Invasive Candidiasis: Candidemia and Acute Disseminated Candidiasis

Candida spp are the most common pathogens of invasive mycoses in the ICU. Invasive candidiasis, as a rule, occurs in patients with risk factors, characterized by severe clinical manifestations and high attributable lethality (10-49%).

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

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

Risk factors for invasive candidiasis

In adults:

• long stay in the ICU,
• widespread (> 2 loci) surface colonization of Candida spp,
• the use of broad-spectrum antibiotics, steroids or immunosuppressants,
• long-term use of the CEC,
• severity of the patient's condition,
• perforation or surgical treatment of the gastrointestinal tract,
• infected pancreatic necrosis,
• complete parenteral nutrition,
• IVL,
• repeated blood transfusion,
• diabetes mellitus and severe neutropenia.

Surface colonization of Candida spp is detected in 40-80% of patients in the ICU.

In newborns:

• gestational age less than 29 weeks,
• birth weight less than 1500 g,
• a low Apgar score,
• use of antibiotics from groups of carbapenems and glycopeptides,
• a common candidiasis of the skin and mucous membranes,
• colonization of Candida spp of the mucous membranes of the gastrointestinal tract.

Up to 10% of cases of candidemia and OCD are associated with outbreaks of nosocomial infection, this may require additional measures (identifying the source of infection, examining 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. Practically all patients for 5-6 days before invasive candidiasis develop a superficial colonization of Candida spp, often multifocus.

Candidemia and acute disseminated candidiasis

Candidemia and acute disseminated candidiasis (i.e., candidemia in combination with a foci / foci of dissemination or multiple foci of dissemination) account for 75-90% of all cases of invasive candidiasis. Candidemia and ODC most often develop in patients in the ICU, hematological and oncology departments, in premature newborns, in patients with widespread burns. The incidence of candidemia and OCD in the ICU varies from 2 to 200 per 1000 hospitalized patients, depending on their risk factors. In the case of candidemia and ODC, the probability of a lethal outcome during hospitalization increases twice, the duration of treatment is 3-30 days, the cost of treatment is 2-5 times.

The majority (93-97%) of the causative agents and OCD are C. Albicans (15-60%), C. Parapsilosis (5-40%), C. Glabrata (5-25%), C. Tropicalis (5-15% ) and C. Krusei (3-7%). About 3-7% of pathogens are C. Lusitaniae, C. Guillermondii, S. Rugosa, S. Kefyr, etc. The spectrum of Candida and JOD pathogens varies widely in different medical institutions and depends on the contingent of patients, the applied methods of treatment and prevention, the effectiveness of methods for monitoring nosocomial infections, etc. The use of azole antimycotics for prophylaxis and empirical therapy leads to a decrease in the proportion of C. Albicans among adults turer of invasive candidiasis. In newborns with low birth weight, the spectrum of Candida and UDC pathogens is significantly different from that in adults. The most frequently detected C. Albicans (40-75%), C. Parapsilosis (7-45%) and C. Tropicalis (5-15%), less often C. Glabrata, C. Krusei, S. Kefyr and C. Guillermondii .

In pathogens of invasive candidiasis, in comparison with pathogens of superficial candidiasis, resistance to antimycotics is much more often detected. This is largely due to the large number of non-albicans of Candida among pathogens of invasive candidiasis, since C albicans are much less likely to be resistant to antifungal agents than other (non-albicans) Candida spp. In addition, the development of secondary resistance as a result of preventive or empirical use of antifungal agents is possible.

[8], [9],

Symptoms of invasive candidiasis

Clinical signs of candidemia are non-specific and do not differ from the symptoms of bacterial sepsis. The increase in body temperature> 38 ° С, refractory to the use of broad-spectrum antibiotics, is revealed in 90-96% of patients, ODN - in 15-21%, infectious-toxic shock - in 15-20%, signs of damage of different organs - in 30 -40%. That is why for the timely detection of candidemia all patients with risk factors and presumed clinical signs showed an examination to identify foci of dissemination, re-sowing blood and material from identified foci.

OCD occurs as a result of hematogenous spread of Candida spp. In organism. With UDC, almost all organs and tissues of the body can be affected, but more often the lungs, kidneys, eyes, 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. In patients, fever, chills, pain in the waist or abdomen, changes in urine analysis, OPN develops in 5-15% of patients with candidemia.

The defeat of the central nervous system develops in 5-15% of patients with UDC. In adults, abscesses of the brain often occur, in newborns - meningitis. Clinical manifestations are nonspecific (headache, photophobia, nausea, vomiting and focal neurological symptoms).

