Nocardiosis

Brijesh Singh Yadav

brijeshbioinfo@gmail.com

Disease Type: Bacterial Disease

Common Name: Nocardiosis
Causative Agent: Nocardia asteroides
Disease Discription: A rare, acute, chronic suppurative infectious disease caused by bacteria
Nocardia asteroides which primarily affects the lung but may also involve the brain, soft
tissues and other organs . It has a pronounced tendency to remission and exacerbation.

Fig.1. Nocardia skin lesion.2. Filamentous bacteria identified as nocardia asteroides in

sputum.

Causes of Disease:
Nocardiosis is an infection caused by bacteria (Nocardia) which live in the soil. If inhaled, the bacterial
infection causes pneumonia-like symptoms leading to blood poisoning (sepsis) and the spread of
nocardiosis to other organs of the body but brain and skin infections are the most common complications.
Nocardia may also infect the skin through a cut, puncture wound, or scratch that occurs while
working outdoors or gardening. The skin infections, which may take different forms, are
called cutaneous nocardiosis. Occupational exposure to soil, as in fieldwork, landscaping,
and farming, increases the risk of contracting cutaneous nocardiosis. Pulmonary and
disseminated infections occur through inhalation and primary cutaneous disease through soil-
contaminated wounds. Rarely, nosocomial postsurgical transmission occurs.

Risk Factors:
Having a risk factor for Nocardiosis makes the chances of getting a condition higher but does
not always lead to Nocardiosis. Severely immunocompromised persons (e.g., persons with
malignancy, connective tissue disorders, bone marrow or solid organ transplantation, high-
dose corticosteroid use, HIV infection, alcoholism or pulmonary alveolar proteinosis, and
males (ratio male: female = 3:1).

Causative Agent Description:

Pathogen Name: Nocardia
Pathogen Description: Nocardia is a genus of Gram-positive, catalase-positive, rod-shaped
bacteria. It has total 85 species. Some species are non pathogenic; some species are
pathogenic (nocardiosis). Nocardia are found worldwide in soil that is rich with organic
matter. Most Nocardia infections are acquired by inhalation of the bacteria or through
traumatic introduction.

Taxonoimic Classification:

Kingdom Bacteria
Phylum Actinobacteria
Order Actinomycetales
Suborder Corynebacterineae
Family Nocardiaceae
Genus Nocardia
Fig.4 Nocardia filamentous bacteria

Other Pathogenic speices: Other pathogenic species include N. farcinica, N. nova,

N.transvalensis,N. brasiliensis, and N. pseudobrasiliensis. A recent report of infections with
Nocardia cornea, Nocardia elegans, Nocardia paucivorans, Nocardia puris, and Nocardia
takedensis has come from Japan. Nocardia brasiliensis is a common cause of localized chronic
mycetoma. A total of approximately 30 strains of Nocardia have been associated with human
disease.

Morphology and toxin production:

The Nocardia do not have complex growth requirements. They grow well on most
commonly used routine bacteriologic media. They usually require a minimum of 48 to72
hours before colonies become visible. They may
manifest extremely variable colonial morphologies on
different culture media. They are dry, chalky, rough,
folded, irregular and powdery. Nocardia colonies
have a variable appearance, but most species appear
to have aerial hyphae when viewed with a dissecting
microscope particularly when they have been grown
on nutritionally-limiting media. Nocardia grow
slowly on non-selective culture media, and are strict
aerobes with the ability to grow in a wide temperature
range. Some species are partially acid fast(meaning
that a less concentrated solution of hydrochloric acid
should be used during the staining procedure) due to
the presence of intermediate-length mycolic acids in their cell wall. Majority of strains
possess the cord factor(trehalose 6-6' dimycolate),an important virulence factor.
History:
Nocard, a French microbiologist and veterinary pathologist, first isolated Nocardia in 1888
and described the species Nocardia faraneux, a lymphatic and visceral disease of oxen.
Nocardia infections in humans range from chronic skin lesions to a progressive pulmonary
disease with documented haematogenous dissemination to virtually any organ in the body.

Epidemiology: Although nocardiosis has been diagnosed in individuals with no detectable

deficiency of humoral or cell-mediated immunity, it usually occurs in patients whose
immune status has been compromised by post-transplant immunosuppressive therapy,
leukemia, lymphoma, dysgammaglobulinemia, pancytopenia, humoral defects, chronic
granulomatous disease, or steroid therapy. The male/female ratio in nocardiosis is
approximately 2:1, and infections occur from infancy to old age. There is no apparent
geographic clustering of cases in the United States, except for cutaneous infection with N
brasiliensis, which is more common in the south.

Disease Host: Both normal and immunocompromised humans and animals.

Disease Transmission:

Nocardiosis is sporadic and person-to-person spread is not well documented. Nocardia are
parasitic bacteria which grow and reproduce on organic material. Their man habitat is
carbon-rich sources such as soils, and plant and animal tissues. In fact, they can be found
almost anywhere. One environmental survey found Nocardia in "beach sand, swimming
pools, house dust, and garden soil". Upon infection of a plant or animal host, it metabolizes
necrotizing tissues for energy and nutrients. Because Nocardia can form endospores,
transmission of the bacteria "aerogenically" from one host to another is relatively easy, and
the bacteria can survive dormantly when food sources are not present.

