Nocardia Infections

NOCARDIOSIS

Nocardiosis occurs as sporadic cases worldwide. Some 70 cases, with about 20 deaths, occur per year in the USA. It is particularly associated with impaired cell-mediated immunity associated with Hodgkin's disease, leukemias, lymphomas, human immunodeficiency virus infection, sarcoidosis, organ transplantation and prolonged corticosteroid or cytotoxic therapy.

About 3/4 of cases involve the lungs (about 1/3 of cases the lungs only). These cases may simulate pulmonary tuberculosis, but the usual presentation is of a subacute chronic pneumonia. Occasionally, there is an extension to the pleura, resulting in empyema and dissemination. Respiratory tract colonisation with Nocardia has been reported in patients with tuberculosis, asthma, bronchitis, aspergillosis and cancer. Overall case-fatality rate for pulmonary infections is about 10%.

The second most frequent infection involves the brain, meninges and spinal cord. Meningitis due to Nocardia has a case-fatality rate of over 50% and may be either pyogenic or lymphocytic. It has a subacute to chronic presentation. 68% of patients exhibit fever, 66% sore neck and 55% headache. CSF usually shows a neutrophil pleocytosis. 83% of specimens have >500 leucocytes/µL and <40 mg glucose/dL, while 61% show >100 mg/dL protein. 43% of cases have an associated brain abscess.

Skin and cutaneous tissue lesions with or without osteomyelitis are next most common. The organism can, on occasions, disseminate from these to affect kidneys, adrenals, eye, liver, lymph nodes, pericardium and myocardium. A lymphocutaneous form, with a presentation similar to sporotrichosis, also occurs. Actinomycetoma, a chronic, progressive disease of skin, subcutaneous tissue and bone usually arising secondary to trauma of a lower extremity, occurs in tropical and subtropical areas, especially Mexico, North Africa and South Asia.

Septic arthritis due to Nocardia is rare and epididymoorchitis extremely so.

Diagnosis of nocardiosis is by staining and culture of sputum, thoracentesis specimens, transtracheal aspirate, bronchial washings or lung biopsy in the case of pulmonary infections, cerebrospinal fluid in the case of meningitis, pus from an abscess or draining sinus, or biopsy from other affected sites. Staining methods should be the Brown-Breen or Hueker modifications of the Gram stain and the Kinyoun or Putt modifications of the Ziehl-Neelsen stain. Nocardia will grow on blood agar but culture on mycobacterial media, modified Thayer-Martin medium, paraffin-containing medium, BMPAa or MWY charcoal yeast extract agar may be necessary to prevent overgrowth by other organisms from specimens with a mixed flora. Serology (immunodiffusion) is available but is rarely used.

The cells of Nocardia are branched filaments which break up into rods and cocci. Because of this, preparations for staining from cultures should be made as squash preparations. The organism is variably Gram positive, often giving a beaded appearance. It is weakly acid-fast but this may be difficult to demonstrate from culture unless the isolate is growing on a high protein medium such as Lowenstein-Jensen or casein medium.

is a strict aerobe. Growth on blood and chocolated blood agars occurs, after 2-5 days, as rough, dry, velvety colonies digging into the agar. Optimum growth occurs at 5-10% CO₂ and 37 degrees C but the organism tolerates a wide temperature range. Colonies have a very earthy odour, though not as overpowering as those of Streptomyces.

The incidence of isolation of Nocardia, especially from cutaneous and sub-cutaneous sites, has increased with the increasing practice of laboratories of incubating for 5 days cultures of specimens showing significant numbers of leucocytes but failing to grow a pathogen.

Speciation of Nocardia isolates and performance of susceptibility tests are best performed in a reference laboratory (usually, a mycobacterial reference laboratory). In Australia, 36% of isolates are N.asteroides, 25% N.nova, 17% N.farcinica, 14% N.brasiliensis, 6% N.transvalensis and 3% N.otidiscaviarum. The other two species, N.brevicatena and N.caviae, are rarely encountered.

The most widely used treatments for nocardiosis are:

• cotrimoxazole (trimethoprim-sulphamethoxazole) 6/30 mg/kg to maximum 320/1600 mg orally 12 hourly for 6-12 months;
• sulphadiazine 100 mg/kg orally daily in 4 divided doses (child: 75 mg/kg initially, then 160 mg/kg daily in 4-6 divided doses to a maximum of 6 g daily) + sodium bicarbonate 50 mg/kg orally daily in 4 divided doses for 4-6 weeks, then sulphisoxazole 60 mg/kg to maximum 6 g orally daily in divided doses for 12-18 months;
• minocycline 300 mg orally 12 hourly.

Ciprofloxacin, cefotaxime, amikacin and imipenem are also used. In the severely ill or in central nervous system disease, cefotaxime 2 g i.v. 8 hourly + imipenem 500 mg i.v. 6 hourly or ceftriaxone 2 g i.v. 12 hourly + amikacin 400 mg i.v. 12 hourly are the recommended regimens.

is a natural inhabitant of soils and almost all infections are acquired from this source - either as inhaled dusts in the case of pulmonary infections are by soil contamination of wounds or other traumatised skin. Person-to-person transmission, if it occurs at all, is an extremely rare event. Rarely, nosocomial post surgical transmission occurs.