Invasive candidiasis is a generalized fungal infection in which candidemia and damage to internal organs by fungi of the genus Candida are observed. Up to half of the cases of the disease are caused by the pathogen C. albicans, the three most common pathogens are C. parapsilosis and C. glabrata. Clinical manifestations of the disease are determined by the localization of the focus of infection and the degree of immune response. Serological and cultural blood tests, instrumental imaging methods are prescribed for diagnosis. Treatment requires an individual selection of antifungal drugs.
Invasive candidiasis is considered one of the most common infections among hospitalized patients. More than 250,000 cases are registered annually, and experts are confident that the true incidence of infection is much higher. The disease develops more often in newborns and elderly people. The high prevalence, unfavorable prognosis and difficulties of timely identification of candidiasis force specialists to look for new ways to diagnose and treat the disease.
The causative agent of the disease is fungi of the genus Candida, which belong to the Saccharomyces family, the Ascomycetes class. More than 20 species pathogenic to humans are known, but up to 90% of cases of invasive candidiasis are provoked by only 5 of them: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei.
The main risk factor for invasive candidiasis is immune insufficiency, since all parts of the immune system are involved in the fight against fungal infection. The disease is mainly found among patients in intensive care units, and the age of the patient under 1 year and older than 65 years dramatically increases the likelihood of fungal infection. There are also other risk factors:
- Transplantation of internal organs. Candidiasis accounts for more than 53% of all invasive mycoses that develop in patients after transplantation. Transplantation of the small intestine, pancreas and liver has the greatest risk. Fungal infection develops in 3-4% of patients with transplanted heart, kidneys, lungs.
- Catheter placement. The central venous catheter is the optimal entrance gate for fungal pathogens. Biofilms from Candida fungi are formed in its lumen, which cause catheter-associated candidemia. Pathology is more common in newborns and is caused by the species C. parapsilosis.
- Antibiotic therapy. Broad-spectrum antimicrobials suppress beneficial intestinal microflora, increase fungal contamination of the gastrointestinal tract. Cephalosporins of the third generation are recognized as the most dangerous, which increase the risk of mycosis by 2 times.
- Oncopathology. Patients with hemoblastosis who have marked neutropenia, impaired production of immunoglobulins and pathology of the complement system are at the greatest risk. In the late stages of solid tumors, the likelihood of invasive candidiasis also increases.
Most cases are associated with endogenous transmission of infection: penetration of fungi through the mucous membranes of the gastrointestinal tract or through damaged hollow organs of the abdominal cavity. Infection is facilitated by an increase in the fungal load in the intestine against the background of antibiotic therapy. Less often, exogenous infection is observed during invasive medical manipulations (catheter placement, parenteral nutrition, surgical intervention).
After the penetration of Candida fungi into the circulatory system, candidemia develops, causing the hematogenic spread of the pathogen and the formation of foci in the internal organs. The main mechanism of tissue invasion is the ability to form pseudomycelia, which prevents the absorption of fungi by macrophages. Pathogenicity factors include enzymes (aspartylproteinases, phospholipases), phenotypic instability.
Invasive candidiasis symptoms
A third of patients have candidemia without organic pathologies of internal organs, which has no specific signs. The main symptom of the addition of fungal invasion is a sharp rise in temperature against the background of antibiotic therapy. Fever often has a wave-like course. With deep immunodeficiency, the manifestations of the systemic inflammatory process are erased or completely absent.
When internal organs are involved in the process, the clinical picture is diverse. The defeat of the abdominal organs is manifested by the classic signs of peritonitis: sharp pains throughout the abdomen, tension of the muscles of the anterior abdominal wall, repeated nausea and vomiting. Infection of the urinary tract is accompanied by candidal cystitis and pyelonephritis. A particular sign of infection is pneumonia, which proceeds without features.
With the installation of liquor shunts and other invasive neurosurgical manipulations, damage to the central nervous system is possible. Invasion by Candida fungi is most often manifested by meningitis with a subacute course. With inflammation of the meninges, there is a severe headache, prolonged fever, photophobia. The difference between fungal meningitis is the absence of rigidity of the occipital muscles.
