Flucloxacillin/paracetamol interaction

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Anion gap metabolic acidosis: case report A 79-year-old woman developed anion gap metabolic acidosis following concomitant administration of flucloxacillin and paracetamol for Staphylococcus aureus infection. The woman was previously admitted to a hospital for total hip replacement surgery. Two weeks after her hospital discharge, she experienced persistent wound leakage and moderate pain. She was again hospitalised to perform surgical wound drainage. Culture identification test was positive for Staphylococcus aureus and she started receiving IV paracetamol [Acetaminophen] 4 g/day and IV flucloxacillin 12 g/day. After 14 days, her clinical status worsened. She experienced mental confusion, icterus, shortness of breath and decompensated heart failure requiring admission to ICU. Arterial blood gas analysis revealed high albumin adjusted anion gap metabolic acidosis and normal lactate with respiratory compensation. Sodium bicarbonate and acetylcysteine therapy was started for 2 days, which showed minor effects. Investigations revealed increase in the blood level of oxoproline indicating accumulation. Flucloxacillin and paracetamol therapy was stopped. A significant improvement was noted after discontinuation of the therapy. Aspiration pneumonia and urinary tract infection complications were observed which required intubation. The woman passed away due to these complications. It was concluded that the long-term administration of paracetamol led to glutathione depletion resulting in extra formation of oxoproline. Whereas, flucloxacillin inhibited the enzyme oxoprolinase causing accumulation. Fijn R, et al. Continuing alert for underdiagnoses of rare oxoproline accumulation: Potentially fatal unexplained anion-gap metabolic acidosis caused by co-administration of acetaminophen (paracetamol) and flucloxacillin. International Journal of Clinical Pharmacy 42 (Poster Abstr. PT027): 283-284, No. 1, Jan 2020. Available from: URL: http:// 803502846 doi.org/10.1007/s11096-019-00945-w [abstract]

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Reactions 26 Sep 2020 No. 1823