AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Nocardiosis is an acute, subacute, or chronic infectious disease that occurs in cutaneous, pulmonary, and disseminated forms. Primary cutaneous nocardiosis manifests as cutaneous infection (cellulitis or abscess), lymphocutaneous infection (sporotrichoid nocardiosis), or subcutaneous infection (actinomycetoma). Pleuropulmonary nocardiosis manifests as an acute, subacute, or chronic pneumonitis, usually in immunocompromised hosts, although isolated cases have been reported in immunocompetent hosts. Disseminated nocardiosis may involve any organ; lesions in the brain or meninges are most common.

Pathophysiology

Members of the genus Nocardia are aerobic actinomycetes that are ubiquitous saprophytes in soil, decaying organic matter, and water. At least 30 species of the genus Nocardia have been identified, and at least 13 of these are reported to cause human disease. New Nocardia species continue to be identified.¹ Nocardia asteroides is responsible for most cases of Nocardia disease among humans in the United States; various other Nocardia species are dominant in other parts of the world. Nocardia species also cause infections in animals, including bovine mastitis and sporotrichoid nocardiosis in horses.

When observed microscopically, either in Gram-stained smears of clinical specimens or cultures or on histopathology in tissues, Nocardia organisms are branching, beaded, filamentous, gram-positive bacteria with a characteristic morphology to a trained observer.


High-power microscopic appearance of Nocardia. Image courtesy of CDC.

Nocardia are typically weakly acid-fast after traditional staining and positive on modified acid-fast staining, but this is not invariable.

The cutaneous, lymphocutaneous, and subcutaneous forms of nocardiosis arise from local traumatic inoculation. These infections are not necessarily associated with immunocompromised host states, but dissemination from these sites of inoculation is more likely in immunocompromised hosts. Pleuropulmonary nocardiosis presumably arises from inhalation exposure. Disseminated nocardiosis results from hematogenous dissemination, usually from a pulmonary focus. Most persons with disseminated nocardiosis have underlying immunocompromising disease or are receiving immunosuppressive therapy.

Frequency

United States

In the 1970s, a survey estimated the incidence of nocardiosis in the United States at 500-1000 cases per year (0.4 cases per 100,000 population per year). However, with the increased prevalence of impaired cell-mediated immunity since then, the incidence of nocardiosis has likely also increased.³

Clusters of nocardiosis have been described in hospitalized patients, related to contaminated fomites from construction or contaminated hands of staff.¹

International

No reliable estimates on the international frequency of nocardiosis are available.

Mortality/Morbidity

Nocardiosis has a variable prognosis, depending on the site of infection, extent of infection, and underlying host factors.⁴

• Cure rates with appropriate therapy are approximately 100% in skin and soft-tissue infections.
• Ninety percent of pleuropulmonary infections can be cured with appropriate therapy.
• The cure rate in disseminated nocardiosis falls to 63%, while only half of patients with brain abscess can be cured with therapy.

Race

Nocardiosis has no apparent racial predilection.

Sex

Nocardiosis is more common in males than in females, with a male-to-female ratio of 3:1. This difference may be related to exposure frequency rather than a gender difference in susceptibility.

Age

All ages are susceptible to nocardiosis. The mean age at diagnosis is in the fourth decade of life.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Clinical manifestations of nocardiosis depend on the site of infection.^{5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16}

