96 NOCARDIOSIS AND ACTINOMYCOSIS
Harrison’s Manual of Medicine
NOCARDIOSIS AND ACTINOMYCOSIS
The term nocardiosis refers to invasive disease due to Nocardia species, aerobic actinomycetes that cause several characteristic syndromes. The two most common syndromes—pneumonia and disseminated infection—may follow inhalation of fragmented nocardial mycelia. Three other syndromes may follow transcutaneous inoculation: cellulitis, a lymphocutaneous syndrome, and actinomycetoma. Finally, nocardial keratitis may result from corneal trauma and nocardial inoculation.
EPIDEMIOLOGY Nocardiae are common inhabitants of soil worldwide. Of the ~1000 cases of nocardiosis that occur annually in the U.S., 85% are either pulmonary or systemic. The risk of pulmonary or systemic disease is increased in persons with impaired cell-mediated immunity, especially those who have lymphoma or AIDS or have undergone solid organ or bone marrow transplantation. Nocardiosis is also associated with pulmonary alveolar proteinosis, tuberculosis, and chronic granulomatous disease.
CLINICAL MANIFESTATIONS Pulmonary Disease Nocardial pneumonia is typically subacute. Cough is prominent and productive of scant, thick, purulent, nonmalodorous sputum. Fever, anorexia, weight loss, and malaise are common. Nodular pulmonary infiltrates and cavitation are frequently evident on radiographs. In half of all cases of pulmonary nocardiosis, extra- pulmonary disease is also evident.
Extrapulmonary Dissemination Disseminated nocardiosis typically manifests as abscesses presenting subacutely. The most common site of dissemination is the CNS, where one or more abscesses—usually supratentorial and often multiloculated—may be found. Other common sites of dissemination include skin and supporting structures, kidneys, bone, and muscle. Around 80% of pts with disseminated nocardiosis have demonstrable concurrent pulmonary involvement.
Disease Following Transcutaneous Inoculation After transcutaneous inoculation, disease may take one of three forms: (1) cellulitis, a subacute illness characterized by painful, firm, warm, nonfluctuant, erythematous lesions; (2) a lymphocutaneous sporotrichoid form; and (3) actinomycetoma, a chronic, deforming, locally invasive entity with minimal systemic manifestations.
Keratitis Nocardia spp. are uncommon causes of keratitis. Nocardial keratitis develops subacutely after eye trauma.
DIAGNOSIS The diagnosis of nocardiosis is suggested by the finding of beaded, branching, gram-positive, weakly acid-fast organisms on stains of sputum or pus. Cultural confirmation usually requires selective media and may take 2–4 weeks.
Sulfonamides are the drugs of choice for the treatment of nocardiosis (Table 96-1). Once disease is controlled, the dose of sulfonamide (sulfadiazine or sulfisoxazole) may be decreased to 1 g qid, or, if TMP-SMZ is used, the dose may be reduced by half. In difficult cases, the dose should be adjusted to maintain serum sulfonamide levels at 100–150 µg/mL. Whether combination therapy is more effective than monotherapy is unknown. The exact duration of treatment is somewhat arbitrary and depends on both the condition being treated and the immune status of the host (Table 96-1). Nocardial abscesses that are large and surgically accessible should be drained.
Table 96-1 Treatment for Nocardiosis
Actinomycosis is an indolent bacterial infection caused by any of several gram- positive, non-spore-forming anaerobic or microaerophilic rods, most but not all of which are in the genus Actinomyces. Characteristic features of actinomycosis include the violation of normal tissue plane barriers by the spreading infection, the formation of draining sinus tracts, and the presence of actinomycotic sulfur granules (yellow aggregates of organisms) in drainage or pus. In certain circumstances, actinomycosis may be easily mistaken for malignancy.
EPIDEMIOLOGY AND PATHOGENESIS The agents of actinomycosis are members of the normal oral flora and may also be found in the bronchi, GI tract, and female genital tract. A critical step in the development of actinomycosis is disruption of the mucosal barrier, which allows actinomycetes to invade beyond their endogenous habitat. Local infection, subsequent extension, and (in rare cases) hematogenous seeding may ensue. Actinomycosis is associated with poor dental hygiene, the use of intrauterine contraceptive devices, HIV infection, transplantation, and chemotherapy.
CLINICAL MANIFESTATIONS Actinomycosis occurs most frequently at an oral, cervical, or facial site and should be considered in the differential diagnosis of any mass lesion or relapsing infection of the head and neck. “Woody” induration is a common finding. Other common presentations include thoracic, abdominal, pelvic, and musculoskeletal disease. CNS infection and disseminated disease are both rare.
DIAGNOSIS The finding of macro- or microscopic actinomycotic sulfur granules in drainage or purulent material is highly suggestive of actinomycosis. The isolation of an actinomycete from granules or from a normally sterile site confirms the diagnosis but takes from 5 days to 4 weeks. Prior antimicrobial therapy greatly decreases the likelihood of isolating the organism. Isolation of the organism from secretions in the absence of sulfur granules indicates that the actinomycete is a commensal.
Treatment recommendations are listed in Table 96-2. Like nocardiosis, actinomycosis typically requires protracted treatment. For extensive or serious infection, IV therapy for 2–6 weeks followed by oral therapy for 6–12 months is suggested. For limited disease, less intensive therapy may suffice. Extending treatment beyond the resolution of demonstrable disease minimizes the likelihood of relapse. Adjunctive surgical treatment is warranted for pts critically ill with actinomycosis and for those infected at a critical site (e.g., the CNS).
Table 96-2 Antibiotic Therapy for Actinomycosis: Regimens Supported by Extensive Clinical Experience
For a more detailed discussion, see Filice GA: Nocardiosis, Chap. 165, p. 1006; and Russo TA: Actinomycosis, Chap. 166, p. 1008, in HPIM-15.