Source: www.clinicaladvisor.com
Author: Carl Sherman

Infection with the ubiquitous fungus Candida cuts across a broad spectrum of severity that ranges from common and superficial mucocutaneous variants to invasive disease that can be life-threatening.

The addition of important new antifungal agents to the candidiasis armamentarium has led the Infectious Diseases Society of America to issue updated Clinical Practice Guidelines for the Management of Candidiasis to replace the 2004 version.

These agents—the echinocandins caspofungin, anidulafungin, and micafungin—are essentially reserved for candidemia and other invasive forms of candidiasis. The Guidelines also incorporate new data on the treatment of mucocutaneous disease and on the prevention of invasive disease in high-risk patients.

Office-based primary-care providers “probably see [relatively benign] aspects of candidiasis most often: oropharyngeal infection (thrush) and vaginitis. They will see Candida in urine, where the question is whether it is causing infection or just hanging out,” says Carol A. Kauffman, MD, professor of internal medicine at the University of Michigan in Ann Arbor, chief of infectious diseases in the VA Ann Arbor Healthcare System, and an author of the Guidelines.

Candidemia and other forms of invasive candidiasis are generally encountered in the hospital setting (candidemia is the fourth most common nosocomial bloodstream infection in the United States) but may develop in community-dwelling patients as well (e.g., those who are leukemic, have an indwelling catheter, are on dialysis, or are receiving cancer chemotherapy via a port or central line), according to Dr. Kauffman.

Muccocutaneous Candidiasis:
Oropharyngeal infection, when mild, is best treated topically, with azole troches, pastilles, or suspension. A seven-day course of fluconazole is an alternative for those who prefer it. When infection is moderate to severe, the Guidelines recommend a 7- to 14-day course of fluconazole. Disease that fails to respond adequately to fluconazole should be treated with one of the other azoles or an echinocandin. For esophageal infection, oral fluconazole for 7-14 days is appropriate as initial therapy.

Oropharyngeal candidiasis may be related to the use of steroid inhalers, or it may follow a course of antibiotics. Patients who have had radiation for head or neck cancer or who have developed xerostomia for other reasons, are also at risk, as are older patients with irritation (usually in the area of the palate) caused by dentures, observes Dr. Kauffman. The possibility of HIV infection should not be overlooked, however, particularly in the absence of other obvious risk factors. The index of HIV suspicion should be higher in the context of esophageal candidiasis, she notes.

Candidemia
Invasive candidiasis, which in many patients represents a life-threatening condition, is “largely a disease of medical progress,” according to the Guidelines. Risk factors include the use of broad-spectrum antibiotics and immunosuppressive agents, central venous catheters, dialysis, parenteral nutrition, and implantable prosthetic devices.

The availability of echinocandins has altered the treatment of candidemia, particularly in neutropenic patients. The mechanism of action of these agents is different from that of older drugs: “Echinocandins attack the cell wall, while azoles and amphotericin B attack the membrane,” Dr. Kauffman states. Since human cells have no cell wall, the echinocandins have far fewer adverse effects than other antifungals.

The echinocandins are also more powerful, killing the target organism outright rather than inhibiting its growth, and active against several Candida species, i.e., C. glabrata and Candida kruzei, that have become increasingly resistant to fluconazole, the most widely used azole. “The chink in the echinocandin armor is Candida parapsilosis; the newer agents are least active against this species,” Dr. Kauffman observes.

The Guidelines recommend an echinocandin as initial therapy for candidemia in neutropenic patients and in non-neutropenic individuals who have moderately severe to severe illness or had recent azole exposure. If the organism is later found likely to be fluconazole-susceptible (e.g., Candida albicans), the Guidelines recommend a switch to fluconazole once the patient is clinically stable. The recommendations for empirical treatment of suspected invasive candidiasis are similar.

Antifungal Prophylaxis
Although antifungal prophylaxis remains an area of controversy, new data have strengthened recommendations for its use under specified circumstances in patients who are judged to be at high risk of invasive candidiasis.

Fluconazole or another antifungal is recommended for organ transplant recipients with additional risk factors and for patients in ICUs, where the incidence of invasive candidiasis is high. As long as neutropenia persists, the Guidelines recommend fluconazole, posaconazole, or caspofungin for patients on chemotherapy and fluconazole, posaconazole, or micafungin for stem-cell transplant recipients.

Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America was published in Clinical Infectious Diseases (2009;48:503-535).

Notes:
1. Mr. Sherman is a freelance medical writer in New York City.
2. From the October 2009 Issue of Clinical Advisor