In the last 2 decades, Nocardia infections have increased significantly, likely as a result of improved detection and identification methods and an expanding immunocompromised population. Therefore, the Infectious Diseases Community of Practice of the American Society of Transplantation updated their guidelines to review the diagnosis, prevention, and management of Nocardia infections and solid organ transplantation (SOT).

Background

Nocardia species are ubiquitous saprophytic gram-positive bacteria in the aerobic actinomycetes group and are found worldwide in soil, freshwater and saltwater, and decaying vegetation. The primary route of transmission of Nocardia is inhalation from environmental sources. Depending on the organ transplanted and the immunosuppressive regimen used, Nocardia infections in SOT recipients varies between <1% and 3.5%. Nocardia commonly affects the lung, brain, and skin and may cause disseminated infection, with spread to the bloodstream, skin, or central nervous system (CNS).

Diagnosis

Good outcomes in patients with nocardiosis is dependent on early recognition. Nocardiosis diagnosis should be considered in patients with nodular and cavitating lung lesions or brain lesions and appropriate cultures and biopsies obtained. In patients with pulmonary and disseminated nocardiosis, brain imaging is recommended to evaluate central nervous system (CNS) involvement. The definitive diagnosis of nocardial disease requires isolation of the organism in culture from a suspected site, particularly given the broad differential diagnosis of pulmonary, brain, and soft tissue infections in transplant recipients. In suspected cases of Nocardia infection, prolonged incubation of diagnostic specimens is recommended. Traditional phenotypic methods for identifying Nocardia species are inadequate and isolates should be speciated at qualified laboratories using molecular methods. Further, obtaining speciation of clinical Nocardia isolates will help guide antimicrobial therapy.

Management

The primary treatment of nocardial infections is antibiotic therapy, although surgical debridement may also be required. However, there have been no controlled clinical trials comparing treatment regimens for nocardiosis; therefore, antibiotic therapy selection should consider the site and severity of disease, the potential drug interactions and adverse effects, and species of Nocardia involved. Antimicrobial susceptibility testing is strongly recommended, as inter- and intra-species susceptibility patterns can vary. Trimethoprim-sulfamethoxazole is the first-line treatment for Nocardia infections. In patients with a sulfa allergy, imipenem, ceftriaxone, or linezolid are options for first-line therapy. In cases of localized skin infection or stable patients with pneumonia, monotherapy is adequate; in cases of severe pulmonary infection, CNS involvement, or disseminated infection, 2 agents (such as trimethoprim-sulfamethoxazole, or imipenem plus amikacin) should be used for initial therapy. In cases of life-threatening disease, 3 drugs can be considered.

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Prevention

Trimethoprim-sulfamethoxazole used daily for the prevention of pneumonia in the first 6 months post-transplantation, also reportedly reduces the rate of nocardial infection in recipients of SOT via prevention of the primary Nocardia infection and prevention of relapse after treatment. However, there are no definitive data on the dose and duration of prophylaxis. Previous studies have used one double-strength trimethoprim-sulfamethoxazole tablet daily, a double-strength tablet 3 times weekly, and other dosing regimens sometimes indefinitely. In terms of secondary prophylaxis, azithromycin has been used successfully.

Reference

Restrepo A, Clark NM. Nocardia infections in solid organ transplantation: guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation [published online February 28, 2019]. doi:10.1111/ctr.13509