Thursday, July 3, 2014

Which antibiotics work best against treatment-resistant Lyme disease (PTLDS)

I take this study as confirmtion from some research institutions that there are indeed "persister" bacteria that survive standard tx with antibiotics such as doxycycline. Ketek is hard to find, at this point (I used it years ago, perhaps 10 years ago) but rumor among LLMDs is that a new formulation (300 mg) is jut around the corner.


BTW, here's a bit of info about keytek from Wikipedia: http://en.m.wikipedia.org/wiki/Telithromycin


Telithromycin is the first ketolide antibiotic to enter clinical use and is sold under the brand name of Ketek. It is used to treatcommunity acquired pneumonia of mild to moderate severity. After significant controversy regarding safety and research fraud, the US Food and Drug Administration sharply curtailed the approved uses of the drug in 2007.

Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting a ketogroup for the cladinose sugar and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the carbon at position 6 has been methylated, as is the case in clarithromycin, to achieve better acid-stability.

-Bob

Jie Feng1, Ting Wang1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul G Auwaerter2 and Ying Zhang1

1.     1Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA

2.     2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA

Correspondence: Y Zhang, E-mail: yzhang@jhsph.edu

Received 17 April 2014; Revised 30 May 2014; Accepted 3 June 2014

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. burgdorferipersisters. 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.

Keywords:

Borrelia burgdorferi; drug discovery; FDA approved drug library; persisters; SYBR Green I 

Read the source:

http://www.nature.com/emi/journal/v3/n7/fig_tab/emi201453t1.html#figure-title



2 comments:

  1. Wow!Looks like those winds of change are coming for us Bob-Hilary

    ReplyDelete
  2. Ketek may have been assoc with several liver fauilures, some resulting in death.

    ReplyDelete

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