Immunosuppressants/amphotericin-B

Abstract

Various toxicities: case report A 58-year-old woman developed aspergillosis during treatment with mycophenolate, prednisone and tacrolimus as an immunosuppression therapy. Additionally, she developed fever, shivering, nausea and vomitus during treatment with amphotericin-B [routes, dosages, durations of treatments to reactions onset and outcomes not stated]. The woman presented for a new-onset, generalised tonic-clonic seizure, which had been well controlled by the midazolam and levetiracetam. Her past medical history included a kidney transplantation due to a focal-segmental glomerulosclerosis 6 months before the admission. She had been receiving an immunosuppressive therapy with mycophenolate, prednisone and tacrolimus. She also received levothyroxine-sodium [levothyroxine] after a total thyroidectomy for papillary thyroid cancer 3.5 years previously. Her other concomitant medication included amlodipine and metoprolol for mitral insufficiency. On admission, her vital signs were found within normal range. An initial aphasia resolved completely within a few hours, and she did not showed any focal deficits on neurological examination. A CT scan of her head showed a space-occupying lesion in the left parietal lobe. Subsequent MRI of the brain confirmed a ring enhancing mass with central diffusion restriction and perifocal oedema in the inferior parietal lobule. In addition, two small haemorrhagic lesions were also observed in the postcentral gyrus and in the centrum semi ovale on the right side. In the absence of any clinical evidence of inflammation and unremarkable cerebrospinal fluid (CSF) analysis, brain metastasis was considered as differential diagnosis. Staging CT (thorax-abdomen) revealed a mass lesion in the right upper lobe of the lung, which was suspected as bronchial carcinoma. Additional nodular lesions were also seen in the left adrenal gland. Clinically, she remained stable under antiepileptic therapy. However, follow-up MRI, 4 days after the initial examination, revealed progression of the left hemispheric lesion and the perifocal oedema. Subsequently, a left parietal craniotomy was performed, and the superficial mass was completely resected. Macroscopically, the lesion appeared firm and indurated without any evidence of pus or necrosis. However, histology did not reveal any evidence for a neoplastic lesion. Instead, a collagenous abscess wall containing mixed inflammatory cells, including abundant neutrophils was observed. The Grocott stain confirmed the presence of branched, septate hyphae consistent with aspergillus. Pan fungal polymerase chain reaction (PCR) linked immunosorbent assay of the resected specimen and fungal cultures was found negative. A diagnosis of aspergillosis secondary to mycophenolate, prednisone and tacrolimus was considered. The postoperative course was uneventful, and the woman was initiated on voriconazole. Subtherapeutic drug values of voriconazole was complemented by amphotericin B. However, she developed fever, shivering, nausea and vomitus secondary to amphotericin B. Later, the antifungal therapy was changed to isavuconazole, which was well tolerated. Initially, she received postoperative empiric antibiotics with ceftriaxone and metronidazole, which were adapted to flucloxacillin [flucloxacilline] and metronidazole after microbiological cultures confirmed growth of Staphylococcus warneri and pasteuri species. A PET-CT scan revealed a metabolically active lesions in the right upper lung and left adrenal gland. Because of the unclear etiology, a video-assisted thoracoscopy surgery wedge resection of the right upper lung lobe was performed. Pathological analysis of the tissue confirmed the diagnosis of aspergillus fumigatus; however, microbiological cultures remained negative. Accordingly, a diagnosis of invasive aspergillosis with cerebral, pulmonal and adrenal manifestations was made. Over the course, antibiotics were deescalated to clindamycin, and antifungal regime was continued with isavuconazole. Later, she was discharged.