Lyme disease in humans is caused by infection of Borreli burgdorferi transmitted by the bite of an Ixodes scapularis. The disease is treatable at all stages, with either oral or intravenous antibiotics. In these two studies, doxycycline therapy is assessed, both as a preventative and as a treatment of Lyme disease.
Study 1: Klempner, et al (N Eng J Med 345:88, 2001) assessed whether a prolonged treatment of antibiotics would be efficacious in patients with documented Lyme disease who have with persistent musculoskelelal pin and/or neurocognitive symptoms despite the recommended course of antibiotic treatment. Patients were randomized to receive either intravenous ceftriaxone (2g qd) for 30 days followed by doxycycline (200mg qd) for 60 days, or matching intravenous and oral placebos. 78 patients were seropositive for B. burgdorferi and 51 were seronegative. An improvement in Medical Outcomes Study (MOS) 36-item Short-Form General Health Survey (SF-36) was used to assess efficacy.
The study was discontinued after the interim analysis of 107 patients found no differences between patients receiving prolonged antibiotic treatment and patients receiving placebo. No differences were observed between the seropositive and seronegative patients. No evidence of persistent infection with B. burgdorferi was found in the serum or cererospinal fluid of any patient.
Study 2: Nadelman, et al (N Eng J Med 345:79, 2001) conducted a randomized, clinical trial to determine if prophylatic treatment with a single dose of doxycycline would prevent Lyme disease following a I. scapularis tick bite. 482 subjects who had removed an attached I. Scapularis tick from their body within the previous 72 hours were treated with either a single dose of 200mg doxycycline or a placebo. Evaluation included serum antibody tests, blood cultures, and detection of erythema migrans at the site of the tick bite.
Erythema migrans developed a median of 12 days after removal of the ticks in 1 of 235 (0.4%) subjects who received doxycycline compared to 8 of 247 (3.2%) subjects in the placebo group. 7 of these 9 subjects with erythema migrans also had laboratory evidence of Lyme disease. In placebo-treated subjects, erythema migrans was significantly more likely to occur following bites from nymphal ticks that had been attached for > 72 hours when compared to adult tick bites and ticks attached for < 72 hours.
Conclusion: The data from these two studies indicate: 1) patients with chronic musculoskeletal pain and or neurocognitive symptoms that persist after antibiotic treatment for Lyme disease do not improve with a prolonged course of antibiotics (either IV or oral); 2) early treatment (within 72 hours of tick bite) with a single dose of 200 mg doxycycline is effective in preventing Lyme disease.
