The effectiveness of a new first-in-class
antibiotic,
tigecycline (
glycylcycline), was evaluated during the early dissemination (1 week), early immune (3 weeks), or late persistent (4 months) phases of
Borrelia burgdorferi infection in C3H mice. Mice were treated with high or low doses of
tigecycline, saline (negative-effect controls), or a previously published regimen of
ceftriaxone (positive-effect controls).
Infection status was assessed at 3 months
after treatment by culture, quantitative ospA real-time PCR, and subcutaneous
transplantation of joint and heart tissue into SCID mice. Tissues from all saline-treated mice were culture and ospA PCR positive, tissues from all
antibiotic-treated mice were culture negative, and some of the tissues from most of the mice treated with
antibiotics were ospA PCR positive, although the
DNA marker load was markedly decreased compared to that in saline-treated mice.
Antibiotic treatment during the early stage of
infection appeared to be more effective than treatment that began during later stages of
infection. The viability of noncultivable spirochetes in
antibiotic-treated mice (demonstrable by PCR) was confirmed by
transplantation of tissue allografts from treated mice into SCID mice, with dissemination of spirochetal
DNA to multiple recipient tissues, and by xenodiagnosis, including acquisition by ticks, transmission by ticks to SCID mice, and survival through molting into nymphs and then into adults. Furthermore, PCR-positive heart base tissue from
antibiotic-treated mice revealed
RNA transcription of several B. burgdorferi genes. These results extended previous studies with
ceftriaxone, indicating that
antibiotic treatment is unable to clear persisting spirochetes, which remain viable and infectious, but are nondividing or slowly dividing.