Candidiasis is an infectious disease affecting the skin, mucous membranes and / or internal organs, caused by yeast-like fungi of the genus Candida. In the structure of nosocomial infections in debilitated patients, candidiasis is up to 12% and in the structure of infectious infectious mortality – up to 40%. The real clinical significance of this pathology is much higher: undiagnosed cases, an increase in hospital stay by 30 bed-days, significant economic losses for the treatment of visceral forms. The rapid growth (almost 11 times) in recent decades in the frequency of candidiasis in inpatients with various immunity disorders gave the specialists from the Center for Disease Control in Atlanta (USA) to call the current situation a nosocomial epidemic .
Microbiology
The main pathogen is Candida albicans, which is associated with more than 80% of candidiasis. But the infection can be caused by other species: C. tropicalis, C. parapsilosis, C. krusei, C. lusitaniae. Yeast-like fungi do not form true mycelium. The length of the pseudomycelium reaches 12-16 microns. Cells multiply by germination and multipolar budding. They can grow on agar culture media and are aerobic. Favorable conditions for growth 21-370C, pH 6.0-6.5. At 400C, growth is inhibited, at 500C, cells die, complete death with a few minutes of boiling.
Often, fungi are detected as saprophytes in the microflora on the skin and mucous membranes of the respiratory and gastrointestinal tract, and the vagina. Widely distributed in nature (fruits, vegetables, dairy products, etc.).
Pathogenesis Yeast-like fungi of the genus Candida in small quantities can be part of the natural microflora of the mucous membranes, and therefore an important role in the development of candidiasis is played by violations of the competitive interaction of fungi with bacteria of the normal microflora of the host, the integrity of the skin and mucous membranes, phagocytosis, immunological reactions, hormonal balance, distress. Generalization of fungal infection is associated with a change in the relationship between the virulence of the fungus and the patient’s immunity.
Almost all parts of the immune system are involved in protection against fungal infections. Neutrophils, macrophages and eosinophils phagocytose candida blastospores, neutrophils and monocytes – their pseudohyphae. Disseminated candidiasis develops in patients with quantitative and functional defects of neutrophils, suppression of the T-cell link of immunity. A deep defect in the T-cell system explains the predisposition to the development of candidiasis in patients with AIDS. Specific conditions include drug neutropenia during treatment with cytostatics and immunosuppressants.
The disease usually occurs as a result of an endogenous infection. The penetration of the fungus into the tissue occurs when the skin and mucous membranes are damaged, for example, with perforations of the gastrointestinal tract, trauma, surgery, the introduction of catheters into the vessels, with peritoneal dialysis, intravenous drug administration, etc. intestinal dysbiosis.
The causative agent has allergenic and antigenic properties, but antibody titers are high only in visceral candidiasis.
Clinic
Depending on the degree of lesion, candidiasis can be superficial and deep. Superficial includes cutaneous, oropharyngeal, urogenital and is characterized by lesions of the corresponding mucous membranes. The most dangerous are disseminated candidiasis and deep visceral forms.
In the cutaneous form, the disease manifests itself in the form of small vesicles, in the place of which erosions quickly form with a shiny, moist, dark red surface, clear irregular boundaries, with a border of exfoliating macerated epidermis. Characterized by “dropouts” on healthy skin in the form of the smallest erosions with a fringe along the edges and erythematous, scaly spots in the center. The third and fourth interdigital folds of the hands and feet, the inguinal and axillary regions, and the anus may be affected. Paronychia develops. Candidiasis of the oral mucosa (pseudomembranous mucositis or “thrush”) manifests itself in the form of white plaques on the mucous membrane of the cheeks, back of the throat, and tongue. The affected area is usually painless. When plaque hardens and cracks form, slight soreness may appear.