Candidial endocarditis develops in 5-13% of patients with OCD, myocarditis or pericarditis occur less frequently. Additional risk factors - the presence of prosthetic heart valves or blood vessels, injecting drug addiction. Clinical manifestations (fever, palpitations, dyspnea and pain in the heart) and echocardiography are not specific and do not differ from the symptoms of bacterial endocarditis.

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

The defeat of the visual organs (candidiasis endophthalmitis) develops in 2-10% of patients with UDC. Characterized by severe pain, impairment and loss of vision Candidative retinitis may be a late complication and develop after systemic manifestations of candidemia. Therefore, all patients with candidemia are shown ophthalmoscopy with pupil dilatation during the initial examination of the patient and in evaluating the effectiveness of the treatment.

In newborns with low birth weight, the incidence of candidemia and OCD is 2 to 6%, but in patients with risk factors it increases to 12-32%. In term infants with normal body weight, invasive candidiasis occurs very rarely. Depending on the time of infection, congenital and acquired candidiasis is allocated. Congenital candidiasis is diagnosed from the first hours of birth to 6 days.

Congenital candidiasis is the result of transplacental or vertical (ascending) infection of the fetus. Clinically congenital and acquired candidiasis can manifest as a lesion of the skin and mucous membranes, candidemia, UDC 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 when viewed looks like erythematous diffuse rash, similar to a superficial burn. Lesion of mucous membranes - acute pseudomembranous candidiasis of the oral cavity. Candida and UDC are usually detected in the period from 15 to 33 days of life. The main clinical manifestations of candidemia and ODC are non-specific, do not differ from bacterial sepsis. A high incidence of candidal meningitis (10-40%) is typical, kidneys, endocardium and vision organs are less often affected.

Candidiasis peritonitis

Candidiasis peritonitis is 10-15% of all cases of invasive candidiasis. Usually develops in patients in the ICU or as a complication of PD.

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

Risk factors

Perforation of the gastrointestinal tract, infected pancreatic necrosis, abdominal surgery, PD The frequency of resistance of pathogens of candidiasis 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 from antibiotic 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 a purulent discharge from the abdominal cavity or clouding of the dialysate. The frequency of development of shock in candidal peritonitis exceeds 15%. In addition, there is a high incidence of candidemia and ODC with damage to various organs and systems.

Diagnostics

Diagnosis is based on the detection of Candida spp in a peritoneal fluid. The examination should exclude the defeat of other organs and systems. Criteria for diagnosing clinical, endoscopic or laboratory signs of peritonitis in combination with the detection of Candida spp in microscopy and / or peritoneal fluid culture.

[17], [18]

Treatment of candidal peritonitis

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

[19], [20], [21]

Candidiasis of the central nervous system

Candidiasis of the central nervous system may be a manifestation of the ODC or complication in premature and small children with risk factors for invasive candidiasis, in neurosurgical patients with ventriculo-peritoneal shunts, injecting drug users, etc.

[22],

Symptoms of candidiasis of the central nervous system

The course is usually protracted, first signs of hypertension-hydrocephalic syndrome predominate, and focal symptomatology is revealed later.

Diagnostics

Diagnosis is based on the detection of Candida spp in CSF, aspirate from an abscess of the brain. Be sure to determine the type of pathogen and its sensitivity to antimycotics. In a general clinical study of CSF, moderate pleocytosis of mixed character, protein-cell dissociation, is revealed. During the examination, it is necessary to exclude damage to the brain substance, other organs and systems (MRI, CT, etc.).

Diagnostic criteria: Detection of Candida spp during microscopy and / or CSF seeding, material from brain abscess.

Treatment

When choosing an antimycotic should take into account the type of pathogen and its sensitivity, the patient's condition, pharmacokinetics and pharmacodynamics of the drug Fluconazole and voriconazole well pass through the BBB. The level of fluconazole in CSF in patients with fungal meningitis is 52-85% of the concentration in the blood plasma, voriconazole - about 50%. In addition, voriconazole creates high concentrations in the brain substance 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 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 substance. The concentration of caspofungin in CSF and brain substance is low.

Preparations for the choice of voriconazole intravenously 6 mg / kg in 2 injections on day 1, then 4 mg / kg in 2 injections, amphotericin B 0.7-1.0 mg / kgg. Fluconazole 6.0 to 12 mg / kgg is prescribed after stabilization of the patient's condition and when a sensitive pathogen is detected, liposomal amphotericin B 3.0-5.0 mg / kgg / day with ineffectiveness or toxicity of standard amphotericin B. Duration of antimycotics application - at least 4 weeks after the disappearance of all signs of infection. An obligatory condition for successful treatment is removal of catheters, shunts and similar instruments, correction of ICP.

