Breakthrough invasive fungal diseases during echinocandin treatment in high-risk hospitalized hematologic patients

Abstract

The frequency of breakthrough invasive fungal diseases (IFDs) during echinocandin therapy is unclear. We retrospectively analyzed 534 hematologic patients treated with echinocandin (caspofungin, N = 55; micafungin, N = 306; anidulafungin, N = 173). Four proven IFDs were found, caused by Candida parapsilosis (N = 2), C. parapsilosis and Candida glabrata (N = 1), and Fusarium species (N = 1). Four cases of possible IFDs were observed, all showing pulmonary infection. One case showed features suggestive of hepatosplenic candidiasis. Six of these eight cases had previously received the purine analog clofarabine. Breakthrough IFD during echinocandin treatment occurred infrequently (1.5 %), caused predominantly by Candida species. Clofarabine usage was an important risk factor.

Primary antifungal prophylaxis with micafungin in patients with haematological malignancies: real‐life data from a retrospective single‐centre observational study

“…, the overall incidence of proven and probable bIFDs was impressively low with only 6/397 (1.5%) patients. A similar low rate of only 1.5% proven bIFDS during echinocandin treatment was recently reported in a large cohort of 534 high‐risk hospitalised patients in a quaternary haematological referral centre . However, results in this study were confounded by several problems such as mixing up patients receiving prophylactic, empirical, preemptive and targeted antifungal treatment and by the lack of standardised diagnostic work‐up procedures, thus making an interpretation of the results in the context of our findings and other studies on this topic difficult.…”

Consensus guidelines for the treatment of invasive mould infections in haematological malignancy and haemopoietic stem cell transplantation, 2014

“…Dissemination may cause endophthalmitis, septic arthritis, meningitis and fungal endocarditis, among other clinical syndromes . Breakthrough infections may occur with resistant strains during treatment with echinocandins and voriconazole, or while on posaconazole prophylaxis …”

Invasive fusariosis masquerading as extramedullary disease in rapidly progressive acute lymphoblastic leukemia

“…There are several reports of immunosuppressed patients developing severe fungal infections despite antifungal prophylaxis . Fluconazole and echinocandins are common well‐tolerated choices for antifungal prophylaxis in patients with ALL; echinocandins, as opposed to fluconazole, have some activity against Aspergillus .…”

“…There are several reports of immunosuppressed patients developing severe fungal infections despite antifungal prophylaxis. [15][16][17][18][19] Fluconazole and echinocandins are common well-tolerated choices for antifungal prophylaxis in patients with ALL 19 ; echinocandins, as opposed to fluconazole, have some activity against Aspergillus. Despite antifungal prophylaxis and the anti-Aspergillus activity of echinocandins, breakthrough invasive fungal infections can still occur, and most echinocandin-associated breakthrough mold infections are still due to aspergillosis, not IF.…”