Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy

Abstract

Zygomycosis is increasingly reported as a cause of lifethreatening fungal infections. A higher proportion of cases reported over the last decades have been in cancer patients, with or without hematopoietic stem cell transplantation (HSCT). The new anti-fungal agent voriconazole is a recently identified risk factor for developing zygomycosis. We reviewed the clinical characteristics and outcomes of a large cohort of cancer patients who developed zygomycosis after exposure to voriconazole. Health care professionals at 13 large cancer centers provided clinical information on cancer patients with zygomycosis and prior exposure to voriconazole. Criteria for inclusion were 5 days or more of voriconazole use and diagnostic confirmation with tissue or histology. Fiftyeight cases were identified among patients with hematologic malignancies, 62% including patients who underwent a HSCT procedure. Fifty-six patients received voriconazole for primary or secondary prophylaxis against fungal infection. In addition to prior exposure to voriconazole, patients also had several of the previously established risk factors for zygomycosis. Amphotericin B was the most commonly prescribed anti-fungal therapy. Overall mortality was 73%. We conclude that zygomycosis after exposure to voriconazole is a recently described entity that is frequently fatal, despite treatment with currently available anti-fungal agents and surgery.

Voriconazole as primary antifungal prophylaxis in children undergoing allo-SCT

“…In our experience, voriconazole is effective as a primary prophylactic agent and is an improvement over previously published results using low-dose amphotericin B deoxycholate/fluconazole (13% IFD) 5 or L-AmB (9.7% of 51 patients underwent 57 allo-SCT had an IFD, whereas none developed an invasive mold infection), 22 which are similar to the results of Kolve et al 29 who used L-AmB as primary or secondary prophylaxis in children (3.5% IFD in the global series), and van Burik et al 19 who used micafungin only during neutropenic phase (2.5% of IFD). In contrast to the published experience of Trifilio et al, 30 who observed breakthrough fungal infections due to opportunistic molds or yeast, in a retrospective study that also included children, we did not observe any of these results.…”

Invasive fungal disease in patients treated for newly diagnosed acute leukemia

“…First, several centers have reported breakthrough IFDs in AL patients treated with posaconazole prophylaxis with difficult-to-treat pathogens such as Scedosporium prolificans, Trichosporon asahii, and Mucorales [13][14][15], similar to that which has been observed with voriconazole prophylaxis [16][17][18]. Furthermore, the number of patients needed to treat with antifungal prophylaxis to prevent one IFD varies significantly between centers based on the background rate of IFD at a particular center, which suggests that the results of antifungal prophylaxis studies in general, and posaconazole in particular, may not be generalizable to all centers-particularly those with relatively low rates of IFD [19].…”

Challenges in the management of invasive aspergillosis in hematopoietic stem cell transplantation

“…As with any antimicrobial class of drugs, widespread and prolonged use of triazoles may lead to the emergence of drug-resistant organisms [14]. Several reports have linked voriconazole use to a rising incidence of zygomycosis [15,16]. Moreover, unlike with fluconazole, many clinicians routinely obtain serum levels of these azoles in order to ensure efficacy and minimize toxicity.…”