaneous infection: 5 mg/kg/day (TMP) + DB
Hypersensitivity reactions :Desensitization
MANAGEMENT
Medication:alternative therapeutic drugs
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Failed sulfonamide Rx: N. otitidiscaviarum
Intolerant : hypersensitivity,GI toxicity, myelotoxicity)
Parenteral : Imipenem & amikacin
: Meropenem
: 3rd-gen cephalosporins Ceftriaxone, cefotaxime
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Oral:Amoxicillin clavulanate
:Minocycline(100–200 mg twice daily)
:Linezolid :new oxazolidinone ;effective orally
(bioavailability~100%), good CSF penetration
MANAGEMENT
Surgical drainage: depend on site
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Extraneural aspirate,drainage, excision
Brain abscesses
1) Accessible and relatively large AND
2.1) Lesions progress within 2 wks or
2.2) No reduction in abscess size within a month.
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Duration of Therapy
Clinical improvement: most 7 -10 days
Parenteral 3 to 6 wks oral regimen
Primary cutaneous infection :1-3 mo.
Nonimmunosuppressed
-Pulmonary /systemic nocardiosis: at least 6 mo
-CNS involvement : for 12 months
 Immunocompromised
HIV-negative
immunosuppressed
:12 mo or longer if there
are intercurrent
increases in
immunosuppression
AIDS
: at least 12 mo. +
low-dose maintenance
(long life)
Outcome of therapy
Cure rates
-skin or soft tissue : almost 100%
-pleuropulmonary disease : 90%
-disseminated infection : 63%
-brain abscess : 50%
 Mortality
-brain abscesses :31%
-multiple abscesses :41%
-immunocompromised patients :55%
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Actinomycosis
Genus : Actinomyces
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Slowly progressive infection
Colonize : mouth, colon, vagina
Infection : mucosal disruption
In vivo : Grains / Sulfur granules
The most misdiagnosed disease
3 clinical presentations
1.chronicity, progress across tissue boundaries,
masslike
2. develop sinus tract, resolve and recur
3. refractory/relapsing after a short course therapy
Etiologic Agents
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A. israelii***
A. naeslundii/viscosus
A. odontolyticus
A. viscosus
A. meyeri
A. gerencseriae
pelvic disease ass. IUCDs & “lumpy jaw”
16S rRNA gene sequencing led to identification of an
ever-expanding list of Actinomyces spp
Concomitant bacteria
Staphylococcus / Streptococcus
 Enterobacteriaceae
 Actinobacillus comitans
 Eikenella corrodens
HACEK
 Fusobacterium
 Bacteroides
 Capnocytophaga (Dog bite)
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Epidemiology
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Members of oral, GI, and genital flora
Never been cultured from nature
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No document of person-to-person transmission
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The peak incidence : mid-decades
 Male > Female
(poorer dental hygiene & oral trauma )
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Pathogenesis & Pathology
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Disruption of the mucosal barrier.
Spreads : slow progressive manner, ignoring tissue planes.
Hallmark : chronic, indolent phase (single /multiple indurations)
Wooden – fibrotic wall
As mature lesion : soft , fluctuant and suppurates centrally.
The fibrous walls :wooden
 absence of suppuration: neoplasm???
 Sinus tracts : spontaneously close and re-form
skin  adjacent organs(bone)
Pathology :Central necrosis consisting of neutrophils + sulfur granules.
Actinomycosis
G/S :Variable cellular morphology, ranging from diphtheroidal
to coccoid filaments มักพบ sulfur granule จากการย้ อม gram ได้ และย้ อมไม่
ติด mAFB
Actinomycosis
Sulfur granules
G/S :sulfur granule
Risk Factors
Foreign bodies : IUCDs
 Abnormal host defense : HIV
 Post transplantation
 Radio-Chemotherapy
 Ulcerative mucosal infection: HSV/CMV
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Clinical Manifestations
Oral-Cervicofacial Disease
 Thoracic Disease
 Abdominal Disease
 Pelvic Disease
 Central Nervous System Disease
 Musculoskeletal & Soft tissue infection
 Disseminated Disease
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Oral-Cervicofacial Disease
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Most frequently site
Soft tissue swelling / mass/ abscess : mistaken
for a neoplasm
Most common site : Angle of jaws
Dx: mass lesion/relapsing infection in head &neck
Complication :-Otitis, sinusitis, and canaliculitis
:-extend to cranium,c- spine, thorax
Most common site : Angle of jaws
Thoracic Disease
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Chest pain, fever, and weight loss ***.
