Invasive candidiasis: candidemia and acute disseminated candidiasis

Candida spp are the most common pathogens causing invasive mycoses in the ICU. Invasive candidiasis usually occurs in patients with risk factors and is characterized by severe clinical manifestations and high (10-49%) attributable mortality.

The most common variants of invasive candidiasis are candidemia, acute disseminated candidiasis (ADC) and candidal peritonitis; other variants are less common, usually in patients with specific risk factors.

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Risk factors for invasive candidiasis

In adults:

• long stay in intensive care unit,
• widespread (>2 loci) superficial colonization with Candida spp,
• use of broad-spectrum antibiotics, steroids or immunosuppressants,
• long-term use of CVC,
• the severity of the patient's condition,
• perforation or surgical treatment of the gastrointestinal tract,
• infected pancreatic necrosis,
• total parenteral nutrition,
• artificial lung ventilation,
• repeated blood transfusions,
• diabetes mellitus and severe neutropenia.

Superficial colonization with Candida spp is detected in 40-80% of patients in the intensive care unit.

In newborns:

• gestational age less than 29 weeks,
• birth weight less than 1500 g,
• low Apgar score,
• the use of antibiotics from the carbapenem and glycopeptide groups,
• widespread candidiasis of the skin and mucous membranes,
• colonization of the gastrointestinal mucosa by Candida spp.

Up to 10% of cases of candidemia and ADC are associated with outbreaks of hospital-acquired infection, which may require additional measures (identification of the source of infection, examination of the hands of medical personnel, etc.). The main sources of the pathogen are catheters in the central vessels, the gastrointestinal tract and the urinary tract of the patient. Almost all patients develop superficial colonization of Candida spp 5-6 days before invasive candidiasis, often multifocal.

Candidemia and acute disseminated candidiasis

Candidemia and acute disseminated candidiasis (i.e. candidemia in combination with a focus/foci of dissemination or multiple foci of dissemination) account for 75-90% of all cases of invasive candidiasis. Candidemia and ADC most often develop in patients in the intensive care unit, hematology and oncology departments, in premature infants, in patients with widespread burns. The incidence of candidemia and ADC in the intensive care unit varies from 2 to 200 per 1000 hospitalized patients, depending on the presence of risk factors. When candidemia and ADC occur, the probability of a fatal outcome during hospitalization increases twofold, the duration of treatment - by 3-30 days, the cost of treatment - by 2-5 times.

The majority (93-97%) of the causative agents of candidemia and ODC are C. albicans (15-60%), C. parapsilosis (5-40%), C. glabrata (5-25%), C. tropicalis (5-15%) and C. krusei (3-7%). Approximately 3-7% of the causative agents are C. lusitaniae, C. guillermondii, C. rugosa, C. kefyr, etc. The spectrum of causative agents of candidemia and ODC in different medical institutions varies widely and depends on the contingent of patients, the methods of treatment and prevention used, the effectiveness of methods for controlling nosocomial infections, etc. The use of azole antimycotics for prevention and empirical therapy leads to a decrease in the proportion of C. albicans among the causative agents of invasive candidiasis. In neonates with low birth weight, the spectrum of causative agents of candidemia and ODC differs significantly from that in adults. The most frequently detected are C. albicans (40-75%), C. parapsilosis (7-45%) and C. tropicalis (5-15%), less frequently - C. glabrata, C. krusei, C. kefyr and C. guillermondii.

Invasive candidiasis pathogens are significantly more likely to be resistant to antifungal agents than superficial candidiasis pathogens. This is largely due to the higher proportion of non-albicans Candida among invasive candidiasis pathogens, since C albicans are significantly less likely to be resistant to antifungal agents than other (non-albicans) Candida spp. In addition, secondary resistance may develop as a result of prophylactic or empirical use of antifungal agents.

