Nocardiosis

 

by Brandon Flammang

 

Disease: 

Nocardiosis – an acute, subacute, chronic, disseminated, suppurative or granulomatous bacterial infection caused by various species of the genus Nocardia (1)(2).  It is a rare disorder that affects the lungs, brain, skin or any other organs (3).  It is especially prevalent among people with weakened immune systems, such as patients with HIV/AIDS (3). The term is used as an umbrella to encompass all infections and diseases caused by species of the Nocardia genus.      

 

Etiologic Agent: 

There is no one unique species that causes these types of diseases.  There are approximately fifty species of Nocardia and thirty of which are known to cause disease of this type (4).  The most common human pathogen causing pulmonary and disseminated infection in at least 50% of reported cases are caused by Nocardia asteroides while other pathogenic species reported include N. farcinica, N. nova, N.transvalensis, and N. brasiliensis (2)(5).  The latter, N.brasiliensis, is the most common etiologic agent for skin infections (2).  To report this disease adequately and efficiently, the Nocardia asteroides will be used as the etiological agent for the disease since it is the primary cause, unless otherwise stated. 

 

Method of Transmission: 

There are two main methods of transmission to acquire an infection.  Pulmonary and disseminated infections occur through inhalation of contaminated dust or soil containing the microorganism (2)(3)(5).  Cutaneous infection occurs open wounds becoming contaminated with dust or soil with the microorganism, or through direct inoculation/puncture of the skin by dust or soil with the microorganism (2)(3)(5).  Postsurgery nosocomial infection is a third method of transmission but it is rare(5).

 

Reservoirs: 

Nocardia species occur naturally and ubiquitously throughout the world as part of the normal ground soil flora, some aquatic habitats, and have been associated with decomposing plant material, dust, and the air if particulates are disturbed in those areas (1)(4)(6).  N. brasiliensis is associated with tropical environments (6).  Person-to-person transmission is rare and not well documented (2).   

 

General Characteristics of Microorganism:

Species of the Nocardia genus are of the phyla Actinobacteria, order Actinomycetes, family Actinomycetaceae (2)(7).  They have high G+C content in their genome and produce antibiotics (7).  They are aerobic, filamentous, branching, beaded, Gram positive rods that are partially acid-fast (8)(9).  They are variably acid fast due to presence of intermediate mycolic acids in cell wall (10).      

 

Key Identification Tests:

The Gram stain procedure is the most sensitive method to visualize Nocardia species from clinical specimens, such as pus or sputum, by seeing filamentous, branched, beaded, Gram positive rods (9)(10).  A modified acid fast stain procedure is used to confirm the results of the Gram stain, with the staining usually giving a positive result (9)(10).  Growing cultures of the bacterium is slow and time consuming, from 2 to 4 weeks (10).  The differentiation of Nocardia species from one another is very difficult using standard biochemical tests (10).  Other tests are diagnostic, such as a BAL, chest X-ray or CT scans (11).      

 

Signs and Symptoms:

Signs and symptoms of nocardiosis vary depending on the organ or systems infected.  Nocardiosis usually begins as a subacute pulmonary infection that resembles actinomycosis, but Nocardia is more likely to disseminate locally, in nearly one half of all pulmonary cases (2)(3). Dissemination with abscess formation may involve any organ but most commonly affects the brain, skin, kidney, bone, or muscle (2).

 

Pulmonary (respiratory/lungs): chest pain while breathing, coughing (with blood), fever, nigh sweats, chills, malaise, anorexia, weight loss and may resemble those of tuberculosis or suppurative pneumonia (2)(3). 

 

Cutaneous (skin):  Skin or subcutaneous abscesses occur frequently, sometimes as a primary local inoculation. They may appear as a firm cellulitis, a lymphocutaneous syndrome, or an actinomycetoma. An actinomycetoma begins as a nodule, suppurates, spreads along fascial planes, and drains through chronic fistulas.  They usually occur on the hands or feet, sometimes the neck or upper back (10). The lymphocutaneous syndrome consists of a primary pyoderma lesion at the inoculation site, subcutaneous lymphatic nodules resembling sporotrichosis, that drain the primary lesion (2)(10).

