ACTINOMYCES
AND
NOCARDIA
Doç.Dr.Hrisi BAHAR
ACTINOMYCETES
AEROBIC ACTINOMYCETES
► Gram-positive branching filaments that
sporulate or fragment:
According to the composition of the cell
wall they are studied in 2 groups.
►1- Aerobic Actinomycetes whose cell walls
contain mycolic acid: Nocardia species and
Rhodococcus species
► 2-Aerobic Actinomycetes whose cell walls
lack mycolic acid: Streptomyces species
ANAEROBIC ACTINOMYCETES
► Anaerobic non-sporulating Gram-
positive rods consist of two groups based
on guanosine (G) plus cytosine (C) DNA
content:
1-Low mole percent (30-53%)
2-High mole percent (49-68%)
► Actinomyces species are member of the
high G+C group.
Pathogenic Genera of
Aerobic Actinomycetes
► Nocardia
► Actinomadura
► Streptomyces
► Rhodococcus
► Gordonia
► Tsukamurella
► Tropheryma whipplei (Non-cultivable)
Aerobic Actinomycetes:
Natural Habitats
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Nocardia species and other aerobic
Actinomycetes are in soil and primarily
responsible for decomposition of organic plant
matter
Rhodococcus species present in the intestinal
bacterial flora of grazing herbivores especially
horses
Streptomyces species (>3,000) widely
distributed in soil
Anaerobic Actinomycetes:
Natural Habitats
Anaerobic Actinomyces species
are normal inhabitants of the
mucous membranes of humans
and animals
Aerobic Actinomycetes:
Modes of Infection
► Actinomadura species (A. madurae, A.
latina, A. pelletieri) produce subcutaneous
infections in tropical and subtropical countries
with those who walk barefooted
► Gordonia and Tsukamurella species are
closely related to Rhodococcus, and are soil
organisms considered opportunistic pathogens
Anaerobic Actinomyces:
Modes of Infection
► Actinomyces invades normally
sterile tissue from endogenous mucous
membrane sites of normal colonization
Aerobic Actinomycetes: Types of
Infectious Disease -1► Rhodococcus equi infects macrophages
inhibiting phagolysosome fusion, and produces
pulmonary disease with cavitation. Infection
occurs in immunocompromised (especially
HIV-infected) individuals who handle horses.
► R. equi disseminates to other organs
including the brain and subcutaneous tissue
Aerobic Actinomycetes: Types of
Infectious Disease -2► Streptomyces (S. anulatus formerly S. griseus,
and S. somaliensis) is associated with
actinomycotic mycetoma in warm climates.
► Streptomyces somaliensis is a frequent cause of
actinomycotic mycetomas of the head and neck.
Aerobic Actinomycetes: Types of
Infectious Disease
► Whipple’s disease: The cause is infection with the
bacterium Tropheryma whipplei. This bacterium
can initially affect the mucosal lining of the small
intestine, forming small lesions within the
intestinal wall. With time, the infection can spread
to other parts of the body. Diarrhea, weight loss,
lymphadenopathy, fever, and arthralgia are
between the symptoms
► Diagnosis is by typical histopathology combined
with PCR)
Actinomycosis
► Actinomyces israelii causes actinomycosis in
which chronic granulomas become suppurative.
► Cervicofacial actinomycosis most common (~60%),
followed by abdominal (20%) and pulmonary
actinomycosis(15%).
► Tissue pus contains “sulfur granules”, a mass of
branching bacteria.
► Presence of sulfur granules establishes a diagnosis
of actinomycosis.
Anaerobic Actinomyces: Types of
Infectious Disease-2-
Aerobic Actinomycetes:
Identification
► Rhodococcus, Gordonia, and Tsukamurella
difficult to characterize biochemically.
