This is the current release of the guideline.

This guideline updates a previous version: Chapman SW, Bradsher RW, Campbell GD, Pappas PG, Kauffman CA. Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America. Clin Infect Dis 2000 Apr;30(4):679-83.

Blastomycosis (disease caused by the fungus Blastomyces dermatitidis)

Management
Treatment

Infectious Diseases
Internal Medicine

Advanced Practice Nurses
Health Care Providers
Nurses
Physician Assistants
Physicians

• To provide recommendations for the optimal treatment of the pulmonary and extrapulmonary forms of blastomycosis
• To update and replace previous management guidelines for blastomycosis published in April 2000

Patients with blastomycosis

1. Antifungal therapy
   • Amphotericin B deoxycholate
   • Lipid preparations of amphotericin B
   • Itraconazole (including monitoring of drug serum levels)
   • Fluconazole
   • Voriconazole
2. Considerations for antifungal therapy in immunosuppressed patients, pregnant women, and children

• Abatement of symptoms and signs of blastomycosis
• Eradication of Blastomyces dermatitidis from involved tissue
• Drug toxicity
• Relapse rates

Searches of Electronic Databases

Literature Review and Analysis

For the 2007 update, the Expert Panel completed the review and analysis of literature on the treatment of blastomycosis that has been published since 2000 and reviewed the older literature as well. Computerized literature searches of PubMed (January 2000 through July 2007) were performed. Only English-language literature was reviewed. Searches focused on studies of humans but included a few experimental animal studies and in vitro studies.

The search yielded 62 articles: 30 case reports, 16 reviews, 1 clinical practice guideline, and 15 studies. Only 1 randomized, comparative treatment trial comparing amphotericin B (AmB) with 2-hydroxystilbamidine for the treatment of blastomycosis has been reported. There are no randomized, blinded trials comparing the currently available agents for the treatment of blastomycosis. However, several prospective, multicenter treatment trials of individual antifungal agents were reviewed and accorded the greatest importance. Prospective and retrospective studies that represented the treatment experience of single institutions and individual case reports were given an intermediate importance. Finally, selected reports dealing with the in vitro susceptibility of Blastomyces dermatitidis and experimental animal models were considered to be relevant but of lowest importance.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Grades reflecting the quality of evidence on which recommendations are based:

1. Evidence from >1 properly randomized, controlled trial
2. Evidence from >1 well-designed clinical trial without randomization, from cohort or case-controlled analytic studies (preferably from >1 center), from multiple time-series studies, or from dramatic results of uncontrolled experiments
3. Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees

Systematic Review

In evaluating the evidence with regard to the treatment of blastomycosis, the Panel followed a process used in the development of other Infectious Diseases Society of America (IDSA) guidelines. The process included a systematic weighting of the quality of the evidence and the grade of recommendation. Recommendations for the treatment of blastomycosis were derived primarily from case reports and nonrandomized treatment trials.

Expert Consensus

A panel of experts prepared these guidelines; the panel was composed of the authors of the guidelines, all infectious diseases specialists from North America with expertise in blastomycosis. The panelists have both clinical and laboratory experience in blastomycosis (see Appendix, Table A1 in the original guideline document).

In evaluating the evidence with regard to the treatment of blastomycosis, the Panel followed a process used in the development of other Infectious Diseases Society of America (IDSA) guidelines.

The Panel met on 7 occasions via teleconference to complete the work of the guideline. The purpose of the teleconferences was to discuss the questions to be addressed, to make writing assignments, and to discuss recommendations. All members of the panel participated in the preparation and review of the draft guideline.

Strength of Recommendation

1. Good evidence to support a recommendation for use
2. Moderate evidence to support a recommendation for use
3. Poor evidence to support a recommendation

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

Feedback from external peer reviews was obtained. The guideline was reviewed and approved by the Standards and Practice Guidelines Committee (SPGC) and the Board of Directors before dissemination.

Each recommendation includes a ranking for the strength and the quality of evidence supporting it. Definitions of the levels of evidence (I-III) and grades of recommendation (A-E) are repeated at the end of the "Major Recommendations" field.

Pulmonary Blastomycosis

1. For moderately severe to severe disease, initial treatment with a lipid formulation of amphotericin B (AmB) at a dosage of 3 to 5 mg/kg per day or AmB deoxycholate at a dosage of 0.7 to 1 mg/kg per day for 1 to 2 weeks or until improvement is noted, followed by oral itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6 to 12 months, is recommended (A-III).
2. For mild to moderate disease, oral itraconazole, 200 mg 3 times per day for 3 days and then once or twice per day for 6 to 12 months, is recommended (A-II).
3. Serum levels of itraconazole should be determined after the patient has received this agent for at least 2 weeks, to ensure adequate drug exposure (A-III)

Disseminated Extrapulmonary Blastomycosis

4. For moderately severe to severe disease, lipid formulation AmB, 3 to 5 mg/kg per day, or AmB deoxycholate, 0.7 to 1 mg/kg per day, for 1 to 2 weeks or until improvement is noted, followed by oral itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day for a total of at least 12 months, is recommended (A-III).
5. For mild to moderate disease, oral itraconazole, 200 mg 3 times per day for 3 days and then once or twice per day for 6 to 12 months, is recommended (A-II).
6. Patients with osteoarticular blastomycosis should receive a total of at least 12 months of antifungal therapy (AIII).
7. Serum levels of itraconazole should be determined after the patient has received this agent for at least 2 weeks, to ensure adequate drug exposure (A-III).

Central Nervous System (CNS) Blastomycosis

8. AmB, given as a lipid formulation at a dosage of 5 mg/kg per day over 4 to 6 weeks followed by an oral azole, is recommended. Possible options for azole therapy include fluconazole, 800 mg per day, itraconazole, 200 mg 2 or 3 times per day, or voriconazole, 200 to 400 mg twice per day, for at least 12 months and until resolution of CSF abnormalities (B-III).

