ACTINOMYCES AND NOCARDIA Doç.Dr.Hrisi BAHAR. ACTINOMYCETES.

ACTINOMYCES ACTINOMYCES AND AND

NOCARDIA 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 Aerobic ActinomycetesActinomycetes whose cell walls whose cell walls contain mycolic acid: contain mycolic acid: Nocardia species and Rhodococcus species

► 2-2-Aerobic Aerobic ActinomycetesActinomycetes whose cell walls whose cell walls lack mycolic acid: Streptomyces species

ANAEROBIC ACTINOMYCETES

► Anaerobic non-sporulating Anaerobic non-sporulating GGram-ram-positive rods consist of two groups based positive rods consist of two groups based on on guanosineguanosine (G) plus (G) plus cytosinecytosine (C) DNA (C) DNA content: content:

1--Low mole percent (30-53%)Low mole percent (30-53%)2-H-High mole percent (49-68%) igh mole percent (49-68%) ► ActinomycesActinomyces speciesspecies are are member of the member of the

high G+C grouphigh G+C group..

Pathogenic Genera of Aerobic Actinomycetes

► NocardiaNocardia

► ActinomaduraActinomadura

► StreptomycesStreptomyces

► RhodococcusRhodococcus

► GordoniaGordonia

► TsukamurellaTsukamurella

► Tropheryma whipplei Tropheryma whipplei (Non-cultivable(Non-cultivable))

Aerobic Actinomycetes: Natural Habitats

NocardiaNocardia species species and other and other aerobic aerobic ActinomycetesActinomycetes are are in soil and primarily in soil and primarily responsible for decomposition of organic plant responsible for decomposition of organic plant mattermatter

Rhodococcus Rhodococcus speciesspecies present in the intestinal present in the intestinal bacterial flora of grazing herbivores especially bacterial flora of grazing herbivores especially horseshorses

Streptomyces Streptomyces speciesspecies (>3,000) widely (>3,000) widely distributed in soildistributed in soil

Anaerobic Actinomycetes: Natural Habitats

Anaerobic Anaerobic Actinomyces Actinomyces speciesspecies

are normal inhabitants of the are normal inhabitants of the

mucous membranes of humans mucous membranes of humans

and animalsand animals

AerobicAerobic ActinomycetesActinomycetes: : Modes of InfectionModes of Infection

► Actinomadura Actinomadura species (species (A. madurae, A. A. madurae, A. latina, A. pelletierilatina, A. pelletieri)) produce subcutaneous produce subcutaneous infections in tropical and subtropical countries infections in tropical and subtropical countries with those who walk barefootedwith those who walk barefooted

► Gordonia Gordonia and and TsukamurellaTsukamurella species are species are closely related toclosely related to RhodococcusRhodococcus, , and are soil and are soil organisms considered opportunistic pathogensorganisms considered opportunistic pathogens

Anaerobic Anaerobic ActinomycesActinomyces:: Modes of Infection Modes of Infection

► ActinomycesActinomyces invades normally invades normally

sterile tissue from endogenoussterile tissue from endogenous mucousmucous

membrane sites ofmembrane sites of normal colonizationnormal colonization

Aerobic Aerobic ActinomycetesActinomycetes: Types of : Types of Infectious DiseaseInfectious Disease -1--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-

► StreptomycesStreptomyces ( (S. anulatusS. anulatus formerly formerly S. griseus, S. griseus, and and S. somaliensisS. somaliensis) ) is is associated with associated with actinomycotic mycetomaactinomycotic mycetoma in warm climates. in warm climates.► SStreptomyces treptomyces somaliensis somaliensis is is a frequent cause of a frequent cause of

actinomycotic mycetomas of the head and neck.actinomycotic mycetomas of the head and neck.

Aerobic Actinomycetes: Types of Infectious Disease

► Whipple’s diseaseWhipple’s disease: : The cause is infection with the The cause is infection with the bacteriumbacterium Tropheryma whippleiTropheryma whipplei. . This bacterium This bacterium can initially affect the mucosal lining of the small can initially affect the mucosal lining of the small intestine, forming small lesions within the intestine, forming small lesions within the intestinal wall. With time, the infection can spread intestinal wall. With time, the infection can spread to other parts of the body.to other parts of the body. DDiarrhea, weight loss, iarrhea, weight loss, lymphadenopathy, fever, and arthralgialymphadenopathy, fever, and arthralgia are are between the symptomsbetween the symptoms

► DDiagnosis iagnosis is is by typical histopathology combined by typical histopathology combined with PCR)with PCR)

ActinomycosisActinomycosis

► Actinomyces israeliiActinomyces israelii causes actinomycosis in causes actinomycosis in which chronic granulomas become suppurative. which chronic granulomas become suppurative.

