Scedosporium apiospermumSoft Tissue Infection Successfully Treated with Voriconazole: Potential Pitfalls in the Transition from Intravenous to Oral Therapy

Abstract

An immunocompromised patient with an invasive soft tissue infection due to Scedosporium apiospermum was successfully treated with voriconazole and surgical debridement. After transition from intravenous to oral therapy, successive adjustments of the oral dose were required to achieve complete resolution. For soft tissue infections due to molds characterized by thin, septate hyphae branching at acute angles, voriconazole should be considered a first-line antifungal agent. The potential usefulness of plasma voriconazole levels for guiding optimal therapy should be investigated. CASE REPORTA 58-year-old woman who had been treated chronically for Behçet's disease with prednisone, at doses ranging from 10 to 40 mg per day over 10 years, developed pain, swelling, and erythema of the left wrist. These symptoms were felt by her rheumatologist to represent an unusually severe exacerbation of arthritis, and a single dose of infliximab at 3 mg/kg was given intravenously. In addition, prednisone was increased from 20 to 100 mg per day, and amoxicillin-clavulanic acid at 875 mg twice daily was empirically started. Due to continued pain and erythema, the patient underwent exploratory surgery of her left wrist 10 days later at a local community hospital. Intraoperatively, thickening and early mucinous degeneration of the tenosynovium of an extensor tendon was noted from the wrist to the distal end of the third metacarpal. Surgically obtained tissue grew rare methicillin-sensitive Staphylococcus aureus but was negative for fungi and mycobacteria based on both cultures and histopathology. Antibiotic therapy was changed from oral amoxicillin-clavulanic acid to intravenous oxacillin at 2 g every 4 h, and her oral prednisone dosage was reduced gradually from 100 mg daily to 20 mg daily over the following week.The patient's symptoms continued to progress, however, with erythema spreading from the dorsum of the left wrist to the elbow. At 4 weeks after the exploratory surgery, the patient was admitted to Stanford University Medical Center. Oxacillin was discontinued, and intravenous vancomycin, given as 1 g every 12 h, was initiated. The following day, surgical exploration and debridement of the left wrist and forearm were performed, and necrosis involving multiple extensor tendons of the wrist was noted intraoperatively. Specimens from her wrist joint and tendons were sent for bacterial, mycobacterial, and fungal cultures. Small, gray colonies of a mold grew in a culture derived from an extensor tendon. Early examination of this mold revealed thin, septate hyphae branching at acute angles. On the basis of this morphology, intravenous voriconazole was initiated at a loading dose of 6 mg/kg every 12 h for two doses, followed by 4 mg/kg given every 12 h; prednisone was continued at 20 mg daily. Two days later, diminished pain and erythema of the patient's forearm and elbow were noted. The mold was ultimately identified as Scedosporium apiospermum. The patient showed continued improvement over a 10-day course of intravenous voriconazole...

Molecular Mycological Diagnosis and Correct Antimycotic Treatments

“…For example, Fig. 2 in our report depicts two filamentous fungi (Scedosporium apiospermum and Aspergillus fumigatus) that exhibit a similar morphology of thin septate hyphae branching at acute angles (9). Although no antifungal agent has reliable efficacy against all molds that share this morphology, amphotericin B has historically proven to be ineffective for the treatment of S. apiospermum infection, whereas voriconazole has a spectrum of in vitro antifungal activity that includes both S. apiospermum and Aspergillus spp.…”

Antifungal therapy and surgical drainage for the treatment of a cerebral abscess caused by Scedosporium apiospermum in a renal transplant patient - a case report

“…Voriconazole has emerged as a possible treatment option, since it shows high activity against several species of fungi, including S. apiospermum 17 . Several reports have shown the successful use of voriconazole synergistically combined with terbinafine against S. apiospermum 18 and S. prolificans.…”

Disseminated Scedosporium apiospermum infection with leprosy responsive to voriconazole

“…Itraconazole 100 mg twice daily was escalated to 400 mg day 21 in two divided doses after 15 days (Kiraz et al, 2001;Schaenman et al, 2005). Anti-hypertensive and anti-diabetic treatment was continued.…”

“…It is becoming an increasingly significant opportunistic agent of potentially life-threatening infection in poor immune responders (Cortez et al, 2008;Kiraz et al, 2001;Munoz et al, 2000). Various malignancies, chronic granulomatous diseases, organ transplants, therapy with corticosteroids, immunosupressants, antimicrobials and human immunodeficiency virus-positive state constitute the main risk factors (Barbaric & Shaw, 2001;Castiglioni et al, 2002;Husain et al, 2005;Lavinge et al, 1999;Schaenman et al, 2005). Clinically, scedosporiosis simulates other fungal infections (Cardoso et al, 2009;Kiraz et al, 2001;Schaenman et al, 2005).…”

“…Various malignancies, chronic granulomatous diseases, organ transplants, therapy with corticosteroids, immunosupressants, antimicrobials and human immunodeficiency virus-positive state constitute the main risk factors (Barbaric & Shaw, 2001;Castiglioni et al, 2002;Husain et al, 2005;Lavinge et al, 1999;Schaenman et al, 2005). Clinically, scedosporiosis simulates other fungal infections (Cardoso et al, 2009;Kiraz et al, 2001;Schaenman et al, 2005). It exhibits resistance to multiple antifungal agents (Barbaric & Shaw, 2001;Castiglioni et al, 2002;Munoz et al, 2000).…”