[23], [24], [25], [26], [27], [28], [29]

Candidiasis endocarditis, pericarditis and phlebitis

Candidiasis endocarditis, pericarditis and phlebitis are usually a manifestation of the OCD Isolated candidiasis endocarditis, pericarditis and phlebitis develop rarely, mainly in patients after cardiac surgery, in injecting drug users.

Symptoms

Clinical manifestations in mycotic endocarditis are similar to endocarditis of bacterial etiology, auscultatory pattern of the defeat of the valves, increasing heart failure, resistant to antibiotics fever. Aortic and mitral valves are involved in the lesion. In Echocardiography, signs of warty endocarditis are revealed. Pericarditis and phlebitis occur rarely, do not have clinical features other than the absence of the effect of antibiotic therapy.

Diagnostics

Diagnosis is based on the detection of Candida spp in the material from the affected heart valves, endocardium, etc. Serological diagnostic methods are not developed. In addition, the diagnosis is established when identifying the characteristic signs of cardiovascular damage in patients with candidemia and UDC. In the course of the examination, it is necessary to exclude the damage of other organs and systems Criteria for diagnosis of clinical and instrumental (echocardiography, etc.) signs of endocarditis, pericarditis or phlebitis in combination with the detection of Candida spp in blood sowing, pericardial fluid, or histological examination and biopsy.

Treatment

The basis of treatment is the surgical removal of infected heart valves, resection of the affected parts of peripheral veins and pericardium combined with prolonged use of antimycotics. The optimal variant of antifungal therapy is not defined. Usually prescribed caspofungin, amphotericin B or fluconazole, depending on the type of pathogen and the patient's condition. The duration of antimycotics usually ranges from 2 to 12 months, at least 6 weeks after surgical treatment. If it is not possible to remove the affected valves, lifelong prophylaxis of recurrence with fluconazole at 3 mg / (kg x 10) is necessary. After completion of the treatment, patients were observed for at least 1 year.

[30]

Candidiasis endophthalmitis

Candida endophthalmitis - caused by Candida spp inflammation of the inner shells of the eye with the formation of an abscess in the vitreous. Candida endophthalmitis develops as a complication in 2-10% of patients with UDC. Isolated candidiasis endophthalmitis occurs rarely, for example, with prolonged intravenous use of drugs or injecting drug users.

[31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41]

Clinical picture

The main complaints are reduced visual acuity, pain in the eye, mild eyelid edema and conjunctiva. The examination reveals corneal edema, hypopion or fibrinous exudate in the anterior chamber of the eye, white-yellow foci with faint margins on the retina, focal or diffuse opacification of the vitreous. Progression can lead to panophthalmitis, loss of the eye, CNS damage.

Diagnostics

The diagnosis is usually established when identifying the characteristic changes in ophthalmoscopy in patients with candidemia and ODC. Isolated damage to the organs of vision is less common. In such cases, a survey is performed 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, blood or other foci of dissemination.

Treatment

The basis of treatment is the long-term use of antimycotics, with the defeat of the vitreous body, surgical treatment is effective. The choice of the drug depends on the type of pathogen and the patient's condition. The duration of antimycotics usually ranges from 6 to 12 weeks. The effectiveness of the administration of antifungal agents to the vitreous is not defined.

[42], [43]

Diagnosis of invasive candidiasis

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

Methods of diagnosis:

• repeated blood cultures for specialized media (Saburo, wort agar) - 2 times a day for at least 3 days,
• tsosev a distal fragment of an intravascular catheter,
• microscopy and sowing of biosubstrates (material from fauces, urine, feces, bronchial flushing fluid, separated from drains and wounds) to determine the degree of surface colonization,
• CT or lung radiography,
• CT or ultrasound of the abdominal cavity,
• ophthalmoscopy with dilated pupil,
• biopsy of lesions,
• microscopy, sowing, histological examination of biopsy material,
• mandatory determination of the type of pathogen detected during the sowing of any sterile normal biosubstrate.

Criteria for diagnosis:

• Candidaemia - a single discharge of Candida spp when sowing blood 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 for 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 sites.

