From: Sewer Rat Date: Wed, 11 Apr 2007 14:13:15 +0200
-------------------------------------------------------------------------------- "The use of tetracyclines for treating bacterial infections has been limited in recent years because of the emergence of resistant organisms with efflux and ribosomal protection mechanisms of resistance. Research to find tetracycline analogues that circumvented these resistance mechanisms has lead to the development of the glycylcyclines." ---------------------------------------------
Drugs. 2004;64(1):63-88.
The glycylcyclines: a comparative review with the tetracyclines.
Zhanel GG, Homenuik K, Nichol K, Noreddin A, Vercaigne L, Embil J, Gin A, Karlowsky JA, Hoban DJ.
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. gghanzel@xxxxxxxxx
The tetracycline class of antimicrobials exhibit a broad-spectrum of activity against numerous pathogens, including Gram-positive and Gram-negative bacteria, as well as atypical organisms. These compounds are bacteriostatic, and act by binding to the bacterial 30S ribosomal subunit and inhibiting protein synthesis. The tetracyclines have been used successfully for the treatment of a variety of infectious diseases including community-acquired respiratory tract infections and sexually transmitted diseases, as well in the management of acne. The use of tetracyclines for treating bacterial infections has been limited in recent years because of the emergence of resistant organisms with efflux and ribosomal protection mechanisms of resistance. Research to find tetracycline analogues that circumvented these resistance mechanisms has lead to the development of the glycylcyclines. The most developed glycylcycline is the 9-tert-butyl-glycylamido derivative of minocycline, otherwise known as tigecycline (GAR-936). The glycylcyclines exhibit antibacterial activities typical of earlier tetracyclines, but with more potent activity against tetracycline-resistant organisms with efflux and ribosomal protection mechanisms of resistance. The glycylcyclines are active against other resistant pathogens including methicillin-resistant staphylococci, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci. Tigecycline is only available in an injectable formulation for clinical use unlike currently marketed tetracyclines that are available in oral dosage forms. Tigecycline has a significantly larger volume of distribution (> 10 L/kg) than the other tetracyclines (range of 0.14 to 1.6 L/kg). Protein binding is approximately 68%. Presently no human data are available describing the tissue penetration of tigecycline, although studies in rats using radiolabelled tigecycline demonstrated good penetration into tissues. Tigecycline has a half-life of 36 hours in humans, less than 15% of tigecycline is excreted unchanged in the urine. On the basis of available data, it does not appear that the pharmacokinetics of tigecycline are markedly influenced by patient gender or age. The pharmacodynamic parameter that best correlates with bacteriological eradication is time above minimum inhibitory concentration. Several animal studies have been published describing the efficacy of tigecycline. Human phase 1 and 2 clinical trials have been completed for tigecycline. Phase 2 studies have been conducted in patients with complicated skin and skin structure infections, and in patients with complicated intra-abdominal infections have been published as abstracts. Both studies concluded that tigecycline was efficacious and well tolerated. Few human data are available regarding the adverse effects or drug interactions resulting from tigecycline therapy; however, preliminary data report that tigecycline can be safely used, is well tolerated and that the adverse effects experienced were typical of the tetracyclines (i.e. nausea, vomiting and headache). Tigecycline appears to be a promising new antibacterial based on in vitro and pharmacokinetic/pharmacodynamic activity; however more clinical data are needed to fully evaluate its potential.
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Posted by dmc (Member # 5102) on :
started it yesterday, will let you know how I do on it.
Posted by yanivnaced (Member # 13212) on :
dmc: How long of a treatment with the Tigecycline does your LLMD anticipate?
Posted by dmc (Member # 5102) on :
my llmd has said 8-12 weeks of treatment if tolerated. Had heard from my other llmd...people have only tolerate fot 3 weeks.
I can believe that...worse I ever felt. During infusion...get woozy then wiped out.
Yesterday was loading dose of 100mg. from now on 2X at 50mg a day.
wow, much hard to do than Rocephen, with the mixing and iv bag and all.
Trying to keep positive, side effects or herx are humdingers.
Posted by Tracy9 (Member # 7521) on :
Hi, Sent you a pm; please respond if you are up to it! I am guessing we have the samd doctors; I go on Monday for the first time to neurologist for Tigecycline and would LOVE to talk to you!!!
Tracy
Posted by jamescase20 (Member # 14124) on :
lets see, its a derivative of minocin, no wonder mino made me herx badly.
Anyway, this drugs gotta be great, its a efflux pump inhibitor in itself.
Posted by kelmo (Member # 8797) on :
My LLMD mentioned it last week. He has big hopes for it. Please keep us posted.
When was it made available?
Posted by dmc (Member # 5102) on :
On 11th day...had turn around on the 7th day. No longer felt horrid while infusing. No longer in bed most of the day. Do get back pain/tightness in middle of back while infusing.
No more nausea, haven't gotten diarrhaea. Over all, sure feel better than last week but too early still.
