Emerging diagnostic and therapeutic options for treating mucormycosis

ABSTRACT

Introduction: Early diagnosis and treatment of mucormycosis remain challenges in clinical practice. Diagnosis typically involves direct tissue sampling and histopathologic examination, which may take days to confirm. Recently, nucleic acid amplification and hybridization has emerged as an adjunctive modality in the diagnosis of mucormycosis.

Areas covered: Nested, semi-nested, and multiplex PCR have tremendous potential for the rapid and reliable diagnosis of invasive fungal infections, but are not routinely used in clinical practice. Here, we review technological hurdles to widespread implementation as well as novel therapeutic options for the treatment of mucormcyosis. These include combination therapy, novel drug targets that draw on structure-activity relationships, and alternative drug development pathways, which rely on pharmacodynamics modeling.

Expert opinion: Mucormycosis is an uncommon yet life-threatening infection, and robust, prospective, randomized clinical trials to define optimal therapeutic strategies are an ongoing challenge for investigators. Advantageous strategies include crossover designs, multicenter collaboration, well-defined contemporaneous control populations, data sharing, and refinement of clinically relevant and biologically tenable endpoints. Support is also needed to bolster the development of novel antifungal agents to treat mucormycosis and other orphan mycoses.

KEYWORDS:

• Isavuconazole
• nested PCR
• multiplex PCR
• microarray
• shotgun sequencing

Article highlights

• Organisms causing mucormycosis have variable susceptibility patterns; identification down to species level may be necessary for appropriate clinical management

• Nested, semi-nested, and multiplex real-time PCR have tremendous potential to hasten both the diagnosis of mucormycosis and the initiation of appropriate treatment

• Similarities between nucleic acid sequences from pathogenic and contaminating fungi can diminish sensitivity and specificity of PCR-based assays

• Timely diagnosis is crucial for appropriate initiation of therapy, which often includes a combination of systemically active antifungal therapy, surgical debridement, and reversal of predisposing factors

• Isothermal amplification methods that do not require expensive thermal cyclers have been developed to potentially supplant PCR amplification

This box summarizes key points contained in the article.

Declaration of interest

MW McCarthy has received consulting fees from Allergan. TJ Walsh receives research grants from Astellas, Cubist, Theravance, The Medicines Company, Allergan, Merck and Pfizer. He has served as a paid consultant to Astellas, Actavis, ContraFect, Drais Pharmaceuticals, Novartis, Pfizer, MethylGene, SigmaTau and Trius. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.