Cavitary disease / hilar adenopathy
>50% pleural thickening / effusion / empyema
pulmonary nodules or endobronchial lesions :
Rare
CT scan:central low attenuation + ringlike rim
enhancement
Complication:
- Mediastinal infection***
: uncommon, usually from thoracic extension
- Breast disease
- Primary Endocarditis
A:Chest
wall
mass
D:Purulent
pleural fluid
(aspiration)
B and C: Chest x-ray + CTscan :pulmonary infiltrate, pleural effusion,
pleural and chest wall extension (arrow).
Abdominal Disease(1)
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Usually pass from inciting event
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Appendicitis
Diverticulitis
PUD
Foreign bodies
Bowel surgery
ascension from IUCD-associated pelvic disease
Abscess, mass, mixed lesion : mistaken—tumor???
CT: heterogeneous enhance+ thick adjacent bowel.
Sinus tracts  abd. wall / perianal/ between bowel
(Mimic inflammatory bowel disease)
Clue : Recurrent dz /wound or fistula : fails to heal
Imaging and percutaneous techniques
:Therapeutic diagnosis
A.CTscan:multiple hepatic abscesses and small splenic lesion extend out side liver.
Inset: Gram's stain of abscess
B.Subsequent formation of a sinus tract.
Abdominal Disease(2)
KUB Disease
 All levels: can be infected
- pyelonephritis
- renal and perinephric abscess
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 Bladder involvement:usually due to pelvic disease
 urine : stains and cultures
Pelvic Disease
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Risk:IUD in place >1yr-months after removed
S&S: Typically indolent
fever, wt loss, abd pain,
abnormal vaginal bleeding or discharge
Endometritis  masses/tuboovarian abscess
delayed Rxfrozen pelvis
Removed as early as possible :but not removal
of the IUCD unless a suitable contraceptive
An IUCD encased by endometrial fibrosis (solid arrowhead)
paraendometrial fibrosis (open arrow)
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CNS Disease
Rare
Single/multiple abscess**
Irregular nodular Rimenhancing thick wall
Meningitis / Epidural /
Subdural space infection
Cavernous sinus syndrome
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MS & Soft tissue
Associated trauma:Fx
Adjacent soft tissue  Bone
Periostitis / Osteomyelitis/
Cutaneous sinus tracts** .
 Disseminated Disease
:Lung* / Liver*
:multiple nodules ~ CA metas
but, indolent
MS & Soft tissue: Cutaneous sinus tracts
Diagnosis
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Avoid unnecessary surgery
Aspirations & Biopsy
Material for C/S + microscopic identification
Sulfur granules : In vivo matrix of bacterial + CaPO4 + host debris
Grossly identified from sinus tract
DDx : Mycetoma / Botryomycosis
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C/S isolated in 5-7 d but 2-4 wk. if previous ATB
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16S rRNA gene amplification and sequencing
: not routinely used
Treatment
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Can cure with medical Rx alone even in extensive dz
Medical Management
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High doses and prolonged period
1. serious infections and bulky disease
Intravenous PGS 18-24 mU /day : 2-6 wk.
then Oral Penicillin / Amoxycillin
: 6-12 mo.
2.Less extensive disease, e.g. oral-cervicofacial
: cured with shorter course.
Combined medical-surgical therapy
initial attempt cure with medical Rx alone, CT and MRI : monitor
 Critical organs : Reproductive /CNS e.g. epidural space
 Fails suitable medical therapy
Thank you for
your attention
Reference
-Mandell, Douglas, and Bennett’s
Principles and Practice of Infectious Diseases,6TH Edition
-Harrison's PRINCIPLES OF INTERNAL MEDICINE,17th Edition
-CLINICAL MICROBIOLOGY REVIEWS, Apr. 2006, p. 259–282