micafungin and Meningitis--Cryptococcal

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.

Topics: Antibiotic Prophylaxis; Antifungal Agents; Calcineurin Inhibitors; Cord Blood Stem Cell Transplantation; Cryptococcus neoformans; Dose-Response Relationship, Drug; Fungemia; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Meningitis, Cryptococcal; Micafungin; Middle Aged; Tacrolimus; Transplantation, Homologous

A 67-year-old woman with systemic lupus erythematosus (SLE) was admitted to our hospital because of lupus nephritis. Methylprednisolone minipulse therapy dramatically reduced her proteinuria; however; she then complained of general fatigue with low-grade fever. Radiological and culture studies revealed no infectious focus, but she was treated with meropenem and micafungin, considering her immunosuppressive state. Cytomegalovirus antigenemia was later determined and ganciclovir was added. She became afebrile, but complained of nausea and headache, and disorientation, without meningeal signs. Because a brain computed tomography (CT) scan showed no abnormality, we initially suspected some kind of drug interaction. Despite the discontinuation of all drugs, however, she still suffered from disturbance of consciousness. A lumbar puncture revealed yeast cells stained by India ink. A diagnosis of cryptococcal meningitis was confirmed. Though fluconazole and meropenem were administered, the patient died. Autopsy findings revealed disseminated cryptococcosis concomitant with pulmonary aspergillosis. Micafungin is a recently approved echinocandin-class antifungal agent that is now widely used in Japan because of its minimal toxicity and broadspectrum activity. However, such echinocandins have limited activity against a number of fungi. Indeed, breakthrough trichosporonosis is becoming a significant problem in patients with hematological malignancies who are receiving echinocandins. To the best of our knowledge, breakthrough cryptococcosis, as seen in our patient, has not been reported previously in patients who were receiving micafungin as an empiric antifungal therapy. This case highlights that cryptococcosis should be kept in mind as a possible breakthrough infection during the administration of echinocandins, especially in patients with cellular immunodeficiency.

Topics: Aged; Antifungal Agents; Drug Resistance, Fungal; Echinocandins; Fatal Outcome; Female; Humans; Lipopeptides; Lipoproteins; Lung Diseases, Fungal; Lupus Erythematosus, Systemic; Meningitis, Cryptococcal; Micafungin