New antibiotics are required to have not only the antibacterial activity against doxycyline-resistant O. tsutsugamushi but also lower risk for resistance or any cross-resistance to others.

In this prospective, open-label, randomized trial, we enroll patients with mild-to-moderate scrub typhus. We compared the efficacy and safety of a 5-day rifampin therapy with those of a 5-day doxycycline therapy at Chosun University Hospital, or one of its two community-based affiliated hospitals which are all located in southwestern Korea between 2006 and 2009.

• Drug: doxycycline
• Drug: rifampin

• Active Comparator: a 5-day course of daily 200-mg doses of doxycycline
• Active Comparator: a 5-day course of daily 600-mg doses of rifampin

Inclusion Criteria:

Inclusion criteria were:

• Adults aged 18 years or older
• A fever of higher than 37.5°C
• The concurrent presence of eschar or a maculopapular skin rash; and the clear presence of more than two symptoms such as headache, malaise, myalgia, coughing, nausea and abdominal discomfort.
• Patients were hospitalized at Chosun University Hospital in Kwangju, Korea or one of its two community-based affiliated hospitals which are all located in southwestern Korea between 2006 and 2009.

Exclusion Criteria:

The exclusion criteria were:

• An inability to take oral medications
• Pregnancy
• Hypersensitivity to the trial drugs
• Previous drug therapy with potential antirickettsial activity (e.g., rifampicin, chloramphenicol, macrolides, fluoroquinolones or tetracyclines) within 48 h prior to admission
• Severe scrub typhus (shock requiring vasopressor therapy for more than one hour
• A stuporous or comatose level of consciousness
• Respiratory failure requiring mechanical ventilation or renal failure requiring immediate dialysis) (4, 10).
• For the differential diagnosis of scrub typhus from other diseases with similar symptoms (e.g., murine typhus, leptospirosis, hemorrhagic fever with renal syndrome and systemic lupus erythematosus), patients underwent diagnostic tests. We thus excluded patients with concurrent infections who had the risk of causing different outcomes.