By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: A review of 24 cases of Nocardia brain abscess, two-fifths of which occurred in apparently non-immunocompromised hosts, had variable outcomes, but antibiotic therapy was effective in most.

SOURCE: Corsini Campioli C, Castillo Almeida NE, O’Horo JC, et al. Clinical presentation, management, and outcomes of patients with brain abscess due to Nocardia species. Open Forum Infect Dis 2021;8:ofab067.

Corsini Campioli and colleagues reviewed the cases of adults with brain abscesses caused by Nocardia spp. seen from Jan. 1, 2009, to June 30, 2020, at the Mayo Clinic in Rochester, MN. The 24 cases represented 9.7% of the 247 brain abscess patients. The median age of the cases was 65 years and 75% were male. Comorbidities were frequent, including chronic kidney disease (45.8%), hypertension (33.3%), and diabetes mellitus (29.1%). Approximately one-half had malignancies. Three (12.5%) were recipients of hematopoietic stem cell transplants and seven (29.1%) had undergone solid organ transplantation (SOT), with a median interval from transplantation to diagnosis of Nocardia brain abscess of 876 days. Nine patients had received a median 10 mg daily dose of prednisone for more than two weeks and seven patients (9.2%) had received other immunomodulatory therapies. Two infections were the result of central nervous system trauma. Four transplant patients were receiving trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis jirovecii pneumonia.

One-third of the patients had more than one brain abscess. Cutaneous nocardiosis was present in 12.5%, and 37.5% had pulmonary involvement, with the latter being present in 71% of the immunocompromised patients but in only 29% of those without known immunocompromise.

The diagnosis was confirmed by culture of brain abscess material in all 24 patients, and the most frequent isolate was Nocardia farcinica, which accounted for nine cases (37.5%). Nocardia was isolated in blood culture from only three patients, although all had had blood cultures.

Various antimicrobials were used alone or in combination with trimethoprim-sulfamethoxazole, to which all 24 isolates were susceptible. Corticosteroids, most often dexamethasone, were initially administered to 10 patients (41.6%). The median duration of parenteral administration of antibiotics was 21 days, and all received at least two antibiotics (counting trimethoprim-sulfamethoxazole as one) for the first six weeks of therapy. Subsequently, 10 patients received monotherapy at some point, with most receiving at least one orally administered antibiotic, most often trimethoprim-sulfamethoxazole and/or linezolid.

Seven patients (29.1%) died after a median interval of 169 days after diagnosis, but four of these deaths were related to comorbidities. Complete clinical and radiographic resolution was achieved by 14 patients (58.3%), while two survived with permanent neurological deficits and one had disease progression ultimately requiring surgical intervention.  

COMMENTARY  

Resistance to trimethoprim-sulfamethoxazole generally is rare and it remains the antimicrobial of choice for the treatment of nocardiosis, including cases of brain abscess. Reports indicate that susceptibility is maintained even in cases in which this infection arises in patients receiving prophylactic doses of trimethoprim-sulfamethoxazole — something that was true in four patients in the series reviewed here. This lack of the emergence of resistance may be the result of the use of low, infrequently administered doses that exert limited selective pressure — or to non-compliance with prophylaxis. At any rate, it is recommended that initial therapy in such patients should include trimethoprim-sulfamethoxazole. Other antibiotics to which Nocardia frequently are susceptible include amikacin, imipenem, linezolid, ceftriaxone, and minocycline. Patients with histories of trimethoprim-sulfamethoxazole allergy may undergo testing and, if indicated, desensitization.

Generally, it is recommended that combination therapy be administered intravenously initially and then for approximately six weeks, after which including orally administered agents can be considered. It should be noted that these recommendations generally are based on low-quality evidence. For SOT patients with cerebral nocardiosis, the Infectious Diseases Community of Practice of the American Society of Transplantation recommends, largely based on expert opinion alone, initial intravenous therapy with imipenem, amikacin, and trimethoprim-sulfamethoxazole.1 They recommend that alternative individual agents that may be substituted in the regimen include linezolid, ceftriaxone, cefotaxime, or minocycline.

REFERENCE

  1. Restrepo A, Clark NM. Nocardia infections in solid organ transplantation: Guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation. Clin Transplant 2019;33:e13509.