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## Complete Summary

#### GUIDELINE TITLE

Clinical practice guidelines for the management of blastomycosis: 2008
update by the Infectious Diseases Society of America.

#### BIBLIOGRAPHIC SOURCE(S)

Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG,
Kauffman CA, Infectious Diseases Society of America. Clinical practice
guidelines for the management of blastomycosis: 2008 update by the
Infectious Diseases Society of America. Clin Infect Dis 2008 Jun
15;46(12):1801-12. \[78 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18462107)

#### GUIDELINE STATUS

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.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Blastomycosis (disease caused by the fungus *Blastomyces dermatitidis*)

#### GUIDELINE CATEGORY

Management\
Treatment

#### CLINICAL SPECIALTY

Infectious Diseases\
Internal Medicine

#### INTENDED USERS

Advanced Practice Nurses\
Health Care Providers\
Nurses\
Physician Assistants\
Physicians

#### GUIDELINE OBJECTIVE(S)

-   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

#### TARGET POPULATION

Patients with blastomycosis

#### INTERVENTIONS AND PRACTICES CONSIDERED

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

#### MAJOR OUTCOMES CONSIDERED

-   Abatement of symptoms and signs of blastomycosis

-   Eradication of *Blastomyces dermatitidis* from involved tissue

-   Drug toxicity

-   Relapse rates

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**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.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Weighting According to a Rating Scheme (Scheme Given)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

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

I.  Evidence from [\>]{.underline}1 properly randomized, controlled
    trial

II. Evidence from [\>]{.underline}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

III. Evidence from opinions of respected authorities based on clinical
     experience, descriptive studies, or reports of expert committees

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

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.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

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.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

**Strength of Recommendation**

A.  Good evidence to support a recommendation for use

B.  Moderate evidence to support a recommendation for use

C.  Poor evidence to support a recommendation

#### COST ANALYSIS

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

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

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.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

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**

I.  Evidence from [\>]{.underline}1 properly randomized, controlled
    trial

II. Evidence from [\>]{.underline}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

III. Evidence from opinions of respected authorities based on clinical
     experience, descriptive studies, or reports of expert committees

**Strength of Recommendation**

A.  Good evidence to support a recommendation for use

B.  Moderate evidence to support a recommendation for use

C.  Poor evidence to support a recommendation

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

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

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Reduced morbidity and mortality

**Subgroups Most Likely to Benefit**

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

#### POTENTIAL HARMS

-   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.

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

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.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

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.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Audit Criteria/Indicators\
Personal Digital Assistant (PDA) Downloads

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG,
Kauffman CA, Infectious Diseases Society of America. Clinical practice
guidelines for the management of blastomycosis: 2008 update by the
Infectious Diseases Society of America. Clin Infect Dis 2008 Jun
15;46(12):1801-12. \[78 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18462107)

#### ADAPTATION

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

#### DATE RELEASED

2000 Apr (revised 2008 Jun 15)

#### GUIDELINE DEVELOPER(S)

Infectious Diseases Society of America - Medical Specialty Society

#### SOURCE(S) OF FUNDING

Infectious Diseases Society of America (IDSA)

#### GUIDELINE COMMITTEE

Infectious Diseases Society of America (IDSA) Practice Guidelines
Committee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*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

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

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.

#### GUIDELINE STATUS

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.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [Infectious Diseases Society of
America (IDSA) Web
site](http://www.journals.uchicago.edu/doi/full/10.1086/588300).

Print copies: Available from Dr. Carol A. Kauffman, Veterans Affairs Ann
Arbor Healthcare System, 2215 Fuller Rd., Ann Arbor, MI 48105, Email:
<ckauff@umich.edu>.

#### AVAILABILITY OF COMPANION DOCUMENTS

A PDA version of the original guideline document is available from
[Infectious Diseases Society of America (IDSA) Web
site](http://www.idsociety.org/content.aspx?id=9200#blas).

Performance measures are available in the [original guideline
document](http://www.journals.uchicago.edu/doi/full/10.1086/588300).

#### PATIENT RESOURCES

None available

#### NGC STATUS

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.

#### COPYRIGHT STATEMENT

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

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008