Heart tissue damage develops in patients after the installation of artificial valves. Clinical manifestations manifest within 2 months after surgery. Patients suffer from fever, shortness of breath, pain in the heart. Signs of heart failure, hepatosplenomegaly, Osler nodules quickly join. There is a risk of involvement of the musculoskeletal system with the development of candidal arthritis and osteomyelitis.
Invasive candidiasis in newborns is characterized by a classic picture of neonatal sepsis. There is inhibition, refusal of feeding, shortness of breath with episodes of apnea. Characterized by cardiovascular instability, prolonged jaundice. Febrile fever is observed only in 50% of cases, while up to 40% of patients have a physiological norm of blood leukocytes.
Despite the achievements of practical infectology, mortality in invasive candidiasis remains consistently high. In adults, the mortality rate is 40%, among immunocompromised patients it can reach 50-70%. The total infant mortality in the invasive form of candidiasis varies between 37-44%, neonatal – 43-54%. A prognostically unfavorable factor is a delay in the identification of the pathogen for 48 hours or more.
The life-threatening consequences of invasive candidiasis are mainly associated with septic shock and multiple organ failure. The causes of death are critical lesions of the brain, cardiopulmonary system and kidneys. Coagulopathy, thromboembolism, disseminated intravascular coagulation syndrome (DIC) are of great danger.
Since invasive candidiasis mainly develops in hospitalized patients, the examination is carried out by the attending physician together with a resuscitator and an infectious disease specialist. Great importance is paid to the collection of anamnesis, clarification of the immune status, analysis of the current pharmacotherapy regimen. Upon examination, signs of systemic inflammation and multiple organ failure are determined. To confirm the diagnosis , the following methods are prescribed:
- Determination of the Candida surface antigen. The presence of mannan and antimannan antibodies in the analysis is specific for candida infection. Positive results are 5-6 days ahead of the response when sowing hemoculture, are important for the timely start of therapy. The sensitivity and specificity of the method are 80-85%.
- Hemoculture research. The detection of Candida fungi in blood samples taken from three different veins is a reliable sign of invasive candidiasis. This method requires a long time and gives positive results only in 75% of patients, so it is not suitable for early diagnosis.
- Instrumental visualization. Ultrasound examination, transesophageal echocardiography, computer and magnetic resonance imaging are used to detect foci of candida infection. It is possible to confirm the fungal etiology of inflammatory foci by analyzing biopsies.
- Predictive scales. The Candida colonization index is used to determine individual risk.
Due to the absence of pathognomonic manifestations, bacterial sepsis, generalized herpetic infection, aspiration and ventilator-associated pneumonia are excluded when making a diagnosis. Differential diagnosis is carried out with malaria, systemic lupus erythematosus, vasculitis. Respiratory distress syndrome should be excluded in newborns.
Invasive candidiasis treatment
The basis of treatment is long-term parenteral administration of antifungal drugs. Medications are prescribed empirically until the results of blood culture are obtained, after taking a biomaterial for microbiological diagnostics. When choosing a drug for the treatment of candidiasis, pay attention to the immune status of the patient, the presence and nature of concomitant diseases, anamnestic data on fungal infections.
Standard therapy protocols include drugs from the group of polyene antibiotics, azole antimycotics, echinocandins. The clinical response to the treatment develops within 3 days. In its absence, a revision of the dosage regimen of antimycotics or their replacement is necessary. The criterion for the completion of antimycotic therapy is negative blood cultures for 14 days.
Pharmacotherapy of invasive candidiasis is combined with the treatment of the underlying disease. Significant efforts are made to normalize the immune status, if possible. To exclude repeated infection with fungi, catheters are replaced. In case of severe immunodeficiency, a condition after bone marrow or internal organ transplantation, patients are treated in a sterile box.
Prognosis and prevention
In patients with preserved immune system functions, who have started antimycotic therapy on time, it is possible to achieve full recovery. With immunodeficiency and severe somatic status, the prognosis remains doubtful even with early and comprehensive medical care. For the prevention of invasive candidiasis, patients from the high-risk group are recommended to take fluconazole in a standard dosage.