Nocardia &

Actinomycosis

Nattaya Mangkalapiwat
28 April 2008
Infect topic
Nocardia :History
Edmond Nocard,
1888
Aerobic actinomycete
from cattle with
bovine farcy


Nocardia
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
.
Nocardia :ECOLOGY& EPIDEMIOLOGY

Ubiquitous environmental saphrophyte
Soil, organic matter,water
Tropical and subtropical regions
:Mexico, Central and South America,Africa and India
Nocardia :ECOLOGY& EPIDEMIOLOGY
Nearly all cases :sporadic
Human-to-human
Animal-to-human not documented
Outbreaks : Contamination of the
hospital environment, solutions,drug
injection equipment.
Nocardia :ECOLOGY& EPIDEMIOLOGY
The risk of pulmonary or
disseminated disease
*deficient cell-mediated *
-Alcoholism
-Diabetes
-Lymphoma
-Transplantation
-Glucocorticoid therapy
-AIDS CD4+ < 250


Transmission

Inhalation
Skin
Nocardia : PATHOLOGY

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.

Mycolic acid polymers:ass.with virulence
CLINICAL MANIFESTATIONS
: 4 main form
Lymphocutaneous syndrome
Pulmonary :Pneumonia
CNS : Brain abscess
Disseminated disease
CNS
Eyes (particularly the retinaKeratitis),
Skin& subcutaneous
Kidneys,
Joints, bone
Heart
Lymphocutaneous syndrome
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

underdiagnosed Mycetoma
Days to months ,typical:distal limb
-Cellulitis
-Lymphocutaneous syndrome
-Actinomycetoma

Nocardial actinomycetoma swelling, multiple sinus tracts,
Pulmonary disease
Pneumonia
Subacute(more acute in immunosuppressed)
Cough**
Small amounts of thick, purulent sputum
Fever, anorexia, weight loss, malaise
Endobronchial inflammatory mass
Lung abscess
Cavitary disease
Inadequate therapy Progressive fibrotic disease
Cerebral imaging,should be performed in all
cases of pulmonary and disseminated
nocardiosis

Nocardial pneumonia. Discrete nodular in midlung on both sides

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

brain abscess ; Nocardia farcinica Nocardial abscess :rt. occipital lobe
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 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
3
rd
generation cephalosporin.
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
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
MANAGEMENT
Surgical drainage: depend on site
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.
Duration of Therapy
HIV-negative
immunosuppressed
:12 mo or longer if there
are 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

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%
Actinomycosis
Genus : Actinomyces
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
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)

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 )



Pathogenesis & Pathology
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 sulfur granule gram
mAFB
Actinomycosis
G/S :sulfur granule
Sulfur granules
Risk Factors
Foreign bodies : IUCDs
Abnormal host defense : HIV
Post transplantation
Radio-Chemotherapy
Ulcerative mucosal infection: HSV/CMV

Clinical Manifestations
Oral-Cervicofacial Disease
Thoracic Disease
Abdominal Disease
Pelvic Disease
Central Nervous System Disease
Musculoskeletal & Soft tissue infection
Disseminated Disease

Oral-Cervicofacial Disease
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
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
B and C: Chest x-ray + CTscan :pulmonary infiltrate, pleural effusion,
pleural and chest wall extension (arrow).
A:Chest
wall
mass
D:Purulent
pleural fluid
(aspiration)

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
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
Bladder involvement:usually due to pelvic disease
urine : stains and cultures

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 removal
of the IUCD unless a suitable contraceptive

An IUCD encased by endometrial fibrosis (solid arrowhead)
paraendometrial fibrosis (open arrow)
CNS Disease
Rare
Single/multiple abscess**
Irregular nodular Rim-
enhancing thick wall
Meningitis / Epidural /
Subdural space infection
Cavernous sinus syndrome

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
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 d but 2-4 wk. if previous ATB
16S rRNA gene amplification and sequencing
: not routinely used
Can cure with medical Rx alone even in extensive dz

Medical Management
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
Treatment

Thank you for
your attention
Reference
-Mandell, Douglas, and Bennetts
Principles and Practice of Infectious Diseases,6TH Edition
-Harrison's PRINCIPLES OF INTERNAL MEDICINE,17th Edition
-CLINICAL MICROBIOLOGY REVIEWS, Apr. 2006, p. 259282