Multiple drugs

Abstract

Various toxicities: case report A 65-year-old man developed disseminated Aspergillus fumigatus sternal osteomyelitis during treatment with tacrolimus, mycophenolate mofetil and prednisone as immunosuppressants, axonal sensorimotor polyneuropathy and phototoxicity during treatment with voriconazole, and acute kidney injury (AKI) during treatment with amphotericin B liposomal for disseminated Aspergillus fumigatus sternal osteomyelitis [not all routes and time to reaction onsets stated]. The man, who had a history of terminal cardiac failure secondary to arrhythmia-induced cardiomyopathy, underwent heart transplant in August 2017. Thereafter, he underwent urgent surgical post-operative pericardial effusion and resection of inferior vena cava anastomosis, requiring re-opening of sternotomy. Subsequently, he was discharged to a rehabilitation center with immunosuppressive regimen consisting of tacrolimus 0.15 mg/kg (with residual target between 8 and 10 ng/mL), mycophenolate mofetil 500 twice/day [unit not stated] and prednisone 12.5 mg/day. Four months post-transplantation, he was admitted due to suspected surgical site infection. Physical examination showed inflammatory scar with no sternal diastasis. Chest tomodensitometry revealed retro-sternal infiltration and multiple abscesses localised close to the sternotomy along with focal condensation of the right upper lobe. He benefited from removal of the steel wires, sternal biopsies and drainage of the collections. Probabilistic antimicrobial therapy was commenced with piperacillin/tazobactam and daptomycin. Direct examination of a retrosternal drain liquid showed numerous hyaline septate hyphae. Drain liquid and sternal biopsies cultures showed positive for Aspergillus fumigatus and radiological presentation was compatible with invasive pulmonary aspergillosis. Investigations revealed increased level of serum 1-3-β-D-glucan. The bacterial cultures were noted to be sterile and antibiotics were discontinued after 14 days. A diagnosis of disseminated Aspergillus fumigatus sternal osteomyelitis associated with immunosuppressive regimen was made. The man started receiving treatment with IV voriconazole 6 mg/kg/12hours on the first day followed by 4 mg/kg/12hours for 7 days. Following completion of IV voriconazole, he started receiving oral voriconazole with satisfying residual blood level, measured at 2.4 mg/L. PET-scan revealed strong hypermetabolic activity on the sternum, lung nodules and retrosternal infiltrate. Two months after voriconazole initiation, clinical and radiological improvement were noted. However, he developed neurological and cutaneous toxicities, and voriconazole therapy was discontinued. Electromyogram confirmed the onset of an axonal sensorimotor polyneuropathy with predominant involvement of the lower limbs compatible with iatrogenic neuropathy. The axonal sensorimotor polyneuropathy, paresthesis and phototoxicity were attributed to the voriconazole therapy, and he was switched to amphotericin B liposomal [liposomal amphoterin B (L-AMB)] 3 mg/kg. After 3 months, the cutaneous phototoxicity lesions and paresthesia resolved. After 7 days of amphotericin B liposomal treatment, he presented with AKI, and increased creatinine level was noted. Tacrolimus overdose was not observed. Amphotericin B liposomal was discontinued and following discontinuation, the renal function recovered and a diagnosis of amphotericin B liposomal-mediated AKI was confirmed. Therefore, he was transitioned to offlabel treatment with isavuconazole. After 10 months, the sternal osteomyelitis and contiguous skin and soft tissue infection resolved. At a follow-up after 12 months, after isavuconazole discontinuation, no relapse was clinically or radiologically evident.