What is candidiasis?

Causes and Symptoms

Candida is a genus of dimorphic fungi found widely in nature. This fungus may be found in soil, inanimate objects, plants, and most important, as a harmless parasite of humans and other mammals. It can exist in two forms: as a yeast and as a mold. In the yeast phase, this fungus exists as a normal inhabitant in and on human bodies. Nearly all infections are of such endogenous origin, but human-to-human transmission may occasionally occur from mother to newborn or between sexual partners. The yeasts reproduce asexually by budding, and a sexual stage has been recognized only in a few species. Pseudohyphae develop when yeasts and their progeny adhere to one another, forming chains. Hyphae, the branching tubular structures of molds, are formed in tissue invaded by the fungus.

Identification of Candida as the causative agent in clinical infections depends largely on the microscopic examination of infected tissue or secretions and on a culture of Candida prepared from infected material. Histopathological examination may reveal yeast forms and/or hyphal or pseudohyphal forms. The microscopic appearance of these organisms is similar to those of some other fungi, and a culture is necessary to confirm this fungus as the responsible pathogen. Candida will grow on many types of artificial microbiologic media and can usually be grown on the same media used to grow bacteria. With some types of infection, however, the use of special media or techniques may lead to a higher yield from cultures. After an unknown yeast is grown on artificial media, tests must be performed to determine its identity. Most laboratories initially use the germ tube test, in which yeast is introduced into rabbit or human plasma at 35 degrees Celsius for one to two hours. In this test, a structure called a germ tube is observed if the yeast is Candida albicans, Candida stelloidea, or rare strains of Candida tropicalis. If this test is positive (a germ tube is produced), then
most laboratories assume that the microorganism is C. albicans—it is by far the most common species causing disease—and conduct no further, and usually more expensive, tests. Simple cultural tests may also be used to identify C. albicans, including the formation of spiderlike colonies on eosin methylene blue agar or the production of chlamydoconidia on cornmeal agar. The identification of Candida antigens in the serum of patients with widespread or disseminated infection is sometimes used to assist in the diagnosis of candidiasis, but this test is neither sensitive nor specific.

The bodies of humans and other mammals possess multiple defense mechanisms against candidiasis. The skin and mucous membranes provide a protective wall, but breaks in the mucocutaneous barrier may occur in many ways, including trauma, surgery, and disease. A balanced microbial flora in the gastrointestinal tract prevents the overgrowth of Candida organisms, which can lead to penetration of this fungus into the lining of the gastrointestinal tract and its entrance into the bloodstream. When invasion occurs, phagocytic cells (including monocytes, neutrophils, and eosinophils) further protect the body by ingesting and killing Candida organisms. Phagocytosis is assisted by serum proteins called opsonins. Lymphocytes are also important defenders against this fungus and are part of the cell-mediated
immune system. Candidiasis may result when cell-mediated immunity is defective, as is the case with the
hereditary condition of chronic mucocutaneous candidiasis or with
Acquired immunodeficiency syndrome (AIDS). Approximately 80 percent of healthy people exhibit delayed hypersensitivity reactions to Candida antigens, indicating the presence of a previously induced cell-mediated immunity directed against such an infection.

Candidiasis may be divided into superficial mucocutaneous and deep-seated, tissue-invasive types. There are more than one hundred fifty species of this fungus, but only ten are recognized as human pathogens, and C. albicans is the most important. Oral candidiasis, or thrush, is a common infection characterized by white patches on the tongue and oral mucosal surfaces (oropharyngeal infection). Scrapings taken from these patches contain masses of yeasts, pseudohyphae, and hyphae. Culturing is not as useful as clinical appearance and microscopic examination, since Candida organisms can be grown from normal mouths. Thrush is particularly common when the immune system is impaired, as in patients with cancer or AIDS or in asthmatics treated with inhaled steroids. Infection of other parts of the gastrointestinal tract, especially the esophagus, may occur in patients with a variety of underlying conditions, including an impaired immune system, gastrointestinal surgery, and antibiotic treatment. Esophageal involvement
often results in difficult or painful swallowing. Only about half of patients with esophageal candidiasis will also have the more easily diagnosed oropharyngeal infection. Some patients with gastrointestinal candidiasis will develop systemic or disseminated infection.