Treatment for Immunosuppressed Patients with Blastomycosis

9. AmB, given as a lipid formulation, 3 to 5 mg/kg per day, or AmB deoxycholate, 0.7 to 1 mg/kg per day, for 1 to 2 weeks or until improvement is noted, is recommended as initial therapy for patients who are immunosuppressed, including those with acquired immunodeficiency syndrome (AIDS) (A-III).
10. Itraconazole, 200 mg 3 times per day for 3 days and then twice per day, is recommended as step-down therapy after the patient has responded to initial treatment with AmB and should be given to complete a total of at least 12 months of therapy (B-III).
11. Serum levels of itraconazole should be determined after the patient has received this agent for at least 2 weeks, to ensure adequate drug exposure (A-III).
12. Lifelong suppressive therapy with oral itraconazole, 200 mg per day, may be required for immunosuppressed patients if immunosuppression cannot be reversed (A-III) and in patients who experience relapse despite appropriate therapy (CIII).

Treatment for Blastomycosis in Pregnant Women and in Children

13. During pregnancy, lipid formulation AmB, 3 to 5 mg/kg per day, is recommended (A-III). Azoles should be avoided because of possible teratogenicity (A-III).
14. If the newborn shows evidence of infection, treatment is recommended with AmB deoxycholate, 1.0 mg/kg per day (A-III).
15. For children with severe blastomycosis, AmB deoxycholate, 0.7 to 1.0 mg/kg per day, or lipid formulation AmB, at a dosage of 3 to 5 mg/kg per day, is recommended for initial therapy, followed by oral itraconazole, 10 mg/kg per day (up to 400 mg per day) as step-down therapy, for a total of 12 months (B-III).
16. For children with mild to moderate infection, oral itraconazole, at a dosage of 10 mg/kg per day (to a maximum of 400 mg orally per day) for 6 to 12 months, is recommended (B-III).
17. Serum levels of itraconazole should be determined after the patient has received this agent for at least 2 weeks, to ensure adequate drug exposure (A-III).

Definitions of Strength of Recommendation and Quality of Evidence Ratings

Quality of Evidence

1. Evidence from >1 properly randomized, controlled trial
2. Evidence from >1 well-designed clinical trial without randomization, from cohort or case-control analytic studies (preferably from >1 center), from multiple time-series studies, or from dramatic results of uncontrolled experiments
3. Evidence from opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees

Strength of Recommendation

1. Good evidence to support a recommendation for use
2. Moderate evidence to support a recommendation for use
3. Poor evidence to support a recommendation

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Reduced morbidity and mortality

Subgroups Most Likely to Benefit

Immunocompromised patients and patients with progressive pulmonary disease or extrapulmonary disease.

• Drug-drug interactions are a major clinical issue in the use of azole antifungal agents.
• All azoles have been reported to cause hepatitis. Hepatic enzymes should be measured before starting therapy, at least at 2 to 4 weeks after therapy has begun, and every 3 months during therapy.

The azoles are teratogenic and embryotoxic in animals and should be avoided during pregnancy, especially during the first trimester. Long-term fluconazole administration during pregnancy has been associated with congenital anomalies.

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same results. Accordingly, the Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient's individual circumstances.

An implementation strategy was not provided.

Getting Better

Effectiveness

Not applicable: The guideline was not adapted from another source.

2000 Apr (revised 2008 Jun 15)

Infectious Diseases Society of America - Medical Specialty Society

Infectious Diseases Society of America (IDSA)

Infectious Diseases Society of America (IDSA) Practice Guidelines Committee

Authors: Stanley W. Chapman, University of Mississippi Medical Center, Jackson; William E. Dismukes, University of Alabama at Birmingham; Laurie A. Proia, Rush Medical Center, Chicago, Illinois; Robert W. Bradsher, University of Arkansas for Medical Sciences, Little Rock; Peter G. Pappas, University of Alabama at Birmingham; Michael G. Threlkeld, Germantown, Tennessee; Carol A. Kauffman, University of Michigan Medical School, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan

All members of the Expert Panel complied with the Infectious Diseases Society of America (IDSA) policy on conflicts of interest, which requires disclosure of any financial or other interest that might be construed as constituting an actual, potential, or apparent conflict. Members of the Expert Panel were provided the IDSA's conflict of interest disclosure statement and were asked to identify ties to companies developing products that might be affected by promulgation of the guideline. Information was requested about employment, consultancies, stock ownership, honoraria, research funding, expert testimony, and membership on company advisory committees. The Panel made decisions on a case-by-case basis as to whether an individual's role should be limited as a result of a conflict. No limiting conflicts were identified.

Potential Conflicts of Interest: L.A.P. has served as a speaker and consultant to Schering-Plough and Pfizer. P.G.P. has received grant support from Schering-Plough, Pfizer, Merck, and Astellas; has been an adhoc consultant for Pfizer; and has been a speaker for Pfizer and Astellas. C.A.K. has received research grants from Merck, Astellas, and Schering-Plough and serves on the speaker's bureau for Merck, Astellas, Pfizer, and Schering–Plough. All other authors: no conflicts.

This is the current release of the guideline.

This guideline updates a previous version: Chapman SW, Bradsher RW, Campbell GD, Pappas PG, Kauffman CA. Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America. Clin Infect Dis 2000 Apr;30(4):679-83.

None available

This summary was completed by ECRI on May 1, 2001. The information was verified by the guideline developer as of June 29, 2001. This summary was updated by ECRI Institute on July 31, 2008. The updated information was verified by the guideline developer on August 19, 2008.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.