Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Topics with information and discussion about published studies related to Lyme disease and other tick-borne diseases.
dlf
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Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by dlf » Wed 25 May 2016 21:55

Front. Microbiol., 23 May 2016

A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

Full text available from:
http://journal.frontiersin.org/article/ ... 00743/full

Jie Feng1, Wanliang Shi1, Shuo Zhang1, David Sullivan1, Paul G. Auwaerter2 and Ying Zhang1*

1Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
2Fisher Center for Environmental Infectious Diseases, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10–20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even when pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.
<snip from discussion section of full text>
Despite the description of drug candidate’s active against the round body forms, their significance in improving the treatment remains to be determined. While evidence that round body form of persisters examined in this study may occur in vivo during infection remains to be confirmed, it is also unknown if antibiotics that target such potential persisters would lead to improved outcomes in human infection compared with standard Lyme disease treatment with doxycycline or amoxicillin that do not have good activity against the round body forms of B. burgdorferi (Brorson et al., 2009; Barthold et al., 2010) or if they even induce such forms in vivo. These studies indicate that it would be difficult to kill the round body form of B. burgdorferi using the current Lyme antibiotics if similar organisms exist in vivo or are incompletely eradicated in the human host under environmental stressors. The drug candidates identified in this study could allow the above possibility to be tested in animal models of persistence using the drug combinations that are active against round body forms of B. burgdorferi in the future.
Interestingly, this research group now includes Paul Auwaerter again and he is listed as a co-author on this paper.

duncan
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by duncan » Wed 25 May 2016 22:25

Like cancer patients, we need a cure for ramifications from the cure.

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ChronicLyme19
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by ChronicLyme19 » Fri 27 May 2016 4:34

duncan wrote:Like cancer patients, we need a cure for ramifications from the cure.
I hope not :/ But then again, some conventional IV antibiotics can cause really rough herxing, to the point at which I wonder if it's doing more harm than good.

Some of the LLMDs have been using daptomycin already. I've only known one person personally who has tried it. Artemisinin supposedly can also be a very rough treatment.
Half of what you are taught is incorrect, but which half? What if there's another half missing?

hv808ct
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by hv808ct » Fri 27 May 2016 20:50

Remember, this is a test tube phenomenon. As the authors noted:

…that round body form of persisters examined in this study may occur in vivo during infection remains to be confirmed.

…also unknown…if they even induce such forms in vivo.

…if similar organisms exist in vivo or are incompletely eradicated in the human host.

Interestingly, the authors note the support of various groups unlikely to make a distinction between in vitro and in vivo.

We acknowledge the support of our work by Global Lyme Alliance*, Johns Hopkins Fisher Center for Environmental Infectious Diseases, and Steven & Alexandra Cohen Foundation. We also thank Lyme Disease Association, NatCapLyme, Steve Sim, and Jonathan Locke for their support. 


*Also known as the rich white people’s alliance against their gardeners, caddies, and nannies getting Lyme disease and calling in sick. (http://globallymealliance.org/press-releases)

duncan
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by duncan » Fri 27 May 2016 20:59

What is not a test tube phenomenon is IDSA-recommended treatment failing 1 out of 5 Lyme patients.

20% of at least 300,000, year after year.

Studies such as this help explain why.


duncan
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by duncan » Fri 27 May 2016 21:03

ALDF? Would that be the same organization about which a petition has been gaining support requesting a Congressional investigation?

nnecker
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by nnecker » Fri 27 May 2016 22:09

Typical Lyme kook patient that IDSA treatment fails and who also signs Lyme petitions:

From Lymenut.kook
anuta
LymeNut Contributor
Member # 22646

Oh, I'm sorry to hear that bcb, my daughter was recently diagnosed by Dr. Klinghardt practitioner in Providence with borrelia and bartonella.

She was never bitten though. I think she got infected at home from me or my husband( who also has Lyme but almost asymptomatic) via food, or somehow else. She had mild symptoms on and off and I suspected that she has a tbd.
I'm treating her with photons and nosodes. She response very well. She has no more symptoms , but C- dilutions of borrelia still test positive.

Think about Babesia too. For me itchy skin was symptom of Babesia

duncan
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by duncan » Fri 27 May 2016 22:32

I think the IDSA and CDC are also recommended in the petition for Congressional investigation over their handling of the on-going Lyme debacle.

The days of cruel indifference toward, and even treatment of, some Lyme sufferers may be numbered. It will be interesting to see how developments unfurl, particularly with the new IDSA Guidelines looming.

Henry
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Re: Drug Combination Active against Amoxicillin-Induced Round Bodies of In Vitro B. burgdorferi Persisters

Post by Henry » Sat 28 May 2016 0:28

Duncan: Obviously, since you prefer to dwell on unrelated matters, rather than the issues considered in the paper, you don't really understand it -- but don't like or disagree with it nevertheless because it emanates from the ALDF.

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