Can antibiotic prophylaxis within 72 hours of a tick bite prevent Lyme disease?

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Nadelman RB, Nowakowski J, Fish D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med 2001; 345:79-84.


BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.


A single dose of 200 mg doxycycline results in a statistically significant reduction in erythema migrans in patients exposed to Lyme-carrying ticks. Since the frequency of Lyme disease from tick bites is extremely low even in areas where Lyme disease is endemic, prophylactic treatment will likely result in a large number of patients treated unnecessarily. No patient in the current study developed an asymptomatic seroconversion, thus it appears safe to continue following the IDSA guidelines and delay treatment until the appearance of erythema migrans.

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