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Pediatric Nocardiosis

  • Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Russell W Steele, MD  more...
 
Updated: Oct 04, 2013
 

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.

A recent report of infections with Nocardia carnea, Nocardia elegans, Nocardia paucivorans, Nocardia puris, and Nocardia takedensis has come from Japan.[1] Nocardia brasiliensis is a common cause of localized chronic mycetoma. A total of approximately 30 strains of Nocardia have been associated with human 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, Nfarcinica, Nabscessus, 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]

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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.

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Epidemiology

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.

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Contributor Information and Disclosures
Author

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Received research grant from: Cubist Pharmaceuticals, Durata Therapeutics, and Biota Pharmaceutical<br/>Received income in an amount equal to or greater than $250 from: HealthyCT insurance<br/>Medico legal consulting for: Various.

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

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa

Disclosure: Received research grant from: Pfizer;GlaxoSmithKline;AstraZeneca;Merck;American Academy of Pediatrics<br/>Received income in an amount equal to or greater than $250 from: Sanofi Pasteur;Astra Zeneca;Novartis<br/>Consulting fees for: Sanofi Pasteur; Novartis; Merck; Astra Zeneca.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

Gary J Noel, MD Professor, Department of Pediatrics, Weill Cornell Medical College; Attending Pediatrician, New York-Presbyterian Hospital

Gary J Noel, MD is a member of the following medical societies: Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

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

Rosemary Johann-Liang, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

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