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

## TL;DR

A rare case shows how piperacillin-tazobactam worsened methotrexate toxicity, leading to kidney injury and requiring glucarpidase treatment.

## Contribution

Highlights a rare but critical drug interaction between HD-MTX and PTZ, emphasizing the role of glucarpidase in rescue therapy.

## Key findings

- Piperacillin-tazobactam likely caused delayed methotrexate clearance and acute kidney injury.
- Glucarpidase administration successfully reduced methotrexate levels and improved renal function without dialysis.
- The case underscores the importance of avoiding drug interactions and improving medication safety systems.

## 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.