• Primary cutaneous nocardiosis may present as cutaneous infection, lymphocutaneous infection, or subcutaneous infection.
• • Cutaneous nocardiosis generally manifests as either cellulitis or, more likely, single or multiple nontender erythematous nodule(s) at the site of traumatic inoculation. These nodules occasionally drain purulent material.
  • Lymphocutaneous nocardiosis manifests as similar lesions accompanied by ascending regional lymphadenopathy. The lymphadenopathy may also occasionally drain purulent material.
  • Nocardial species can cause mycetoma, a chronic, swollen, purulence-draining, subcutaneous infection of the extremities, typically encountered in tropical areas of the world.¹⁵
• Postoperative wound infections due to Nocardia species are rare.
• Traumatic inoculation nocardial arthritis has occurred but is rare. This presents as a subacute or chronic monarthritis, typically involving the knee.
• Traumatic inoculation nocardial endophthalmitis has also occurred in rare instances.
• Pulmonary disease is the predominant clinical finding in most patients with nocardiosis.^{8, 16}
• • Pulmonary nocardiosis may be acute, subacute, or chronic.
  • Clinical manifestations include inflammatory endobronchial masses or localized or diffuse pneumonias, which may be accompanied by cavitation, abscess formation, pleural effusion, or empyema.
  • Symptoms in patients with nocardiosis are indistinguishable from those in patients with similar pulmonary infections of other microbial etiology. Cough with sputum production and fever are the dominant symptoms.
  • At least 40% of patients with disseminated nocardiosis have pulmonary infection; therefore, the clinical presentation may be dominated by the pulmonary symptoms.
• Patients with nocardiosis may present with deep abscess at any site, particularly in the lower extremities or the CNS. In patients with extra-CNS abscesses, fever and local symptoms predominate.
• • Up to 25% of nocardiosis cases (other than those involving mycetoma) involve the CNS. When occurring in isolation, CNS nocardiosis manifests as a slowly progressive mass lesion, with a host of specific neurologic findings related to the specific location of the abscess.
  • CNS nocardiosis is detected in 20-40% of disseminated nocardial infections. In two thirds of patients with CNS nocardiosis, clinical findings indicate abscess with or without meningitis, including fever, headache, stiff neck, and/or altered mental status.

Physical

The physical findings of nocardiosis also vary based on the site of infection.

• Patients with primary cutaneous nocardiosis present with cellulitis, cutaneous nodules, nodules with ascending lymphadenopathy, or with a mycetoma that is clinically indistinguishable from similar infections due to other pathogens.
• Patients with pulmonary nocardiosis present with findings of pulmonary consolidation with or without evidence of pleural effusions.
• The presentation of disseminated nocardiosis depends on the sites of infection.
• • Pulmonary findings frequently predominate.
  • 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.
  • Patients with meningitis present with fever, altered consciousness, and meningismus.

Causes

Pulmonary and disseminated nocardiosis are clearly associated with immunocompromising conditions, with approximately 60% of cases of nocardiosis other than mycetoma occurring in individuals with some compromise of host defense systems. Conditions associated with an increased risk of pulmonary and disseminated nocardiosis include the following:

• Chronic pulmonary disease: Although pulmonary nocardiosis has been described in association with various chronic pulmonary diseases, patients with pulmonary alveolar proteinosis are at particular risk.
• Alcoholism
• Cirrhosis
• Lymphoreticular malignancy
• Solid-organ transplantation¹⁷
• Bone marrow or stem cell transplantation
• Long-term corticosteroid use or Cushing syndrome
• Systemic lupus erythematosus
• Systemic vasculitis
• Ulcerative colitis
• Sarcoidosis
• Renal failure
• Whipple disease
• Hypogammaglobulinemia
• Treatment with anti–tumor necrosis factor antibody
• HIV infection and AIDS: Nocardiosis in individuals with advanced HIV disease usually presents as a relentlessly progressive infiltrative pulmonary infection. The median CD4 count in patients infected with HIV who develop nocardiosis is approximately 50 cells/µL.¹³

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

WORKUP

Section 5 of 10  

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• Clinical
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• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• The diagnosis of nocardiosis is established with culture of the causative organism from the infection site(s). Because nocardiae grow slower than common bacteria, the microbiology laboratory should always be notified when nocardiosis is clinically suspected. This is particularly true when sputum is the submitted specimen. Respiratory secretions, skin biopsy samples, and aspirates from abscesses are the most common specimens from which Nocardia species are identified. Direct smears or histopathologic stains of these specimens can be highly suspicious, as noted above. Nocardia species can usually be isolated in 3-5 days.
• Blood cultures are positive for Nocardia organisms in a minority of patients, but they always should be obtained when pulmonary or disseminated nocardiosis is suspected.
• Immunodominant antigens of Nocardia species have been identified and used in serological assays. However, no serologic technique or molecular technique is yet available for routine clinical use. Similarly, nucleic acid amplification assays have been described but are not available for routine clinical use.

Imaging Studies

• Plain chest radiography and, often, CT chest scanning are useful in evaluating pulmonary nocardiosis and in monitoring the course of the infection. However, no characteristic radiographic findings have been described. Radiographic findings may include irregular nodules (which may cavitate), reticulonodular or diffuse alveolar pulmonary infiltrates, lung abscess formation, and pleural effusion.
  
  
  Plain chest radiograph in a patient with nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
• 
  
  
  Chest CT scan in a patient with pleuropulmonary nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.