The defeat of the esophagus by candidal infection is characterized by the appearance of dysphagia and single phagia. When the intestines are involved in the process, abdominal pain, bloating, diarrhea are noted. There may be pain and itching in the anus. Stool often contains blood. With agranulocytosis, infiltration and necrosis of the intestinal wall lead to the development of intestinal obstruction, peritonitis, gastrointestinal bleeding, and conditions characterized by high mortality.
Urogenital candidiasis has three clinical forms: candidiasis, acute and chronic (recurrent) urogenital candidiasis. Candidacy is characterized by the absence of complaints. But with microbiological research, fungi are found in small quantities. The acute form is characterized by a pronounced inflammatory picture: redness, swelling, rashes on the skin and mucous membranes of the urogenital organs. The duration of the disease with an acute form of candidiasis does not exceed 2 months. The chronic form is characterized by a disease duration of more than 2 months. Clinically, urogenital candidiasis is manifested by profuse or moderate cheesy discharge, itching, burning, irritation in the external genital area, increased itching during sleep or after water procedures and intercourse, an
unpleasant odor that intensifies after sexual intercourse. When the urethra is damaged, discharge from the urethra of a pale yellow color appears, often scanty. Candidal urethritis in men can be complicated by candidal prostatitis, epididymitis, cystitis.
Candidal endocarditis is similar in flow with bacterial, manifested by prolonged fever and the formation of vegetations on the heart valves. Against the background of immunity disorders, fungal microabscesses in the myocardium can develop, leading to arrhythmias. Sometimes fungal thromboembolism of the coronary arteries develops with the development of ischemia and heart failure.
Lung involvement usually results from hematogenous spread of infection. In such patients, sputum is almost not separated, and the symptoms of pneumonia are similar to bacterial, although they are less constant. There is a discrepancy between severe respiratory failure and scant auscultatory and radiological signs.
Candidal meningitis is typical for newborns and premature babies, and also as a secondary complication of neurosurgical interventions. It is most difficult in patients with impaired immunity. It manifests with severe cerebral and meningeal symptoms, in the case of intracerebral abscesses – focal symptoms with neutrophilic or lymphocytic pleocytosis (depending on the degree of neutropenia). Skin lesions in acute disseminated candidiasis occur in 5-10% of cases. It manifests itself in the form of dense, rising above the surface of the nodes 0.5-1 cm in diameter, pink-red in color, which do not disappear with pressure, papular or maculopapular rash, similar to drug.
For chronic disseminated candidiasis (“hepatolienal”), the most characteristic is the defeat of the liver and spleen with their increase and the development of multiple microabscesses. The disease is accompanied by prolonged fever, sometimes with the development of jaundice and pain in the right hypochondrium. In half of the patients, high leukocytosis and severe hyperbilirubinemia (mainly due to the direct fraction) are noted in the blood. The level of transaminases increases inconsistently and no more than 3 times. Often such liver damage looks like cholestatic hepatitis and is mistaken for toxic liver damage by cytostatics, especially in the absence of characteristic changes according to ultrasound data.
Hematogenously disseminated forms of candidiasis (candidal sepsis) are characterized by a severe course, high fever and severe symptoms of general intoxication. Fever of an irregular type, with repeated chills alternating with profuse perspiration. The disease is accompanied by damage to various organs (lungs, gastrointestinal tract, brain, kidneys, etc.), and the presence of several foci is characteristic. Often, the retina is involved in the process and spread to the vitreous body. Patients are worried about pain in the eyes and visual disturbances. When the lungs are damaged, a strong cough appears,
at first dry, then with a small amount of viscous mucopurulent sputum, sometimes streaked with blood. X-ray examination reveals infiltrates, more often in the lower lobes, prone to fusion. Disintegration with the formation of cavities is often observed. The pleura may be involved. The hilar lymph nodes are enlarged and indurated. Occasionally, hematogenous, deep, localized infections of Candida such as osteomyelitis, arthritis, endophthalmitis, and liver abscess occur. Blood cultures remain negative, and if they become positive, it is often only late. If granulocytopenia persists and the neutrophil count does not increase, the likelihood of death is very high, even with antifungal treatment.