 

Brain (cerebral nocardiosis): May include fever, headache, nausea, vomiting, mental status changes, seizures, loss of neurological functions (depending on the area of the brain infected) (3)(10).  Brain disease typically takes the forms of subacute abscesses and may be asymptomatic at the time of recognition of pulmonary disease (10).

 

Eye Infections:  Include subacute keratitis, follwed by eye trauma with pain redness, blurred vision, ocular discharge, corneal ulceration, endophthalmitis and may become disseminated (10).

 

Historical Information:

The genus Nocardia is named after its discoverer, Edmund Nocard, a French veterinarian and microbiologist (12).  He lived from 1850 to 1903, discovering the genus in 1888 and initially naming it Streptothrix farcinica (12).  It has a high prevalence of being an opportunistic pathogen by infecting immunocompromised persons (2).  It has been found that some Nocardia species can produce antibacterial agents, specifically Nargencin, that is effective against methicillin resistant Staphylococcus aureus (1).   

 

Nocardia species identification and taxonomy have been improved by molecular methods such as 16S rRNA and hsp65 gene sequence analysis. These procedures are rapid, accurate, and reproducible and can better discriminate among strains of actinomycetes than is possible with phenotypic methods (4).

 

Virulence Factors:

Nocardia species 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 (1)(13).

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, fulminate 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 (1)(13).

 

Treatment and Control:

Long-term antibiotic therapy (usually with sulfonamides) for 6 months to a year (or longer depending on the individual and the parts of the body involved) is needed to treat nocardia.  Patients who develop abscesses caused by this infection may need surgery to completely drain the abscesses (3). 

 

Sulfa-containing antimicrobials remain the drugs of choice for nocardiosis. They have been proven to improve survival when used alone or in combination with other antimicrobials. Primary agents that have been used successfully in treatment of nocardiosis include minocycline, amikacin, ceftriaxone, imipenem and linezolid. Combining one or more of these agents with sulfa-containing antimicrobials has been recommended for serious systemic infections (8).  Trimethoprim (TMP) and sulfamethoxazole (SMX) is a primary combination in treating many types of nocardiosis (10).   

 

Without treatment, pulmonary and disseminated nocardiosis are usually fatal. Among patients who are treated with appropriate antibiotics, the mortality rate is highest (> 50%) in immunocompromised patients with disseminated infections and lowest (about 10%) in immunocompetent patients with lesions restricted to the lungs. Cure rates for patients with skin infection are usually > 95%. (2)

 

Prevention and Vaccination:

While individuals with normal immune systems can get this infection, the main risk factors for getting nocardiosis are a weakened immune system (with deficient cell mediated immunity (10)) or chronic lung disease. People on long-term steroid therapy, those with cancer, organ or bone marrow transplants or HIV/AIDS (3).  As such, these immunocompromised persons should avoid extensive exposure to soil or dust. 

The incidence of nocardiosis is low enough that specific antimicrobial prophylaxis for this infection is not recommended. (10)

Adults are at a higher risk than children and males have a 3:1 ratio to females of acquiring the disease (10).  Patients with bone marrow transplants have a 340x greater incidence rate and patients with HIV/AIDS have a 140x greater incidence rate, as compared to non-immunocompromised patients (10).

 

Local Cases/Outbreaks:

In the United States, an estimated 500-1,000 new cases of Nocardia infection occur annually. An estimated 10%-15% of these patients also have HIV infection.  Approximately 10% of cases with uncomplicated pneumonia are fatal. Case-fatality rate increases with overwhelming infection, disseminated disease, or brain abscess (5).

 

Although incidence data are extremely limited, the number of cases probably has increased recently because of the overall increased number of severely immunocompromised persons as well as improved methods for pathogen isolation and molecular identification (4)(5).

 

Higher rates of infection are observed in the hotter, drier areas, perhaps because of easier entry of infectious organisms into the lungs from dust blown into the air (1).

 

Global Cases/Outbreaks:

The annual incidence is ~0.375 cases per 100,000 persons worldwide (10).   

