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NOCARDIA
Dr.T.V.Rao MD
Dr.T.V.Rao MD 1

Edmond Nocard - Nocardia

Named after Edmond Nocard, in 1888 described the organism in cattle with bovine farcy. First human case of nocardiosis was reported in 1890 by Eppinger.
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What are Nocardia

Nocardia is a genus of weakly staining Gram-positive, catalase-positive, rodshaped bacteria. It forms partially acidfast beaded branching filaments (acting as fungi, but being truly bacteria). It has a total of 85 species. Some species are non-pathogenic while others are responsible for nocardiosis.
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Nocardia
Genus : aerobic Actinomyctes G+ branching filamentous bacteria Subgroup: aerobic nocardiform actinomycetes -Mycobacterium -Corynebacterium -Nocardia -Rhodococcus -Gordona -Tsukamurella
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Nocardia :ECOLOGY& EPIDEMIOLOGY

Ubiquitous environmental saprophyte Soil, organic matter, water Tropical and subtropical regions
:Mexico, Central and South America, Africa and India

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Nocardia is present as commensal In Humans

Nocardia are found worldwide in soil that is rich with organic matter. In addition, Nocardia are oral microflora found in healthy gingiva as well as periodontal pockets. Most Nocardia infections are acquired by inhalation of the bacteria or through traumatic introduction.
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Other Species of Nocardia

Gram-positive bacteria.
On microscopy have branching filamentous cells. The more common human pathogen are Nocardia asteroids sensu stricto, Nocardia farcinica, Nocardia nova, Nocardia brasiliensis, Nocardia pseudobrasiliensis, Nocardia otitidiscaviarum, and Nocardia transvalensis
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Microbiology
Branching, beaded, filamentous bacteria Can cause "Sulfur granules" like actinomycosis, in nocardial mycetomas. Stains acid fast in tissue unlike the Actinomyces.

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Nocardia :ECOLOGY& EPIDEMIOLOGY

Transmission
The risk of pulmonary or disseminated disease
*deficient cell-mediated * -Alcoholism -Diabetes -Lymphoma -Transplantation -Glucocorticoid therapy -AIDS CD4+ < 250

Inhalation Skin

General approach to Diagnose the Infection with Nocardia

Bronchial wash specimens sent to laboratory were to be examined microscopically by gram stain. If numerous gram positive branching bacilli were observed raising suspicion of Nocardia. A partial acid-fast stain will confirm suspicions that the organism was indeed partially acid-fast and consistent with Nocardia. Gram stain results and presumptive diagnosis were to be reported
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Microscopy and Culturing essential for establishing Diagnosis

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Transmission
Pulmonary, disseminated and CNS infections are acquired through inhalation; primary cutaneous disease is acquired through inoculation of the skin. Rarely, nosocomial postsurgical transmission occurs.
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Risk Factors
Immunocompromised: 60% of all reported nocardiosis is associated with preexisting immune dysfunction. Organ transplantation, hematologic malignancy, alcoholism, steroid use, diabetes, acquired immunodeficiency syndrome (AIDS). Patients with chronic pulmonary disorders, especially, pulmonary alveolar proteinosis, Given its ubiquity in the environment and the increasing numbers of poor hosts, this organism should become increasingly common.
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Virulence Factors
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 human and animal infections and perhaps account for treatment failure.

Virulence Factors
The inability to be killed my normal white cells takes on additional significance in the immunoincompetant who have WBC dysfunction that tips the battle between host and pathogen in favor of the Nocardia. Patients with CGD have increased risk for Nocardia infections, a double whammy where the patients cannot generate an oxidative burst and some strains have the ability to make superoxide dismutase,

Virulence Factors
There are species tissue tropism's:
N. asteroides complex including N. farcinica cause 80% of noncutaneous invasive disease and for most systemic and CNS disease. N. brasiliensis: cutaneous and lymphocutaneous disease. N. pseudobrasiliensis: systemic infections, including the CNS. N. transvalensis and N. otitidiscavarium: Noncutaneous disease

Clinical presentation of Nocardia

Overall, 80% of nocardiosis cases present as invasive pulmonary infection, disseminated infection, or brain abscess; 20% present as cellulitis. Pulmonary infection commonly presents with fever, cough, or chest pain. Central nervous system (CNS) symptoms include headache, lethargy, confusion, seizures, or sudden onset of neurologic deficit.
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Clinical Syndromes: mucocutaneous