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Symptoms of invasive candidiasis

Clinical signs of candidemia are non-specific and do not differ from the symptoms of bacterial sepsis. An increase in body temperature >38 °C, refractory to the use of broad-spectrum antibiotics, is detected in 90-96% of patients, ARF - in 15-21%, infectious toxic shock - in 15-20%, signs of damage to various organs - in 30-40%. That is why, for the timely detection of candidemia, all patients with risk factors and suspected clinical signs are shown an examination to identify foci of dissemination, repeated blood cultures and material from the identified foci.

ODC occurs as a result of hematogenous spread of Candida spp. in the body. With ODC, almost all organs and tissues of the body can be affected, but most often the lungs, kidneys, organs of vision, brain, heart, bones, skin and subcutaneous fat are involved in the pathological process.

Kidney damage occurs in 5-20% of patients with candidemia and is usually accompanied by the development of microabscesses. Patients develop fever, chills, pain in the lower back or abdomen, changes in urine analysis. ARF develops in 5-15% of patients with candidemia.

CNS damage develops in 5-15% of patients with ODC. In adults, brain abscesses occur more often, in newborns - meningitis. Clinical manifestations are non-specific (headache, photophobia, nausea, vomiting and focal neurological symptoms).

Candidal endocarditis develops in 5-13% of patients with ODC, myocarditis or pericarditis occur less frequently. Additional risk factors are the presence of prosthetic heart valves or vessels, injection drug addiction. Clinical manifestations (fever, palpitations, shortness of breath and pain in the heart area) and echocardiographic signs are nonspecific and do not differ from the symptoms of bacterial endocarditis.

Lesions of the skin and subcutaneous fat are observed in 3-10% of patients with ODC, characterized by the appearance of a papular rash with a diameter of 0.5-1.0 cm or the development of subcutaneous abscesses.

Visual impairment (candidal endophthalmitis) develops in 2-10% of patients with ODC. Severe pain, visual impairment and loss are typical. Candidal retinitis may be a late complication and develop after systemic manifestations of candidemia. Therefore, all patients with candidemia are recommended to undergo ophthalmoscopy with pupil dilation during the initial examination of the patient and when assessing the effectiveness of treatment.

In low birth weight infants, the incidence of candidemia and ODC ranges from 2 to 6%, but increases to 12-32% in patients with risk factors. In full-term infants with normal birth weight, invasive candidiasis is very rare. Depending on the time of infection, congenital and acquired candidiasis are distinguished. Congenital candidiasis is diagnosed from the first hours after birth to 6 days.

Congenital candidiasis is a result of transplacental or vertical (ascending) infection of the fetus. Clinically, congenital and acquired candidiasis may manifest as lesions of the skin and mucous membranes, candidemia, ODC and invasive candidiasis of various organs. Candidiasis of the skin and mucous membranes is usually diagnosed in the second week of life (range from 6 to 14 days) with a frequency of 6 to 8%. Candidiasis of the skin on examination looks like an erythematous diffuse rash similar to a superficial burn. Lesions of the mucous membranes - acute pseudomembranous candidiasis of the oral cavity. Candidemia and ODC are usually detected in the period from 15 to 33 first days of life. The main clinical manifestations of candidemia and ODC are nonspecific, do not differ from bacterial sepsis. A high frequency of candidal meningitis is characteristic (10-40%); less frequently, the kidneys, endocardium and organs of vision are affected.

Candidal peritonitis

Candidal peritonitis accounts for 10-15% of all cases of invasive candidiasis. It usually develops in patients in the intensive care unit or as a complication of PD.

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Risk factors

Gastrointestinal perforation, infected pancreatic necrosis, abdominal surgery, PD The frequency of resistance of pathogens causing candidal peritonitis to fluconazole is 15-20%, in some hospitals it exceeds 30%.

Symptoms

Clinical symptoms of candidal peritonitis have no specific signs, except for the lack of effect of antibacterial therapy. In 90-100% of patients, antibiotic-resistant fever and other signs of a systemic inflammatory reaction are noted, as well as the presence of purulent discharge from the abdominal cavity or turbidity of the dialysate. The incidence of shock in candidal peritonitis exceeds 15%. In addition, a high incidence of candidemia and ADC with damage to various organs and systems is characteristic.