► Cervicofacial actinomycosis most common (~60%), Cervicofacial actinomycosis most common (~60%), followed by abdominal (20%) and pulmonary followed by abdominal (20%) and pulmonary actinomycosisactinomycosis(15%).(15%).

► Tissue pus contains Tissue pus contains ““sulfur granulessulfur granules””, a mass of , a mass of branching bacteriabranching bacteria. .

► Presence of sulfur granules establishes a diagnosis Presence of sulfur granules establishes a diagnosis of actinomycosisof actinomycosis..

Anaerobic Anaerobic ActinomycesActinomyces: Types of : Types of Infectious DiseaseInfectious Disease-2--2-

Aerobic Aerobic ActinomycetesActinomycetes: : IdentificationIdentification

► RhodococcusRhodococcus, , Gordonia, Gordonia, and and TsukamurellaTsukamurella difficult to characterize biochemicallydifficult to characterize biochemically.. IIdentification dentification is is based on partial acid-fastness, based on partial acid-fastness, colony morphology, and 16S rRNA gene colony morphology, and 16S rRNA gene sequence analysissequence analysis

► RhodococcusRhodococcus:: slimy, salmon-pink colonies slimy, salmon-pink colonies► GordoniaGordonia: smooth, beige to salmon-pink : smooth, beige to salmon-pink

coloniescolonies► TsukamurellaTsukamurella:: cerebroid, cream colonies cerebroid, cream colonies

Anaerobic Actinomyces: Identification

► Actinomyces israeliiActinomyces israelii is is anaerobic with anaerobic with clinical strains varying from obligate clinical strains varying from obligate anaerobes to microaerophilicanaerobes to microaerophilic

► AA. . israeliiisraelii definitively is identified by detection using gas liquid chromatography (GLC) of acetic and lactic acid as end products of carbohydrate metabolism


There are at least five (5) types of actinomycosisThere are at least five (5) types of actinomycosis

► Cervicofacial actinomycosis

► Thoracic actinomycosisThoracic actinomycosis

► Abdominal actinomycosisAbdominal actinomycosis

► Pelvic actinomycosisPelvic actinomycosis

► Generalized actinomycosisGeneralized actinomycosis


► Cervicofacial actinomycosisCervicofacial actinomycosis occurs in the mouth, occurs in the mouth, neck and head region. neck and head region.

► The bacterium enters through the periodontium soft The bacterium enters through the periodontium soft tissue wounds or salivary glands. tissue wounds or salivary glands.

► Cervicofacial actinomycosis develops slowly. The Cervicofacial actinomycosis develops slowly. The area becomes hard, the overlying skin becomes area becomes hard, the overlying skin becomes reddish and swelling appears in the mouth and neck.reddish and swelling appears in the mouth and neck.

► Abscesses develop within and eventually drain to the Abscesses develop within and eventually drain to the surface where surface where sulfur granulessulfur granules ,masses of ,masses of filamentous organisms, may be found in the pus.filamentous organisms, may be found in the pus.


► Thoracic actinomycosisThoracic actinomycosis involves the lungs involves the lungs and mediastinum and mediastinum

► The disease begins with fever, cough, and The disease begins with fever, cough, and sputum production. The patient becomes sputum production. The patient becomes weak, loses weight and may have night sweats weak, loses weight and may have night sweats and shortness of breath.and shortness of breath.

► Cervicofacial and thoracic disease may result Cervicofacial and thoracic disease may result in nervous system complications ; most in nervous system complications ; most commonly brain abscesses or meningitis. commonly brain abscesses or meningitis.


► Abdominal actinomycosisAbdominal actinomycosis are mostly are mostly preceded by surgery . preceded by surgery .

► Infection usually begins in the gastrointestinal Infection usually begins in the gastrointestinal tract and spreads to the abdominal wall. tract and spreads to the abdominal wall.

► Fever and chills, intestinal colic, vomiting, Fever and chills, intestinal colic, vomiting, and weight loss, a palpable (can be felt) mass and weight loss, a palpable (can be felt) mass and an external sinus are evident in this type of and an external sinus are evident in this type of actinomycosis. actinomycosis.


► Pelvic actinomycosisPelvic actinomycosis affects the women's affects the women's pelvic area and may cause lower abdominal pelvic area and may cause lower abdominal pain, fever, and bleeding between menstrual pain, fever, and bleeding between menstrual periods. This form of the infection has been periods. This form of the infection has been associated with the use of IUDs (intra-uterine associated with the use of IUDs (intra-uterine devices) that do not contain copperdevices) that do not contain copper..

