Abstract

BackgroundCoccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Current understanding of serologic kinetics and serologic features are largely based on serologic studies from the 1950s before antifungals were widely available. The effects of antifungal therapy on serologic characteristics has not previously been evaluated.MethodsWe retrospectively analyzed chart history and complement fixation titer trends of 434 patients classified by infectious disease physicians as having either uncomplicated pulmonary coccidioidomycosis (UPC) (n = 248), chronic pulmonary coccidioidomycosis (CPC) (n = 64), disseminated coccidioidomycosis not including meningitis (DC) (n = 86), or coccidioidal meningitis (CM) (n = 36). All patients received azole antifungal therapy. Serologic kinetics and features were analyzed and compared between groups.ResultsRoughly 94% of UPC, 61% of CPC, 29% of DC, and 56% of CM patients developed maximum complement fixation titers ≤1:32. Surprisingly, 25.4% of UPC, 6.3% of CPC, 2.3% of DC, and 8.3% of CM patients did not develop a detectable complement fixation titer during the study period (at least 3 years after diagnosis for each patient). The median maximum titer was 1:4 (range <1:2 – 1:512) for UPC, 1:24 (range <1:2 – 1:2,048) for CPC, 1:128 (range <1:2 – 1:4,096) for DC, and 1:32 (range <1:2 – 1:4,096) for CM patients. Few significant differences were observed in the mean time to maximum titer (overall mean 31 days, 95% CI 13–50) and serologic resolution rates (average 3–4 months/dilution reduction). However, 9% of UPC, 36% of CPC, 50% of DC, 52% of CM patients exhibited serologic reactivations (defined as ≥2 dilution titer increase >90 days from initial positive serology). Meanwhile, 15% of UPC, 25% of CPC, 31% of DC, and 25% of CM patients exhibited a serofast phenotype despite antifungal therapy.ConclusionOur findings provide an update to serologic studies performed prior to long-term triazole therapy. An understanding of the serologic features and kinetics for patients with varying forms of coccidioidomycosis receiving antifungal therapy is key to clinical evaluation and therapeutic decision making.Disclosures All authors: No reported disclosures.

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