Diagnostics

Diagnosis is based on the detection of Candida spp in the peritoneal fluid. During the examination, it is necessary to exclude damage to other organs and systems. Diagnostic criteria are clinical, endoscopic or laboratory signs of peritonitis in combination with the detection of Candida spp by microscopy and/or culture of peritoneal fluid.

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Treatment of candidal peritonitis

The choice of drug depends on the type of pathogen and the patient's condition. It is necessary to take into account the high frequency of resistance of pathogens of candidal peritonitis to fluconazole. Therefore, drugs with a low frequency of resistance (caspofungin, amphotericin B) are usually prescribed first, and fluconazole is used after determining the type of pathogen and stabilizing the patient's condition. The use of antimycotics is continued for 2 weeks after the disappearance of clinical and laboratory signs of peritonitis. Intraperitoneal administration of amphotericin B is contraindicated due to the high probability of developing chemical peritonitis. A prerequisite for successful treatment is surgical intervention, drainage of the abdominal cavity, removal of the catheter for PD.

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CNS candidiasis

CNS candidiasis may be a manifestation of ADC or a complication in premature and low birth weight infants with risk factors for the development of invasive candidiasis, in neurosurgical patients with ventriculoperitoneal shunts, injection drug addicts, etc.

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Symptoms of CNS candidiasis

The course is usually protracted, at first the signs of hypertensive-hydrocephalic syndrome predominate, focal symptoms are detected later.

Diagnostics

The diagnosis is based on the detection of Candida spp in the CSF, aspirate from a brain abscess. The type of pathogen and its sensitivity to antimycotics are determined. General clinical examination of the CSF reveals moderate mixed pleocytosis, protein-cell dissociation. During the examination, it is necessary to exclude damage to the brain tissue, other organs and systems (MRI, CT, etc.).

Diagnostic criteria: detection of Candida spp by microscopy and/or culture of CSF, material from a brain abscess.

Treatment

When selecting an antifungal agent, the type of pathogen and its sensitivity, the patient's condition, and the pharmacokinetics and pharmacodynamics of the drug should be taken into account. Fluconazole and voriconazole pass through the BBB well. The level of fluconazole in the CSF of patients with fungal meningitis is 52-85% of the concentration in the blood plasma, and voriconazole is about 50%. In addition, voriconazole creates high concentrations in the brain tissue. Itraconazole poorly passes through the BBB and creates very low concentrations in the CSF. Amphotericin B poorly passes through the BBB; its effectiveness in the treatment of fungal meningitis is explained by its high concentration in the meningeal membranes and fungicidal action. Liposomal amphotericin B creates a low concentration in the CSF and a high concentration in the brain tissue. The concentration of caspofungin in the CSF and brain tissue is low.

The drugs of choice are voriconazole intravenously 6 mg/kg in 2 doses on the 1st day, then 4 mg/kg in 2 doses, amphotericin B 0.7-1.0 mg/(kg x day). Fluconazole 6.0-12 mg/(kg x day) is prescribed after the patient's condition has stabilized and a sensitive pathogen has been identified, liposomal amphotericin B 3.0-5.0 mg/(kg x day) - if standard amphotericin B is ineffective or toxic. The duration of antifungal use is at least 4 weeks after all signs of infection have disappeared. A prerequisite for successful treatment is the removal of catheters, shunts and similar instruments, and correction of ICP.

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Candidal endocarditis, pericarditis and phlebitis

Candidal endocarditis, pericarditis and phlebitis are usually a manifestation of ODC. Isolated candidal endocarditis, pericarditis and phlebitis develop rarely, mainly in patients after cardiac surgery, in injection drug addicts.

