IDSA updates treatment recommendations for blastomycosis

Amphotericin B recommended as primary therapy for more serious blastomycosis.

Issue: July 2008

The Infectious Diseases Society of America recently updated its clinical practice guidelines for the treatment and management of patients with blastomycosis.

The guidelines were updated because several new antifungal agents have become available since the previous guidelines were issued in 2000. The new guidelines recommend amphotericin B followed by an oral azole for the treatment of more severe forms of blastomycosis.

Itraconazole (Sporanox, Janssen) is recommended as follow-up to initial treatment with amphotericin B and as initial therapy for mild to moderate blastomycosis.

The IDSA panel addressed treatment options for patients with pulmonary and disseminated extrapulmonary blastomycosis, central nervous system (CNS) blastomycosis and blastomycosis in pregnant women, children and immunosuppressed patients.

The information was published in Clinical Infectious Diseases.

Clinical trials

The IDSA panel examined the results of recent clinical trials of amphotericin B when designing the new guidelines. Results of clinical trials of amphotericin B at a dose of greater than 1 g have indicated that 77% to 91% of severe patients were cured and did not have a relapse, according to investigators from several U.S. sites. There has been a 97% cure rate for patients receiving doses greater than 2 g. Itraconazole has become the recommended azole as second-line therapy for severe incidences of the disease and as primary therapy for most nonlife-threatening incidences. In clinical studies, itraconazole has shown a lower relapse rate, lower toxicity and more enhanced antimycotic activity.

“The availability and increasing use of lipid formulations of amphotericin B had to be addressed, as did the common practice of step-down therapy to an azole after amphotericin B is used,” Carol A. Kauffman, MD, professor of internal medicine at the University of Michigan and chief of the infectious diseases section, VA Ann Arbor Healthcare System, told Infectious Disease News.

Dosage recommendations

The recommendations for immunosuppressed patients and adults and children with moderately severe to severe pulmonary and disseminated extrapulmonary blastomycosis are similar. Amphotericin B administered as a lipid formulation at a dose of 3 mg/kg to 5 mg/kg daily or amphotericin B deoxycholate administered at a dose of 0.7 mg/kg to 1 mg/kg daily for one to two weeks or until improvement is noted is recommended as primary therapy. For immunosuppressed patients and patients with disseminated extrapulmonary blastomycosis, this therapy should be followed by oral itraconazole at a dose of 200 mg three times daily for three days, then 200 mg twice daily for at least 12 months. For patients with pulmonary blastomycosis, the twice-daily azole treatment should last six to 12 months. Recommended step-down therapy for children is oral itraconazole 10 mg/kg daily for 12 months. Children should not receive more than 400 mg of oral itraconazole daily.

For adults with mild to moderate pulmonary or extrapulmonary disease, oral itraconazole at 200 mg three times daily for three days followed by a twice-daily regimen for six to 12 months is recommended. Children with mild to moderate disease should receive a daily 10 mg/kg dose of oral itraconazole to a maximum of 400 mg per day for six to 12 months.

Patients with CNS blastomycosis should receive a 5 mg/kg dose of amphotericin B as a lipid formulation daily for a period of four to six weeks. This treatment should be followed by an oral azole. Acceptable azole regimens include fluconazole (Diflucan, Pfizer) at 800 mg daily, itraconazole at 200 mg two or three times daily or voriconazole (Vfend, Pfizer) 200 mg to 400 mg twice daily for at least 12 months and until cerebrospinal fluid abnormalities are resolved.

For pregnant women, lipid formulation amphotericin B 3 mg/kg to 5 mg/kg daily is recommended. Due to the possibility of teratogenicity, azoles should be avoided. Amphotericin B deoxycholate at 1.0 mg/kg daily is recommended if the infant appears to be infected.

Further comments

“Severe pulmonary blastomycosis with adult respiratory distress syndrome, although rare, is a life-threatening disease that demands quick diagnosis and therapy. Physicians need to be aware of this entity which often happens in previously healthy patients,” said Kauffman.

Though the guidelines for CNS blastomycosis have become more defined, the most appropriate azole to be used as follow-up therapy for CNS blastomycosis is currently not clear. However, Kauffman offered insight on appropriate azole therapy.

“Physicians cannot give acid-blocking agents with itraconazole. They should preferentially use the itraconazole solution, if the patient will take it, because absorption is better. They should always mention itraconazole blood levels to be sure the patient is absorbing the drug. Additionally, whenever an azole is used, especially itraconazole or voriconazole, they should be very careful about drug–drug interactions, which are many and can be serious,” she said.

There are not yet guidelines to diagnose the severity of pulmonary and disseminated extrapulmonary blastomycosis. It is recommended that treatment extend a few months beyond the time when skin and focal lesions and other clinical symptoms have been resolved. However, the exact length of time until treatment can be safely discontinued in pulmonary and disseminated extrapulmonary blastomycosis of all severity levels has yet to be determined. – by Rob Volansky

For more information:

Chapman S, Dismukes W, Proia L, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801-1802.