Multiple drugs

Abstract

Development of resistance and various toxicities: case report A 65-year-old woman developed resistance to anidulafungin, voriconazole and caspofungin while being treated for infective endocarditis by Candida glabrata. Additionally, she also developed chest pain, dyspnoea and itchy rash during treatment with amphotericin-B liposomal for infective endocarditis by C. glabrata [not all dosages and routes stated]. The woman, who had infective endocarditis (IE) by C. glabrata, received a double dose of anidulafungin 200mg daily along with voriconazole. She had various co-morbidities including hepatitis-C virus (HCV)-related cirrhosis, autoimmune haemolytic anaemia, thrombocytopenia and pancytopenia due to spleen enlargement. She had undergone various cardiac surgeries (in 1980), aortic and mitral valve substitution (in 2001), prosthetic mitral valve implant for IE, implantation of bioprosthetic tricuspid valve and intravascular electrocatheters (in 2005) and last surgical tricuspid valve replacement in May 2011. The treatment with anidulafungin and voriconazole was proved to be successful for the IE. About 24 months later (in March 2013), she was admitted due to weight loss, fever and asthenia. Due to the known previous history of IE, samples were taken for blood culture. She started receiving antifungal therapy with caspofungin 70mg in day 1 followed by 50 mg/day. Blood cultures resulted positive for C. glabrata. In-vitro sensitivity test showed sensitivity to caspofungin 16 mg/L, fluconazole >256 mg/L, micafungin 2 mg/L, anidulafungin 4 mg/L, voriconazole 16 mg/L, itraconazole >16 mg/L, amphotericin-B 1 mg/L and posaconazole >8 mg/L. Trans-oesophageal echocardiography (TEE) demonstrated vegetation on bioprosthetic tricuspid valve and prosthetic mitral valve. Cardio-surgery was delayed due to intra-operative risk, and anti-fungal therapy with caspofungin and voriconazole 200mg twice daily. After two weeks of anti-fungal therapy, TEE showed decrease in vegetation, following which she underwent cardio-surgery. The intra-operative cultures were found to be positive for C. glabrata with the same sensitivities as prior. The FKS mutation in C. glabrata was detected in the FKS2 gene characterized as S663P mutation, which indicated development of resistance to anidulafungin, voriconazole and caspofungin. The woman’s anti-fungal therapy was therefore changed to amphotericin-B liposomal [liposomal amphotericin B] infusion 3 mg/kg/day. After two days, amphotericin-B liposomal was stopped due to infusion-related intolerance, which was presented as dyspnoea, chest pain and a slowly resolving itchy rash on the whole body. She reported that she had experienced these symptoms in 2011 also. Thereafter, she received micafungin for IE. Her post-operative recovery was complicated by renal failure with anasarcatic status [aetiology of renal failure and anasarca not stated], which led to death in June 2013 [not all times to reactions onsets and outcomes stated]. Author comment: [A] 65-year-old woman who developed acquired FKS mutation 24 months after successful treatment of infective endocarditis by C. glabrata with a double dosage of anidulafungin followed by oral voriconazole . According to the previous reported results antifungal therapy was switched to liposomal amphotericin B (3 mg/kg/die) that was interrupted after two days, because [of] infusion intolerance (chest pain, dyspnea and a slow resolution itchy rash extended to all body) .