Symptoms

Clinical manifestations of mycotic endocarditis are similar to endocarditis of bacterial etiology: auscultatory picture of valve damage, increasing heart failure, antibiotic-resistant fever. The aortic and mitral valves are involved in the lesion. EchoCG reveals signs of warty endocarditis. Pericarditis and phlebitis are rare, have no clinical features except for the lack of effect from the antibacterial therapy.

Diagnostics

The diagnosis is based on the detection of Candida spp in the material from the affected heart valves, endocardium, etc. Serological diagnostic methods have not been developed. In addition, the diagnosis is established when characteristic signs of cardiovascular damage are detected in patients with candidemia and ODC. During the examination, it is necessary to exclude damage to other organs and systems. Diagnostic criteria are clinical and instrumental (echoCG, etc.) signs of endocarditis, pericarditis or phlebitis in combination with the detection of Candida spp during blood culture, pericardial fluid or during histological examination and biopsy culture.

Treatment

The basis of treatment is surgical removal of infected heart valves, resection of affected areas of peripheral veins and pericardium in combination with long-term use of antifungal agents. The optimal option of antifungal therapy has not been determined. Caspofungin, amphotericin B or fluconazole are usually prescribed, depending on the type of pathogen and the patient's condition. The duration of antifungal use is usually from 2 to 12 months, at least 6 weeks after surgical treatment. If it is impossible to remove the affected valves, lifelong prophylaxis of relapse with fluconazole at 3 mg / (kg x day) is necessary. After completion of treatment, observation of patients for at least 1 year is indicated.

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Candidal endophthalmitis

Candidal endophthalmitis is an inflammation of the inner membranes of the eye caused by Candida spp with the formation of an abscess in the vitreous body. Candidal endophthalmitis develops as a complication in 2-10% of patients with ODC. Isolated candidal endophthalmitis occurs rarely, for example, with prolonged intravenous use of medications or in injection drug users.

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Clinical picture

The main complaints are decreased visual acuity, eye pain, moderate swelling of the eyelids and conjunctiva. Examination reveals corneal edema, hypopyon or fibrinous exudate in the anterior chamber of the eye, white-yellow foci with fuzzy edges on the retina, focal or diffuse opacification of the vitreous body. Progression can lead to panophthalmitis, loss of the eye, and damage to the central nervous system.

Diagnostics

The diagnosis is usually established by identifying characteristic changes during ophthalmoscopy in patients with candidemia and ODC. Isolated damage to the visual organs is detected less often. In such cases, an examination is indicated to identify foci of dissemination in other organs. The diagnostic criteria are clinical and ophthalmoscopic signs of endophthalmitis in combination with the isolation of Candida spp from the vitreous body, blood or other foci of dissemination.

Treatment

The basis of treatment is the long-term use of antifungal drugs; in case of damage to the vitreous body, surgical treatment is effective. The choice of drug depends on the type of pathogen and the patient's condition. The duration of antifungal use is usually from 6 to 12 weeks. The effectiveness of the introduction of antifungal drugs into the vitreous body has not been determined.

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Diagnosis of invasive candidiasis

Diagnostics is based on the detection of Candida spp. in blood and other normally sterile substrates. Standardized serological diagnostic methods have not been developed. In patients with risk factors and suspected clinical signs of candidemia and ODC, diagnostic measures should be carried out immediately. It is necessary to determine the type of pathogen, since the choice of antifungal drug depends on this. It is very important to assess the prevalence of the pathological process and identify foci of dissemination, since this affects the nature of the treatment.

Diagnostic methods:

• repeated blood cultures on specialized media (Saburo, wort agar) - 2 times a day for at least 3 days,
• center of the distal fragment of the intravascular catheter,
• microscopy and culture of biosubstrates (material from the pharynx, urine, feces, bronchial lavage fluid, discharge from drains and wounds) to determine the degree of superficial colonization,
• CT or X-ray of the lungs,
• CT or ultrasound of the abdominal cavity,
• ophthalmoscopy with pupil dilation,
• biopsy of lesions,
• microscopy, culture, histological examination of biopsy material,
• mandatory determination of the type of pathogen detected during the sowing of any normally sterile biosubstrate.