As stated, Nocardia infections can be transmitted aerogenically to host respiratory systems or

cutaneous wound sites, they can be introduced by innoculation (puncture wounds with the
bacteria contaminant), and through fluid contact (ex: case reported of keratitis due to
contaminated contact lenses). Infection, once contracted, may spread systemically
(dissemination).
Fig. Pathogenesis of Nocardiosis

Mechanism:

Introduction of N. asteroides via the respiratory tract results in pulmonary lesions that most
often manifest as multiple abscesses. Nocardia abscesses are characteristically confluent,
with little evidence of encapsulation, which probably accounts for the ready dissemination
from the initial pulmonary focus. This organism also evades the host's bactericidal
mechanisms. Host neutrophil mobilization can inhibit Nocardia but does not kill them. Cell-
mediated immunity triggered by activated macrophages and the induction of a T-cell
population capable of direct lymphocyte-mediated cytotoxicity are necessary to kill
Nocardia. Infection progresses after the initial inhibition by neutrophils unless antimicrobial
therapy or cytotoxic lymphocytes take over.

Nocardia exhibit specific organ tropisms. Log-phase cells of Nocardia, which contain
specific cell wall mycolic acids, are more virulent and may influence the ability of nocardiae
to localize in certain tissues, such as the brain. Nocardial metastasis manifests as multiple
abscesses without granules in different organs. In patients with poor neutrophil activity or
impaired cell-mediated immunity, fulminant pulmonary or systemic nocardiosis is an
uncommon but opportunistic infection. It is curable but has a high mortality rate (exceeding
50% in some reports), probably because of delayed diagnosis and treatment. A high index of
suspicion, followed by aggressive diagnosis and treatment, is necessary for optimal results.
Signs and Symptoms of disease:
Symptoms vary and depend on the organs involved.

• Lungs (pulmonary nocardiosis):

Fevers
Night sweats
Weight loss
Coughing blood
Chest pain upon breathing(may occue slowly or suddenly)
• Brain (cerebral nocardiosis):
Fever
Headache
Loss of neurological function (may be seen, depending the part of the brain
affected)
Confusion
Disorientation, which means a loss of awareness of people, place, and time
Dizziness
Nausea
Seizures
• Skin:
Red bump or Ulcer
Swollen lymph gland

Diagnosis:
Nocardiosis is diagnosed by tests that identify the bacteria. Depending on the site involved
this may involve obtaining a tissue sample by way of the following:
 Sputum culture
 Bronchoscopy
 Lung biopsy
 Skin biopsy
 Brain biopsy
 Generalized infections
 Chest radiographic findings vary and include fluffy infiltrates, scattered nodules, and
confluent lobar infiltrates progressing to complete consolidation and cavitation.
 Chest CT scanning is necessary to visualize the extent of disease and to rule out
empyema.
 CT scanning with contrast or MRI may be necessary to visualize cerebral abscesses.
 Perform abdominal and/or pelvic sonography and CT scanning to rule out intra-
abdominal, hepatic, splenic, or renal abscesses
 Use 2-dimensional echocardiography to rule out vegetations
 Perform CT scanning with contrast or MRI to rule out cerebral abscesses.
  Because of the high incidence of spread to the brain, all patients with pulmonary
nocardiosis should have a neuroimaging study, even in the absence of CNS
symptoms.

Treatment:
Individuals with Nocardiosis, either disseminated or cutaneous, require long-term antibiotic
treatment (for 6 months) for the infection.
 Sulfamethoxazole-trimethoprim (Bactrim) is used most frequently, and can be
taken in pill form. Skin lesions may need to be surgically drained or removed.
Diseased tissue may need to be removed from mycetomas.
 Linezolid has a growing literature in support of its use in combination and
even monotherapy for treatment of Nocardia infections. It has good CNS penetration,
is available in an oral form, and is the only antibiotic known to be active against all
strains of Nocardia.

 Other medications for the pediatric age group include extended-spectrum

cephalosporins, imipenem/meropenem, ampicillin, and amoxicillin-clavulanate.
Tetracycline derivatives used in treatment include minocycline or doxycycline (in a
child >8 y with sulfa hypersensitivity)

 Patients who are immunocompetent with lymphocutaneous disease are usually

treated for 6-12 weeks. Therapy includes incision and drainage of abscesses. Patients
with immunocompromising conditions are treated for at least 3 months after clinical
cure (usually up to 1 y of therapy

 Individuals who are immune compromised, though, may have a more difficult
time recovering

Geographical Distribution:
Nocardia asteroides, the bacteria that causes nocardiosis, is found worldwide in the natural
environment.
Nocardiosis in India: Nocardiosis, an uncommon infection of the past, is being increasingly
reported in recent years with rise of immunosuppressed patients. In India, very few centers
have reported this disease. The present report describes twelve consecutive cases of
nocardiosis reported over a period of 26 months (January 2004 to March 2006) from a
tertiary care center in north India.

Disease Statistics:

o Incidence (annual) of Nocardiosis: estimated 500-1,000 annual cases in USA

(DBMD). An estimated 10%-15% of these patients also have HIV infection.
o Incidence Rate: approx 1 in 544,000 or 0.00% or 500 people in USA
o Incidence extrapolations for USA for Nocardiosis: 500 per year, 41 per month, 9
per week, 1 per day, 0 per hour, 0 per minute, 0 per second.
o In patients who undergo renal transplant, the incidence rate is 0-20%.
 o In patients who undergo bone marrow transplant, the incidence rate is 0.3%, and in
patients with systemic lupus erythematosus, the incidence rate is 2.8%.

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http://www.histopathology-india.net/Nocard.htm
http://www.fujita-hu.ac.jp/~tsutsumi/photo/photo072-1.htm
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http://microbewiki.kenyon.edu/index.php/Image:PHIL_3144_lores.jpg
http://microbewiki.kenyon.edu/index.php/Image:PHIL_3145_lores.jpg
http://microbewiki.kenyon.edu/index.php/Image:PHIL_3147_lores.jpg

Brijesh Singh Yadav