Can occur after minor trauma and animal or insect bites; may also colonize open wounds. Often in normal hosts. Misdiagnosis common. N. brasiliensis commonly causes a progressive cutaneous and lymphocutaneous (sporotrichoid) disease.
presents as an ascending nodules

N. asteroides more commonly causes selflimited infection.

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CLINICAL MANIFESTATIONS
: Main form
Lymphocutaneous syndrome Pulmonary :Pneumonia CNS : Brain abscess Disseminated disease CNS Eyes (particularly the retina Keratitis), Skin& subcutaneous Kidneys, Joints, bone Heart
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Nocardial actinomycetoma swelling, multiple sinus tracts,

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Clinical Syndromes: Mucocutaneous

Mycetoma: a chronic progressive, destructive disease, occurring days to months after inoculation located distally on the limbs (classically the foot) and presents 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 (due to actinomycete).

Lymphocutaneous syndrome
-Cellulitis

-Lymphocutaneous syndrome -Actinomycetoma 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

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Clinical Syndromes: pulmonary

Clinical Presentations:
endobronchial inflammatory masses pneumonia lung abscess, cavitary disease empyema pneumonia (often progressive in HIV) it can invade through surrounding tissues like actinomycosis
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Pulmonary disease
Pneumonia

Endobronchial inflammatory mass Lung abscess Cavitary disease

Subacute(more acute in immunosuppressed) Cough** Small amounts of thick, purulent sputum Fever, anorexia, weight loss, malaise

Inadequate therapy Progressive fibrotic disease

Cerebral imaging, should be performed in all cases of pulmonary and disseminated nocardiosis
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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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Nocardiosis can manifest in any region

Local findings associated with metastatic abscesses may be present at almost any site but are typically in the lower extremities. The combination of pneumonia and lower-extremity abscess is particularly suggestive of nocardiosis, although this is not seen exclusively in nocardiosis. Patients with brain abscess may present with altered mental status, personality changes, or various localizing neurologic findings.
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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 therapy no specific therapy Susceptibility testing -Deep-seated /disseminated dz. fail initial therapy -Relapse after therapy -Alternatives to sulfonamides are being considered
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Culturing of Nocardia
Plate culture of the bacteria Nocardia asteroides grown on 7H10 agar plates at 37 C. Photo courtesy
CDC/Dr.William Kaplan
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Specific Methods in Diagnosis

specimens with mixed flora can over grow the Nocardia colonies Selective media may increase yield:
Thayer-Martin agar with antibiotics paraffin agar. Buffered charcoal-yeast extract (BCYE) medium Decontamination methods used for mycobacterial culture kill Nocardia and may decrease culture yield.
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Diagnosis
Slow growing, Nocardia may take from 48 hours to several weeks. typical colonies are buff or pigmented waxy cerebriform colonies and/or as chalky white and are usually seen from 3 to 5 days. biochemical testing and antibiotic resistance patterns can differentiate some species, but PCR83,84 and 16S rRNA sequencing are the most reliable for giving a precise spp.
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Treatment
I&D depending of the location reversal of immunosuppression sulfas the mainstay of therapy, but susceptibilities vary; for example N. farcinica usually resistant to third generation cephalosporins sulfonamide mono therapy in immuno competent or severe disease has a 50% mortality rate in vitro sensitivity and resistance does not predict in vivo response send for susceptibility testing is reasonable
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Treatment
Long-term antibiotic therapy (usually with sulphonamides) for 6 months to a year (or longer depending on the individual and the parts of the body involved) is needed to treat Nocardia. Frequently, chronic suppressive therapy (long-term, low-dose antibiotic therapy) is needed.
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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 divide24times

-Cerebral abscesses,severe,disseminated,AIDS
:15 mg/kg TMP and 75 mg/kg SMX) -Cutaneous infection: 5 mg/kg/day (TMP) + DB

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Treatment: duration
Expect a clinical response in 3 - 10 days Duration is until cure. Often 3-6 months total treatment. Cutaneous disease usually is cured in a month or two Non CNS disease is usually treated for 6 months; CNS disease is treated for a year. Relapses can occur up to a year after stopping therapy; AIDS patient and perhaps other immuno incompetent should be maintained on lifelong suppressive TMP/SULFA

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.
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 Programme Created by Dr.T.V.Rao MD for Medical and Paramedical Students in the Developing World

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