Retrospective Comparison of Gastrointestinal Toxicity in Dogs With Lymphoma Receiving Doxorubicin With or Without Prophylactic Trimethoprim‐Sulfadiazine

ABSTRACT Doxorubicin is commonly used in the treatment of canine lymphoma and other malignancies but is associated with adverse effects, including gastrointestinal toxicity and myelotoxicosis. Previous veterinary studies have suggested that prophylactic antimicrobial administration may reduce chemotherapy‐associated toxicity and hospitalisation. However, the potential benefits of prophylactic antimicrobials must be balanced against risks, including antimicrobial resistance and dysbiosis. This retrospective study evaluated the effect of prophylactic trimethoprim‐sulfadiazine administration on gastrointestinal and haematologic adverse events in dogs with high‐grade multicentric lymphoma receiving doxorubicin for the first time. Medical records from three referral hospitals in Queensland, Australia were reviewed for dogs treated between January 2008 and November 2025. Adverse events occurring within 14 days of doxorubicin administration were retrospectively graded using the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events. Sixty dogs met the inclusion criteria, including 21 dogs receiving prophylactic TMS and 39 receiving no prophylactic antibiotics. Gastrointestinal toxicity occurred in 14/21 (66.7%) dogs receiving TMS compared with 13/39 (33.3%) dogs receiving no antibiotics ( p = 0.013). After controlling for lymphoma stage, prophylactic TMS administration was associated with a 3.69‐fold increase in the odds of GI toxicity (95% CI 1.13–12.11, p = 0.031). No significant differences were identified between groups in severity of GI toxicity, haematologic toxicity, neutropenia or hospitalisation rates. Prophylactic TMS administration during doxorubicin chemotherapy was associated with increased GI toxicity in this cohort, contrasting with previous reports and supporting the need for prospective evaluation of prophylactic antimicrobial use in contemporary geographically distinct canine chemotherapy populations.