Abstract
Methotrexate (MTX) toxicity can affect multiple organ systems, manifesting as nephrotoxicity, myelosuppression, hepatotoxicity, mucositis, and gastrointestinal upset. Serious adverse events are rare in patients prescribed low-dose methotrexate. We present a case of an 86-year-old female on a weekly dose of oral MTX 12.5 mg for rheumatoid arthritis presenting with painful gingiva and oral bleeding during outpatient antimicrobial therapy (OPAT) for osteomyelitis with vancomycin and piperacillin-tazobactam. She had acute kidney injury (AKI), elevated serum MTX levels, thrombocytopenia, neutropenia, and a vancomycin level three times therapeutic concentration. MTX toxicity was suspected to have been triggered by vancomycin and piperacillin-tazobactam causing AKI and impaired renal clearance of MTX which itself is nephrotoxic. The patient was managed with leucovorin, alkalinized intravenous fluids, and filgrastim injections over a 2-week period. Her renal function continued to be reduced at 5-week outpatient follow-up, far after other markers of toxicity normalized. This case demonstrates the importance of considering potential drug-drug interactions and the need for robust monitoring for OPAT in select groups.
Highlights
Outpatient parenteral antimicrobial therapy (OPAT) is a cost-saving alternative to hospitalization in the management of stable patients with infections that require prolonged antibiotic therapy [1]
Besides the direct effect on renal function, an additional consideration in using nephrotoxic agents in OPAT is the effect on the serum concentration of medications that depend on renal clearance
We here present a case of severe MTX toxicity occurring in an elderly patient receiving concomitantly low-dose methotrexate (LDM) for rheumatoid arthritis (RA), and intravenous vancomycin and TZP for osteomyelitis
Summary
Outpatient parenteral antimicrobial therapy (OPAT) is a cost-saving alternative to hospitalization in the management of stable patients with infections that require prolonged antibiotic therapy [1]. The Infectious Diseases Society of America (IDSA) published updated recommendations in 2018 regarding patient selection, monitoring, and integration into antimicrobial stewardship [3]. Certain populations such as intravenous drug users and the elderly are recognized as high risk for complications or failure of OPAT [4,5]. The IDSA recommends regularly monitoring vancomycin levels and renal function during OPAT, though frequency is not specified and this guideline is based on “very low-quality evidence” [3]. We here present a case of severe MTX toxicity occurring in an elderly patient receiving concomitantly low-dose methotrexate (LDM) for rheumatoid arthritis (RA), and intravenous vancomycin and TZP for osteomyelitis
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