Nocardia&Amp Actinomycosis

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    Nocardia&

    Actinomycosis

    Nattaya Mangkalapiwat

    28 April 2008

    Infect topic

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    Nocardia:History

    Edmond Nocard,

    1888

    Aerobic actinomycete

    from cattle with

    bovine farcy

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    Nocardia

    Genus: aerobic actinomycetes

    G+ branching filamentous bacteria

    Subgroup: aerobic nocardiform actinomycetes-Mycobacterium

    -Corynebacterium

    -Nocardia

    -Rhodococcus-Gordona-Tsukamurella

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    Nocardia

    At least 13 species : cause human infection 7most important

    1. Nocardia asteroidescomplex:80% of noncutaneous dz.

    :most systemic & CNS nocardiosis ***2. Nocardia farcin ica: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

    Ubiquitous environmental saphrophyte Soil, organic matter,water

    Tropical and subtropical regions

    :Mexico, Central and South America,Africa and India

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    Nocardia:ECOLOGY& EPIDEMIOLOGY

    Nearly all cases :sporadic

    Human-to-human

    Animal-to-human not documented

    Outbreaks: Contamination of the

    hospital environment, solutions,druginjection equipment.

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    Nocardia:ECOLOGY& EPIDEMIOLOGY

    The risk of pulmonary ordisseminated disease

    *deficient cell-mediated*-Alcoholism

    -Diabetes

    -Lymphoma

    -Transplantation

    -Glucocorticoid therapy-AIDS CD4+ < 250

    Transmission

    Inhalation Skin

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    Nocardia: PATHOLOGY

    Acute pyogenic inflammatory reaction.Branching, beaded, filamentous bacteria

    G/S from a nocardial lung abscess G/S from nocardial pneumonia

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    Nocardia:PATHOGENESIS

    Neutralization of oxidants

    Prevention of phagosome-lysosome fusion

    Prevention of phagosome acidification.

    Mycolic acid polymers:ass.with virulence

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    CLINICAL MANIFESTATIONS

    : 4 main form

    Lymphocutaneous syndrome

    Pulmonary :Pneumonia

    CNS : Brain abscess

    Disseminated disease

    CNS

    Eyes (particularly the retinaKeratitis),

    Skin& subcutaneousKidneys,

    Joints, boneHeart

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    Lymphocutaneous syndrome

    Ubiquitous in soil

    inoculation injuries, Insect and animal bitescontaminated abrasions

    N. brasiliensis: most common

    N. asteroides: self-limited

    Because initial response Rx as staphylococcus

    underdiagnosed Mycetoma

    Days to months ,typical:distal limb

    -Cellulitis-Lymphocutaneous syndrome-Actinomycetoma

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    Nocardial actinomycetomaswelling, multiple sinus tracts,

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    Pulmonary disease

    PneumoniaSubacute(more acute in immunosuppressed)

    Cough**

    Small amounts of thick, purulent sputum

    Fever, anorexia, weight loss, malaise Endobronchial inflammatory mass

    Lung abscess

    Cavitary disease Inadequate therapyProgressive fibrotic disease

    Cerebral imaging,should be performed in allcases of pulmonary and disseminated

    nocardiosis

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    Nocardial pneumonia.Discrete nodular in midlung on both sides

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    CT scan (A),CXR (B)from : multiple abscesses : Nocardia farcinica

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    CNS : Brain abscess

    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

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    brain abscess ; Nocardia farcinic a Nocardial abscess:rt. occipital lobe

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    LABORATORY DIAGNOSIS

    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 therapyno specific therapy

    Susceptibility testing

    -Deep-seated /disseminated dz. fail initial therapy

    -Relapse after therapy-Alternatives to sulfonamides are being considered

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    MANAGEMENT

    :Medication

    Sulfonamides : the mainstay of therapy

    treatment of choice :N. brasiliensis

    N. asteroidescomplexN. transvalensis.

    severely ill patients, CNS /disseminated/immunosuppressed patients=/> 2 drugs

    Amikacin and Carbapenem or3rdgeneration cephalosporin.

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    MANAGEMENT

    :Medication

    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

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    MANAGEMENT

    Medication:alternative therapeutic drugs Failed sulfonamide Rx: N. otitidiscaviarum Intolerant : hypersensitivity,GI toxicity, myelotoxicity)

    Parenteral : Imipenem & amikacin: Meropenem

    : 3rd-gen cephalosporins Ceftriaxone, cefotaxime

    Oral:Amoxicillin clavulanate

    :Minocycline(100200 mg twice daily)

    :Linezolid :new oxazolidinone ;effective orally

    (bioavailability~100%), good CSF penetration

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    MANAGEMENT

    Surgical drainage: depend on site Extraneuralaspirate,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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    Durat ion o f Therapy

    HIV-negative

    immunosuppressed

    :12 mo or longer if thereare intercurrent

    increases in

    immunosuppression

    AIDS

    : at least 12 mo. +

    low-dose maintenance

    (long life)

    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

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    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

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    Genus : Act inomyces

    Slowly progressive infection

    Colonize : mouth, colon, vagina

    Infection : mucosal disruption

    In vivo : Grains / Sulfur granules The most misdiagnosed disease

    3 clinical presentations1.chronicity, progress across tissue boundaries,masslike

    2. develop sinus tract, resolve and recur3. refractory/relapsing after a short course therapy

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    Etiologic Agents

    A. israelii***

    A. naeslundii/v iscosus

    A. odontolyticus

    A. viscosus

    A. meyeri

    A. gerencseriae

    pelvic disease ass. IUCDs & lumpy jaw16S rRNA gene sequencing led to identification of anever-expanding list ofActinomycesspp

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    Concomitant bacteria

    Staphylococcus / Streptococcus

    Enterobacteriaceae

    Ac t inobac i llus com i tans

    Eikenel la co rrodens HACEK

    Fusobacter ium

    Bacteroides Capnocytophaga (Dog bite)

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    Epidemiology

    Members of oral, GI, and genital flora

    Never been cultured from nature

    No document of person-to-person transmission

    The peak incidence : mid-decades Male > Female

    (poorer dental hygiene & oral trauma)

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    Pathogenesis & Pathology

    Disruption of the mucosal barrier.

    Spreads : slow progressive manner