Actinomycetomas occur mainly in tropical and subtropical regions, especially in Mexico, Central and South America, Africa, and India, however worldwide incidence is sporadic (10).  There have been newly reported cases from Japan, Sudan, Europe,and Kuwait (1).  These new cases also coincide with newly discovered species or species that were not previously believed to cause nocardiosis (1). 

  

References:

(1)        Authors: Nicholas John Bennett, MB, BCh, PhD, Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University; “Nocardiosis”; Updated August 28, 2009; http://emedicine.medscape.com/article/966919-overview Last Accessed December 12, 2009

 

(2)        Robert S. Porter, MD, Editor-in-chief; Merck Sharp & Dohme Corp; “Nocardiosis: Gram Positive Bacilli Merck Manual Professional”; November 2005

http://www.merck.com/mmpe/sec14/ch172/ch172f.html Last Accessed December 12, 2009

 

(3)        Linda Vorvick, MD, Jatin M. Vyas, MD, PhD, David Zieve, MD, MHA; A.D.A.M., Inc; “Nocardia infection”; Update Date: 9/28/2008

http://www.nlm.nih.gov/medlineplus/ency/article/000679.htm Last Accessed December 12, 2009

 

(4)        Robert Schlaberg , Richard C. Huard , Phyllis Della-Latta; J. Clin. Microbiol. doi:10.1128/JCM.00937-07; “Nocardia cyriacigeorgica is an emerging pathogen in the United States” November 14, 2007 http://jcm.asm.org/cgi/reprint/JCM.00937-07v1.pdf Last Accessed December 12, 2009

 

(5)        National Center for Zoonotic, Vector-Borne, and Enteric Diseases (ZVED); CDC: Division of Foodborne, bacterial and mycotic diseases; “Disease Listing: Nocardiosis Technical Information”; March 27, 2008 http://www.cdc.gov/nczved/dfbmd/disease_listing/nocardiosis_ti.html Last Accessed December 12, 2009

 

(6)        Michael A. Saubolle and Den Sussland; Journal of Clinical Microbiology, October 2003, p. 4497-4501, Vol. 41, No. 10; “Nocardiosis: Review of Clinical and Laboratory Experience” October 2003. http://jcm.asm.org/cgi/content/full/41/10/4497 Last Accessed December 12, 2009

 

(7)        Todar, Kenneth PhD; Todar’s Online Textbook of Bacteriology; “Important Groups of Procaryotes (page 10)”; 2009 http://www.textbookofbacteriology.net/procaryotes_10.html

Last Accessed December 12, 2009

 

(8)        Hakawi, A.M., Al Rabiah, F.A.; “Clinical pattern of nocardiosis in Saudi Arabia: a case series”; La Revue de Sante de la Mediterranee orientale; Vol. 14 No 4, 2008;

12/04/06 http://www.emro.who.int/emhj/1404/14_4_2008_0966_0971.pdf Last Accessed December 12, 2009

 

(9)        Michael Melia, M.D. and Paul G. Auwaerter, M.D; “Nocardiosis”;  09-29-2009 http://www.hopkins-aids.edu/diagnosis/opportunistic_infections/bacterial/nocardiosis.html

Last Accessed December 12, 2009

 

(10)      GA Filice; Harrison’s Principle of Internal Medicine 17th edition, chapter 155; “Nocardiosis”; May 21, 2009;

http://www.harrisonspractice.com/practice/ub/view/Harrisons%20Practice/141060/all/Nocardiosis Last Accessed December 12, 2009

 

(11)      Benjamin Medoff, MD, David Zieve, MD, MHA; A.D.A.M., Inc; “Pulmonary nocardiosis” 9/13/2008 http://www.nlm.nih.gov/medlineplus/ency/article/000083.htm Last Accessed December 12, 2009


(12)      Chauvau, E Leclainche, E Roux, Edmond Nocard 1850-1903, Paris, Masson and Co éd., 1906, 85 p http://en.wikipedia.org/wiki/Edmond_Nocard Last Accessed December 12, 2009

 

(13)      Samuel Baron; Medical Microbiology 4th Edition:  The UTMB of Galveston; “Nocardia”; 1996 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mmed&part=A1842

Last Accessed December 12, 2009