Adverse events of trimetroprim-sulphonamide treatment of cats and dogs: a systematic review

Potentiated sulphonamides (TMS) are recommended first-line antimicrobials in veterinary medicine, yet their use may be limited by concerns about adverse events (AEs). This systematic review aimed to evaluate the frequency, nature, and potential risk factors for TMS-associated AEs in dogs and cats. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) reporting standards, 110 studies published between 1943 and 2024 were included, covering > 4200 treated animals. A pairwise meta-analysis of eight comparative studies did not suggest a clinically relevant increased risk of AEs with TMS compared to other antimicrobials in either cats or dogs. A proportional meta-analysis of 31 studies in dogs showed an estimated prevalence of mild (2.3%) and severe (0.2%) AE. AE were described in more detail in 80 studies. The most commonly described severe AE were keratoconjunctivitis sicca, immune-mediated polyarthritis, hepatic necrosis, and haematological disorders. Severe AEs were reported in 64 studies and 247 animals, while mild AEs were reported in 23 studies. The most frequently implicated combinations were sulfadiazine- or sulfamethoxazole-trimethoprim. Time to onset ranged from hours to weeks and appeared longer for severe reactions. AEs were more frequently reported after treatment durations exceeding seven days. In breed-specific analyses, Doberman Pinschers were overrepresented among cases with polyarthritis. These findings suggest that while TMS can cause serious AEs, the incidence is low, and judicious use may reduce reliance on critically important antibiotics.