Invasive aspergillosis

Invasive aspergillosis (IA) is becoming an increasingly common disease in immunocompromised patients. The incidence of IA in patients in the intensive care unit can reach 1-5.2%.

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What causes invasive aspergillosis?

The main causative agents of invasive aspergillosis are A. fumigatus (=80-95%), A flavus (=5-15%) and A niger (=2-6%), others (A. terreus, A. nidulans etc.) are encountered less frequently. The causative agents of aspergillosis are sensitive to amphotericin B, voriconazole, itraconazole and caspofungin, and resistant to fluconazole. Determination of the type of causative agent of invasive aspergillosis is of clinical importance due to their different sensitivity to antifungal drugs. For example, A. fumigatus, A. flavus and A niger are sensitive to amphotericin B, A. terreus and A. nidulans may be resistant.

The main risk factor for invasive aspergillosis in patients in the intensive care unit is the use of systemic steroids. The development of IA in the intensive care unit has been described in patients with COPD, ARDS, acute respiratory failure, widespread burns, severe bacterial infection, etc. In addition, outbreaks of invasive aspergillosis can be associated with high concentrations of Aspergillus spp conidia in the air during repairs, damage to the ventilation system, ventilators, etc.

Infection usually occurs through inhalation of Aspergillus spp conidia with air; other routes of infection (food, traumatic implantation of the pathogen, burns, etc.) are less important. Transmission of any form of aspergillosis from person to person does not occur.

Mortality in IA in patients in the intensive care unit is 70-97%. The duration of the incubation period is not defined. In many patients, superficial colonization of the respiratory tract and paranasal sinuses by Aspergillus spp is determined before the appearance of clinical signs of invasive aspergillosis.

Primary lung damage is determined in 80-90% of patients with invasive aspergillosis, paranasal sinuses - in 5-10%. Aspergillus spp are angiotropic, capable of penetrating into vessels and causing thrombosis, this leads to frequent (15-40%) hematogenous dissemination with damage to various organs, such as the brain (-3-30%), skin and subcutaneous tissue, bones, thyroid gland, liver, kidneys, etc.

Symptoms of invasive aspergillosis

Clinical symptoms of invasive aspergillosis in patients in the intensive care unit are nonspecific. Antibiotic-refractory fever is observed in only half of patients, typical signs of angioinvasion, such as hemoptysis or "pleural" chest pain, are detected even less often. This is why the disease is usually diagnosed late, often posthumously.

Early clinical signs of mycotic rhinosinusitis (fever, unilateral pain in the affected paranasal sinus, dark nasal discharge) are nonspecific and are often mistaken for manifestations of a bacterial infection. Rapid progression of the process leads to pain in the orbit, visual impairment, conjunctivitis and eyelid edema, destruction of the hard and soft palate with the appearance of black scabs. Hematogenous dissemination occurs very quickly, and all organs and tissues can be affected (most often the brain, skin and subcutaneous tissue, bones, intestines, etc.). CNS aspergillosis usually occurs as a result of hematogenous dissemination, as well as the spread of infection from the paranasal sinus or orbit. The main types of cerebral aspergillosis are abscess and hemorrhage into the brain tissue; meningitis develops rarely. Clinical manifestations (headache, dizziness, nausea and vomiting, focal neurological symptoms and impaired consciousness) are nonspecific.

Diagnosis of invasive aspergillosis

Diagnosis of invasive aspergillosis is often difficult. Clinical signs of the disease are nonspecific, radiological signs are not specific enough, obtaining material for microbiological confirmation of the diagnosis is often difficult due to the severity of the patient's condition and the high risk of severe bleeding. In CT of the lungs, the "halo" symptom is noted in less than a quarter of patients in the intensive care unit, in about half of the patients foci of destruction and cavities in the lungs are detected, but the specificity of these signs is low. Even in disseminated invasive aspergillosis, the pathogen is very rarely isolated in blood culture.

Diagnostic methods:

• CT or X-ray of the lungs, paranasal sinuses,
• in case of neurological symptoms - CT or MRI of the brain (or other organs if symptoms of dissemination are detected),
• determination of Aspergillus antigen (galactomannan) in blood serum (Platelia Aspergillus, Bio-Rad),
• bronchoscopy, BAL, biopsy of lesions,
• microscopy and culture of BAL, sputum, nasal discharge, biopsy material.

The diagnosis is established by identifying risk factors, radiological signs of invasive pulmonary mycosis in combination with the detection of Aspergillus antigen (galactomannan) in the blood serum or Aspergillus spp during microscopy, histological examination and/or sowing of material from lesions, sputum, BAL.

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Treatment of invasive aspergillosis

Treatment of invasive aspergillosis includes antifungal therapy, elimination or reduction of risk factors, and surgical removal of affected tissue.

The drug of choice is voriconazole intravenously 6 mg/kg every 12 hours on the first day, then intravenously 4 mg/kg every 12 hours or orally 200 mg/day (body weight <40 kg) or 400 mg/day (body weight >40 kg).

Alternative drugs:

• caspofungin 70 mg on the first day, then 50 mg/day,
• amphotericin B at 1.0-1.5 mg/(kg x day),
• liposomal amphotericin B at 3-5 mg/(kg x day).

Combination therapy with caspofungin in combination with voriconazole or lipid amphotericin B.

Antifungal therapy is continued until the clinical signs of the disease disappear, the pathogen is eradicated from the site of infection, radiological signs are stopped or stabilized, and the period of neutropenia is over. The average duration of treatment until the patient's condition stabilizes is 20 days, and complete remission is 60 days. Antifungal therapy is usually continued for at least 3 months. However, patients with persistent immunosuppression require longer treatment.

Elimination or reduction of the severity of risk factors is achieved by successful treatment of the underlying disease, discontinuation or reduction of the dose of steroids or immunosuppressants.

Surgical treatment

The main indication for lobectomy or resection of the affected lung area is a high risk of pulmonary hemorrhage (pronounced hemoptysis, location of lesions near large vessels). In CNS aspergillosis, removal or drainage of the lesion reliably increases the probability of patient survival. In addition, obtaining material from a lesion located on the periphery can help establish a diagnosis, especially when other diagnostic measures are ineffective.