Over a 20-year period, 40 nontuberculous mycobacteria (NTM) were isolated from 6259 hematopoietic stem cell transplant (HSCT) recipients (0.64%), of which 28 were considered to have probable or definite infection (0.44%). Only 3 of 15 lower respiratory isolates obtained by bronchoalveolar lavage (BAL) and/or biopsy; (Mycobacterium avium complex [n = 2] and M. gordonae [n = 1]) caused definite or probable lower respiratory tract disease, whereas 12 of 15 were considered to cause possible lower respiratory tract disease according to Centers for Disease Control and Prevention definitions. The median time to diagnosis was 251 days following HSCT. All 3 patients with definite NTM disease were successfully treated with 3 antimicrobials for several months. Twenty-three patients had catheter-related infections, including exit site infection (n = 5), tunnel infection (n = 7), and catheter-related bacteremia (n = 11). All were caused by rapidly growing mycobacteria. The median time to diagnosis was 61 days following HSCT. All patients with catheter-related infections were successfully treated with an average of 2 antibiotics for a median of 3 weeks for exit site infection and 6 weeks for tunnel infection and catheter-related bacteremia. Soft tissue debridement was performed in all cases with tunnel infection. The catheter was removed in 21 of 23 patients with catheter-related infections. Two additional patients were diagnosed, one with lymphadenitis and one with skin lesion, due to NTM. In conclusion, NTM infections are infrequent in HSCT recipients and carry a good clinical prognosis. In the majority of lower NTM respiratory isolates obtained by BAL, a pathogenic role could not be established. However, lower respiratory tract disease can occur late after HSCT and should be considered if patients fail to respond to the treatment of concomitant infections or if evidence of tissue infection or concomitant bacteremia is present. Therapy should be performed with 2 to 3 antimicrobials, guided by antimicrobial susceptibilities, with additional surgical debridement in patients with tunnel infection.
Proinflammatory cytokines have been proposed as adjunctive therapeutic agents to enhance the host immune response during infections caused by opportunistic fungi. The study compared the differential in vitro priming effects of interferon-gamma (IFN-gamma), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on hyphal damage of opportunistic fungi mediated by isolated neutrophils (polymorphonuclear leukocytes, PMNL) and buffy coat cells (polymorphonuclear leukocytes/peripheral blood mononuclear cells, PMNL/PBMC) from healthy donors. IFN-gamma (1000 U/mL) effectively primed both PMNL and PMNL/PBMC for enhanced hyphal damage of Aspergillus fumigatus, Fusarium solani, and Candida albicans. G-CSF (100 ng/mL) increased hyphal damage mediated by both PMNL and PMNL/PBMC against F. solani, and GM-CSF (100 ng/mL) augmented the antifungal activity of PMNL/PBMC against hyphal forms of both F. solani and C. albicans. IFN-gamma may be superior to G-CSF or GM-CSF for enhancing the microbicidal activity of PMNL and PMNL/PBMC against opportunistic fungi.
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