title: A sustained-release formulation of doxycycline hyclate (Atridox) prevents simultaneous infection of Anaplasma phagocytophilum and Borrelia burgdorferi transmitted by tick bite.
abstract: 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 microg (ml plasma)(-1); sustained release, 1.9 microg (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.
authors: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.
authors: Nordin S
authors: NS
authors: Zeidner
authors: Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Robert F
authors: RF
authors: Massung
authors: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.
authors: Marc C
authors: MC
authors: Dolan
authors: QLT Laboratories, Fort Collins, CO 80525, USA.
authors: Eric
authors: E
authors: Dadey
authors: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.
authors: Elizabeth
authors: E
authors: Gabitzsch
authors: Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, USA.
authors: Gabrielle
authors: G
authors: Dietrich
authors: Division of Viral and Rickettsial Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Michael L
authors: ML
authors: Levin
mesh_terms: D041081:Anaplasma phagocytophilum / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D025065:Borrelia burgdorferi / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use*; D004318:Doxycycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016873:Ehrlichiosis / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007299:Insect Bites and Stings / Q000382:microbiology*; D018884:Ixodes / Q000382:microbiology; D008193:Lyme Disease / Q000150:complications / Q000382:microbiology / Q000517:prevention & control*; D051379:Mice; D008809:Mice, Inbred C3H; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004318:Doxycycline