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A Rare Case of High-Dose Methotrexate Toxicity Precipitated by Piperacillin-Tazobactam: Delayed Clearance, Acute Kidney Injury, and Rescue with Glucarpidase

Year: 2026

Type: article

Abstract: One of the fundamental pillars of central nervous system (CNS)-directed therapy of aggressive lymphomas is high-dose methotrexate (HD-MTX). The use of this drug is offset by a well-defined risk of renal pharmacokinetic retardation and extreme toxicity, often compounded by drug-drug interactions, especially penicillin-class antibiotics. A 58-year-old female patient who had primary high-grade B-cell lymphoma was administered high-dose methotrexate (HD-MTX) standard prophylaxis. Piperacillin-tazobactam (PTZ) was empirically initiated within 24 hours, which is against documented avoidance instructions. The 24-hour MTX level was critically high at 193 umol/L, and acute kidney injury (creatinine increase: 74 to 259 umol/L) was also present. The administration of glucarpidase was performed approximately 48 hours after the administration of MTX, after folinic acid escalation and consultation with toxicology. Renal performance improved without dialysis, and the MTX levels dropped. The importance of the clinically significant interaction of HD-MTX and PTZ is critically highlighted in this case. It brings out the urgency of rigorous antimicrobial stewardship, the life-saving significance of timely glucarpidase, and reveals the system-level crises in medication visibility and electronic prescribing safeguards.

Source: Cureus

DOI: 10.7759/cureus.103715

Authors: Hashir Abdullah, Hassan Waraich, Kainat Atta, Fatima Atta

Institutions: Manchester University NHS Foundation Trust, Countess of Chester Hospital NHS Foundation Trust, Royal Berkshire Hospital

Language: English

Topic: Chemotherapy-induced organ toxicity mitigation

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7129043581