Diagnosis
Diagnosis of cutaneous lesions of Candida spp. is put on the basis of clinical manifestations.
Candidiasis of the digestive tract is determined by the characteristic thrush in combination with symptoms of damage to other organs. It is possible to reveal the involvement of the esophagus, stomach, and large intestine in the process by endoscopic examination (with taking material from the affected areas for laboratory research).
In genitourinary candidiasis, colposcopy after staining with Lugol’s solution reveals colpitis in the form of small-point inclusions (“semolina”), often with a pronounced vascular pattern. Microscopy of a vaginal smear stained with methylene blue is performed. Scanty sputum discharge in pneumonia still allows the pathogen to be isolated in it.
The clinical manifestations of candidal meningitis are nonspecific, and morphological examination of the cerebrospinal fluid of the drusen of fungi or pseudomycelium cannot be detected. The nature of the disease is often established posthumously.
A reliable diagnosis is considered with the laboratory isolation of yeast-like fungi (from ulcerative lesions of the mucous membranes, pus, bile, and in case of candidal sepsis – from blood and punctuate of closed cavities). It is important to detect fungi in histological preparations obtained with targeted biopsy, re-isolation of the same type of fungi from an open affected surface, and their antigens in the blood serum. High titers (1: 160-1: 1600) or an increase in antibody titers during the course of the disease are considered positive.
Of the immunological methods in the diagnosis of candidiasis, enzyme immunoassay, agglutination reactions, complement binding, direct hemagglutination, and immuno-electrophoresis are used. The main ones are enzyme-linked immunosorbent assay, polycepid reaction, crops. In HIV-infected patients, serological tests remain negative.
At present, in addition to classical microbiological methods, the determination of D-arabinitol and mannose markers of candidiasis by gas chromatography is used, which allows not only to establish a diagnosis, but also to evaluate the effectiveness of treatment.
Treatment
Treatment is carried out in a hospital and is aimed at eliminating the factors contributing to the occurrence of candidiasis. In case of skin lesions, local treatment is carried out in an open way using antifungal ointments.
For lesions of the mucous membranes, an antifungal suspension is used. With lesions of the gastrointestinal mucosa, antifungal drugs can be administered orally, intravenously, and in the form of rectal suppositories.
For urogenital candidiasis, antifungal drugs are administered in the form of tablet forms, vaginal balls, tablets and ointments. For visceral and disseminated forms of candidiasis, antifungal drugs are prescribed intravenously in the form of drip infusions. Fluconazole occupies a special status among antifungal drugs. It is distinguished by high bioavailability and efficiency at any localization of the process – from common skin lesions to meningitis, penetration into all biological fluids and body tissues, a good effect of oral forms, the possibility of intravenous use in a serious condition of the patient and the introduction of a shock (double) dose on the first day of treatment , lack of toxicity and low frequency of adverse reactions. The drug can be used in premature babies. In all cases, fluconazole is prescribed once a day.
When fluconazole therapy is ineffective, one should think about candidiasis caused by naturally resistant Candida species, such as C. krusei. In these cases, antifungal therapy is recommended with an effective, but potentially toxic, amphotericin B. Treatment is carried out only in a hospital under close laboratory supervision. Doses of amphotericin B due to the danger of nephrotoxic reactions should not exceed 0.5-1 mg / kg per day intravenously once a day or every other day. For microabscesses in the liver, brain and other organs, the liposomal form of amphotericin B is most effective.
In stubborn cases, along with antibiotic therapy, a multivalent vaccine from Candida cultures, antihistamines, solutions of sodium or potassium iodide inside, B vitamins, ascorbic acid are used.
Prognosis
With superficial forms, the prognosis is favorable, with generalized and visceral forms, it is more serious.
Prevention
Long-term antibiotic therapy requires the appointment of antifungal drugs.