1Gosford Hospital , North Gosford, Australia

Background: Pyrogluamic acid (also known as 5- oxoproline) accumulation is a rare cause of high anion gap metabolic acidosis. The combination of paracetamol and flucloxacillin has been implicated in a number of case reports. Paracetamol depletes glutathione levels which increases 5-Oxoproline production. Concomitant use of flucloxacillin inhibits 5-oxoprolinase that is required to metabolize the 5-Oxoproline.
Case Report: A 78 year old female with an extensive past medical history presented to local Emergency Department with headache, back pain, and general malaise for 4 days. The findings on physical examination were fever, tachycardia and back tenderness. A septic screen was performed and Gentamicin and Flucloxacillin were administered for presumed sepsis. Blood cultures grew methicillin sensitive Staphylococcus Aureus.Her subsequent workup demonstrated spondylodiscitis and infective endocarditis on the mitral and aortic valves. She continued to received Flucloxacillin, and her regular medications including paracetamol. During the admission the serum bicarbonate declined from 25mmol/L on the day of admission to 12mmol/L on day 34 and the patient became confused with an altered level of consciousness. Blood gas analysis demonstrated a raised anion gap metabolic acidosis. Investigation for common causes of raised anion gap acidosis yielded no diagnosis. A comprehensive urine metabolic screen was requested to assess for elevated 5-oxoproline levels (also known as pyroglutamic acid). The 5-oxoproline level was significantly raised. Flucloxacillin and paracetamol were ceased and the patient was give N-Acetyl Cysteine. Shortly after the diagnosis was made the patient and family elected to withdraw active care.
Conclusions: Pyroglutamic Acidosis should be considered as a cause of high anion gap metabolic acidosis in patients treated with flucloxacillin and paracetamol.

Dr Kumar is a Nephrologist who practices General Nephrology in Gosford,NSW with particular expertise in peritoneal dialysis. Dr Max Ray is a Basic Physician Trainee.


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