Mucormycosis treated with posaconazole: review of 96 case reports

Abstract

Mucormycosis is an emerging invasive fungal infection, primarily affecting immunocompromised patients. The disease is difficult to diagnose and mortality reaches 40% even if treated adequately. Depending on site of infection and risk factors, surgical debridement in combination with systemically active antifungal drugs are the mainstay treatment strategies. Lipid-based amphotericin B is the treatment of choice for first-line therapy while posaconazole may be a promising alternative. We performed a PubMed search on reports of patients with mucormycosis treated with posaconazole. From 2003 to 2011, 96 cases have been published. Diagnosis was based on histology alone in 2 (2.1%) and microbiological evidence in 67 (69.8%), while no data on the diagnostic approach was reported in 27 (28.1%) patients. The most frequent pathogens were Rhizopus spp. (31.2%), followed by Mucor spp. (14.6%). The site of infection was predominantly rhino-orbital (38.5%, of which 43% also had central nervous system [CNS] involvement), followed by disseminated disease (22.1%). A complete response was achieved in 62 (64.6%), partial response in 7 (7.3%) patients, and stable disease in 1 (1%). Overall mortality was 24% (lacking data for three patients). In published case reports on posaconazole treatment for mucormycosis, the drug was frequently and successfully used in combination or as second line therapy.

New facets of antifungal therapy

“…Currently, only amphotericin B, posaconazole, and isavuconazole have sufficient activity against these organisms to be used clinically. 49,115,116 As with treatment of invasive aspergillosis, ineffective monotherapy and serious side effects of amphotericin B have prompted clinicians to attempt alternative strategies, including combination therapy. Two retrospective analyses of combination therapy for treatment of mucormycosis infections have recently been published.…”

Multicenter Evaluation of MIC Distributions for Epidemiologic Cutoff Value Definition To Detect Amphotericin B, Posaconazole, and Itraconazole Resistance among the Most Clinically Relevant Species of Mucorales

“…The recommended therapy for infections caused by the Mucorales is usually surgery and/or one of the amphotericin B lipid formulations; despite its toxicity, amphotericin B deoxycholate continues to be used routinely in some areas (5,8). More recently, posaconazole has been recommended as salvage therapy and/or prophylaxis (9)(10)(11); itraconazole and other triazoles are also used as prophylactics (9). Despite antifungal therapy, mucormycosis is associated with a great deal of morbidity and about a 50% mortality rate; breakthrough infections caused by Mucorales species among patients receiving triazole prophylaxis, especially voriconazole, are frequently reported (3,6).…”

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

“…Despite aggressive antifungal therapy and, in selected cases, extensive surgical debridement, the overall mortality due to mucormycosis remains unacceptably high (9). Primary antifungal therapies for mucormycosis are amphotericin B (AMB) lipid formulations, whereas open-label salvage studies suggest posaconazole (POS) as an option for patients who are refractory to or intolerant of polyenes (10,11). Furthermore, recent data also demonstrated the activity of isavuconazole (ISAV), which was approved by the U.S. Food and Drug Administration on 6 March 2015 for the primary treatment of invasive aspergillosis and mucormycosis, against Mucorales in vitro and in vivo, adding a second triazole antifungal for the therapy of patients with mucormycosis (12)(13)(14).…”