Comparative Efficacy of Once-Daily versus Twice-Daily Doxycycline Regimens in Dogs Naturally Infected with Ehrlichia canis: A Randomized Clinical Trial

• BID doxycycline significantly reduces treatment duration. • Divided dosing accelerates early platelet recovery. • Standard 28-day therapy may fail to clear E. canis DNA. • Treat-to-target protocol ensures complete molecular cure. This prospective, randomized clinical trial compared the therapeutic efficacy and rate of platelet recovery of doxycycline 10 mg/kg once daily (SID) (Group A, n=17) versus 5 mg/kg twice daily (BID) (Group B, n=12) in 29 dogs naturally infected with Ehrlichia canis . Using a "treat-to-target" protocol that mandated both molecular clearance and platelet normalization prior to cessation, results showed that while both regimens achieved 100% molecular clearance, the BID regimen demonstrated significantly more rapid hematological recovery (P 28 days) was observed exclusively in the SID group, and post-treatment recrudescence was detected in two dogs at Day 98. We conclude that the 5 mg/kg BID protocol offers superior pharmacodynamic performance, and a "treat-to-target" strategy involving long-term monitoring is recommended over a fixed 28-day course to ensure complete clinical and parasitological resolution.