Risk Factors for Fungal Infection in Patients with Malignant Hematologic Disorders: Implications for Empirical Therapy and Prophylaxis

Abstract

To determine which patients are at high risk for disseminated fungal infection and should be given systemic prophylaxis, we studied the charts of 341 patients with malignant hematologic disorders who were admitted to our institution during 10 consecutive years. These patients represented 636 admissions; during these admissions, 60 invasive fungal infections occurred, with deaths in 44 cases. All patients who died of these infections either had persisting granulocytopenia and a poor prognosis for the underlying disease or suffered from chronic graft-vs.-host disease. Two of 58 patients who had no or low-level candidal colonization developed this infection (P < .001). Nine of the 10 patients with candidal infection had microbiologically proven bacteremia within the week preceding the candidal infection. After bone marrow transplantation, 8 of 10 patients with chronic graft-vs.-host disease vs. 2 of 36 without this disease (P < .001) developed fatal infection with Aspergillus species. The results of our study reveal that patients with high-level candidal colonization who were treated for microbiologically proven bacteremia and patients with chronic graft-vs.-host disease might benefit from systemic antifungal prophylaxis.

A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation

“…In order to achieve effective prophylaxis with an acceptable safety profile, it is crucial to determine doses associated with a minimal risk of toxicity. 11 Micafungin, recently approved in Japan and USA, is a new echinocandin lipopeptide synthesized through the chemical modification of a fermentation product from Coleophoma empetri. 12 In vitro, the minimum concentration of micafungin required to inhibit the growth of 90% of isolates (MIC 90 ) for yeast-like organisms was lower than that for fluconazole, itraconazole or amphotericin B.…”

Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study

“…The risk period following an allogeneic hematopoietic stem cell transplant (HSCT) even extends beyond the neutropenic phase, particularly in cases of graft-versus-host disease. [1][2][3] Despite appropriate treatment and an initially favorable outcome, the risk of recurrence of an invasive fungal infection following HSCT is high (30-50%). 4 Documented previous invasive fungal infections may be a major obstacle to the success of HSCT and may affect patients' survival [5][6][7] to such an extent that transplant centers have been unwilling to carry out HSCT in patients with a history of an invasive fungal infection.…”

Late onset of invasive aspergillus infection in bone marrow transplant patients at a university hospital

“…6 Specific knowledge of the usual time of onset and identifiable risk factors for IA is essential to the development of more effective prevention strategies and the application of new therapeutic techniques. Previously identified risk factors include age, 3,7 unrelated donor, 3,4 transplant outside of a laminar air flow room, 5 low cell dose, 7 recipient CMV seropositivity, 7 persistent or prolonged neutropenia, 5,8 early corticosteroid use for acute graft-versus-host disease (GVHD) prophylaxis, 9 high-grade acute GVHD, 1,3,4 chronic GVHD 4,8 and graft rejection. 10 Decreased risk for IA has been ascribed to housing patients in a high-efficiency particulate air (HEPA) filtered environment.…”