• All patients with nocardiosis, except those with mycetoma, should undergo brain imaging with either CT scanning or MRI (likely preferred). Intracranial abscess is the most common abnormality found. Spread of intracranial abscesses to contiguous structures is particularly suggestive of nocardiosis.
  
  
  Brain CT scan in a patient with nocardial brain abscess. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
• Localized symptoms other than pulmonary or CNS should be evaluated with appropriate site-specific imaging.

Other Tests

• If meningitis is suspected, cerebrospinal fluid (CSF) should be obtained for analysis unless this is contraindicated by mass effect on brain imaging. Nocardial meningitis typically results in findings typical of bacterial meningitis (ie, neutrophilic pleocytosis, hypoglycorrhachia, and a mildly elevated CSF protein level).

Procedures

• Biopsy of skin lesions or aspiration of deep abscesses may be required for diagnosis of nocardiosis.
• Similarly, in patients with pulmonary nocardiosis, bronchoalveolar lavage and/or transbronchial lung biopsy may be required if the microbial etiology is not definitively established based on examination and culture of expectorated sputum.

Histologic Findings

Suppurative infection with organisms of characteristic morphology and staining attributes is the typical histopathologic finding in nocardiosis. Granulomatous infection is occasionally encountered.

TREATMENT

Section 6 of 10  

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Medical Care

• Protracted specific antimicrobial therapy is the mainstay of medical care for nocardiosis. Therapy is generally recommended for at least 6 months.¹
• In patients who require immunosuppressive therapy, such therapy can generally be continued while appropriate specific therapy for nocardiosis is administered.

Surgical Care

• For lesions outside the CNS, surgical management is the same as standard recommendations for other infections; that is, localized abscesses generally require prompt surgical therapy.
• In patients with nocardial brain abscesses, surgery should be performed if the lesions are large, if they are readily accessible, or if they progress beyond 2 weeks of antimicrobial therapy.⁹

Consultations

An infectious diseases specialist is recommended for coordinating protracted antimicrobial therapy. Depending on the infection site(s), consultation with a pulmonologist, thoracic surgeon, general surgeon, and/or neurosurgeon may be appropriate.

Diet

No specific dietary recommendations are warranted.

Activity

Activity can be as tolerated by the patient.

MEDICATION

Section 7 of 10  

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Sulfonamides have long been the first-line antimicrobial therapy for nocardiosis. Among the sulfonamides, sulfadiazine is generally preferred because of its CNS and CSF penetration. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered by most an acceptable alternative to sulfadiazine. The addition of trimethoprim has not been shown convincingly to enhance the efficacy of sulfonamide. Therefore, this drug must be dosed to provide a dose of sulfamethoxazole equivalent to that given with sulfadiazine alone. TMP-SMX may be the preferred therapy when parenteral therapy is required because it is generally the only available parenteral sulfonamide agent.

In patients who are unable to take sulfonamides, therapy may be guided by in vitro susceptibility testing, although such testing for Nocardia species is difficult technically, poorly standardized, and not fully correlated with in vivo results of therapy. No data exist from comparative clinical trials to guide the choice among alternative therapies.

In Vitro Susceptibility Data¹

Alternative oral therapies include minocycline and amoxicillin/clavulanate. These may be used initially in mild to moderately severe disease or as sequential therapy after an induction course of parenteral therapy. Modern fluoroquinolones often have demonstrable in vitro activity against Nocardia species but have failed therapeutically.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

FOLLOW-UP

Section 8 of 10  

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In/Out Patient Meds

• Antimicrobial therapy for pulmonary or disseminated nocardiosis should be continued for 6-12 months and at least 1 month following resolution of all evidence of infection.
• Follow-up radiographic studies should be obtained to monitor treatment.
• Follow-up laboratory studies are required to monitor for adverse effects of prolonged antimicrobial therapy.

Deterrence/Prevention

Although not clearly established, prophylactic therapy for Pneumocystis jiroveci pneumonia (PCP) with TMP-SMX in patients with AIDS whose CD4 count is less than 200 cells/µL probably decreases the likelihood of nocardiosis. (For an excellent discussion of PCP prophylaxis, see the eMedicine article Prevention of Opportunistic Infections in Patients Infected With HIV.) Similarly, TMP-SMX prophylaxis in solid-organ transplant or hematopoietic stem cell transplant recipients may decrease the likelihood of nocardiosis. However, prophylaxis is not fully effective in either circumstance.