Identification is based on partial acid-fastness,
colony morphology, and 16S rRNA gene
sequence analysis
► Rhodococcus: slimy, salmon-pink colonies
► Gordonia: smooth, beige to salmon-pink
colonies
► Tsukamurella: cerebroid, cream colonies
Anaerobic Actinomyces:
Identification
► Actinomyces israelii is anaerobic with
clinical strains varying from obligate
anaerobes to microaerophilic
► A. israelii definitively is identified by
detection using gas liquid chromatography
(GLC) of acetic and lactic acid as end products
of carbohydrate metabolism
Actinomycosis
There are at least five (5) types of actinomycosis
► Cervicofacial actinomycosis
► Thoracic actinomycosis
► Abdominal actinomycosis
► Pelvic actinomycosis
► Generalized actinomycosis
Actinomycosis
► Cervicofacial actinomycosis occurs in the mouth,
neck and head region.
► The bacterium enters through the periodontium soft
tissue wounds or salivary glands.
► Cervicofacial actinomycosis develops slowly. The
area becomes hard, the overlying skin becomes
reddish and swelling appears in the mouth and neck.
► Abscesses develop within and eventually drain to the
surface where sulfur granules ,masses of
filamentous organisms, may be found in the pus.
Actinomycosis
► Thoracic actinomycosis involves the lungs
and mediastinum
► The disease begins with fever, cough, and
sputum production. The patient becomes weak,
loses weight and may have night sweats and
shortness of breath.
► Cervicofacial and thoracic disease may result
in nervous system complications ; most
commonly brain abscesses or meningitis.
Actinomycosis
► Abdominal actinomycosis are mostly
preceded by surgery .
► Infection usually begins in the gastrointestinal
tract and spreads to the abdominal wall.
► Fever and chills, intestinal colic, vomiting,
and weight loss, a palpable (can be felt) mass
and an external sinus are evident in this type of
actinomycosis.
Actinomycosis
► Pelvic actinomycosis affects the women's
pelvic area and may cause lower abdominal
pain, fever, and bleeding between menstrual
periods. This form of the infection has been
associated with the use of IUDs (intra-uterine
devices) that do not contain copper.
► Generalized actinomycosis may involve the
skin, brain, liver and urogenital system.
Treatment
► Treatment for actinomycosis is long term,
generally with up to one month of intravenous
penicillin G, followed by weeks to months of
penicillin taken by mouth.
► Additionally, surgical excision and drainage
of abscesses may be necessary.
NOCARDIA SP
NOCARDIA SP
NOCARDIA SP
►Named after Edmond
Nocard,
► In 1888 described the
organism in cattle
► First human case of
Nocardiosis was
reported in 1890
by Eppinger.
NOCARDIA :Classification
► Gram-positive bacteria.
► On microscopy have branching filamentous cells.
► Members of the group are often only distantly
related phylogenetically.
► Part of a subgroup of aerobic nocardiform
actinomycetes includes: Mycobacterium,
Corynebacterium, Nocardia, Rhodococcus,
Gordona, and Tsukamurella and the cause of
Whipple's disease (Tropheryma whippeli).
NOCARDIA :Classification
► Standard laboratory techniques are limited in their ability
to differentiate these organisms.
► Molecular genetics have identified at least 30 species, 13
of which cause human infection.
► The more common human pathogen are Nocardia
asteroides sensu stricto, Nocardia farcinica, Nocardia
nova, Nocardia brasiliensis, Nocardia pseudobrasiliensis,
Nocardia otitidiscaviarum, and Nocardia transvalensis.
NOCARDIA :Epidemiology
► Nocardia is everywhere in the environment: soil,
organic matter, and water.
► Human infection usually occurs from minor trauma
and direct inoculation of the skin or soft tissues or
by inhalation. It is also a common animal infection
► Outbreaks in oncology and transplant wards and
surgical wounds have occurred from fomites, hospital
construction with resultant contaminated dust, and
health care worker hands.
NOCARDIA:Characteristics
► Branching, beaded,
filamentous bacteria
►In Nocardial mycetomas ,it
can cause "Sulfur
granules" like
actinomycosis.
► Stains acid fast in tissue.
