Abstract
Background
Rare invasive fungal infections (IFIs) such as chromoblastomycosis (CBM), fungal mycetoma (mycetoma), hyalohyphomycosis/phaeohyphomycosis (hyalo/phaeo), and mucormycosis (mucor) cause significant morbidity and mortality in immunocompromised patients. Few effective treatment options are available for these IFIs, therefore we assessed the clinical efficacy of posaconazole, a broad-spectrum triazole antifungal compound with demonstrated activity against IFIs.
Methods
We performed a systemic literature review of Medline and EMBASE to identify studies published from 2005 (year of posaconazole approval) to October 30, 2019, reporting the efficacy/effectiveness of posaconazole monotherapy or combination therapy for treating CBM, mycetoma, hyalo/phaeo, and mucor. Two reviewers screened and extracted data based on predefined PICOS criteria. Effectiveness outcomes included cure, response, relapse, radiologic improvement; mortality and any other effectiveness measures reported. Study quality was assessed using National Institute for Health and Care Excellence-recommended checklists. A narrative descriptive summary was used to summarize study findings.
Results
Of 2612 articles identified, 351 articles (mostly case reports) were included. Positive clinical outcomes with posaconazole therapy were observed in most patients with CBM (73.9%, 17/23), mycetoma (100%, 2/2), hyalo/phaeo (53.3%, 49/92), and mucor (66.7%, 564/845). The population for mycetoma was small; only 2 positive cases (Figure). Overall survival was ~70% or greater across the IFIs examined. Posaconazole efficacy and mortality differed by line of therapy as well as for monotherapy versus combination therapy. Positive response was higher in second line monotherapy than first line monotherapy in CBM and mucor. Higher mortality was observed with combination therapy than monotherapy in hyalo/phaeo and mucor infections (except for first line use in mucor).
Figure. Overall Results of Posaconazole Treatment
Conclusion
Despite the rarity of these IFIs, substantial data have been published since posaconazole’s initial approval in the year 2005, and the evidence demonstrates that posaconazole is an effective therapeutic option alone or in combination for the treatment of these rare IFIs.
Disclosures
Mark Bernauer, BPharm, RPh, Merck & Co, Inc. (Consultant) Hetty Waskin, MD/MPH, Merck & Co, Inc. (Employee) Nicole Cossrow, PhD, Merck & Co, Inc. (Employee) Allysen Kaminski, BA, Merck & Co, Inc. (Consultant) Havilland Campbell, BS, Merck & Co, Inc. (Employee) Dipen Patel, BPharm, PhD, Merck & Co, Inc. (Consultant)
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