Diagnostic criteria:

• candidemia - a single isolation of Candida spp during blood culture obtained from a patient with a body temperature >38 °C or other signs of a generalized inflammatory reaction,
• acute disseminated candidiasis - candidemia in combination with the detection of Candida spp during histological examination and/or sowing of material from deep tissues (including subcutaneous tissue) or the detection of Candida spp during histological examination and/or sowing of material from deep tissues of two or more localizations.

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Treatment of invasive candidiasis

If signs of invasive candidiasis are detected, antifungal therapy is started immediately; late administration of antimycotics only after repeated isolation of Candida spp from blood and other substrates increases mortality. Drugs for the treatment of invasive candidiasis are caspofungin, fluconazole, voriconazole, and amphotericin. The effectiveness of these drugs in candidemia and ODC ranges from 66 to 81%. Ketoconazole and itraconazole are not used due to variable bioavailability when taken orally. All patients with invasive candidiasis are recommended to have early removal (replacement) of all intravascular catheters and other possible sources of the pathogen (urinary catheters, shunts, prostheses, etc.).

An important component of treatment is the elimination or reduction of risk factors (discontinuation or reduction of the dose of glucocorticoids, optimization of the use of antibacterial drugs, compensation of diabetes mellitus, etc.).

Due to the insufficient efficiency of diagnostics and the high attributable mortality of invasive candidiasis, empirical antifungal therapy is widely used - the prescription of antimycotics to patients with a high risk of invasive candidiasis before laboratory confirmation.

The choice of antifungal drug depends on the clinical condition and age of the patient, as well as the type of pathogen and its sensitivity to antifungal agents.

Choice of antifungal drug for the treatment of candidemia, acute disseminated candidiasis

The patient's condition is unstable (shock, convulsive respiratory failure, etc.)	Caspofungin intravenously 70 mg/day on day 1, then 50 mg/day intravenously on subsequent days, amphotericin B 0.6 mg/(kg x day), voriconazole intravenously at 6 mg/kg in 2 doses on day 1, then 4 mg/kg in 2 doses
Very low birth weight newborns	Amphotericin B 0.6-1.0 mg/(kg day), fluconazole 5-12 mg/(kg day)
The type of pathogen has not been determined.	Caspofungin intravenously 70 mg/day on day 1, on subsequent days 50 mg/day intravenously amphotericin B 10 mg/(kg x day)
Pathogen C. glabrata	Amphotericin B 0.8-1.0 mg/(kg x day), caspofungin intravenously 70 mg/day on the 1st day, on the following days 50 mg/day intravenously fluconazole 12 mg/(kg x day)
The causative agent is C. krusei	Caspofungin intravenously 70 mg/day on day 1, then 50 mg/day intravenously on subsequent days, voriconazole intravenously 6 mg/kg in 2 doses on day 1 then 4 mg/kg in 2 doses
The causative agent is C. lusitaniae C. guillermondii	Fluconazole 6.0 mg/(kg x day), caspofungin intravenously 70 mg/day on day 1, 50 mg/day intravenously on subsequent days, voriconazole intravenously 6 mg/kg in 2 doses on day 1, then 4 mg/kg in 2 doses
Pathogen C. albicans, C. tropicalis, C. parapsilosis	Fluconazole 6.0 mg/(kg x day), amphotericin B 0.6 mg/kg/day, caspofungin intravenously 70 mg/day on day 1, then 50 mg/day intravenously on subsequent days, voriconazole intravenously 6 mg/kg in 2 doses on day 1, then 4 mg/kg in 2 doses

In clinically unstable patients, as well as until the pathogen is identified, an antifungal drug with a low risk of pathogen resistance (e.g., caspofungin or amphotericin B) should be prescribed. In such patients, the use of fluconazole is not indicated due to its mycostatic activity and a high probability of pathogen resistance to fluconazole. Fluconazole is used after the patient's condition has stabilized and the pathogen, usually sensitive to fluconazole, has been identified (C albicans, C tropicalis, C parapsilosis, C lusitaniae, C guillermondii).

