The prophylactic potential of a single injection of sustained-release doxycycline hyclate (Atridox) was compared to that of a single oral dose of doxycycline hyclate in a murine model of Lyme borreliosis. Prophylaxis, as measured by the lack of cultivable spirochetes and demonstrable pathology, was noted for 43% of orally treated mice; in contrast, the sustained-release doxycycline hyclate completely protected mice from infection and resultant pathology.Since Lyme borreliosis became a reportable disease in 1982, it has consistently been the most common vector-borne disease reported in the United States (3). Given the lack of an available vaccine, the prophylaxis of tick bite infection consists of personal protective measures directed against ticks in areas where Borrelia burgdorferi is endemic (4). Reports on the efficacy of post-tick exposure antimicrobial prophylaxis in animals and humans demonstrate a high degree of variability, and opinions vary greatly as to the necessity of such prophylactic treatment (5,11,16,17,19). The need for effective prophylaxis is underscored by the increase in cases of Lyme disease and the seriousness of untreatable sequelae in a subset of infected individuals (7,8). This study compares the effectiveness of a single oral dose of doxycycline hyclate, designed to mimic levels in the plasma of humans given 200 mg orally (6,14), to that of a subcutaneous injection of sustained-release doxycycline (Atridox; Atrix Laboratories, Fort Collins, Colo.) in a mouse model of Lyme borreliosis (22).Laboratory-reared nymphal ticks (Ixodes scapularis) that were raised as previously described (13) and that have previously been shown to be free of Anaplasma phagocytophila and Babesia microti (2, 21) were infected with B. burgdorferi strain B31. Five infected ticks were placed on the heads and neck areas of specific-pathogen-free, 7-week-old female C3H/HeJ mice (Jackson Laboratories, Bar Harbor, Maine). Seventy-two hours after tick infestation, the partially engorged ticks were removed from all of the mice. Since three or four infected ticks (average, 3.4) fed on each mouse, the mice were then randomly assigned to receive 2 mg of oral doxycycline hyclate in water, 4.2 mg of a sustained-release doxycycline hyclate copolymer formulation (Atrix Laboratories), or a water or poly (DL-lactide) in N-methyl-2-pyrrolidone copolymer (Atrix Laboratories) control. The oral doxycycline or water vehicle was delivered by gavage in 0.1 ml of tissue-grade water. Sustainedrelease doxycycline hyclate was mixed according to the manufacturer's instructions and transferred to a 1-ml Luerlock syringe (Becton Dickinson, Chicago, Ill.) fitted with a 25-gauge needle for subcutaneous injection. A total of 0.05 ml was delivered to each mouse. At 4 weeks posttreatment, an ear biopsy was obtained and cultured in Barbour-Stoenner-Kelly medium (15) to determine B. burgdorferi infection status (18). The mice were euthanized (by exposure to CO 2 ) 8 weeks after tick infestation, and heart and bladder tissues were placed in culture me...

Current prophylaxis for infected tick bites consists of personal protective measures directed towards ticks. This study compared the efficacy of a single oral dose of doxycycline with that of a single injection of sustained-release doxycycline in a model of Lyme borreliosis and Anaplasma phagocytophilum infection. Dosages of doxycycline were equilibrated based on previously determined peak plasma levels in mice [oral, 2.4 μg (ml plasma)−1; sustained release, 1.9 μg (ml plasma)−1] determined 8 h after inoculation. In challenge experiments where five Borrelia burgdorferi-infected and five A. phagocytophilum-infected nymphs were used per mouse, only 20 and 30 % of mice were protected from B. burgdorferi and A. phagocytophilum infection, respectively, using oral doxycycline. In contrast, 100 % of mice receiving sustained-release doxycycline were protected from A. phagocytophilum infection, as indicated by real-time PCR of blood samples, quantitative PCR and culture isolation of spleen samples, and protected against B. burgdorferi infection as demonstrated by culture of ear, heart and bladder. Although 15–40 copies of A. phagocytophilum could be amplified from the spleens of mice treated with sustained-release doxycycline, no viable A. phagocytophilum from these spleens could be cultured in HL-60 cells. In contrast, 7/10 mice receiving oral doxycycline were PCR- and culture-positive for A. phagocytophilum, with copy numbers ranging from 800 to 10 000 within the spleen, as determined by quantitative PCR. Other correlates with A. phagocytophilum infection included a significant difference in spleen mass (mean of 110 mg for sustained-release treatment versus a mean of 230 mg for oral treatment) and the number of splenic lymphoid nodules (mean of 8 for sustained-release treatment versus mean of 12.5 for oral doxycycline) as determined by histopathology. These studies indicate that a single injection of a sustained-release formulation antibiotic may offer a viable prophylactic treatment option for multiple infectious agents in patients presenting with tick bites.