Nocardiosis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Nocardiosis is an acute, subacute, or chronic infection occurring primarily in cutaneous, pulmonary, and disseminated forms in patients who are immunocompromised or have chronic pulmonary disease. Nocardiosis produces suppurative necrosis and abscess formation at sites of infection.Primary cutaneous nocardiosis presents as cutaneous infection (cellulitis or abscess), lymphocutaneous infection (similar to sporotrichosis), or subcutaneous infection (actinomycetoma).Pulmonary infection presents as an acute, subacute, or chronic pneumonitis.Disseminated nocardiosis may involve any organ (lesions in the brain or meninges are most frequent).System(s) affected: Nervous; Pulmonary; Renal/Urologic; Skin/ExocrineUnusual nocardial infections: Keratoconjunctivitis associated with contact lenses or penetrating injury or ophthalmologic surgeryPeritonitis in patients on continuous ambulatory peritoneal dialysisUpper respiratory and digestive tract infectionsPericarditis and cardiac tamponadeHematogenous endophthalmitisProsthetic joint infectionsNatural or prosthetic valve endocarditisInfections of the male genitourinary tractIntravascular access device–related infection

Epidemiology

Incidence

0.4/100,000 person-years overall53/100,000 person-years among individuals with AIDS128/100,000 person-years among bone marrow transplant (BMT) recipients1,122/100,000 person-years among solid-organ transplant recipientsPredominant age: All ages are susceptible; mean age at diagnosis is the 4th decade of life.Predominant sex: Male > Female (3:1)

Prevalence

It is estimated that 500–1,000 new cases occur per year in the US.

Risk Factors

Most cases occur as opportunistic infection of immunocompromised hosts or hosts with predisposing pulmonary abnormalities.Solid-organ transplantation, chronic granulomatous disease of childhood, dysgammaglobulinemias, pemphigus, Cushing disease, hemochromatosis, cirrhosis, bronchiectasis, tuberculosis, sarcoidosis, anthracosilicosis, pulmonary alveolar proteinosis, lymphoma, leukemia, glucocorticoid and cytotoxic therapy, solid malignancies, and AIDSImmunologically normal individuals may develop primary cutaneous disease days to weeks after receiving a wound contaminated with soil.

Pediatric Considerations

An association has been reported between chronic granulomatous disease of childhood and nocardiosis.

Pathophysiology

Nocardiosis is an acute suppurative bacterial infection.

Etiology

Inhalation or traumatic inoculation of Nocardia sp. bacteria (predominantly N. asteroides, as well as N. brasiliensis, N. caviae, N. farcinica, N. transvalensis, N. otitidiscaviarum, and N. nova, although a host of new species continues to be described) from soil

Commonly Associated Conditions

Chronic pulmonary diseaseLymphoid malignancyBone marrow or solid-organ transplantationChronic corticosteroid useAutoimmune disease with immune suppressive agentsTreatment with antitumor necrosis factor antibodySarcoidosisKidney failureCirrhosis and alcoholismHypogammaglobulinemiaHIV infection

Diagnosis

History

Presentation in the immunocompromised host depends on site of infection.

Physical Exam

Pulmonary nocardiosis: Fever (70%)Cough (52%)Pleuritic chest pain (32%)Dyspnea (16%)AnorexiaWeight lossHemoptysisTachypneaRalesCNS dysfunction in those with CNS involvementOther focal infections in those with disseminated infectionCutaneous nocardiosis: Disseminated nocardiosis: ConfusionDisorientationDizzinessHeadacheNausea and/or vomitingSeizuresShortness of breathPatients with primary cutaneous nocardiosis present with cellulitis, cutaneous nodules, lymphadenopathy, or a mycetoma that is clinically indistinguishable from other etiologies.Patients with pulmonary nocardiosis present with pulmonary consolidation ± pleural effusions.Patients with disseminated nocardiosis present with symptoms that depend on sites of infection.

Diagnostic Tests & Interpretation

Lab

The diagnosis is established by observing the characteristic microscopic appearance of the organism in Gram-stained and modified acid-fast-stained preparations of sputum or pus or histopathologic samples. Confirmation is by culture of these same specimens.When attempting recovery of Nocardia from sputum, clinical microbiology laboratory should be so advised because of the organism’s slow growth and propensity to be overgrown by oral flora.Blood cultures should be obtained in all cases of suspected nocardiosis.

Imaging

Radiography: Confluent bronchopneumonia ± cavitationPleural effusion is common (up to 50%).Other CXR presentations include masses, nodules, cavities, and interstitial infiltrates.CT scan or MRI of the brain may reveal single or multiple intracranial abscesses and is indicated in all patients with pulmonary or disseminated nocardiosis.Other sites of focal infection may be identified by imaging in disseminated disease.

Diagnostic Procedures/Surgery

If evaluation of sputum is nondiagnostic, bronchoscopy for bronchoalveolar lavage and transbronchial lung biopsy may prove valuable for diagnosis.Percutaneous aspiration of lung lesion is often useful.

Pathological Findings

Histopathology reveals a suppurative lesion with acute necrosis and abscess formation and the microorganism, which may stain positive on modified acid-fast stains.