Patient Education

• Patients with nocardiosis must be educated about the need for protracted antimicrobial therapy.
• Patients with nocardiosis should be informed of the potential adverse effects of protracted antimicrobial therapy and which circumstances require reporting to their physician promptly.

MULTIMEDIA

Section 9 of 10  

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• Clinical
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• Workup
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• Follow-up
• Multimedia
• References

Media file 1:  High-power microscopic appearance of Nocardia. Image courtesy of CDC.
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Media file 2:  Photomicrograph of tissue biopsy stained with Gomori methenamine silver demonstrating acute inflammatory response and organisms compatible with Nocardia.
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Media type:  Micrograph

Media file 3:  Plain chest radiograph in a patient with nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Media type:  Radiograph

Media file 4:  Chest CT scan in a patient with pleuropulmonary nocardiosis. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Media type:  Radiograph

Media file 5:  Brain CT scan in a patient with nocardial brain abscess. Image courtesy of Applied Radiology, Anderson Publishing, LTD.
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Media type:  Radiograph

REFERENCES

Section 10 of 10

• Authors and Editors
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1. Sorrell TC, Mitchell DH, Iredell JR. Nocardia species. In: Mandell, Bennett, Dolin. Principles and Practice of Infectious Diseases. volume 2. 6^th edition. Churchill Livingstone; 2005.
2. Beaman BL, Beaman L. Nocardia species: host-parasite relationships. Clin Microbiol Rev. Apr 1994;7(2):213-64. [Medline].
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4. Smego RA Jr, Moeller MB, Gallis HA. Trimethoprim-sulfamethoxazole therapy for Nocardia infections. Arch Intern Med. Apr 1983;143(4):711-8. [Medline].
5. Boiron P, Locci R, Goodfellow M, et al. Nocardia, nocardiosis and mycetoma. Med Mycol. 1998;36 Suppl 1:26-37. [Medline].
6. Castro JG, Espinoza L. Nocardia species infections in a large county hospital in Miami: 6 years experience. J Infect. Apr 2007;54(4):358-61. [Medline].
7. Filice GA. Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations. J Lab Clin Med. Mar 2005;145(3):156-62. [Medline].
8. Hui CH, Au VW, Rowland K, et al. Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med. Jun 2003;97(6):709-17. [Medline].
9. Kilincer C, Hamamcioglu MK, Simsek O, et al. Nocardial brain abscess: review of clinical management. J Clin Neurosci. May 2006;13(4):481-5. [Medline].
10. Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine (Baltimore). Sep 2004;83(5):300-13. [Medline].
11. Lerner PI. Nocardiosis. Clin Infect Dis. Jun 1996;22(6):891-903; quiz 904-5. [Medline].
12. Matulionyte R, Rohner P, Uckay I, et al. Secular trends of nocardia infection over 15 years in a tertiary care hospital. J Clin Pathol. Aug 2004;57(8):807-12. [Medline].
13. Pintado V, Gomez-Mampaso E, Cobo J, et al. Nocardial infection in patients infected with the human immunodeficiency virus. Clin Microbiol Infect. Jul 2003;9(7):716-20. [Medline].
14. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. Oct 2003;41(10):4497-501. [Medline].
15. Pilsczek FH, Augenbraun M. Mycetoma fungal infection: multiple organisms as colonizers or pathogens?. Rev Soc Bras Med Trop. Jul-Aug 2007;40(4):463-5. [Medline].
16. Martinez Tomas R, Menendez Villanueva R, Reyes Calzada S, et al. Pulmonary nocardiosis: risk factors and outcomes. Respirology. May 2007;12(3):394-400. [Medline].
17. Peleg AY, Husain S, Qureshi ZA, et al. Risk factors, clinical characteristics, and outcome of Nocardia infection in organ transplant recipients: a matched case-control study. Clin Infect Dis. May 15 2007;44(10):1307-14. [Medline].
18. Jodlowski TZ, Melnychuk I, Conry J. Linezolid for the treatment of Nocardia spp. infections. Ann Pharmacother. Oct 2007;41(10):1694-9. [Medline].
19. Sridhar MS, Gopinathan U, Garg P, et al. Ocular nocardia infections with special emphasis on the cornea. Surv Ophthalmol. Mar-Apr 2001;45(5):361-78. [Medline].

Article Last Updated: Oct 14, 2008