- Author: Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP; Chief Editor: Russell W Steele, MD more...
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. 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, and Nocardia africana, from respiratory secretions of patients with pneumonia in the Sudan. Most recently, Nocardia ignorata, a new agent of human nocardiosis, was isolated from respiratory specimens in Europe and soil samples from Kuwait. 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.
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. Nocardia lactamdurans has also been found to produce a cephamycin under the right conditions.
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.
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.
Nocardiosis occurs sporadically worldwide.
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.
No racial predilection is known.
No age predilection is recognized.
Watanabe K, Shinagawa M, Amishima M, et al. First clinical isolates of Nocardia carnea, Nocardia elegans, Nocardia paucivorans, Nocardia puris and Nocardia takedensis in Japan. Nippon Ishinkin Gakkai Zasshi. 2006. 47(2):85-9. [Medline]. [Full Text].
Marchandin H, Eden A, Jean-Pierre H, et al. Molecular diagnosis of culture-negative cerebral nocardiosis due to Nocardia abscessus. Diagn Microbiol Infect Dis. 2006 Jul. 55(3):237-40. [Medline].
Hamid ME, Maldonado L, Sharaf Eldin GS, et al. Nocardia africana sp. nov., a new pathogen isolated from patients with pulmonary infections. J Clin Microbiol. 2001 Feb. 39(2):625-30. [Medline].
Rodriguez-Nava V, Couble A, Khan ZU, et al. Nocardia ignorata, a new agent of human nocardiosis isolated from respiratory specimens in Europe and soil samples from Kuwait. J Clin Microbiol. 2005 Dec. 43(12):6167-70. [Medline]. [Full Text].
Conville PS, Witebsky FG. Organisms designated as Nocardia asteroides drug pattern type VI are members of the species Nocardia cyriacigeorgica. J Clin Microbiol. 2007 Jul. 45(7):2257-9. [Medline]. [Full Text].
Sohng JK, Yamaguchi T, Seong CN, Baik KS, Park SC, Lee HJ, et al. Production, isolation and biological activity of nargenicin from Nocardia sp. CS682. Arch Pharm Res. 2008 Oct. 31(10):1339-45. [Medline].
Kagliwal LD, Survase SA, Singhal RS. A novel medium for the production of cephamycin C by Nocardia lactamdurans using solid-state fermentation. Bioresour Technol. 2009 May. 100(9):2600-6. [Medline].
Hashizume Y, Takise A, Kawata T, Suzuki K, Endou K, Horie T. [Pulmonary nocardiosis with elevation of serum beta-D-glucan in a patient with polymyositis]. Nihon Kokyuki Gakkai Zasshi. 2011 Oct. 49(10):750-5. [Medline].
Harada S, Hatakeyama S, Kitazawa T, Itoyama S, Ota Y, Koike K. [A case of disseminated nocardiosis followed by pneumocystis pneumonia in a patient prescribed corticosteroid and cyclosporin A and having elevated blood (1-->3)-beta-D-glucan]. Kansenshogaku Zasshi. 2009 Sep. 83(5):538-43. [Medline].
[Guideline] Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005 Nov 15. 41(10):1373-406. [Medline].
American Academy of Pediatrics. Nocardiosis. Red Book: Report of the Committee on Infectious Diseases. 29th ed. 2012.
Barone MA. Formulary. The Harriet Lane Handbook. 14th ed. 1996. 474-667.
Blackwell Synergy. Nocardia infections. American Journal of Transplantation. 2004. Vol 4 Issue S10:47. [Full Text].
Bruckner DA, Colonna P, Bearson BL. Nomenclature for aerobic and facultative bacteria. Clin Infect Dis. 1999 Oct. 29(4):713-23. [Medline].
Dinulos JG, Darmstadt GL, Wilson CB, et al. Nocardia asteroides septic arthritis in a healthy child. Pediatr Infect Dis J. 1999 Mar. 18(3):308-10. [Medline].
Dorman SE, Guide SV, Conville PS, et al. Nocardia infection in chronic granulomatous disease. Clin Infect Dis. 2002. 35 (4):390-4. [Medline].
Fabre S, Gilbert C, Lechiche C, et al. Primary cutaneous Nocardia otitiscaviarum infection in a patient with rheumatoid arthritis treated with infliximab. J Rheumatol. 2005. 32 (12):2432-3. [Medline].
Feigin RD, Cherry JD. Actinomycosis and nocardiosis. Textbook of Pediatric Infectious Diseases. 1992. Vol 1: 1042-44.
Hitti W, Wolff M. Two cases of multidrug-resistant Nocardia farcinica infection in immunosuppressed patients and implications for empiric therapy. Eur J Clin Microbiol Infect Dis. 2005 Feb. 24(2):142-4. [Medline].
Kontoyiannis DP, Ruoff K, Hooper DC. Nocardia bacteremia. Report of 4 cases and review of the literature. Medicine (Baltimore). 1998 Jul. 77(4):255-67. [Medline].
Leitersdorf I, Silver J, Naparstek E, Raveh D. Tetracycline derivatives, alternative treatment for nocardiosis in transplanted patients. Clin Nephrol. 1997 Jul. 48(1):48-51. [Medline].
Mok CC, Yuen KY, Lau CS. Nocardiosis in systemic lupus erythematosus. Semin Arthritis Rheum. 1997 Feb. 26(4):675-83. [Medline].
Paredes BE, Hunger RE, Braathen LR, Brand CU. Cutaneous nocardiosis caused by Nocardia brasiliensis after an insect bite. Dermatology. 1999. 198(2):159-61. [Medline].
Schlaberg R, Huard RC, Della-Latta P. Nocardia cyriacigeorgica is an emerging pathogen in the United States. J Clin Microbiol. Nov 14 2007. Epub ahead of print:[Medline].
Singh NP, Goyal R, Manchanda V, Gupta P. Disseminated nocardiosis in an immunocompetent child. Ann Trop Paediatr. 2003 Mar. 23(1):75-8. [Medline].
van Burik JA, Hackman RC, Nadeem SQ, et al. Nocardiosis after bone marrow transplantation: a retrospective study. Clin Infect Dis. 1997 Jun. 24(6):1154-60. [Medline].