In newborns, most pathogens are sensitive to amphotericin B and fluconazole, and the nephrotoxicity of amphotericin B is lower than in adults. The drugs of choice are amphotericin B and fluconazole; when using the latter, the pharmacokinetic characteristics of premature infants should be taken into account. Fluconazole is not prescribed to patients who have previously received this drug prophylactically. If amphotericin B or fluconazole is ineffective or toxic, caspofungin can be used.

In addition, when prescribing antifungal agents, the local epidemiological situation should be taken into account. If the frequency of detection of non-albicans Candida spp. is high in a medical institution or department, a broad-spectrum drug, such as caspofungin or amphotericin B, is prescribed first, and after the patient's condition has been stabilized and the pathogen has been identified, fluconazole is prescribed. The choice of drug is also influenced by previous antifungal prophylaxis or empirical therapy. If the patient received fluconazole or itraconazole before the onset of invasive candidiasis, drugs of other classes are prescribed, i.e. caspofungin or amphotericin B.

The effect of antifungal therapy in the absence of rapid deterioration of the patient's condition is assessed on the 4th-7th day. Ineffectiveness of candidemia and ODC treatment may be due to resistance of the pathogen to the antifungal agent, colonization of the intravascular and urinary catheter, vascular prostheses or heart valves, persistent immunosuppression, the presence of foci of dissemination requiring surgical treatment (endocarditis, phlebitis, abscesses, etc.). That is why, if the initial treatment is ineffective, an antifungal agent of a different class is prescribed, taking into account the type and sensitivity of the pathogen, the patient is re-examined to identify foci of dissemination, possible sources of infection are removed and, if necessary, surgical treatment is performed.

Antifungal therapy is continued for at least 2 weeks after the disappearance of all clinical signs of invasive candidiasis and the last detection.

Candida spp in blood and biosubstrate cultures from lesions. After completion of treatment, observation for at least 2 months is indicated to exclude the occurrence of late foci of hematogenous dissemination, including retinitis, osteomyelitis, etc.

Antifungal prevention of invasive candidiasis

The use of antimycotics for primary prevention of invasive candidiasis is indicated only for patients with a high (at least 10%) risk of this complication. The incidence of invasive mycoses is reduced only by prophylactic use of systemic antimycotics in adequate doses (for example, fluconazole), and the use of non-absorbable oral polyenes (nystatin, natamycin, levorin) is ineffective.

Prophylactic use of low doses of fluconazole, as well as antifungal prophylaxis in groups of patients with a low risk of invasive candidiasis, are useless and harmful, since they lead to adverse events and drug interactions, contribute to the selection of pathogens resistant to antifungal drugs, and increase the cost of treatment.

In addition to the use of antifungal agents, an important condition for reducing the incidence of invasive candidiasis is strict adherence to aseptic rules (including thorough hand washing), optimal care of vascular and urinary catheters, and adequate use of antibacterial drugs.

Primary prophylaxis of superficial candidiasis is not indicated. Effective methods of primary antifungal prophylaxis of invasive aspergillosis and other mycoses in patients in the intensive care unit have not been developed.

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Prevention of invasive candidiasis after surgery

Antifungal prophylaxis in the ICU should not be routine. It should be reserved for units with a high incidence of invasive candidiasis, despite aseptic technique, meticulous catheter care, and optimization of antibacterial use.

Antifungal prophylaxis is only appropriate in groups of patients with a frequency of invasive candidiasis development of more than 10%, for example, in patients with repeated gastrointestinal perforation. In addition, the following combinations of risk factors are used to identify patients with a risk of invasive candidiasis of more than 10%. An important predictor of invasive candidiasis in patients in the intensive care unit is multifocal superficial colonization of Candida spp of mucous membranes and skin, which develops 5-6 days before invasive candidiasis in almost all patients.