► Generalized actinomycosisGeneralized actinomycosis may involve the may involve the skin, brain, liver and urogenital system.skin, brain, liver and urogenital system.

Treatment

► Treatment for actinomycosis is long term, Treatment for actinomycosis is long term, generally with up to one month of intravenousgenerally with up to one month of intravenous penicillin Gpenicillin G, , followed by weeks to months of followed by weeks to months of penicillin taken by mouthpenicillin taken by mouth. .

► Additionally, surgical excision and drainage Additionally, surgical excision and drainage of abscesses may be necessary. of abscesses may be necessary.

NOCARDIA SP

NOCARDIA SP

NOCARDIA SP

►Named after Edmond Named after Edmond Nocard, Nocard, ► IIn 1888 described the n 1888 described the organism in cattle organism in cattle ► First human case of First human case of NNocardiosis was ocardiosis was reported in 1890reported in 1890 by Eppinger.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 Nocardia asteroides sensu stricto, Nocardia farcinica, Nocardia asteroides sensu stricto, Nocardia farcinica, Nocardia nova, Nocardia brasiliensis, Nocardianova, Nocardia brasiliensis, Nocardia pseudobrasiliensis, pseudobrasiliensis,

Nocardia otitidiscaviarum, and Nocardia transvalensis. Nocardia otitidiscaviarum, and Nocardia transvalensis.

NOCARDIA :Epidemiology

► Nocardia is everywhere in the environment: soil, Nocardia is everywhere in the environment: soil, organic matter, and water.organic matter, and water.

► Human infection usually occurs from minor trauma Human infection usually occurs from minor trauma andand direct inoculation of the skin or soft tissues or direct inoculation of the skin or soft tissues or by inhalation.by inhalation. It is also a common animal infectionIt is also a common animal infection

► Outbreaks in oncology and transplant wards and Outbreaks in oncology and transplant wards and surgical wounds have occurred from fomites, hospital surgical wounds have occurred from fomites, hospital construction with resultant contaminated dust, and construction with resultant contaminated dust, and health care worker hands.health care worker hands.

NOCARDIA:Characteristics

► Branching, beaded, Branching, beaded, filamentous bacteriafilamentous bacteria

►Inn NNocardial mycetomasocardial mycetomas ,it ,it ccan causean cause "Sulfur "Sulfur granules"granules" like like actinomycosisactinomycosis. .

► SStains tains acid fastacid fast in tissue. in tissue.

NOCARDIA:Virulence

► Virulent strains are relatively resistant to neutrophil-Virulent strains are relatively resistant to neutrophil-mediated killing.mediated killing.

► OOrganisms in the logarithmic growth phase are more rganisms in the logarithmic growth phase are more toxic to macrophagestoxic to macrophages. .

► IInhibitnhibit phagosome-lysosome fusion more phagosome-lysosome fusion more successfully in vitro, which gives rise to L-forms, successfully in vitro, which gives rise to L-forms, which can survive in macrophages for days which can survive in macrophages for days

► L-forms have been foundL-forms have been found in in human and animal human and animal infections and perhaps account for treatment failureinfections and perhaps account for treatment failure..

NOCARDIA:Virulence

TThere are species tissue tropism's:here are species tissue tropism's:

► NN. asteroides complex including . asteroides complex including

N. farcinica causeN. farcinica cause 80% of noncutaneous invasive 80% of noncutaneous invasive

disease and most systemic and CNSdisease and most systemic and CNS (Central Nervous (Central Nervous

System)System) disease. disease.► N. brasiliensisN. brasiliensis: : CCutaneous and lymphocutaneous disease.utaneous and lymphocutaneous disease.

► N. pseudobrasiliensisN. pseudobrasiliensis: : SSystemic infections, including the ystemic infections, including the CNS.CNS.

► N. transvalensis and N. otitidiscavariumN. transvalensis and N. otitidiscavarium: Noncutaneous : Noncutaneous diseasedisease

NOCARDIA:Diagnosis

► Stains show gram-positive, branching Stains show gram-positive, branching filaments, that are usually acid fast. filaments, that are usually acid fast.

NOCARDIA:Diagnosis

Nocardia organisms Nocardia organisms grew in sgrew in standard bloodtandard blood

culture media culture media in in prolonged incubationprolonged incubation

NOCARDIA:Lab Diagnosis

► TTypical colonies are ypical colonies are pigmented pigmented ,,cerebriform cerebriform colonies and/or white colonies and/or white colonies colonies and are usually seen and are usually seen from 3 to 5 days.from 3 to 5 days.

► BBiochemical testing and iochemical testing and antibiotic resistance patterns antibiotic resistance patterns can differentiate some can differentiate some speciesspecies..

