Antibacterials

Abstract

Drug-induced hepatotoxicity: case reportA 51-year-old man developed drug-induced hepatotoxicity following treatment with anakinra for haemophagocytic lymphohistiocytosis (HLH) and off-label amoxicillin/clavulanic acid and piperacillin/tazobactam for COVID-19.The man presented with worsening shortness of breath, pyrexia and persistent dry cough. His past medical history was remarkable for an episode of community acquired pneumonia. Upon examination, he was noted to have mild jaundice with nontender hepatomegaly. Based on further investigational findings, COVID-19 was strongly suspected. He was hospitalised. Swabs taken on day 1 and day 3 of admission were found to be negative by RT-PCR for SARS-CoV-2 and were considered as false negative. On admission day 1, he was treated with oral amoxicillin/clavulanic acid [amoxicillin-clavulanic acid] 625mg for one day, followed by IV piperacillin/tazobactam [piperacillin-tazobactam] 4.5g three times a day scheduled to be administered for 5 days, as off-label therapy for COVID-19. On day 2 of admission, HLH was suspected. Therefore, he started receiving anakinra 100mg once a day scheduled to be administered for six days [route not stated]. He also received methylprednisolone and prednisolone. On day 5 of admission, his liver function test findings started to deteriorate. Liver function test revealed bilirubin 346 µmol/L, ALT 161 U/L, GGT 624 U/L and ALP 256 U/L. At that point, he had completed 5 days of antibiotic therapy and 3 days of anakinra therapy. Drug-induced hepatotoxicity secondary to anakinra, amoxicillin/clavulanic acid and piperacillin/tazobactam was suspected. Clinically, biochemically and radiologically no features of chronic liver disease portal hypertension were observed. Ultrasound revealed an enlarged fatty liver with normal ducts and splenomegaly of 20cm. A further third combined nose and throat swab taken on day 10 of admission was positive for SARS-CoV-2, confirming COVID-19. On day 13, MRCP revealed hepatic haemosiderosis. Significant interval reduction in lymphadenopathy was noted. On day 14, he experienced progressive respiratory deterioration and became increasingly hypoxic. He was trialled with continuous positive airway pressure with no improvement. He became progressively encephalopathic and died on day 17 of admission. Approximately three weeks after his death, results of genetic testing were obtained that showed a homozygous C282Y mutation of the Human Homeostatic Iron Regulator (HFE) gene. He was diagnosed with hereditary haemochromatosis (HH). A post-mortem was performed. The liver showed extensive deposition of haemosiderin in hepatocytes consistent with HH and fatty changes consistent with a history of alcohol excess [outcome not stated].