Ineffectiveness of Tigecycline Against Persistent Borrelia burgdorferi

Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine,
University of California at Davis, One Shields Avenue, Davis, California 95616;
Division of Infectious Diseases, Department of Medicine, State University of New
York at Stony Brook, Stony Brook, New York 11794.

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 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 non-cultivable 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. Results extended
previous studies with ceftriaxone, indicating that antibiotic treatment is
unable to clear persisting spirochetes, which remain viable and infectious, but
are non- or slowly dividing.

http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=19995919&retmode=ref&cmd=prlinks
PMID: 19995919  [PubMed – as supplied by publisher]

Antimicrob Agents Chemother. 2009 Dec 7; [Epub ahead of print]

Ineffectiveness of Tigecycline Against Persistent Borrelia burgdorferi.

Barthold SW, Hodzic E, Imai DM, Feng S, Yang X, Luft BJ.

Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine,
University of California at Davis, One Shields Avenue, Davis, California 95616;
Division of Infectious Diseases, Department of Medicine, State University of New
York at Stony Brook, Stony Brook, New York 11794.