It takes an hour just to infuse (empty iv bag) so I'm catching up on magazine reading the 2 times a day.
Posted by oxygenbabe (Member # 5831) on :
Thanks. Please keep us posted on this.
Posted by djf2005 (Member # 11449) on :
any updates?
Posted by oxygenbabe (Member # 5831) on :
Tigecycline sounds great--except--even the regular folks can barely tolerate 3 weeks (per a previous post) and 8-12 is the goal?
I can barely tolerate 3 weeks of a normal antibiotic!
Is it the herx? Any thoughts? 8-12 weeks is still short term in lyme.
Posted by jamescase20 (Member # 14124) on :
Tiger has a built in Efflux pump inhibitor, this is why I believe its so effective.
Natural efflux pump inhibitors are claimed to be the following, UNDER tonuge AND orally.
Black pepper Rosemary Tyme PAXIL (maybe most effective)
Posted by CD57 (Member # 11749) on :
Up-- can you folks taking weigh in? I think I just heard from a friend that it may turn your skin black and cause one to vomit uncontrollably...?
Posted by njgirl14 (Member # 14174) on :
Any other info - I am seeing my LLMD tomorrow.
Posted by merrygirl (Member # 12041) on :
Bumping this post because My doc has offered this to me as well as an option.
Anyone have any idea what the cost is?
I heard it is more expensive than Rocephin.
Thanks Melissa
Posted by Mathias (Member # 5298) on :
I'm sure it is more expensive than Rocephin which is now available as a generic.
Glad to read about a new antibiotic being available. Haven't researched it but is there any hope of making it available in a capsule or tablet like the rest of the tetracycline class?
Posted by CD57 (Member # 11749) on :
I heard it is VERY pricey. Looks promising against bartonella (gram negative bacteria).
Posted by djf2005 (Member # 11449) on :
anyone using this or planning on it have a bad case of bart?
thanks
derek
Posted by Tracy9 (Member # 7521) on :
Please update us! I was trying to get on it myself, but so far it seems patients experiences have been dismal.
I know my LLD had three people on it, another well known LLD had three people on it, none of whom could tolerate it and he stopped using it.
My LLD wouldn't give it to me because all three people he has on it were not doing well.
I'm anxious to hear from DMC and anyone else who has tried this.
Posted by METALLlC BLUE (Member # 6628) on :
The reports I've been receiving have been disappointing. I'll keep everyone posted as usual if anything useful comes my way. I've been following the drug for about a year now. When patients first began using it, we were all excited.
So far, it has not been a silver bullet. More research will be necessary.
Posted by djf2005 (Member # 11449) on :
this is the same thing my dr is saying.
no magic yet..
derek
Posted by peter j (Member # 11825) on :
METALLIC BLUE, thank's for bumping it. I am very interested in hearing about experiences.
You say what you've heard have been disapointing. Could you write a summary of it? How many patients are you in contact with, and how long were they using etc. etc.
Posted by peter j (Member # 11825) on :
I've found this article about it (in vitro testing) which naturally, doesn't have to correlate with in vivo, but nontheless - it may give indications:
1116 Tigecycline is Highly Effective against Borrelia burgdorferi
ANDREW NGUYEN, MD , DAN QIU, MD, BENJAMINE J. LUFT, MD; Stony Brook University Medical Center, Stony Brook, NY
Background: Borrelia burgdorferi, the etiologic agent of Lyme disease, is a slowly dividing organism. Previously reported sensitivity data indicated that although Doxycycline is the preferred drug for treatment of Lyme disease, it is associated with a relatively high minimal bactericidal concentration in vitro. Tigecycline is a new glycylcycline that shows pronounced activity against most gram-positive and many gram-negative organisms.
Methods: In-vitro activity of Tigecycline and Doxycycline were compared in time-kill studies of 3 strains of B. burgdorferi in both mid-log and stationary phase growth. Cultures were co-incubated with varying concentrations of antibiotics and aliquots were examined by dark field microscopy.
Results: Tigecycline was remarkably more effective than Doxycycline against B. burgdorferi in both stationary and midlog phase growth. Doxycycline was bacteriostatic against the B31 strain of B. burgdorferi in the mid-log phase growth and achieved its greatest effect at 72 hours of culture. In contrast, Tigecycline was bactericidal at a concentration 0.097 ug/ml at 24 hours and 0.006 ug/ml at 72 hours. With Borrelia in the stationary phase, Tigecycline killed the three different strains of Borrelia at 0.012–0.097 ug/ml. Doxycycline had little effect on the stationary phase at concentrations greater than 6.25 ug/ml.
Conclusion: Borrelia burgdorferi is remarkably more sensitive to Tigecycline than Doxycycline. Tigecycline appears to be bactericidal and is able to inhibit the replication of the organism more rapidly than Doxycycline. Further studies are in progress to determine whether antibiotic efflux pumps in Borrelia may explain the differences.
