Seven months after implantation in October 2001, the knee prosthesis was finally removed after consent of the patient. Fungal and
bacterial cultures taken at this time remained negative. The patient showed a fast clinical improvement with a reduction of ESR and CRP to 23 and 16, respectively. Itraconazole therapy was continued with 400 mg day−1 for another 6 months. Serum levels were not measured during ITZ treatment. One Gefitinib month after the termination of ITZ administration, the patient developed a recurrence of infection with a draining fistula close to the knee. Therefore, in March 2002, the patient was referred for a second opinion to a tertiary care orthopaedic reference centre. The consultant advised to amputate the leg just above the knee to allow the proper fitting of a limb prosthesis. The patient refused to follow the advice of limb amputation. But in September 2002 he agreed to an arthrodesis of the knee with an external fixation devise. Cultures taken during the arthrodesis were negative. Four months after placement, the external fixation devise was removed but in January 2003 (only 1 month after removal) the patient presented again with
pain, mild swelling, skin lesions and one pus-producing fistula in a scar above the proximal left tibia (Fig. 3). Magnetic resonance imaging YAP-TEAD Inhibitor 1 manufacturer (MRI) showed a multi-loculated abscess on the anteromedial side of the left tibia and infiltration of the local tissue (Fig. 4a,b), while MRI of the upper leg was without pathological findings. During surgical exploration of the lower leg, several subcutaneous collections of fluid were excised and again P. apiosperma was cultured. In vitro next susceptibility testing according to CLSI 38A2 broth microdilution15 after almost 1 year of ITZ therapy showed that the causative P. apiosperma strain had high minimal inhibitory concentrations (MIC) of amphotericin B (16 mg l−1), ITZ (>16 mg l−1), and isavuconazole
(16 mg l−1). The lowest MICs/MECs (minimal effective concentrations) were found for voriconazole (VORI; 1 mg l−1), posaconazole (1 mg l−1), caspofungin (1 mg l−1), anidulafungin (0.5 mg l−1) and micafungin (0.125 mg l−1). Because VORI was just registered in the European Union in 2003, with the label to treat Scedosporium and Pseudallescheria infections and based on our in vitro susceptibility results, previous case reports with favourable outcome,16–18in vitro studies19,20 and in vivo results21,22 with Scedosporium strains, the antifungal therapy was changed from ITZ to oral VORI (loading dose: 2 dd 400 mg for two days, followed by 1 dd 400 mg). As the patient was not clinically improving and ulcerous skin lesions persisted, suggesting progression and spreading of the Scedosporium infection, an above knee amputation was carried out in April 2003, six weeks after initiation of VORI therapy.