Flucloxacillin/paracetamol interaction
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High anion gap metabolic acidosis and 5-oxoproline acidosis: case report A 79-year-old woman developed high anion gap metabolic acidosis and 5-oxoproline acidosis following concomitant treatment with flucloxacillin and paracetamol for Staphylococcus aureus infections [outcome not stated; not all routes stated]. The woman was admitted to the ICU following a surgical interposition graft for a thoracoabdominal aortic aneurysm. She had a significant history of chronic obstructive pulmonary disease, hypertension, chronic kidney disease, transcatheter aortic valve implantation, a vascular graft of the abdominal aorta, the percutaneous coronary intervention of the right coronary artery, acute-onchronic kidney failure, third-degree atrioventricular block with the implantation of a pacemaker, tracheostomy and persistent chylous leakage with re-thoracotomy. After 5 weeks of initial surgery, she had a Staphylococcus aureus bacteraemia originating from an infected thoracotomy wound. Pleural fluid cultures were also positive for the Staphylococcus aureus. Therefore, she started receiving continuous IV flucloxacillin 12 g/24h. However, a blood concentration of flucloxacillin was increased to 119000 mg/L with the 2 days of flucloxacillin treatment. Hence, the dose of flucloxacillin was decreased to 3 g/24h. After 6 days, the dose of flucloxacillin was changed to 6 g/24h based on a new flucloxacillin blood concentration (48000 mg/L). Additionally, she was treated with paracetamol [acetaminophen] 3 g/day. After 10 days of Staphylococcus aureus bacteraemia, she developed appendicitis which was treated with piperacillin/tazobactam and supportive care. After 3 weeks from initiation of flucloxacillin treatment, she developed reduced consciousness again, requiring controlled mechanical ventilation. Subsequent arterial blood gas analysis showed a severe respiratory and high anion gap metabolic acidosis. After ruling out other factors, a 5-oxoprolinaemia i.e. 5-oxoproline acidosis was considered to be the most likely reason for high anion gap metabolic acidosis. Therefore, the woman’s paracetamol was discontinued. On the next day, her abdominal pain deteriorated. Subsequent abdomen CT scan showed intra-abdominal abscesses. After consultation with a family member, the physician discontinued ICU treatment and she died several hours later [immediate cause of death not stated]. The high anion gap metabolic acidosis due to 5-oxoproline accumulation was confirmed by urinary analysis. Hence, it was concluded that, long-lasting concomitant use of flucloxacillin and paracetamol can lead to 5-oxoproline accumulation i.e. 5-oxoproline acidosis and severe high anion gap metabolic acidosis. van den Bersselaar LR, et al. Acetaminophen use concomitant with long-lasting flucloxacillin therapy: A dangerous combination. European Journal of Case Reports in Internal 803501213 Medicine 7: no pagination, No. 7, 23 Apr 2020. Available from: URL: http://doi.org/10.12890/2020_001569
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