Billet Sarah, Vanbiervliet Philippe, Remery Mark, Dekoninck Julien, Janssens Wim
Department of Geriatric Medicine, Ghent University Hospital, Ghent, Belgium.
Department of Internal Medicine, AZ Oudenaarde, Oudenaarde, Belgium.
Acta Clin Belg. 2023 Dec;78(6):509-515. doi: 10.1080/17843286.2023.2246226. Epub 2023 Aug 13.
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.
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.
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.
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.
本文描述了两名老年女性患者在感染甲氧西林敏感金黄色葡萄球菌（MSSA）时发生高阴离子间隙代谢性酸中毒（HAGMA）的情况。两名患者均接受了氟氯西林和对乙酰氨基酚治疗。她们最初病情有所改善，但在治疗两到三周后迅速恶化。她们发展为严重的HAGMA并导致死亡。本文的目的是确定在将对乙酰氨基酚与氟氯西林联合使用时，老年是否是发生HAGMA的主要危险因素。
使用MEDLINE数据库、PubMed进行文献研究。使用的医学主题词为“氟氯西林、对乙酰氨基酚、谷胱甘肽合成酶缺乏症和酸中毒”。此外，我们用两个病例来说明我们的发现。
高阴离子间隙代谢性酸中毒的根源是5-氧脯氨酸的积累，已知当氟氯西林与对乙酰氨基酚联合使用时，由于它们与γ-谷氨酰循环的不同酶相互作用，会发生这种情况。这会导致谷胱甘肽耗竭并形成5-氧脯氨酸。这种现象在体弱的老年人中发生风险更高，因为他们中的大多数人有几个易感危险因素，这些因素导致基线谷胱甘肽储备较低。这些危险因素包括老年、营养不良、出生时被指定为女性、既往存在的肾脏和/或肝脏功能障碍、未控制糖尿病以及败血症。
本文的目的是提高对这种现象及其在体弱老年人中更高发生率的认识，希望这将导致更早的诊断，从而为患者带来更好的结果。
