Zygomycosis

Zygomycosis is an invasive mycosis caused by lower zygomycete fungi, which belong to the Zygomycetes class. Zygomycosis is characterized by an extremely severe course. Without early surgical treatment and active antifungal therapy, it usually leads to death.

The most common causative agent of zygomycosis is Rhizopus oryzae; less common are R. microsporus, M. indicus, M. circinelloides, C. bertholletiae, A. corymbifera, etc.

Zygomycosis pathogens are resistant to clinically used azoles and echinocandins, but are usually susceptible to amphotericin B in vitro. Some zygomycetes, such as C. bertholletiae, may be resistant to amphotericin B.

Risk factors for zygomycosis

Decompensated diabetes mellitus, long-term use of high doses of glucocorticoids and immunosuppressants, long-term agranulocytosis, organ and tissue transplantation, prematurity at birth, AIDS, skin trauma and invasive procedures, widespread deep burns, long-term intravenous drug administration, treatment with deferoxamine. 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 prophylactic or empirical use of fluconazole, itraconazole, voriconazole and amphotericin B.

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Symptoms of Zygomycosis

Zygomycosis is characterized by an extremely aggressive course with very rapid destruction of all tissue barriers, damage to blood vessels, hematogenous dissemination with subsequent development of thrombosis, infarctions and tissue necrosis. Infection usually occurs when the pathogen is inhaled or implanted through injured skin, less often - through the gastrointestinal tract when eating contaminated food. With zygomycosis, any organs can be affected, but most often the paranasal sinuses, lungs, skin and subcutaneous fat, gastrointestinal tract are involved in the process.

Diagnosis of zygomycosis

Diagnosis of zygomycosis is difficult, and the disease is often detected at autopsy. Zygomycosis should be excluded in patients with atypical sinusitis, pneumonia, or fever of unknown genesis against the background of decompensated diabetes mellitus, severe neutropenia, and immunosuppression. Diagnosis is based on identifying the pathogen in material from lesions; serological diagnostic methods have not been developed. Zygomycetes are more often identified by microscopy of the studied substrates than by sowing. In this case, a characteristic wide, non-septate or sparsely septate mycelium is detected, branching at a right angle. The mycelium size is 10-50 μm. Due to the low diagnostic sensitivity of microscopy and sowing of nasal aspirate, sputum, and BAL, a repeat examination is often necessary. Even in disseminated zygomycosis, the pathogen is very rarely isolated by blood sowing.

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Treatment of zygomycosis

Treatment should be started as early as possible. Antifungal therapy is limited by the polyresistance of zygomycetes. The drug of choice is lipid amphotericin B [3.0-5.0 mg/(kg x day) intravenously], the use of standard amphotericin B [1.0-1.5 mg/(kg x day) intravenously] is usually insufficiently effective and is accompanied by severe toxicity. The maximum tolerated doses of the drug are used.

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

Empirical antifungal therapy

Empirical antifungal therapy is administered to patients with suspected clinical signs of invasive mycosis until laboratory confirmation. The basis for empirical use of antifungals is the very high attributable mortality, relatively low efficacy, and significant diagnostic time.

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

Unjustified empirical use of antifungals in groups with a low risk of invasive candidiasis is accompanied by adverse events and drug interactions, contributes to the selection of pathogens refractory to antifungal drugs, and increases the cost of treatment.

In non-neutropenic ICU patients, the efficacy of empirical antifungal therapy has not been established in controlled clinical trials. However, antifungals are often prescribed to patients with risk factors and suspected clinical signs of invasive candidiasis. The choice of drug depends on the type of pathogen and the patient's condition. The duration of therapy is at least 5 days after normalization of body temperature and disappearance of other possible signs of invasive candidiasis.

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Indications for therapy

A combination of the following symptoms:

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

Selecting an antifungal drug:

• fluconazole 6.0 mg/(kgxday) intravenously,
• caspofungin intravenously 70 mg/day on day 1, on subsequent days 50 mg/day intravenously,
• amphotericin B 0.6-0.7 m/(kg x day) intravenously.