Vaginal candidiasis, the most common type of vaginitis, is a common form of the infection associated with an overgrowth of Candida organisms in the vagina followed by mucocutaneous invasion. The patient will have a thick, curdlike vaginal discharge and itching of the surrounding skin areas. Antibiotic therapy, pregnancy, birth control pills, diabetes, and AIDS all predispose women to this form of infection. Recurrent or chronic infection can occur and may be associated with tissue invasion or impaired response of lymphocytes to the infection in some patients.

Cutaneous infection is common with candidiasis. This fungus is often the cause of diaper rash in infants; the condition often results from infection of skin under wet diapers by Candida organisms from the gastrointestinal tract. Intertrigo is another skin condition produced by candidiasis in the warm, moist area of skin folds, and similar environments result in perianal or scrotal infections that cause intense itching (pruritus). A widespread eruption of infection involving the trunk, thorax, and extremities is occasionally seen in both children and adults. Disseminated candidiasis, usually in association with persistent candidemia (the presence of the fungus in the bloodstream), may be associated with widely distributed, nodular skin lesions. Candidiasis of the skin, mucous membranes, hair, and nails beginning early in life and associated with defective cell-mediated immunity has been called chronic mucocutaneous candidiasis. This disease is often associated with a variety of endocrine diseases, including diabetes mellitus and decreased function of the parathyroid, thyroid,
and adrenal glands.

Deep-organ involvement with candidiasis is serious and often life-threatening. The placement in the body of foreign material used for medical therapy may provide the initial breeding ground for the infection. Examples of these devices are vascular catheters, artificial heart valves, artificial vascular grafts, and artificial joints and other orthopedic implants. The environment created by these foreign materials makes it impossible for the normal defense mechanisms of the body to function.

Urinary tract infection with Candida organisms is seen in association with urinary catheters, especially when usage is chronic. Colonization of the urine with Candida organisms may also occur following a course of antibiotics or in diabetic patients. Infection of the kidney can result if the candidiasis spreads upward from the bladder through the ureter or via the bloodstream. Renal involvement has been reported in up to 80 percent of patients with disseminated candidiasis. In disseminated disease, infection is spread to the kidney through the bloodstream, with the formation of renal abscesses. Primary renal infection occurs when the kidney is invaded directly without concomitant invasion through the blood. Such direct infection may occur in association with urinary catheters or following surgical procedures involving the genital and urinary tracts. A particularly severe form of ascending renal infection, more frequent in diabetic patients, causes necrosis of the renal papillae and
renal failure.

Ocular candidiasis (endophthalmitis) may occur when the eye is infected with Candida organisms either by direct invasion or through the bloodstream. Virtually any portion or structure of the eye may be involved. Examination of the retina using an ophthalmoscope can reveal white spots, resembling cotton balls, indicating Candida organisms in the blood vessels of the eye. This finding may also be a clue to infection elsewhere in the body that has spread through the bloodstream to the eye.

Endocarditis
(inflammation of the lining of the heart) occurs when a native or artificial heart valve becomes infected. Candidiasis is an increasingly frequent cause of endocarditis of the native valves of intravenous drug abusers and artificial valves of all varieties. Such endocarditis is presumptively diagnosed when the organism is grown from blood specimens in the presence of a heart murmur. Abnormal growth on the heart valves, called vegetation, can usually be demonstrated using echocardiography. Fragments of vegetation may break off and circulate in the bloodstream, leading to the obstruction of vessels in many organs of the body, including the brain, eyes, lungs, spleen, and kidneys. Without treatment, this disease is uniformly fatal.

Disseminated candidiasis is seen in the most susceptible patients, including those with cancer, prolonged postoperative illness, and extensive burns. In these patients, further risk is associated with the use of central venous or arterial catheters, broad-spectrum antibiotic therapy, artificial feeding, or abdominal surgery. Dysfunction of neutrophils, or neutropenia, may increase the susceptibility of the patient to widespread infection with Candida organisms and can also be seen with AIDS. The kidney, brain, heart, and eye are the most common organs to be involved. Despite severe and extensive disease, specific diagnosis of disseminated candidiasis is difficult during life and is often only made at the time of postmortem examination.

