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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, ignoring tissue planes.
Hallmark: chronic, indolent phase (single /multiple indurations)
Woodenfibrotic wallAs 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.
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Actinomycosis
G/S :Variable cellular morphology, ranging from diphtheroidalto coccoid filaments sulfur granule gram
mAFB
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Actinomycosis
G/S :sulfur granuleSulfur granules
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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
Most frequently site
Soft tissue swelling / mass/ abscess : mistaken
for a neoplasm Most common site : Angle of jaws
Dx: mass lesion/relapsinginfection in head &neck
Complication
:-Otitis, sinusitis, and canaliculitis:-extend to cranium,c- spine, thorax
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Most common site : Angle of jaws
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Thoracic Disease
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 rimenhancement
Complication:- Mediastinal infection***
:uncommon, usually from thoracic extension
- Breast disease
- Primary Endocarditis
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Band C:Chest x-ray + CTscan :pulmonary infiltrate, pleural effusion,
pleural and chest wall extension (arrow).
A:Chest
wallmass
D:Purulent
pleural fluid
(aspiration)
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Abdominal Disease(1)
Usually pass from inciting event Appendicitis
Diverticulitis
PUD
Foreign bodies
Bowel surgery ascension from IUCD-associated pelvic disease
Abscess, mass, mixed lesion : mistakentumor???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
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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.
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Abdominal Disease(2)
KUB Disease
All levels: can be infected
- pyelonephritis
- renal and perinephric abscess
Bladder involvement:usually due to pelvic disease
urine : stains and cultures
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Pelvic Disease
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 Rxfrozen pelvis
Removed as early as possible:but not removalof the IUCD unless a suitable contraceptive
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An IUCD encased by endometrial fibrosis (sol id arrowh ead)
paraendometrial fibrosis (open arrow)
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CNS Disease
Rare
Single/multiple abscess**
Irregular nodular Rim-enhancing thick wall
Meningitis / Epidural /Subdural space infection
Cavernous sinus syndrome
MS & Soft t issue
Associated trauma:Fx
Adjacent soft tissue Bone
Periostitis / Osteomyelitis/
Cutaneous sinus tracts** .
Disseminated Disease:Lung* / Liver*
:multiple nodules ~ CA metasbut, indolent
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MS & Soft t issue: Cutaneous sinus tracts
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Diagnosis
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
C/S isolated in 5-7 dbut 2-4 wk. if previous ATB
16S rRNA gene amplification and sequencing: not routinely used
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Can cure with medical Rx alone even in extensive dz
Medical ManagementHigh 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 therapyinitial attempt cure with medical Rx alone, CT and MRI : monitor Critical organs : Reproductive /CNS e.g. epidural space Fails suitable medical therapy
Treatment
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Thank you for
your attention
Reference
-Mandell, Douglas, and BennettsPrinciples and Practice of Infectious Diseases,6TH Edition
-Harrison's PRINCIPLES OF INTERNAL MEDICINE,17th Edition-CLINICAL MICROBIOLOGY REVIEWS, Apr. 2006, p. 259282