The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Comparison of Oral Fluconazole and Itraconazole for Progressive, Nonmeningeal Coccidioidomycosis: A Randomized, Double-Blind Trial

John N. Galgiani, MD; Antonino Catanzaro, MD; Gretchen A. Cloud, MS; Royce H. Johnson, MD; Paul L. Williams, MD; Laurence F. Mirels, MD; Faris Nassar, MD; Jon E. Lutz, MD; David A. Stevens, MD; P. Kay Sharkey, MD; Vipul R. Singh, MD; Robert A. Larsen, MD; Kathy L. Delgado, LPN; Cynthia Flanigan, BS; and Michael G. Rinaldi, PhD
[+] Article, Author, and Disclosure Information

for the National Institute of Allergy and Infectious Diseases–Mycoses Study Group

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 2000;133(9):676-686. doi:10.7326/0003-4819-133-9-200011070-00009
Text Size: A A A

Background: In previous open-label noncomparative clinical trials, both fluconazole and itraconazole were effective therapy for progressive forms of coccidioidomycosis.

Objective: To determine whether fluconazole or itraconazole is superior for treatment of nonmeningeal progressive coccidioidal infections.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: 7 treatment centers in California, Arizona, and Texas.

Patients: 198 patients with chronic pulmonary, soft tissue, or skeletal coccidioidal infections.

Intervention: Oral fluconazole, 400 mg/d, or itraconazole, 200 mg twice daily.

Measurements: After 4, 8, and 12 months, a predefined scoring system was used to assess severity of infection. Findings were compared with those at baseline.

Results: Overall, 50% of patients (47 of 94) and 63% of patients (61 of 97) responded to 8 months of treatment with fluconazole and itraconazole, respectively (difference, 13 percentage points [95% CI, −2 to 28 percentage points]; P = 0.08). Patients with skeletal infections responded twice as frequently to itraconazole as to fluconazole. By 12 months, 57% of patients had responded to fluconazole and 72% had responded to itraconazole (difference, 15 percentage points [CI, 0.003 to 30 percentage points]; P = 0.05). Soft tissue disease was associated with increased likelihood of response, as in previous studies. Azole drug was detected in serum specimens from all but 3 patients; however, drug concentrations were not helpful in predicting outcome. Relapse rates after discontinuation of therapy did not differ significantly between groups (28% after fluconazole treatment and 18% after itraconazole treatment). Both drugs were well tolerated.

Conclusions: Neither fluconazole nor itraconazole showed statistically superior efficacy in nonmeningeal coccidioidomycosis, although there is a trend toward slightly greater efficacy with itraconazole at the doses studied.


Grahic Jump Location
Figure 1.
Box plots of baseline abnormalities associated with coccidioidal infection in patients treated with fluconazole (white bars) or itraconazole (gray bars).

Center lines represent the median value. Error bars indicates the 5th and 95th percentiles, and dots represent individual results that fall outside these ranges.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Flow of patients through the study.

HMO = health maintenance organization.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Patients responding after different mean durations of protocol therapy with fluconazole (dotted line) or itraconazole (solid line).
Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Journal Club
Topic Collections
PubMed Articles
Coccidioidomycosis with diffuse miliary pneumonia. Proc (Bayl Univ Med Cent) 2016;29(1):39-41.
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.