► PCR and 16S rRNA PCR and 16S rRNA sequencing are the most sequencing are the most reliable for giving a precisereliable for giving a precise identification.identification.

Nocardia on blood agar

Risk Factors for Nocardiosis

► ImmunocompromiseImmunocompromise host host: : 60% of all60% of all reported nocardiosis is associated with reported nocardiosis is associated with preexisting immune dysfunction.preexisting immune dysfunction.

►OOrgan transplantation, hematologic rgan transplantation, hematologic malignancy, alcoholism, steroid use, diabetes, malignancy, alcoholism, steroid use, diabetes, acquired immunodeficiency syndrome (AIDS). acquired immunodeficiency syndrome (AIDS).

andand Patients with chronic pulmonary disorders Patients with chronic pulmonary disorders are in risk.are in risk.

Clinical Syndromes: Mucocutaneous

► CCan occur after minor trauma and animal or an occur after minor trauma and animal or insect bites; may also colonize open woundsinsect bites; may also colonize open wounds..

► N. brasiliensisN. brasiliensis commonly causes a commonly causes a progressive cutaneous and lymphocutaneous progressive cutaneous and lymphocutaneous (sporotrichoid) disease.(sporotrichoid) disease.

► N. asteroidesN. asteroides more commonly causes more commonly causes self-limited infection.self-limited infection.

Clinical Syndromes: Mucocutaneous

► MycetomaMycetoma: a chronic progressive, destructive : a chronic progressive, destructive disease, occurring days to months after inoculationdisease, occurring days to months after inoculation

► LLocated distally on the limbs (classically the foot) ocated distally on the limbs (classically the foot) and and is is present with present with Suppurative granulomataSuppurative granulomata PProgressive fibrosis and necrosisrogressive fibrosis and necrosis SSinus formation and destruction of adjacent structures, inus formation and destruction of adjacent structures, MMacroscopically visible infective granules acroscopically visible infective granules Mimics fungal mycetoma and actinomycetomataMimics fungal mycetoma and actinomycetomata

Mucocutaneous Nocardiosis

Clinical Syndromes: Pulmonary

●●Pulmonary disease Pulmonary disease is the is the most common reported most common reported ..●● BacteriaBacteria colonize sputum of COPD patients colonize sputum of COPD patients ..●● Clinical Presentations:Clinical Presentations:

► endobronchial inflammatory masses pneumoniaendobronchial inflammatory masses pneumonia► lung abscess, lung abscess, ► cavitary disease cavitary disease ► empyemaempyema► pneumonia (often progressive in HIV)pneumonia (often progressive in HIV)► it can invade through surrounding tissues like it can invade through surrounding tissues like

actinomycosisactinomycosis

Clinical Syndromes

► Cardiac ConditionsCardiac Conditions

Nocardia has been highly linked to endocarditisNocardia has been highly linked to endocarditis

as a main symptom .In recorded cases,it hasas a main symptom .In recorded cases,it has

caused damage to heart valves.caused damage to heart valves.

► Ocular diseaseOcular disease

Very rarely Nocardia cause keratitis,generallyVery rarely Nocardia cause keratitis,generally

after traumaafter trauma

Disseminated Nocardiosis

► Disseminated infection can occur in veryDisseminated infection can occur in very

immunocompromised patients, through theimmunocompromised patients, through the

spreading enzymes possessed by the bacteriaspreading enzymes possessed by the bacteria..

►It generally involves both lungs and brain It generally involves both lungs and brain

► Multiple cavitating pulmonary infiltrates developMultiple cavitating pulmonary infiltrates develop

► Cerebral abscesses arise laterCerebral abscesses arise later

► If untreated,the prognosis is poor for this form of If untreated,the prognosis is poor for this form of diseasedisease

Treatment

► Nocardiosis requires at least 6 months of treatment, Nocardiosis requires at least 6 months of treatment, preferably withpreferably with co-trimoxazoleco-trimoxazole or highor high doses ofdoses of sulfonamides.sulfonamides.

► In patients who don’t respond to sulfonamide In patients who don’t respond to sulfonamide treatment, other drugs, such astreatment, other drugs, such as ampicillin,ampicillin,

erythromycin,or minocyclineerythromycin,or minocycline may be addedmay be added..► Treatment also includesTreatment also includes surgical drainagesurgical drainage of of

abscesses and excision of necrotic tissue. abscesses and excision of necrotic tissue. ► A new combination drug therapyA new combination drug therapy ( (sulfonamide, sulfonamide,

ceftriaxone and amikacinceftriaxone and amikacin) ) is also in usageis also in usage..

ACTINOMYCES AND NOCARDIA Doç.Dr.Hrisi BAHAR. ACTINOMYCETES.

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