Zygomycosis

Zygomycosis is an invasive mycosis due to the lower fungi of zygomycetes belonging to the class Zygomycetes. For zygomycosis is characterized by extremely severe course. Without early surgical treatment and active antifungal therapy, it usually leads to death.

The most frequent causative agent of zygomycosis is Rhizopus oryzae, less often R. Microsporus, M. Indicus, M. Circinelloides, S. Bertholletiae, A. Corymbifera, etc.,

The causative agents of zygomycosis are resistant to the azole and echinocandin used in the clinic, but are usually sensitive to amphotericin B in vitro. Some zygomycetes, for example C. Bertholletiae, can be resistant to amphotericin B.

Factors of risk of zygomycosis

Decompensated diabetes mellitus, prolonged use of high doses of glucocorticoids and immunosuppressors, prolonged agranulocytosis, organ and tissue transplantation, preterm birth, AIDS, skin trauma and invasive procedures, widespread deep burns, prolonged intravenous medication, deferoxamine treatment. The most common risk factor for the development of zygomycosis is diabetic ketoacidosis, which is detected in 40-50% of patients. Zygomycosis can occur against the background of a preventive or empirical application of fluconazole, itraconazole, voriconazole, and amphotericin B.

[1], [2], [3], [4], [5], [6], [7], [8], [9]

Symptoms of zygomycosis

For zygomycosis is characterized by an extremely aggressive course with a very rapid destruction of all tissue barriers, damage to blood vessels, hematogenous dissemination followed by the development of thromboses, infarcts and tissue necrosis. Infection usually occurs by inhaling the pathogen or implantation through the injured skin, less often through the gastrointestinal tract when eating contaminated foods. With zygomycosis, any organs can be affected, but more often the paranasal sinuses, lungs, skin and subcutaneous fatty tissue, GIT are involved in the process.

Diagnosis of zygomycosis

Diagnosis of zygomycosis is complex, often the disease is detected in autopsy. Zygomycosis should be excluded in patients with atypically occurring sinusitis, pneumonia or fever of unknown origin against decompensated diabetes mellitus, severe neutropenia and immunosuppression. Diagnosis is based on identifying the causative agent in the material from the lesions, serological diagnostic methods are not developed. Zygomycetes are more often determined by microscopy of the substrates studied than in sowing. At the same time, a characteristic wide, unsepted or sparse mycelium is revealed, branching at a right angle. The size of the mycelium is 10-50 μm. Due to the low diagnostic sensitivity of microscopy and sowing of aspirates from the nose, sputum and BAL fluid, repeated research is often necessary. Even with disseminated zygomycosis, the pathogen is very rarely isolated when blood is sown.

[10], [11], [12], [13], [14], [15], [16], [17]

Treatment of zygomycosis

Treatment should be started as soon as possible. The antifungal therapy is limited by multidrug resistance of zygomycetes. The drug of choice - lipid amphotericin B [3,0-5,0 mg / (kghsut) intravenously], the use of standard amphotericin B [1,0-1,5 mg / (kghsut) intravenously] is usually not effective enough and is accompanied by severe toxicity. Use the maximum tolerated dose of the drug.

In addition to antifungal therapy, the most important condition for success is active surgical removal of all affected tissues, but it can be difficult due to the patient's severe condition, expressed by thrombocytopenia and the prevalence of the process. Effective therapy is usually impossible without eliminating or reducing the severity of risk factors (diabetes mellitus, cancellation or reduction of glucocorticoid dose, etc.).

Empirical antifungal therapy

Empirical antifungal therapy is given to patients with suspected clinical signs of invasive mycosis before laboratory confirmation. The basis for the empirical use of antimycotics is a very high attributable lethality, a relatively low efficacy and a significant duration of diagnosis.

Currently, empirical antifungal therapy is prescribed for patients with antibiotic-resistant neutropenic fever, with a high risk of invasive candidiasis in some categories of patients without neutropenia.

Unjustified empirical use of antimycotics in groups with a low risk of invasive candidiasis is accompanied by undesirable phenomena and drug interactions, promotes the selection of refractory antifungal agents of mycosis pathogens, and also increases the cost of treatment.

In patients with ICU without neutropenia, the efficacy of empiric antifungal therapy has not been established in controlled clinical trials. However, antimycotics are often prescribed to patients with risk factors and presumed clinical signs of invasive candidiasis. The choice of the drug depends on the type of pathogen and the patient's condition. The duration of therapy is at least 5 days after the normalization of body temperature and the disappearance of other possible signs of invasive candidiasis.

[18], [19], [20], [21], [22], [23]

Indications for therapy

Combination of the following features:

• a fever of an obscure etiology lasting more than 4-6 days, resistant to adequate therapy with antibacterial drugs of a wide spectrum of action, 
• widespread (from 2 localizations) colonization of Candida spp., 
• presence of two or more risk factors for the development of invasive candidiasis (intravenous catheter, abdominal surgery, pronounced mucositis, complete parenteral nutrition, use of glucocorticoids or immunosuppressants).

Choosing an antifungal drug:

• fluconazole 6.0 mg / (kilogram) intravenously, 
• caspofungin intravenously 70 mg / day on the 1st day, in the following days 50 mg / day intravenously, 
• amphotericin B 0,6-0,7 m / (kghsut) intravenously.