Article

Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice

Center for Comparative Medicine, School of Medicine, University of California at Davis, One Shields Avenue, Davis, CA 95616, USA.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.48). 06/2008; 52(5):1728-36. DOI: 10.1128/AAC.01050-07
Source: PubMed

ABSTRACT

The effectiveness of antibiotic treatment was examined in a mouse model of Lyme borreliosis. Mice were treated with ceftriaxone
or saline solution for 1 month, commencing during the early (3 weeks) or chronic (4 months) stages of infection with Borrelia burgdorferi. Tissues from mice were tested for infection by culture, PCR, xenodiagnosis, and transplantation of allografts at 1 and 3
months after completion of treatment. In addition, tissues were examined for the presence of spirochetes by immunohistochemistry.
In contrast to saline solution-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 on by Ixodes scapularis ticks (xenodiagnosis), spirochetes were acquired by the ticks, as determined based upon PCR results, 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 nondividing but infectious spirochetes, particularly when antibiotic
treatment was commenced during the chronic stage of infection.

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    • "Unfortunately, continued antibiotic treatment is not recommended as its long-term effectiveness has not been observed or proven (Delong et al. 2012; Stanek et al. 2012). The increasing trend with new and relapsing Lyme disease cases was noted and attributed mainly to inadequate prevention, ineffective therapy and/or bacterial persistency (Straubinger et al. 1997; Bockenstedt et al. 2002; Peltomaa et al. 2003; Hodzic et al. 2008; Feng et al. 2014). "
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    • "Considerations may include persisting immunological responses that may be independent of continued infection or possibly driven by the continued presence of antigenic debris,8 as well as persisting organisms. The question of whether B. burgdorferi may persist in some patients after antibiotic therapy and further evade host immune clearance has been raised by some researchers, but the idea is controversial.9,10 "
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    • "Embers et al138 addressed several of the key issues identified by Wormser and Schwartz140 in their 2009 review that focused on studies by Bockenstedt et al,141 Hodzic et al,142 and Straubinger et al,143 all of which documented the persistence of Bb in the tissues of animals despite the antibiotic challenge. "
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    ABSTRACT: Is chronic illness in patients with Lyme disease caused by persistent infection? Three decades of basic and clinical research have yet to produce a definitive answer to this question. This review describes known and suspected mechanisms by which spirochetes of the Borrelia genus evade host immune defenses and survive antibiotic challenge. Accumulating evidence indicates that Lyme disease spirochetes are adapted to persist in immune competent hosts, and that they are able to remain infective despite aggressive antibiotic challenge. Advancing understanding of the survival mechanisms of the Lyme disease spirochete carry noteworthy implications for ongoing research and clinical practice.
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