NOCARDIA:Virulence
► Virulent strains are relatively resistant to neutrophilmediated killing.
► Organisms in the logarithmic growth phase are more
toxic to macrophages.
► Inhibit phagosome-lysosome fusion more
successfully in vitro, which gives rise to L-forms,
which can survive in macrophages for days
► L-forms have been found in human and animal
infections and perhaps account for treatment failure.
NOCARDIA:Virulence
There are species tissue tropism's:
► N. asteroides complex including
N. farcinica cause 80% of noncutaneous invasive
disease and most systemic and CNS (Central Nervous
System) disease.
► N. brasiliensis: Cutaneous and lymphocutaneous disease.
► N. pseudobrasiliensis: Systemic infections, including the
CNS.
► N. transvalensis and N. otitidiscavarium: Noncutaneous
disease
NOCARDIA:Diagnosis
► Stains show gram-positive, branching
filaments, that are usually acid fast.
NOCARDIA:Diagnosis
Nocardia organisms grew in standard blood
culture media in prolonged incubation
NOCARDIA:Lab Diagnosis
► Typical colonies are
pigmented ,cerebriform
colonies and/or white
colonies and are usually seen
from 3 to 5 days.
► Biochemical testing and
antibiotic resistance patterns
can differentiate some
species.
► PCR and 16S rRNA
sequencing are the most
reliable for giving a precise
identification.
Nocardia on blood agar
Risk Factors for Nocardiosis
► Immunocompromise host: 60% of all
reported nocardiosis is associated with
preexisting immune dysfunction.
►Organ transplantation, hematologic
malignancy, alcoholism, steroid use, diabetes,
acquired immunodeficiency syndrome (AIDS).
and Patients with chronic pulmonary disorders
are in risk.
Clinical Syndromes: Mucocutaneous
► Can occur after minor trauma and animal or
insect bites; may also colonize open wounds.
► N. brasiliensis commonly causes a
progressive cutaneous and lymphocutaneous
(sporotrichoid) disease.
► N. asteroides more commonly causes
self-limited infection.
Clinical Syndromes: Mucocutaneous
► Mycetoma: a chronic progressive, destructive
disease, occurring days to months after inoculation
► Located distally on the limbs (classically the foot)
and is present with
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Suppurative granulomata
Progressive fibrosis and necrosis
Sinus formation and destruction of adjacent structures,
Macroscopically visible infective granules
Mimics fungal mycetoma and actinomycetomata
Mucocutaneous Nocardiosis
Clinical Syndromes: Pulmonary
●Pulmonary disease is the most common reported .
● Bacteria colonize sputum of COPD patients .
● Clinical Presentations:
► endobronchial inflammatory masses pneumonia
► lung abscess,
► cavitary disease
► empyema
► pneumonia (often progressive in HIV)
► it can invade through surrounding tissues like
actinomycosis
Clinical Syndromes
► Cardiac Conditions
Nocardia has been highly linked to endocarditis
as a main symptom .In recorded cases,it has
caused damage to heart valves.
► Ocular disease
Very rarely Nocardia cause keratitis,generally
after trauma
Disseminated Nocardiosis
► Disseminated infection can occur in very
immunocompromised patients, through the
spreading enzymes possessed by the bacteria.
►It generally involves both lungs and brain
► Multiple cavitating pulmonary infiltrates develop
► Cerebral abscesses arise later
► If untreated,the prognosis is poor for this form of
disease
Treatment
► Nocardiosis requires at least 6 months of treatment,
preferably with co-trimoxazole or high doses of
sulfonamides.
► In patients who don’t respond to sulfonamide
treatment, other drugs, such as ampicillin,
erythromycin,or minocycline may be added.
► Treatment also includes surgical drainage of
abscesses and excision of necrotic tissue.
► A new combination drug therapy (sulfonamide,
ceftriaxone and amikacin) is also in usage.
Nocardiosis:Treatment
From Mandel et al The Principals and Practice of Infectious disease
Copyright © 2006 Elsevier