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» LymeNet Flash » Questions and Discussion » Medical Questions » New Antibiotic - Cubicin (daptomycin)

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Author Topic: New Antibiotic - Cubicin (daptomycin)
dan67
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Has anyone heard of this? I think it has to be taken by IV but the mechanism of action looks promising:

"Cubicin is daptomycin, is a lipopeptide. Its main mechanism of action is to bind to the bacterial cell membrane leading to a loss of the membrane potential, which results in the inhibition of protein, DNA and RNA synthesis. Ultimately, this causes cell death. Daptomycin is indicated for complicated skin and skin structure infections, bacteraemia and right-sided endocarditis caused by S. pyogenes, S. aureus (including MRSA), S. dysglactiae subsp. equisimilis and Enterococci including GRE and VRE."

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bettyg
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anyone? on page 2 ...

dan, please break up your techinical paragraph; perhaps that's why we neuros skipped reading this one and you have no replies ...

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METALLlC BLUE
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I'm looking at this drug right now.

--------------------
I am not a physician, so do your own research to confirm any ideas given and then speak with a health care provider you trust.

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marcholland81
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found this on lymenet europe:

Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline

Jie Feng, Paul G. Auwaerter, Ying Zhang

Published: March 25, 2015DOI: 10.1371/journal.pone.0117207

"Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin) or an energy inhibitor (clofazimine). Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations. These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection."

web page

Anyone any experience with this. Its in vitro but still looks promising.

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Rhiagel
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quote:
Originally posted by marcholland81:
found this on lymenet europe:

Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline

Jie Feng, Paul G. Auwaerter, Ying Zhang

Published: March 25, 2015DOI: 10.1371/journal.pone.0117207

"Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefoperazone or carbenicillin) or an energy inhibitor (clofazimine). Daptomycin plus doxycycline and cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three drug combinations. These findings may have implications for improved treatment of Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human infection."

web page

Anyone any experience with this. Its in vitro but still looks promising.

Thanks for posting this interesting article. The in vivo problem with the study may be the poor penetration into the BBB for daptomycin (molecular mass = 1,619) and Cefoperazone (molecular mass = 645). Doxy (molecular mass - 444), of course, does pass through into the brain.

I hope these researchers keep experimenting with the combinations to give us the best 1-2-3 punch into the brain.

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Rhiagel
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Table 2 in this study seems kind of odd. The table is entitled, "Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline." In the chart, it shows the combination of dapto, cefo, and doxy with 19% of live cell persisters. If all borrelia were eradicated, shouldn't this be 0%?
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marcholland81
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@rhiagel

The penetration of the bbb for daptomycin and cefoperazone is indeed quite poor. Daptomycin however is quite potent so maybe its enough in vivo (lets say dosage 5/6 mg/kg). There is research where both substances are used succesfully for meningitis.

daptomycin csf

"The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUCCSF)/(AUCserum ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%."

cefoperazone csf

Regarding the 19%; I think they mentioned that the remaining cells weren't viable anymore for replication.

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Rhiagel
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Well, that's encouraging, at least for those with inflamed meninges. I hope we hear soon from those who try this abx trifecta. The original study, which alerted everyone to daptomycin, was last summer and I still haven't read of anyone actually trying it. Perhaps, it's too expensive.

Thanks for the clarification on the 19% that remained.

quote:
Originally posted by marcholland81:
@rhiagel

The penetration of the bbb for daptomycin and cefoperazone is indeed quite poor. Daptomycin however is quite potent so maybe its enough in vivo (lets say dosage 5/6 mg/kg). There is research where both substances are used succesfully for meningitis.

daptomycin csf

"The mean daptomycin penetration, determined by the area under the concentration-time curve in CSF (AUCCSF)/(AUCserum ratio), was 0.8%. Corrected for protein binding, the overall CSF penetration was 11.5%."

cefoperazone csf

Regarding the 19%; I think they mentioned that the remaining cells weren't viable anymore for replication.


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marcholland81
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yes its very expensive.

131 euro for 350mg!

link

The patent might expire june 2016.

link

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Rhiagel
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Let's hope the patent does expire next year and more lyme sufferers get a chance to try a less expensive daptomycin combo.

From the study, the spirochetes were only subjected to the abx for 7 days. That could make a human trial less costly.

Also, daptomycin seems to have cyst-busting and biofilm-penetrating abilities. That would be a godsend to not have to rely on flagyl or tini. It's too bad that there isn't an oral version of it, but it reportedly has poor bioavailability in that form.

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Rhiagel
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The Maryland LLMD blogger has an interesting take on the study, while blasting the IDSA apologists in the process.

"We may not be able to readily adopt this study for clinical purposes. Daptomycin is an extremely expensive drug and is currently reserved for the sickest hospitalized patients. Infectious disease physician's "stewardship" over antibiotics will likely be a roadblock against the use of this potent drug, and, third party payers, hiding behind the banner of FDA approval will likely not pay for it. Cefoperazone I have tried to prescribe; pharmacists have told me it is not available.

Only a veritable nuclear bomb of antibiotics could kill all the Lyme in a test tube. Still, Dr. Auewater (at his other job), along with the coterie of Steerites will continue to tell us the pea shooter therapy is all our patients should ever need."

http://lymemd.blogspot.com

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Lepidopterophile
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Regarding the expense. I contacted my insurance before I started and they determined that my out of pocket cost would be about $1500 for the 2 weeks. Today as I was walking out they grabbed me to fill out some paperwork. It seems that the compnay that makes Cubicin is offering to pay doctors to use it but they want info about who and how it is being used. I'm not sure yet how much of it will be written off but I was thrilled that I may not have to pay that whole $1500! I'll let you guys know what my total bill is.

--------------------
Positive Western Blot IGM - First in 2013; most recently June 2015. IGG always negative but bands 41,45,58,66 positive.

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nellypointis
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Hi,
Apart from insurance issues, how did the combo you tried help you?
Really want to try it but very few people giving any proper feedback
thanks

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willbeatthis
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Isn't Dr.H doing research on this right now- you can pull a facebook link on it.

Just an FYI.

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