Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies

Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.

Clinical Utility of Molecular Diagnosis of Blood Stream Infections in Allogeneic Hematopoietic Stem Cell Transplantation Recipients with Hematologic Malignancies

Blood stream infections (BSIs) are a serious problem in patients with hematologic malignancies receiving allogeneic hematopoietic stem cell transplantation (ASCT). We evaluated the clinical utility of molecular diagnosis for the management of BSIs in such patients. We prospectively performed a polymerase chain reaction (PCR) analysis of microbial DNA in blood samples from 10 consecutive patients with hematological malignancies at least once a week for one month after ASCT. In total, 51 and 54 samples were analyzed by bacterial and fungal PCR assays, respectively. Bacteria were detected in 24 samples from 8 patients by PCR, but in only 2 samples from one patient by blood culture. Notably, the bacteria detected in at least half of the 24 samples were considered to have originated from the oral cavity. Fungi were detected in 5 samples from 3 patients by PCR, but not by blood culture. Most cases with positive PCR results were manageable with empirical antimicrobial therapy without disclosure of DNA data. Our DNA analyses did not directly contribute to management of BSIs, but did provide valuable microbiological evidence for the patients. Additionally, oral management appears to require a critical re-evaluation to reduce the occurrence of BSIs in ASCT recipients.

Utility of Miconazole Therapy for <i>Trichosporon</i>Fungemia in Patients with Acute Leukemia

Invasive trichosporonosis is an extremely rare mycosis, but Trichosporon fungemia (TF) in patients with hematologic malignancies has been increasingly recognized to be a fulminant and highly lethal infection. Although the utility of azole therapy has been demonstrated in several observations, little is known about the efficacy of one of azoles, miconazole (MCZ). To assess its therapeutic role, we retrospectively investigated 6 cases of TF in patients with acute leukemia receiving MCZ containing regimens. Successful outcome was obtained in 4 patients [MCZ + amphotericin B (AmB) in 2, MCZ only and MCZ + fluconazole (FLCZ) + AmB in one each], but not in 2 (MCZ + FLCZ + AmB and MCZ + FLCZ in one each). Although MCZ and AmB exhibited good in vitro activities against isolates from all patients, FLCZ had such finding from only one patient. Considering the reportedly limited utility of AmB, MCZ seemed to play a critical role even in the combination therapies for TF. Despite the release of newer azoles and other classes of antifungals, the use of MCZ remains a potential therapeutic approach for TF in patients with acute leukemia.