NOCARDIOSIS
Nocardiosis is an uncommon, suppurative, bacterial infection caused by aerobic actinomycetes in the genus Nocardia. Although the lungs, skin, and subcutaneous tissues are ordinarily involved, the disease may spread to any other organ, particularly to the central nervous system (CNS). Another characteristic of nocardiosis is its tendency to relapse or progress despite appropriate therapy.
The genus Nocardia
includes more than 50 species, at least 33 of which cause human disease,
most commonly Nocardia asteroides complex. Nocardia is a
gram-positive, nonmotile, nonencapsulated, partially acid-fast, aerobic, highly
evolved bacterium with characteristic filamentous branching that fragments into
bacillary or coccoid forms. Acid-fastness and growth in aerobic conditions help
to distinguish Nocardia from Actinomyces.
Nocardia spp. occur
worldwide and exist in soil, decaying vegetable matter, and aquatic
environments as saprophytes. Inhalation is the most common route of infection,
although ingestion, direct inoculation, and nosocomial transmission have also
been described. Individuals of all ages may be infected, and males con- tract
the disease more frequently, presumably because of occupational exposure.
Nocardiosis is usually an opportunistic infection; however, one-third of cases
occur in immunocompetent hosts. Immunocompromising illnesses that commonly
predispose to nocardiosis include glucocorticoid therapy, malignancy, organ and
hematopoietic transplantation, and HIV infection. Less common predispositions
include diabetes mellitus, alcoholism, chronic granulomatous disease, pulmonary
alveolar proteinosis, tumor necrosis factor-inhibitor therapy, and
tuberculosis.
The location
and extent of disease can be used to classify nocardiosis as pulmonary, CNS,
cutaneous, and disseminated disease. In the lungs, nocardiosis produces chronic
to fulminating disease; in other viscera and skin, it causes chronic
suppuration, sinuses, and abscess formation. Hematogenous dissemination can
occur to almost any organ.
Presenting
symptoms of pulmonary nocardiosis are often similar to those of pneumonia or
tuberculosis. Radiographic manifestations include single or multiple nodules
(with or without cavitation), lobar consolidation, reticulonodular or
interstitial infiltrates, and pleural effusions. Empyema, mediastinitis,
pericarditis, and superior vena cava syndrome may occur after contiguous
spread.
Nocardial brain
abscess may occur in any region of the brain and present clinically with fever,
headache, meningismus, seizures, and focal neurologic deficits. CNS nocardiosis
may also present as a mass lesion in immunocompetent patients or infrequently
as subacute or chronic meningitis.
Manifestations
of cutaneous nocardiosis include ulcerations, pyoderma, cellulitis, nodules,
and subcutaneous abscesses. Involvement of regional lymphatics and formation of
a mycetoma involving subcutaneous tissues and bones with draining sinuses may
also occur. Disseminated nocardiosis is defined as two noncontiguous sites of
involvement.
Nocardiosis
should be suspected in any patient who presents with brain, soft tissue, or
cutaneous lesions and a concurrent or recent pulmonary process. Nocardial
infection should also be suspected in patients with suppurative pneumonia
unresponsive to conventional antimicrobial agents, particularly with
immunosuppression. The differential diagnosis primarily includes mycobacterial,
fungal, parasitic, and bacterial infections as well as malignancy.
Definitive
diagnosis depends on pathogen isolation from clinical specimens. Invasive
sampling is often necessary, and the clinical laboratory needs to use specific
media and staining procedures. The characteristic appearance on Gram stain and
partial acid fastness on direct examination of clinical samples can yield a
rapid presumptive diagnosis. Nocardia spp. require 5 to 21 days to grow
in culture. If possible, isolates of Nocardia should be sent to a
reference laboratory for precise identification and confirmation of
susceptibility testing.
TREATMENT
Nocardia spp. clinical
isolates are variably resistant to antibiotics. Monotherapy with an oral agent is appropriate
for cutaneous infection in an immunocompetent host. Trimethoprim/sulfamethoxazole is the drug of choice.
Empiric coverage with two or three agents is recommended in severe infection
(e.g., trimethoprim/ sulfamethoxazole in combination with amikacin); with CNS
involvement, a third-generation cephalosporin or imipenem should be added.
Initial treatment should be administered intravenously for 3 to 6 weeks and until
clinical improvement occurs. Therapy should be continued with two oral drugs,
such as trimethoprim/sul-famethoxazole, minocycline, or amoxicillin/clavulanate
for a total duration of 6 to 12 months. Surgical intervention may be required
for brain and large soft tissue abscesses unresponsive to antibiotics, empyema,
mediastinal fluid collection, and pericarditis. Prolonged oral maintenance
therapy to prevent relapse is required in persistently immunosuppressed patients.
The rate for patients with in pulmonary nocardiosis ranges from 14% to 40%.
Disseminated disease has a mortality rate of 7% to 44% in immu ocompetent and
85% in immunocompromised
hosts.