Differential Diagnosis

Includes other causes of acute, subacute, or chronic pneumonitis, particularly those occurring principally in immunocompromised hosts:

Tuberculosis or atypical mycobacteriaHistoplasmosisPneumocystis jiroveci infectionPolymicrobial bacterial lung abscessCarcinoma

Treatment

Medication

First Line

Survival may be improved if a sulfa-containing regimen is used (1)[B]. Some prefer sulfadiazine because of possibly better CNS penetration (1)[B]; should be given as 4–8 g/d PO in 4 divided doses. Dosage should be adjusted to maintain sulfonamide serum levels in the range of 8–16 mg/dL.Some prefer to use trimethoprim-sulfamethoxazole (1)[B]. This agent must be used if parenteral sulfonamide therapy is required. Initial dose based on trimethoprim component: 640 mg daily. Base subsequent doses on sulfamethoxazole level. Dosage should provide sulfonamide dosing and levels equivalent to those of sulfonamide when used alone.Duration of therapy is usually at least 3 months for immunocompetent hosts and 6–12 months for those who are immunocompromised, with treatment at least 1 month past resolution of evidence of infection.Contraindications: Sulfonamides: During the last month of pregnancy (should be used only when the potential benefits outweigh the risks)All antimicrobial agents above are contraindicated in the presence of known hypersensitivity to the agent.Precautions: With the use of high-dose sulfadiazine, high urine flow should be maintained to minimize risk of crystalluria. Generally, patients should be advised to drink 2–3 L/d.Significant possible interactions: Sulfonamides may increase the therapeutic effects of oral anticoagulants, phenytoin, sulfonylurea hypoglycemic agents, methotrexate, and thiopental.Decreased absorption of digoxin may be encountered.Ceftriaxone, 2 g IV q12h, or meropenem, 1 g IV q8h, plus amikacin, 15 mg/kg IV daily, should be considered as initial combination therapy with sulfonamide in critically or acutely ill patients.

Second Line

Alternatives for sulfonamide-allergic patients include doxycycline or minocycline, ampicillin plus erythromycin, amikacin, meropenem, ß-lactam/ß-lactamase inhibitor combinations, cefotaxime or ceftriaxone, and linezolid (2)[A],(3)[B]. Clinical experience with these alternative regimens is limited.Species-specific trends in susceptibility have been identified; therefore, therapy should be guided by in vitro antimicrobial susceptibility.Empirical therapy for the acutely ill patient: Ceftriaxone, 2 g IV q12h, or meropenem, 1 g IV q8h, plus amikacin, 15 mg/kg IV daily

Additional Treatment

General Measures

Respiratory support is often necessary in hospitalized patients.

Issues for Referral

Patients with suspected or confirmed nocardiosis should have therapy directed by an infectious diseases specialist.

Surgery/Other Procedures

Surgical drainage of abscesses other than intrapulmonary abscesses is generally indicated if technically feasible.

In-Patient Considerations

Initial Stabilization

Patients with moderate or severe illness generally require hospitalization.

Admission Criteria

Patients with nocardiosis are often immune suppressed and are generally ill. They usually require hospitalization.

IV Fluids

Often required in critically ill patients

Ongoing Care

Follow-Up Recommendations

Acute phase usually requires bed rest; increase activity as condition improves.

Patient Monitoring

Patients on high-dose sulfonamide therapy should have a complete blood count (CBC) and assessment of hepatic and renal function at least every other week.

Diet

Appropriate supportive care

Patient Education

Not a contagious diseaseAdvise patients of the need for long-term antimicrobial therapy to reduce the likelihood of relapse and inform patients of potential adverse reactions.

Prognosis

Overall modern mortality is 7–44%.Mortality in renal transplant recipients: 25% overall0% with isolated cutaneous involvement29% with localized pleuropulmonary disease42% with CNS involvementIn patients with AIDS, mortality is 30%.

Complications

CNS infection (brain abscess or meningitis; 16%)Secondary cutaneous nocardiosis (13%)Septic arthritis (2%)Hematogenous osteomyelitis (1%)Other focal manifestations of disseminated infection (13%)

References

1. Lerner PI. Nocardiosis. Clin Infect Dis. 1996;22:891–903; quiz 904–5.

2. Jodlowski TZ, Melnychuk I, Conry J. Linezolid for the Treatment of Nocardia spp. Infections (October). Ann Pharmacother. 2007.

3. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003;41:4497–501.

Additional Reading

Castro JG, Espinoza L. Nocardia species infections in a large county hospital in Miami: 6 years experience. J Infect. 2006(14).

Filice GA. Nocardiosis in persons with human immunodeficiency virus infection, transplant recipients, and large, geographically defined populations. J Lab Clin Med. 2005;145:156–62.

Márquez-Diaz F, Soto-Ramirez LE, Sifuentes-Osornio J. Nocardiasis in patients with HIV infection. AIDS Patient Care STDS. 1998;12:825–32.

Timóteo AT, Branco LM, Pinto M et al. Nocardial endocarditis after mitral valve replacement: case report and review of the literature. Rev Port Cardiol. 2010;29:291–7.

Codes

ICD9

039.1 Pulmonary actinomycotic infection039.8 Actinomycotic infection of other specified sites039.9 Actinomycotic infection of unspecified site

Snomed

29227009 nocardiosis (disorder)2087000 pulmonary nocardiosis (disorder)64650008 cutaneous nocardiosis (disorder)240443003 disseminated nocardiosis (disorder)

Clinical Pearls

When attempting recovery of Nocardia from sputum, clinical microbiology laboratory should be so advised because of the organism’s slow growth and propensity to be overgrown by oral flora.Most common signs and symptoms of pulmonary nocardiosis: Fever (70%), cough (52%), pleuritic chest pain (32%), and dyspnea (16%)CT scan or MRI of the brain may reveal single or multiple intracranial abscesses and is indicated in all patients with pulmonary or disseminated nocardiosis.Patients on high-dose sulfonamide therapy should have a CBC and assessment of hepatic and renal function at least every other week.