Persistence of Borrelia burgdorferi Following Antibiotic Treatment in Mice Antimicrobial Agents and Chemotherapy, published online ahead of print on 3 March 2008 Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone or saline for one month, commencing during the early, 3 weeks, or chronic, 4 months, stages of infectionwith Borrelia burgdorferi. Tissues from mice were tested for infection by culture, polymerase chain reaction, PCR, xenodiagnosis, and transplantation of allografts at 1 and 3 months after completion of treatment. In addition, tissues were examined for spirochetes by immunohistochemistry. In contrast to saline-treated mice, mice treated with antibiotic were consistently culture-negative, but tissues from some of the mice remained PCR-positive, and spirochetes could be visualized in collagen-rich tissues. Furthermore, when some of the antibiotic treated mice were fed upon by Ixodes scapularis ticks, xenodiagnosis, spirochetes were acquired by the ticks, based upon PCR, and ticks from those cohorts transmitted spirochetes to naïve SCID mice, which became PCR-positive, but culture-negative. Results indicated that following antibiotic treatment, mice remained infected with non-dividing but infectious spirochetes, particularly when antibiotic treatment was commenced during the chronic stage of infection