Q&A: Risk Factors for Nocardiosis Infection

Nocardia was first identified by Nocard in 1888 in bovine farcy. The first human disease was described by Eppinger in 1890. Nocardia is a gram-positive, branching, filamentous, weakly acid-fast bacterium. These organisms are not part of normal flora and are very rarely laboratory contaminants. Pathogenic Nocardia are members of the family Nocardiaceae, the aerobic Actinomycetes. Nocardia asteroides is the principal cause of nocardiosis in the United States (responsible for 80% of human infection). Nocardia is ubiquitous in the soil and decaying vegetables and is found worldwide.

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In this article:
Nocardiosis
MCQ: clinical scenario
MCQ: answer
MCQ: explanation

Nocardiosis

Roughly 500-1000 new Nocardia infections are diagnosed each year, and often in an opportunistic setting; up to 20% of patients with renal transplants develop nocardiosis. The organism can cause pulmonary, extrapulmonary, CNS, or cutaneous disease; CNS involvement is more common in the immunocompromised host. The route of infection is generally by inhalation or wound inoculation. Clinical manifestations can be acute, subacute, or chronic suppurative infections.

Nocardia is responsible for 2% of all brain abscesses; 15% to 45% of infected patients develop CNS involvement. In 36% of patients, the abscesses are multiloculated, which may be of diagnostic significance when seen on MRI scans. In all, 41% of patients have multiple abscesses, and an extraneural source is identified in 66%. The diagnosis requires isolation and identification from the clinical specimen. Nocardia are gram-stain-positive and modified acid-fast stain-positive. Cultures can take 1-3 weeks to develop and speciation is difficult.

No prospective, randomized trials exist addressing the most appropriate treatment of these infections. For more than 50 years, the mainstay of treatment has been trimethoprim-sulfamethoxazole. Second-line agents include imipenem-cilastatin, amikacin, minocycline, ceftriaxone, and dapsone. Successful outcome has also been reported with meropenem, a newer carbapenem with a spectrum of activity comparable to that of imipenem-cilastatin. Resistance to both sulfonamides and cephalosporins is most common among Nocardia farcinicia isolates. Duration of treatment is prolonged and may require up to 1 year of treatment. Generally, the maximum dose of medications is given for 6 weeks, followed by reduced-dose treatment for 6 months to 1 year. Surgical treatment is often required.

MCQ: clinical scenario

A 35-year-old woman is admitted with history of worsening left-sided weakness, multiple falls and finally inability to walk because of her weakness. She had headaches which were getting worse and associated with nausea. She had a past medical history of diabetes mellitus type 2, had undergone a hysterectomy a few years earlier for cervical cancer, and also had been diagnosed with pulmonary alveolar proteinosis (PAP). She lived with her husband, had no children, and reported a 20-year, 2-packs-per-day smoking history, but had recently cut down to 1 pack per day. She denied any alcohol or illicit drug use. Testing showed she was HIV-negative. Toxoplasma immunoglobulin (Ig)M and IgG were negative. Routine blood cultures were negative.

During the initial incision of an open brain biopsy, a large amount of purulent material under pressure was rapidly exposed within 1 mm of the surface of her brain. The STAT gram stain showed light-to-moderate polymorphonucleated cells with heavy branching, gram-positive rods that were modified acid-fast positive. The pathogen was definitively diagnosed as Nocardia.

What risk factor does this patient have for nocardial infection?

a). History of smoking
b). Obesity
c). Immunocompromise
d). PAP
e). Nulliparity

MCQ: answer

The correct answer is D.
The risk factor for developing nocardiosis was PAP.

MCQ: explanation

In the patient described, the risk factor for developing nocardiosis was PAP. This condition was first described in 1958. PAP is characterized by intra-alveolar accumulation of lipid and proteinaceous PAS+ material and is clinically associated with increased work of breathing and derangement of gas exchange. It exists both as a primary and secondary condition (ie, in the setting of infection, malignancy, or inhalation). There is a strong male predominance (2:1-4:1), and the peak age of diagnosis is 20-50 years. Heavy smoking appears to be a risk factor.

The condition is caused by abnormal clearance of surfactant forming in the alveolar spaces and associated with macrophage dysfunction. The diagnosis is made by chest CT, pulmonary function tests, bronchoalveolar lavage, and biopsy. Treatment is with periodic whole lung lavage and administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). Infectious complications associated with this disease are nocardiosis, Pneumocystis carinii pneumonia, and Mycobacterium avium-intracellulare. Recent data suggest a mortality between 0% and 8%.

Reference(s)
1). Irene Cortese, MD, Fellow and Avindra Nath, MD, Professor: Case 11: A Young Woman With Ring-Enhancing Brain Lesions. MedGenMed. 2006; 8(1): 3. Published online 2006 Jan 5. PMCID: PMC1681925 PMID: 16915133