eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Nocardiosis

Author: Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University
Coauthor(s): Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York-Upstate Medical University; Rosemary Johann-Liang, MD, Medical Officer, Infectious Diseases and Pediatrics, Division of Special Pathogens and Immunological Drug Products, Center for Drug Evaluation and Research, Food and Drug Administration
Contributor Information and Disclosures

Updated: Aug 28, 2009

Introduction

Background

Nocardia are weakly gram-positive, filamentous bacteria found worldwide in soils. Human disease from this microbe was first described by Eppinger in 1890, after bovine disease was described by Nocard in 1888. Pathogenic Nocardia are members of the family Nocardiaceae, the aerobic actinomycetes. Nocardia asteroides is the principal cause of systemic nocardiosis in the United States. Nocardia pseudobrasiliensis, Nocardia otitidis-caviarum (formerly Nocardia caviae), Nocardia farcinica, Nocardia nova, and Nocardia transvalensis have also been rarely associated with human systemic disease.

Two newly described species have been associated with disease in humans: Nocardia abscessus, from soft-tissue abscesses,² and Nocardia africana, from respiratory secretions of patients with pneumonia in the Sudan.³ Most recently, Nocardia ignorata, a new agent of human nocardiosis, was isolated from respiratory specimens in Europe and soil samples from Kuwait.⁴ Case reports of Nocardia cyriacigeorgica occurring in the United States have been published, with several infections being retrospectively identified from stored samples.

Molecular DNA hybridization techniques (usually involving the 16S ribosomal RNA [rRNA]) have better characterized the Nocardia species; this identification is useful in identifying antibiotic resistance patterns. Several of the species mentioned above (N nova, N farcinica, N abscessus, N cyriacigeorgica) had been considered as N asteroides isolates in some reports.⁵

Nocardiosis is an acute, subacute, or chronic suppurative infection caused by Nocardia. It has a pronounced tendency to remission and exacerbation. Infections are localized or disseminated. Localized cutaneous or lymphocutaneous infections usually occur after contamination of an abrasion, resulting in cutaneous or lymphocutaneous abscess. In children with immunocompetence, systemic spread from the primary skin site is extremely rare.

Disseminated and fulminant disease mainly occurs in immunocompromised hosts (among persons with deficient cell-mediated immunity) with underlying illnesses, such as chronic granulomatous disease or human immunodeficiency virus (HIV) infection, and in children undergoing cytotoxic chemotherapy, bone marrow transplantation, or prolonged glucocorticoid treatment.

Nocardiosis has also been associated with pulmonary alveolar proteinosis, tuberculosis and other mycobacterial diseases, and interleukin 12 deficiency. Inhalation of the free-living organism is the likely route of infection. The primary disease occurs in the pulmonary system and may mimic tuberculous, staphylococcal, or mycotic infections. Hematogenous dissemination may occur to all organs of the body. The brain, kidneys, and liver are the most common metastatic sites.

Interestingly, Nocardia species have been found to produce effective antibacterial agents, including one agent (nargencin) that shows promise against methicillin resistant Staphylococcus aureus.⁶ Nocardia lactamdurans has also been found to produce a cephamycin under the right conditions.⁷

Pathophysiology

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.

Frequency

United States

Nocardiosis is sporadic and person-to-person spread is not well documented. Rare outbreaks have been associated with contamination of the hospital environment. Incidence estimates vary in immunocompromised populations. In patients who undergo renal transplant, the incidence rate is 0-20%. 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%.

Higher rates of infection are observed in the hotter, drier states, perhaps because of easier entry of infectious organisms into the lungs from dust blown into the air.

International

Nocardiosis occurs sporadically worldwide.

Mortality/Morbidity

Death occurs from sepsis, overwhelming pneumonia, or brain abscess, rather than the untreated underlying disease. Mortality is increased in patients with acute infection and in those with disseminated disease involving 2 or more contiguous organs or the CNS. Mortality is also increased in patients taking corticosteroids or antineoplastic agents.

Race

No racial predilection is known.

Age

No age predilection is recognized.

Clinical

History

• Generalized nocardiosis
  • In patients with cutaneous disease, elicit history of trauma at the site of mycetoma (eg, scrape from thorn), firm subcutaneous abscesses (eg, cat scratch, insect bite, open cut), and/or cervical adenitis (eg, dental injury). Signs of infection tracking along lymph node chains or a draining sinus may be present.
  • Slowly progressive joint swelling and pain, with or without fever, may occur, resulting in Nocardia septic arthritis if the trauma was deep (eg, puncture from rooster's claw).
  • The pulmonary course begins with nonspecific complaints, including fever (night sweats), malaise, chest or abdominal pain (may be sudden onset), persistent cough (rarely hemoptysis), and anorexia.
• Disseminated nocardiosis
  • If dissemination occurs from a pulmonary infection, a constellation of acute and chronic symptoms develops, ranging from headache to obtundation (CNS), pyuria (kidneys), and right upper abdominal pain (liver). CNS infection may have no signs or symptoms or may present with focal neurological deficits, seizures, and coma.
  • Children at risk for nocardiosis as an opportunistic infection include patients with the following:
    • Lymphoreticular neoplasms
    • Chronic pulmonary disorders (most notably alveolar proteinosis)
    • Prolonged corticosteroid usage
    • Systemic lupus erythematosus
    • Severe asthma
    • Chronic granulomatous disease
    • Children with acquired immune deficiency syndrome (AIDS)
  • Patients undergoing transplant for the following are at risk:
    • Renal
    • Cardiac
    • Liver
    • Bone marrow

Physical

• Subcutaneous abscesses are palpable at the site of trauma and generally feel firmer than fluctuant. Contiguous lymph nodes may indicate infection tracking along lymphatics.
• A lung examination may reveal diffuse or localized abnormal breath sounds.
• Mild-to-severe respiratory distress that progresses to respiratory failure may occur.
• Disseminated miliary appearance can occur with diffuse organ abscesses that mimic miliary tuberculosis.
• Clinical manifestations may include the following:
  • Bronchopneumonia
  • Lobar pneumonia
  • Necrotizing pneumonia
  • Persistent meningitis
  • Cerebral abscesses
  • Peritonitis
  • Intra-abdominal abscesses
  • Hematogenous endophthalmitis
  • Sinusitis
  • Endocarditis
  • Aortitis
  • Mediastinitis
  • Pyelonephritic abscesses
  • Septic arthritis

Causes

• Nocardia are usually found in soil and dust, and infection results from inoculation of a wound or inhalation. Person-to-person transmission has not been reported, and Nocardia are not commensal in humans or animals.
• Nosocomial cases have been reported. In some cases, N asteroides were detected in the dust and air of the hospital unit.

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