The drug of choice for antifungal prophylaxis in the intensive care unit is fluconazole at a dose of 400 mg per day, used until the patient's condition stabilizes and risk factors for the development of invasive candidiasis disappear.

The use of low doses of fluconazole, as well as other azoles (ketoconazole, itraconazole) or polyenes (nystatin, etc.) is ineffective and leads to the selection of Candida spp. resistant to antifungals. Indications for prophylaxis:

• repeated perforation of the gastrointestinal tract,
• infected pancreatic necrosis,
• the presence of two or more risk factors for invasive candidiasis (intravenous catheter, use of broad-spectrum antibiotics, pancreatitis, HD, parenteral nutrition, use of systemic steroids within 3 days before ICU, use of immunosuppressants within 7 days before ICU), in combination with widespread (two or more unrelated loci) superficial colonization with Candida spp.
• ICU stay for more than 3 days, presence of three risk factors for invasive candidiasis (intravenous catheter, mechanical ventilation, use of broad-spectrum antibiotics for more than 3 days), in combination with one of the following risk factors: abdominal surgery, parenteral nutrition, HD, pancreatitis, use of systemic steroids within 3 days before ICU, use of immunosuppressants within 7 days before ICU.

The choice of antifungal drug is fluconazole 400 mg/day - until the patient's condition is stable.

Prevention of invasive candidiasis in very low birth weight preterm infants

Antifungal prophylaxis is used in departments with a high incidence of invasive candidiasis, despite compliance with aseptic rules, careful care of catheters, and optimization of the use of antibacterial drugs. The effectiveness of antifungal prophylaxis has been established in controlled clinical trials. In such patients, prophylactic use of fluconazole leads to a decrease in attributable mortality.

The frequency of administration of fluconazole depends on the age of the child. Antifungal prophylaxis is continued throughout the entire period of the child's stay in the intensive care unit.

Indications for prophylaxis: newborns with a gestation period of less than 32 weeks and a body weight of less than 1500 g at birth.

The choice of antifungal drug is fluconazole 3 mg/kg 1-2 weeks of life - every 72 hours, 3-4 weeks of life - every 48 hours, from the 5th week of life - every 24 hours.

Prevention of invasive candidiasis in liver transplant recipients

The effectiveness of antifungal prophylaxis has been established in controlled clinical trials. Prophylaxis is performed if the liver transplant recipient has risk factors. The duration of use of liposomal amphotericin B is 5 days, fluconazole - 10 weeks or until the risk factors are relieved.

Indications for prevention:

• the presence of two or more of the above risk factors in liver transplant recipients,
• repeat liver transplant,
• creatinine level over 2.0 mg,
• choledochojejunostomy,
• use of more than 40 units of blood components during surgery,
• detection of superficial colonization with Candida spp within two days before and three days after surgery.

Selecting an antifungal drug:

• fluconazole 400 mg/day,
• liposomal amphotericin B at 1 mg/(kg x day).

What is the prognosis for invasive candidiasis?

It was found that with candidemia, the probability of a fatal outcome of patients during hospitalization increases by 1.8-2.5 times. In adults, the overall mortality within 30 days after detection of candidemia and ADC is 30-70%, the attributable mortality is 10-49%. At the same time, about half of the patients die in the first 14 days after detection of candidemia. It was found that the overall and attributable mortality significantly decreases with removal (replacement) of the CVC, early and prolonged antifungal therapy. Prognostically unfavorable factors are the APACHE index and more than 18, malignant neoplasm, use of urinary and arterial catheter, male gender, use of glucocorticoids. In premature infants, the overall mortality within 30 days after detection of candidemia and ADC is 32-40%. The type of pathogen also has prognostic significance. For example, candidemia and C. krusei, C. glabrata and C. albicans cause high rates of overall and attributable mortality compared to C. parapsilosis.