The concomitant use of paracetamol and flucloxacillin. A rare cause of high anion gap metabolic acidosis in the frail oldest old.

OBJECTIVES: This article describes the occurrence of a high anion gap metabolic acidosis (HAGMA) in two older, female patients with a methicillin sensitive staphylococcus aureus (MSSA) infection. Both patients received flucloxacillin and paracetamol. Both of them initially improved but declined rapidly after two to three weeks of treatment. They developed a severe HAGMA resulting in their death. The objective of this article is to determine whether old age is a major risk factor for developing HAGMA when combining paracetamol with flucloxacillin.

METHODS: A literature study was conducted using the MEDLINE database, PubMed. The used MeSH terms were 'flucloxacillin, acetaminophen, glutathione synthetase deficiency and acidosis'. Furthermore, we used two cases to illustrate our findings.

RESULTS: The origin of the high anion gap metabolic acidosis is the accumulation of 5-oxoproline which is known to occur when combining flucloxacillin with paracetamol due to their interaction with different enzymes of the gamma glutamyl cycle. This leads to the depletion of glutathione and the formation of 5-oxoproline. This phenomenon has a higher risk of occurring in frail older adults as most of them have several predisposing risk factors which result in lower baseline glutathione reserve. These risk factors include old age, malnutrition, assigned female at birth, pre-existing kidney and/or liver dysfunction, uncontrolled diabetes and sepsis.

CONCLUSION: The purpose of this article is to raise awareness of this phenomenon and its higher occurrence in frail older adults, which hopefully will lead to an earlier diagnosis with a better outcome for the patient.