Aspergillus nidulans infection in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a rare inherited disorder of the NADPH oxidase complex in which phagocytes are defective in generating reactive oxidants. As a result, patients with CGD suffer from recurrent bacterial and fungal infections. The most common fungal infections are caused by Aspergillus species. Aspergillus nidulans is a rare pathogen in most patient populations with quantitative or qualitative neutrophil defects. We have reviewed all cases in which A. nidulans was isolated from patients at the National Institutes of Health (Bethesda, MD) between 1976 and 1997. A. nidulans infection occurred in 6 patients with CGD, but was not a pathogen in any other patient group. Aspergillus fumigatus was a more common pathogen in CGD compared with A. nidulans, but A. nidulans was more virulent. A. nidulans was significantly more likely to result in death compared with A. fumigatus, to involve adjacent bone, and to cause disseminated disease. Patients with A. nidulans received longer courses of amphotericin B therapy than patients with A. fumigatus, and were treated with surgery more often. In contrast to A. fumigatus, A. nidulans was generally refractory to intensive antifungal therapy, suggesting that early surgery may be important. These data show that A. nidulans is a distinct pathogen in CGD and its isolation carries more severe implications than that of A. fumigatus.

Severe Burkholderia (Pseudomonas) gladioli infection in chronic granulomatous disease: report of two successfully treated cases.

Chronic granulomatous disease (CGD) is characterized by a defect in phagocytic cells that leads to recurrent superficial and deep pyogenic infections. Burkholderia (Pseudomonas) gladioli is a gram-negative bacillus in the pseudomallei group of pseudomonads that is known primarily as a plant pathogen. We report two cases of pneumonia, one accompanied by septicemia, caused by B. gladioli in patients with CGD and their successful treatment with antibiotics. We believe these represent the first reports of human disease caused by this organism. We conclude that B. gladioli should be considered a potential pathogen in patients with CGD.

Treatment with intralesional granulocyte instillations and interferon-gamma for a patient with chronic granulomatous disease and multiple hepatic abscesses.

We present the case of a 16-year-old girl with p22-deficient chronic granulomatous disease in whom multiple hepatic abscesses secondary to Staphylococcus aureus infection developed. Infection persisted despite extensive surgery and aggressive antibiotic therapy. Conventional intravenous granulocyte transfusions were not tolerated because of the development of alloantibodies to HLA. Treatment with interferon-gamma and intralesional granulocyte infusions was associated with dramatic clinical and radiographic improvement. No morbidity was associated with this therapy. To our knowledge, this is the first report of treatment with intralesional granulocyte instillations. Intralesional granulocyte instillation in association with interferon-gamma administration may result in clinical improvement in the conditions of patients with chronic granulomatous disease and hepatic abscesses for whom conventional therapy has failed.

In vivo interferon-gamma therapy augments the in vitro ability of chronic granulomatous disease neutrophils to damage Aspergillus hyphae.

During the recently completed double-blind, placebo-controlled, randomized trial of recombinant interferon-gamma (rIFN-gamma) therapy in chronic granulomatous disease (CGD), a metabolic assay of neutrophil damage to Aspergillus fumigatus hyphae was used to monitor neutrophil function before and during therapy. In this assay, 5 x 10(4) conidia that had germinated into hyphae were exposed to 5 x 10(5), 15 x 10(5), or 50 x 10(5) CGD neutrophils. By analysis of variance, neutrophils from patients on rIFN-gamma were found to produce significantly more damage to hyphae than those from the placebo group (P less than .01). In subgroup analysis, this effect was best seen in the hyphae exposed to 50 x 10(5) CGD neutrophils, where neutrophils from patients receiving rIFN-gamma produced significantly more damage to the hyphae than those from the placebo group (P less than .05). In vivo rIFN-gamma therapy improves the ability of CGD neutrophils to damage Aspergillus fumigatus hyphae in an in vitro assay.