[44], [45], [46]

Treatment of invasive candidiasis

When revealing signs of invasive candidiasis, antifungal therapy is started urgently; later administration of antimycotics only after repeated isolation of Candida spp from blood and other substrates increases lethality. Preparations for the treatment of invasive candidiasis - caspofungin, fluconazole, voriconazole and amphotericin. The effectiveness of these drugs with candidemia and ODC is from 66 to 81%. Ketoconazole and itraconazole are not used due to the variable bioavailability when ingestion. All patients with invasive candidiasis show 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 the severity of risk factors (cancellation or reduction of the dose of glucocorticoids, optimization of the use of antibacterial drugs, compensation for diabetes mellitus, etc.).

In connection with the insufficient effectiveness of diagnosis and the high attributable lethality of invasive candidiasis, empirical antifungal therapy is widely used - the administration of antimycotics to patients with a high risk of invasive candidiasis to laboratory confirmation.

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

The choice of an antifungal agent for the treatment of candidemia, acute disseminated candidiasis

The patient's condition is unstable (shock, shock, etc.)	Caspofungin intravenously 70 mg / day on the 1st day, on subsequent days 50 mg / day intravenously, amphotericin B 0.6 mg / kgg, voriconazole intravenously in 6 mg / kg in 2 injections on day 1, then 4 mg / kg in 2 administrations
Newborns with very low body weight	Amphotericin B 0.6-1.0 mg / (kg x 10), fluconazole 5-12 mg / (kgxut)
Type of pathogen not defined	Caspofungin intravenously 70 mg / day on the 1st day in the following days 50 mg / day intravenously amphotericin B 1 0 mg / (kghsut)
Pathogen C. Glabrata	Amphotericin B 0.8-1.0 mg / kgg, cappofungin intravenously 70 mg / day on the 1st day, on the following days 50 mg / day intravenously fluconazole 12 mg / kg kg)
Pathogen C. Krusei	Caspofungin intravenously 70 mg / day on the 1st day, on subsequent days 50 mg / day intravenously, voriconazole intravenously 6 mg / kg in 2 injections on the 1st day then 4 mg / kg in 2 injections
Pathogen C. Lusitaniae S. Guillermondii	Fluconazole 6.0 mg / kgg, caspofungin intravenously 70 mg / day on the 1st day on subsequent days 50 mg / day intravenously, voriconazole intravenously 6 mg / kg in 2 injections on day 1, then 4 mg / kg in 2 introductions
Pathogen C. Albicans, C. Tropicalis, C. Parapsilosis	Fluconazole 6.0 mg / kgg, amphotericin B 0.6 mg / kg / day, caspofungin intravenously 70 mg / day on the first day, on subsequent days 50 mg / day intravenously, voriconazole intravenously 6 mg / kg in 2 administration on day 1, then 4 mg / kg in 2 injections

In clinically unstable patients, as well as before identifying the pathogen, an antifungal drug with a low risk of resistance of the causative agent (eg, caspofungin or amphotericin B) should be prescribed. In such patients the use of fluconazole is not shown in connection with its mycostatic activity and high probability of the causative agent to fluconazole. Apply fluconazole after stabilizing the patient's condition and identifying the pathogen usually sensitive to fluconazole (C albicans, C tropicalis, C parapsilosis, C lusitaniae, C guillermondii).

In newborns, most pathogens are sensitive to amphotericin B and fluconazole, and amphotericin B nephrotoxicity is lower than in adults. Drugs of choice - amphotericin B and fluconazole, when using the latter should take into account the features of pharmacokinetics in premature newborns. Fluconazole is not prescribed to patients who previously received this medication prophylactically. If amphotericin B or fluconazole is ineffective or toxic, then caspofungin may be used.

In addition, the appointment of antimycotics should take into account the local epidemiological situation. If a high frequency of non-albicans Candida spp. Is detected in a medical institution or department, a wide-spectrum preparation, for example caspofungin or amphotericin B, is first prescribed, and after stabilization of the patient's condition and determination of the pathogen, fluconazole. The choice of the drug is also influenced by previous antifungal prophylaxis or empirical therapy. If the patient received fluconazole or itraconazole before the occurrence of invasive candidiasis, then prescribe drugs of other classes, te caspofungin or amphotericin B.

Evaluation of the effect of antifungal therapy in the absence of rapid deterioration of the patient is carried out on the 4-7th day. Ineffectiveness of treatment of candidemia and ODC may be due to resistance to the antimycotic agent, colonization of the intravascular and urinary catheter, prosthesis of the vessels or valves of the heart, persisting immunosuppression, the presence of surgical treatment for dissemination (endocarditis, phlebitis, abscesses, etc.). That is why, if the initial treatment is ineffective, antimycotics of another class are prescribed, taking into account the type and sensitivity of the pathogen, re-examining the patient to identify foci of dissemination, remove possible sources of infection and, if necessary, perform surgical treatment.

