Infections Remains Difficult

Entomophthorales. Treatment of  Rhizopus infections remains difficult due to its ability to invade vascular tissues, infarction of the infected tissue is common and mortality rates are very high.  Surgical debridement or surgical resection and well as antifungal therapy are usually required.  The most commonly used antifungal agent is amphotericin B.   In some cases of zygomycosis, liposomal amphotericin B  and other lipid – based amphotericin B formulations such as amphotericin B colloidal dispersion have also been used as treatment. Frequently, clinical response to therapy is unsatisfactory in zygomycosis.  Enhanced clinical response has been anecdotally associated with adjuvant therapy with cytokines, especially the colony stimulating factors.  For further validation is the successful use of fluconazole and terbinafine as treatment for zygomycosis.  Furthermore, a combination of fluconazole with trovafloxacin or ciprofloxacin proved to be effective in a murine model of pulmonary zygomycosis.
Definition:

Entomophthorales Zygomycoses are angioinvasive fungal infections due to fungi belonging to the genera of Mucorales (Rhizopus sp., Mucor sp., Rhizomucor sp., Absidia sp., Apophysomyces sp., Cunninghamella sp., and Saksenaea sp.)
Background

Zygomycosis is an infection caused by fungi in the orders Mucorales and Entomophthorales. The Mucorales order contains 2 families exist—Mucoraceae and Cunninghamellaceae.[1]Mucormycosis is another common name applied to this same group of diseases. This designation reflected the predominance of the Mucorales in causing disease in humans. However, this term ignored the role of the Entomophthorales (Conidiobolus species and Basidiobolus species). The currently accepted designation is zygomycosis, reflecting all disease processes caused by the members of the class Zygomycetes. During the past decade, the Zygomycetes have emerged as common causes of invasive fungal infections.

The pathogens that cause zygomycosis are commonly found in the environment on fruit, on bread, and in soil and are common components of decaying organic debris.[2] These organisms are ubiquitous and generally saprophytic, rarely causing disease in immunocompetent hosts, but they are the third-most-common cause of invasive fungal infection in immunocompromised patients, especially stem cell transplant recipients and patients with underlying hematologic malignancies.

Fungi are ubiquitous in the natural world, often found in association with plants, mammals, and insects. Accordingly, humans are continually exposed to multiple genera of fungi via various routes, including the respiratory and gastrointestinal routes, which allow the possibility of colonization. Depending on the interaction between host mucosal defense mechanisms and fungal virulence factors, colonization may be transient or persistent, or local disease may ensue.

Entomophthorales:

Entomophthorales Zygomycosis (or mucormycosis) describes in the broadest sense any infection due to a member of the Zygomycetes.Zygomycosis (mucormycosis, phycomycosis) is an opportunistic infection caused by “bread mold fungi,” including Rhizopus, Absidia, Cunninghamella, and Mucor, which belong to the class Zygomycetes.These fungi are widely distributed in nature and cause no harm to immunocompetent individuals, but they infect immunosuppressed patients, albeit somewhat less frequently than do Candida and Aspergillus. The major predisposing factors are neutropenia, corticosteroid use, diabetes mellitus and breakdown of the cutaneous barrier (e.g., as a result of burns, surgical wounds, trauma).
Pathogenesis Entomophthorales:

Similar to Aspergillus, zygomycetes are transmitted by airborne asexual spores. Most commonly, inhaled spores produce infection in the sinuses and the lungs, but spores can also lead to infection following percutaneous exposure or ingestion. Macrophages provide the initial defenses by phagocytosis and oxidative killing of germinating spores.Neutrophils have a key role in killing fungi during established infection. Proteolytic and lipolytic enzymes and mycotoxins have been identified for some of the zygomycetes, but whether these contribute to disease is not yet known. The thermotolerance of the spores of some species of zygomycetes might contribute to their spread.
Morphology Entomophthorales:

Zygomycetes form nonseptate, irregularly wide (6 to 50 μm) fungal hyphae with frequent right-angle branching, which are readily demonstrated in the necrotic tissues by hematoxylin and eosin or special fungal stains.The three primary sites of invasion are the nasal sinuses, lungs, and gastrointestinal tract, depending on whether the spores (which are widespread in dust and air) are inhaled or ingested. Most commonly in diabetics, the fungus may spread from nasal sinuses to the orbit and brain, giving rise to rhinocerebral