Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment

James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Journal of Clinical Microbiology (Impact Factor: 3.99). 02/1997; 35(1):111-6.
Source: PubMed


In specific-pathogen-free dogs experimentally infected with Borrelia burgdorferi by tick exposure, treatment with high doses of amoxicillin or doxycycline for 30 days diminished but failed to eliminate persistent infection. Although joint disease was prevented or cured in five of five amoxicillin- and five of six doxycycline-treated dogs, skin punch biopsies and multiple tissues from necropsy samples remained PCR positive and B. burgdorferi was isolated from one amoxicillin- and two doxycycline-treated dogs following antibiotic treatment. In contrast, B. burgdorferi was isolated from six of six untreated infected control dogs and joint lesions were found in four of these six dogs. Serum antibody levels to B. burgdorferi in all dogs declined after antibiotic treatment. Negative antibody levels were reached in four of six doxycycline- and four of six amoxicillin-treated dogs. However, in dogs that were kept in isolation for 6 months after antibiotic treatment was discontinued, antibody levels began to rise again, presumably in response to proliferation of the surviving pool of spirochetes. Antibody levels in untreated infected control dogs remained high.

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Available from: Reinhard K Straubinger, Oct 04, 2015
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    • "Although animals do not experience symptoms that might be judged to be PTLDS, in various animal models (mice, dogs and rhesus macaque monkeys), antibiotic therapy with doxycycline, ceftriaxone or tigecycline has not fully eradicated B. burgdorferi, as determined by methods including xenodiagnosis, although viable organisms have not been able to be cultured in conventional culture media.11,12,13,14 Others have raised concerns about such findings, including the use of high concentration inocula and the use of stationary-phase organisms for infection, insufficient antibiotic dosing and other methodological issues, including concerns that rodents are a natural reservoir of B. burgdorferi and that studies of persistence would not approximate human infections.15,16 "
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    ABSTRACT: Although antibiotic treatment for Lyme disease is effective in the majority of cases, especially during the early phase of the disease, a minority of patients suffer from post-treatment Lyme disease syndrome (PTLDS). It is unclear what mechanisms drive this problem, and although slow or ineffective killing of Borrelia burgdorferi has been suggested as an explanation, there is a lack of evidence that viable organisms are present in PTLDS. Although not a clinical surrogate, insight may be gained by examining stationary-phase in vitro Borrelia burgdorferi persisters that survive treatment with the antibiotics doxycycline and amoxicillin. To identify drug candidates that can eliminate B. burgdorferi persisters more effectively, we screened an Food and Drug Administration (FDA)-approved drug library consisting of 1524 compounds against stationary-phase B. burgdorferi by using a newly developed high throughput SYBR Green I/propidium iodide (PI) assay. We identified 165 agents approved for use in other disease conditions that had more activity than doxycycline and amoxicillin against B. burgdorferi persisters. The top 27 drug candidates from the 165 hits were confirmed to have higher anti-persister activity than the current frontline antibiotics. Among the top 27 confirmed drug candidates from the 165 hits, daptomycin, clofazimine, carbomycin, sulfa drugs (e.g., sulfamethoxazole), and certain cephalosporins (e.g. cefoperazone) had the highest anti-persister activity. In addition, some drug candidates, such as daptomycin and clofazimine (which had the highest activity against non-growing persisters), had relatively poor activity or a high minimal inhibitory concentration (MIC) against growing B. burgdorferi. Our findings may have implications for the development of a more effective treatment for Lyme disease and for the relief of long-term symptoms that afflict some Lyme disease patients.
    Emerging Microbes and Infections 07/2014; 3(7):e49. DOI:10.1038/emi.2014.53 · 2.26 Impact Factor
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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.
    International Journal of General Medicine 04/2013; 6:291-306. DOI:10.2147/IJGM.S44114
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    • "Some patients develop chronic persistent disease , and borreliae can be isolated in spite of previous treatment with antibiotics (Maraspin et al., 1995). Clinical and experimental data showed that after so-called adequate treatment in patients with Lyme borreliosis, Borrelia could persist in tissue, and failures of treatment have been reported for almost every suitable antimicrobial agent (Hassler et al., 1990; Preac-Mursic et al., 1989; Preac-Mursic et al., 1996a; Straubinger et al., 1997; Strle et al., 1993 Strle et al., 1996b; Wormser et al., 2003). In some cases, the failure of treatment could be due to irreversible tissue damage during active borrelial infection or inflammation in association with the infection, the induction of autoimmune mechanisms, and possible misdiagnosis (Strle, 1999b). "
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    ABSTRACT: Lyme borreliosis is the most common vector-borne disease in the northern hemisphere. The agents of Lyme borreliosis are borrelia, bacteria of the family Spirochaetaceae, which are grouped in Borrelia burgdorferi sensu lato species complex. Borreliae are fastidious, slow-growing and biochemically inactive bacteria that need special attention and optimal conditions for cultivation. The isolation of Borrelia from clinical material and their cultivation is a time-consuming and demanding procedure. Cultivation lasts from 9 up to 12 weeks, which is much longer than is necessary to grow most other human bacterial pathogens. Although B. burgdorferi sensu lato is susceptible to a wide range of antimicrobial agents in vitro, up to now the susceptibility of individual Borrelia species to antibiotics is defined only partially.
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