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 Inläggsrubrik: Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Mic
InläggPostat: ons 26 okt 2016, 14:42 
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Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/Doxycycline/Cefuroxime Drug Combination without Pulse Dosing

Jie Feng1, Shuo Zhang1, Wanliang Shi1 and Ying Zhang1*
1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, USA
Although the majority of Lyme disease patients can be cured, at least 10-20% of the patients continue to suffer from persisting symptoms such as fatigue, muscular and joint pain, and neurologic impairment after standard 2-4 week antibiotic treatment. While the causes for this post-treatment Lyme disease symptoms are unclear, one possibility is due to B. burgdorferi persisters that are not effectively killed by current antibiotics such as doxycycline or amoxicillin used to treat Lyme disease. A previous study showed that four rounds of ceftriaxone pulse dosing treatment eradicated B. burgdorferi persisters in vitro using a relatively young late log phase culture (5 day old). In this study, we investigated if ceftriaxone pulse dosing could also eradicate B. burgdorferi persisters in older stationary phase cultures (10 day old) enriched with more resistant microcolony form of persisters. We found that ceftriaxone pulse dosing could only eradicate planktonic log phase B. burgdorferi spirochetal forms and round body forms but not more resistant aggregated biofilm-like microcolony persisters enriched in stationary phase cultures. Moreover, we found that not all drugs are suitable for pulse dosing, with bactericidal drugs ceftriaxone and cefuroxime being more appropriate for pulse dosing than bacteriostatic drug doxycycline and persister drug daptomycin. We also showed that drug combination pulse dosing treatment was more effective than single drug pulse dosing. Importantly, we demonstrate that pulse dosing treatment impaired the activity of the persister drug daptomycin and its drug combination against B. burgdorferi persisters and that the most effective way to kill the more resistant biofilm-like microcolonies is the daptomycin/doxycycline/ceftriaxone triple drug combination without pulse dosing. Our findings indicate pulse dosing may not always work as a general principle but rather depends on the specific drugs used, with cidal drugs being more appropriate for pulse dosing than static or persister drugs, and that drug combination approach with persister drugs is more effective at killing the more resistant microcolony form of persisters than pulse dosing. These observations may have implications for more effective treatment of Lyme disease. Future studies are required to validate these findings in animal models of B. burgdorferi persistence.

Keywords: Borrelia burgdorferi, Persisters, Biofilm, pulse dosing, drug combination

Citation: Feng J, Zhang S, Shi W and Zhang Y (2016). Ceftriaxone Pulse Dosing Fails to Eradicate Biofilm-like Microcolony B. burgdorferi Persisters Which Are Sterilized by Daptomycin/Doxycycline/Cefuroxime Drug Combination without Pulse Dosing. Front. Microbiol. 7:1744. doi: 10.3389/fmicb.2016.01744

Received: 13 Aug 2016; Accepted: 19 Oct 2016.
Edited by:
Octavio L. Franco, Universidade Católica de Brasília, Brazil
Reviewed by:
Miriam Barlow, University of California, Merced, USA
Nicolau Brito Da Cunha, Universidade Católica de Brasília, Brazil
Copyright: © 2016 Feng, Zhang, Shi and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Ying Zhang, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA, yzhang@jhsph.edu

http://journal.frontiersin.org/article/ ... 4/abstract


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