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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