Treatment and Therapy

Candidiasis may be prevented by avoiding or ameliorating the underlying predisposing factor or disease state and by decreasing or halting growth of the fungi. Dry or cracked skin can be treated with dermatologic lubricants. Invasive devices used for medical treatment should be placed in the body under the most sterile conditions and only employed when absolutely necessary. Care of these devices, including urinary catheters, intravascular lines, and peritoneal renal dialysis catheters, must be performed by skilled personnel using the most sterile approach possible. If antibacterial therapy is used excessively, fungal overgrowth may occur; Candida organisms can grow with ease in the gastrointestinal tract and vagina when bacteria are inhibited or killed by antibiotics, and overgrowth can lead not only to local infection but also to bloodstream invasion and secondary infection elsewhere in the body. Moreover, the treatment of underlying disease states such as diabetes mellitus, neoplasia, and AIDS will lessen the detrimental effects of candidiasis on the immune system.

Growth of Candida organisms can be decreased by altering the local conditions that favor their proliferation. For example, changing a baby’s diaper frequently and applying a drying powder can avoid the wet and warm conditions that can result in
diaper rash. Obese patients can lose weight, which will minimize skin fold infections. Wearing nonocclusive clothing, especially cotton fabrics, is often helpful in discouraging candidiasis.

Antifungal agents are often used to prevent candidiasis. Hospitalized patients recovering from surgery who have received antibacterial agents are given nystatin, an oral, nonabsorbed antifungal, to prevent the overgrowth of Candida organisms in the gastrointestinal tract. For cancer patients receiving chemotherapy, systemic antifungal drugs are often employed during the period when the cancer chemotherapy has had the most deleterious effects on the immune system.

Antifungals are employed by the topical, oral, parenteral (through a blood vessel or muscle), or irrigation routes for treatment of candidiasis. Among the many antifungal agents, nystatin, flucytosine, amphotericin B, and a variety of imidazole agents are the most commonly used. Antifungals utilize a number of different mechanisms that impede the metabolic activities of the organism or disrupt the integrity of the cell membrane on the outer surface of the fungus. Amphotericin B and fluconazole are useful in the treatment of systemic or deep-organ disease. Amphotericin B is produced by the fungus Streptomyces nodosus and is administered intravenously for systemic and deep-organ disease and by bladder irrigation for lower urinary tract infection (cystitis). When administered intravenously, amphotericin B has serious side effects, including fever, chills, kidney failure, liver abnormalities, and bone marrow suppression.
Fluconazole has fewer adverse effects and can be administered by the oral or intravenous routes; for these reasons, it is now commonly used as the initial therapy for candidiasis. Amphotericin B remains the treatment of choice for serious or life-threatening infection or when a Candida species isolated from a patient has been demonstrated by laboratory testing to be resistant to other antifungal agents.

In addition to antifungals, removal of foreign material or infected tissue is often necessary to treat severe candidiasis. Catheters, vascular grafts, artificial heart valves, artificial joints, and other devices must be removed and then replaced, if necessary, while the patient is receiving antifungal therapy or after the infection is cured. In some cases, such as with endocarditis, the infected tissue must be surgically removed to ensure a cure.

As with prevention, treatment of the underlying disease state greatly assists other measures directed against candidiasis. Gaining control of hyperglycemia in diabetes mellitus patients, viral infection in AIDS patients, and bone marrow suppression in cancer patients will aid in the treatment of candidiasis when it is present.

Perspective and Prospects

More than two thousand years ago, the Greek physicians Hippocrates and Galen described oral lesions that were probably thrush, but it was not until 1839 that fungi were found in such lesions. Deep-seated infection was first described in 1861, and endocarditis was identified in 1940. Candidiasis was recognized as an indicator disease in the 1987 surveillance definition for AIDS by the Centers for Disease Control in the United States. Candida ranks among the most common pathogens in hospital-acquired infections.

Candidiasis is on the increase largely because of increasingly sophisticated medical therapies and the worldwide epidemic of AIDS. Medical devices, immunosuppressive medical therapies, and organ transplantation are all becoming more common, and it is anticipated that candidiasis will increase in a corresponding manner. Likewise, as patients infected with human immunodeficiency virus (HIV) progress to clinical illness, the cases of candidiasis are expected to rise dramatically.

More effective preventive and therapeutic measures will be necessary to combat such an increase in cases of candidiasis. New antifungal agents will need to be developed to treat resistant strains of Candida. Laboratory testing to determine whether various antifungal agents can kill or inhibit the growth of Candida species isolated from patients will need to be more widely available and more frequently performed if organisms resistant to antifungals are to be identified. Early identification of resistant organisms will benefit patients by providing more effective antifungal therapy early in the course of treatment. Testing procedures will need to employ better methodology that is standardized to enable laboratories in different locations to compare results and determine regional or national trends in antifungal resistance.

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