Appropriate antibiotic treatment should be initiated immediately when there is a strong suspicion of ehrlichiosis on the basis of clinical and epidemiologic findings. Treatment should not be delayed until laboratory confirmation is obtained. Fever generally subsides within 24-72 hours after treatment with doxycycline or other tetracyclines. In fact, failure to rapidly respond to a tetracycline antibiotic argues against a diagnosis of ehrlichiosis. Preventative therapy in non-ill patients who have had recent tick bites is not warranted.

Doxycycline (100 mg twice daily for adults or 4.4 mg/kg body weight per day in two divided doses for children under 45.4 kgs (100 lbs)) is the drug of choice for patients with ehrlichiosis. The optimal duration of therapy has not been established, but current regimens recommend continuation of treatment for at least 3 days after the fever subsides and until evidence of clinical improvement, for a minimum total course of 5 to 7 days. Severe or complicated disease may require longer treatment courses. Because tetracyclines are contraindicated in pregnancy, rifampin has been used successfully in a limited number of pregnant women with documented HGE.