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CANDIDA

IMPACT OF CANDIDA

Opportunistic infections caused by Candida species have increased substantially over the past 10 to 15 years. National data from the Centers for Disease Control and Prevention (CDC) indicate that Candida species caused 7.7% of bloodstream infections nationwide.

RISK FACTORS FOR ACQUISITION, DISEASE, AND DEATH

Seriously ill, immunocompetent patients and severely immunocompromised patients are at particular risk for candidal infections. Included in these groups are neonates, patients with various forms of cancer who are leukopenic, and patients who have had major surgery (especially gastrointestinal and pancreatic), severe burns.

Given the presence of high-risk diagnoses (especially gastrointestinal and pancreatic), some identified risk factors for acquisition of candidemia include exposure to multiple antibiotics and steroids, presence of Swan-Ganz catheters, length of stay in the intensive care unit, artificial respiratory assistance, use of steroids, candida colonization, and repeated transfusions. In the study by Wey et al, four independent risk factors were identified by multivariate analysis: (1) number of antibiotics received, (2) isolation of Candida species from a site other than blood, (3) prior hemodialysis.

NEWBORNS

Weese-Mayer et al looked at factors important in the development of candidemia in 20 case patients less than 4 months of age who were matched with control infants by birth weight and date of admission to the neonatal intensive care unit. Univariate analysis identified duration of hyperalimentation, administration of fat emulsion, endotracheal intubation or tracheostomies or both ( p = 0.01), and antibiotic therapy ( p = 0.0002) as risks.

NEW SIGNS AND SYMPTOMS

Differentiating infection from colonization is difficult and is a major handicap in the prevention and therapy of candidiasis in hospitalized patients. Helpful clinical findings that may be suggestive of infection caused by candida species include endophthalmitis, macronodular skin lesions, suppurative peripheral thrombophlebitis, hepatitis, purpura fulminans, bullous dermatitis, epiglottitis, and candida osteomyelitis. It usually is not possible to differentiate bacterial infections from local or systemic candidiasis by these clinical signs and symptoms.

CANDIDA AND ANTIBIOTIC ASSOCIATED DIARRHEA

Nosocomial diarrhea is a well-recognized problem in several hospitals across the United States, with Clostridium difficile being one of the most common etiologic agents. Candida species also are being associated with diarrhea. Danna et al evaluated the role of candida in antibiotic-associated diarrhea in elderly patients. The 24 patients with antibiotic-associated diarrhea were matched by age and sex with two selected controls who were either on antibiotics and had no diarrhea or were not on antibiotics and had no diarrhea. They concluded that 7 of 24 patients with stools negative for Clostridium difficile and other intestinal pathogens.

NEW DERMATOLOGIC SIGNS AND SYMPTOMS

Traditional clinical findings in skin presentations of candida infection include erythematous papules and nodules, ecthyma-gangrenosum-like ulcerations and verrucous plaques. Purpura fulminans and disseminated intravascular coagulation were described by Silverman et al.

DIAGNOSIS OF CANDIDEMIA

The growing importance of fungal species as agents of septicemia-candidemia has resulted in increased efforts to diagnose these infections accurately. Stone et al evaluated the pathogenesis and principles of treatment of Candida species and demonstrated the remarkable efficiency with which the liver cleared candida from venous blood (ratio of 10,000:1); the lungs, striated muscle, and kidneys were less effective but also filtered yeasts from the blood.

THERAPY OF CANDIDIASIS

A wider array of antifungal agents has become available in the last 10 years (Table 3) (Table Not Available) . The availability of new agents or newer formulations of older agents have had a positive impact on the treatment of infections caused by Candida species.

The in vitro susceptibility of amphoteracin B in a clinical study by Powderly et al was better for blood isolates of yeasts in immunocompetent patients than immunocompromised patients (allogenic or autologous bone marrow transplantation and/or myelosuppressive chemotherapy). In that study, all episodes (10 of 10) of bloodstream infection in immunocompromised patients.

Many oncology units and infectious disease physicians now advocate the use of amphotericin B empirically in neutropenic patients on broad-spectrum antibiotics if they remain pyrexic after 4 to 7 days of antibiotic therapy. The use of amphotericin B, a polyene macrolide.

Rifampin has no intrinsic antifungal property but augments the in vitro antifungal activity of amphotericin B against some Candida species including Candida albicans.

Antagonism is observed in vitro between amphotericin B, which binds to ergosterol in the fungal cell membrane, and the antifungal imidazoles, which inhibit synthesis of ergosterol.

Flucytosine has been used with amphotericin B in patients with endophthalmitis, renal candidiasis, overt central nervous system (CNS) infection, or persistent fungemia. Flucytosine is well absorbed from the gastrointestinal tract and is excreted mainly unchanged (90%).

Patients with candida meningitis or hepatosplenic candidiasis seem to benefit from combined amphotericin and flucytosine. The initial dose of flucytosine is 150 mg/kg when renal function is normal.

Ketoconazole is available in an oral preparation; it is an N-substituted antifungal imidazole. Its metabolism occurs predominantly in the liver and it is excreted in bile as an inactive compound. No dose adjustment is required in renal or hepatic insufficiency.

Fluconazole is a bis-triazol-fiflourophenyl-2-propanol antifungal available for both parenteral and enteral administration. Excretion is predominantly renal. Protein binding is only 11%.