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

Candida spp when sowing blood and biosubstrates from lesions. After completion of treatment, observation of at least 2 months is shown to exclude the occurrence of late foci of hematogenous dissemination, including retinitis, osteomyelitis, etc.

Antifungal prophylaxis of invasive candidiasis

The use of antimycotics for the primary prevention of invasive candidiasis has been shown only in patients with a high (at least 10%) risk of this complication. The frequency of invasive mycoses reduces only the preventive use of systemic antimycotics in adequate doses (eg, fluconazole), and the administration of unabsorbed oral polyenes (nystatin, natamycin, levorin) is ineffective.

Prophylactic use of small 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 undesirable phenomena and drug interactions, promote the selection of mycosis-resistant pathogens, and increase the cost of treatment.

In addition to the use of antimycotics, an important condition for reducing the incidence of invasive candidiasis is strict adherence to asepsis rules (including thorough hand washing), optimal care for 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 ICU have not been developed.

[47], [48], [49], [50], [51], [52]

Prevention of invasive candidiasis after surgery

Antifungal prophylaxis in the ICU should not be routine. It should be performed in departments with a high incidence of invasive candidiasis, despite compliance with asepsis rules, careful care of catheters and optimization of the use of antibacterial drugs.

Antifungal prophylaxis is suitable only in groups of patients with the incidence of invasive candidiasis more than 10%, for example, in patients with repeated perforation of the gastrointestinal tract. In addition, the following combinations of risk factors are used to identify patients at risk of invasive candidiasis of more than 10%. An important predictor of invasive candidiasis in patients in the ICU is multifocus surface colonization of Candida spp of the mucous membranes and skin that develops 5-6 days before invasive candidiasis in almost all patients.

The drug of choice for antifungal prophylaxis in ICU is fluconazole at a dose of 400 mg per day, applied before the patient stabilizes and the risk factors for the development of invasive candidiasis disappear.

The use of small doses of fluconazole, as well as other azoles (ketoconazole itraconazole) or polyenes (nystatin and others) is ineffective and leads to the selection of antimycotic-resistant Candida spp. Indications for prevention:

• repeated perforation of the gastrointestinal tract,
• infected pancreatic necrosis,
• 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 for 3 days prior to ICU, immunosuppressive use for 7 days before ICU), combined with common ( two or more unrelated loci) by the surface colonization of Candida spp.
• stay in the ICU for more than 3 days, the presence of three risk factors for invasive candidiasis (intravenous catheter, ventilator, use of broad-spectrum antibiotics for more than 3 days), combined with one of the following risk factors: abdominal surgery, parenteral nutrition, HD, pancreatitis, steroids for 3 days prior to ICU, the use of immunosuppressors for 7 days before ICU.

Choice of an antifungal drug Fluconazole 400 mg / day - until stable stabilization of the patient.

Prevention of invasive candidiasis in preterm infants with very low birth weight

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

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

Indication for the prevention of newborns with a gestation period of less than 32 weeks with a body weight of less than 1500 g at birth.

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

Prevention of invasive candidiasis in liver transplant recipients

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

Indications for prevention:

• the presence of two or more of these risk factors in liver transplant recipients,
• repeated liver transplantation,
• the level of creatinine is more than 2.0 mg,
• choledochoejunostomy,
• the use of more than 40 units of blood components during surgery,
• detection of superficial colonization of Candida spp for two days before and three days after surgery.

Choosing an antifungal drug:

• fluconazole 400 mg / day,
• Liposomal amphotericin B at 1 mg / (kilogram).

What prognosis does invasive candidiasis have?

It was found that when a candidemia occurs, the likelihood of a lethal outcome of patients during hospitalization increases 1.8-2.5 times. In adults, the overall lethality within 30 days after the detection of candidemia and UDC is 30-70%, attributable lethality - 10-49%. At the same time, about half of the patients die within the first 14 days after the detection of candidemia. It is established that the total and attributable lethality significantly decreases with the removal (replacement) of CIC, early and prolonged antifungal therapy. Prognostically unfavorable factors APACHE index And more than 18, malignant neoplasm, application of urinary and arterial catheter, male sex, use of glucocorticoids. In preterm infants, the overall lethality within 30 days after the detection of candidemia and UDC is 32-40%. The type of pathogen also has prognostic significance. For example, candidemia and ODC caused by S. Krusei, C. Glabrata and C. Albicans, are distinguished by high rates of general and attributable lethality in comparison with C. Parapsilosis.