Various toxicities: 2 case reports

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      An event is serious (based on the ICH definition) when the patient outcome is:
    • * death

    • * life-threatening

    • * hospitalisation

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    In a case report, a 63-year-old man developed worsening of underlying acute kidney injury (AKI) due to amphotericin B liposomal for Yeasts infection, and an approximately 33-year-old woman developed respiratory syncytial virus infection, Elizabethkingia miricola and invasive Fusarium due to tacrolimus, followed by AKI due to antifungal therapy with posaconazole and isavuconazole and amphotericin B liposomal [times to reactions onsets not stated; not all dosages and routes stated].

    The 63-year-old man presented to an accident and emergency department with haematemesis. At presentation, he was tachycardic and hypotensive, with clinical signs of ongoing bleeding and chronic liver disease, including ascites. He had underlying stage 2 AKI. He was on ciprofloxacin prophylaxis. He was resuscitated with intravenous fluids and transferred to the ICU, where he received further fluid resuscitation, including a two-unit blood transfusion. Urgent endoscopy under general anaesthesia revealed bleeding oesophageal varices which were treated by sclerotherapy and banding. However, he was subsequently detected with invasive aspergillosis. He additionally had fever. During that time of the fever, he was initially diagnosed with sepsis of unknown cause. He eventually developed worsening multiorgan failure, requiring increasing vasopressor support [specific drugs not stated] and higher concentrations of oxygen in order to maintain adequate organ perfusion. Vancomycin was added empirically on day 9, and the central line was changed. Following the growth of unspecified yeasts on day 10, amphotericin B liposomal [liposomal amphotericin B] 3 mg/kg/day was started because of its broad spectrum of activity against a wide variety of fungal pathogens. However, his serum creatinine and CRP levels continued to rise and peaked at 273 µmol/L on day 13 and 455 mg/L on day 11, respectively. A worsening of underlying AKI due to amphotericin B liposomal was considered. Of note, the creatinine and CRP values improved thereafter. He had a normal urine output throughout this period. On day 12, vasopressor support started decreasing and his oxygen requirements decreased from 60% to 45%. On day 13, when Aspergillus species were identified as the causative agent, it was elected that he would continue on amphotericin B liposomal. On day 16, he was weaned off of vasopressor support. On day 33, he was discharged from the ICU. His serum creatinine returned to baseline levels, and he was discharged home 2 weeks later. At the time of report, he would require ongoing, long-term monitoring of his kidney function.

    An approximately 33-year-old woman underwent a bilateral lung transplant at the age of 32 years, for cystic fibrosis. She required long-term daily maintenance immunosuppression with tacrolimus. Thirteen months following transplant (at an approximate age of 33 years), she presented with a productive cough and breathlessness, and a decrease in forced expiratory volume in 1s (FEV1). She was hospitalised. Following admission, her serum creatinine level was found to be normal, and she was taking prophylactic oral posaconazole (gastro-resistant tablets) due to history of aspergillosis, and long-term prophylactic isavuconazole (hard capsules) due to history Fusarium infection. However, FEV1 declined further. A CT-scan showed chest abnormalities. A bronchoscopy and culture of bronchoalveolar lavage (BAL) fluid showed the presence of Fusarium and Elizabethkingia miricola. Invasive Fusarium was considered. As she presented with a productive cough, a bacterial or a fungal infection was speculated. A histology, collected during a bronchoscopy demonstrated interstitial changes, with no evidence of obliterative bronchiolitis. Therefore, an acute rejection of the lung transplant was unlikely. Reverse-transcriptase PCR (RT-PCR) was performed, in order to investigate a panel of fourteen respiratory viruses, including coronavirus OC43 infection. Nasopharyngeal aspirates (NPA) were collected in order to test for infection with respiratory syncytial virus (RSV). On admission (day 0), she was immediately treated with empiric broad-spectrum antibiotics (piperacillin/tazobactam and tigecycline) in order to provide cover for suspected bacterial infections of unknown type. An RT-PCR was negative for all fourteen unknown respiratory viruses tested. NPA testing confirmed the presence of RSV. The infections (RSV, Elizabethkingia miricola and invasive Fusarium) occurred in the setting of immunosuppression. She was then treated with methylprednisolone and ribavirin. On day 1, amphotericin B liposomal [liposomal amphotericin B] 3 mg/kg/day was started as treatment for Fusarium. Additionally, isavuconazole dosage was increased. She was discharged from hospital on day 13. However, due to progressive respiratory decline, she continued to receive amphotericin B liposomal at home, through a peripherally inserted central catheter. Her serum creatinine level increased throughout this period, peaking at 186 µmol/L on day 26. She developed AKI due to antifungals. However, the AKI was managed by excluding obstruction, and optimising fluid and haemodynamic status. A bronchoscopy was performed on day 27, which was culture-negative. At the time of report, she remained well, with no further episodes of fungal infection. Additionally, her renal function recovered, with no lasting impairment.


    1. Armstrong-James D, et al. Optimal management of acute kidney injury in critically ill patients with invasive fungal infections being treated with liposomal amphotericin B. BMJ Case Reports 13: No. 5, 2020. Available from: URL:

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    Antifungals/tacrolimus. Reactions Weekly 1809, 32 (2020).

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