Invasive aspergillosis

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

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

What causes invasive aspergillosis?

The main pathogens of invasive aspergillosis A. Fumigatus (= 80-95%), A flavus (= 5-15%) and A niger (= 2-6%), others (A. Terreus, A. Nidulans, etc.) Aspergillosis pathogens are sensitive to amphotericin B, voriconazole, itraconazole and caspofungin, are resistant to fluconazole. Determination of the type of causative agent of invasive aspergillosis is of clinical importance due to their different sensitivity to antimycotics. For example, A. Fumigatus, A. Flavus and A niger are sensitive to amphotericin B, A. Terreus and A. Nidulans can be resistant.

The main risk factor for invasive aspergillosis in patients in the ICU is the use of systemic steroids. The development of IA in the ICU is described in patients with COPD, ARDS, acute PN, widespread burns, severe bacterial infection, etc. In addition, outbreaks of invasive aspergillosis may be associated with a high concentration of conidia Aspergillus spp in the air during repair, damage to these fungi by the ventilation system , ventilators, etc.

Infection usually occurs with inhalation of conidia Aspergillus spp with air, other ways of infection (food, traumatic implantation of the pathogen, with burns, etc.) are of less importance. The transmission of any form of aspergillosis from person to person does not occur.

Mortality with IA in patients in the ICU is 70-97%. The duration of the incubation period is not determined. In many patients, before the appearance of clinical signs of invasive aspergillosis, the surface colonization of Aspergillus spp of the respiratory tract and accessory sinuses of the nose is determined.

Primary lung disease is defined in 80-90% of patients for invasive aspergillosis, sinus paranasal sinuses - in 5-10%. Aspergillus spp angiotropic, capable of penetrating into blood vessels and causing thrombosis, this leads to frequent (15-40%) hematogenous dissemination with lesions of different organs, for example, the brain (-3-30%), skin and subcutaneous tissue, bones, thyroid, liver, kidneys, etc.

Symptoms of invasive aspergillosis

The clinical symptoms of invasive aspergillosis in patients in the ICU are non-specific. Refractory to antibiotics fever is noted only in half of patients, typical signs of angioinvasia, for example hemoptysis or "pleural" pain in the chest, are even more rare. That is why the disease is usually diagnosed late, often posthumously.

Early clinical signs of mycotic rhinosinusitis (a rise in body temperature, unilateral pain in the region of the affected paranasal sinus, the appearance of a dark discharge from the nose) are nonspecific, they are often mistaken for bacterial infection. Rapid progression of the process leads to the appearance of pain in the eye area, visual impairment, conjunctivitis and edema of the eyelids, the destruction of the hard and soft palate with the appearance of black scabs. Hematogenous dissemination occurs very rapidly, and all organs and tissues can be affected (most often the brain, skin and subcutaneous tissue, bones, intestines, etc.). Aspergillosis of the CNS usually occurs as a result of hematogenous dissemination, as well as the spread of infection from the paranasal sinus or orbit. The main variants of cerebral aspergillosis are abscess and hemorrhage into the brain substance, 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 - are not specific enough, obtaining a material for microbiological confirmation of the diagnosis is often difficult due to the severity of the condition of patients and a high risk of severe bleeding. With CT of the lungs, the halo symptom is noted in less than a quarter of patients in the ICU, about half of the patients are diagnosed with foci of destruction and cavity in the lungs, but the specificity of these signs is not high. Even with disseminated invasive aspergillosis, it is very rare to excrete a pathogen when sowing blood.

Methods of diagnosis:

• CT or radiography of the lungs, paranasal sinuses, 
• with neurological symptoms - CT or MRI of the brain (or other organs in detecting symptoms of dissemination), 
• the determination of Aspergillus antigen (galactomannan) in serum (Platelia Aspergillus, Bio-Rad), 
• bronchoscopy, BAL, biopsy lesions, 
• microscopy and seeding of BAL fluid, sputum, separated from the nose, biopsy material.

Diagnosis is established by identifying risk factors, radiological signs of invasive lung mycosis in combination with the detection of Aspergillus antigen (galactomannan) in serum or Aspergillus spp by microscopy, histological examination and / or seeding of the lesion, sputum, BAL fluid.

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Treatment of invasive aspergillosis

Treatment of invasive aspergillosis includes antifungal therapy, elimination or reduction of the severity of risk factors, surgical removal of affected tissues.

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

Alternative preparations:

• caspofungin at 70 mg on the first day, then 50 mg / day, 
• Amphotericin B 1.0-1.5 mg / (kg x 10), 
• Liposomal amphotericin B by 3-5 mg / (kilogram).

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

Antifungal therapy is continued until the disappearance of clinical signs of the disease, the eradication of the pathogen from the focus of infection, arresting or stabilizing the radiological signs, as well as the end of the neutropenia period. The average duration of treatment to stabilize the patient is 20 days, achieving a complete remission - 60 days. Usually, antifungal therapy continues for at least 3 months. However, in patients with persistent immunosuppression, longer treatment is needed.

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

Surgery

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