I found it on page 29 (it's a pdf). here Posted by CD57 (Member # 11749) on :
I have an LLMd appt next week and will ask about why the experiences have been dismal. is it because no one can stay on it or because it doens't work?
Posted by peter j (Member # 11825) on :
great CD57!
I've heard one report with a patient with symptoms of paralysis which had some improvement, but not 'dramatic' improvement. Is anyone here treated by Dr. s in ct?
Posted by CD57 (Member # 11749) on :
I have an LLMd appt next week and will ask about why the experiences have been dismal. is it because no one can stay on it or because it doens't work?
Posted by Tracy9 (Member # 7521) on :
I am seen by the LLDs in CT. My main LLD is very excited about it and all the research, and referred me to the neuro LLD who can actually prescribe it longterm.
When I got to him, he refused to give it to me because all three of the patients he had on it were experiencing much worse, profound fatigue and he wasn't willing to try it on anyone else until he saw how they did for a while.
I begged and pleaded with him to give it to me. He said he might make an exception and do it. He sent me for tons of tests before deciding.
I am still in the process of getting all the tests done. In the meantime, I have become a little wary of it after speaking to one of his patients by phone, who also posts here, and hearing her say how awful it was making her feel.
I am really hoping she will update us. The last I heard from her was at least a month ago. I don't know if she was able to stay on it or if it is helping her at all.
I was really excited about it, now I guess I'll probably just go for IV Rocephin and give that a try first. Wish it was better news. Very, very disappointing.
Posted by METALLlC BLUE (Member # 6628) on :
It's really too early to tell in my opinion. I think patients will possibly need to be on this in combination with many other things, like any combo therapy -- for it to be effective, but it also has to be tolerable and at appropriate doses.
The patients who have reported to me gave me time lines from everything from 1 month up to 3 months, and some discontinued. Some improvements were seen, some were not.
At this time, it's still too early.
Posted by peter j (Member # 11825) on :
How did that LLMD appointment go CD57?
Posted by GADaisy (Member # 12964) on :
bump
Posted by CD57 (Member # 11749) on :
I forgot to ask him at my last appt, will try at next one.
Posted by djf2005 (Member # 11449) on :
please update for those of you who are on it...
very curious especially because dr b recently said this drug is very promising
Posted by amk33 (Member # 13206) on :
I just read about this drug in Pamela Weintraub's book. It sounds promising. Rocephin (6 wks) did nothing for me, except possibly make me worse in the long run.
Those of you who are on tigecycling-please keep us posted! Thanks.
Posted by djf2005 (Member # 11449) on :
so whos on this drug???
my llmd only has/had THREE people on it.
do i have to be a test rat??
actually i am going to push hard for it once i get medicare if they will cover it so well see.
by then im counting on being 50-60% functional and will be able to take the brutal herxing from it..
cheers
derek
Posted by Tracy9 (Member # 7521) on :
Derek, Yes you would be a test rat. Very few people have been put on it so far. Remember in order for an LLD to prescribe it, they are prescribing it off label, which is yet another red flag they dont' need in this IDSA world.
There are not yet any peer reviewed journal articles published on its use for Lyme Disease. Most of the few patients who have been put on it have experienced crippling side effects, causing further hestitation on the LLD's part to use it.
I will let you know if I end up on it; I am seeing an LLD who uses it just for that purpose. I still have a few tests to complete (of the gazillion he sent me for) before I will know for sure if he is going to let me give it a whirl.
Posted by merrygirl (Member # 12041) on :
I was going to try this but lLMD told me the out of pocket expense would be $6000 just for the dry powder in vials.
YIKES>
I am doing bicillin first,
Melissa
Posted by njgirl14 (Member # 14174) on :
any updates??
Posted by peter j (Member # 11825) on :
updates anyone? CD57, have you been to your LLMD since last time I wrote?
Posted by onmyway (Member # 17607) on :
I am getting ready to start this for Lyme and Bart and my LLID- Infectious Disease Dr. is putting me on it!
I guess they see some good in it! He speaks very highly of it because the capabilitis of crossing into the blood brain barrier!
I will keep you updated and let you know how it goes!
Take Care, Onmyway
Posted by Kreynolds (Member # 15117) on :
yanivnaced:
On it for a month....nothin great about it... at least for me...it is very hard on the stomach and i get many headaches with it...
Posted by stressed out (Member # 16480) on :
hello
whats up
no response on this since oct 2008
we see DR J in SC 2 weeks - my wife might be using this drug -
he said he runs 3 to 4 days on and then only fluids to flush the remainder of week - this is suppose to prevent toxicity and allow longer treatment regimans
we really wanted to research it b4 spending big bucks - insurance wont cover a dime
but all tht have tried it never give final report
im sorry for those sufferin from the drug reactions - but need to know if the suffering is worth it in the end
hasnt anyone been able to bare it? if yes was it worth it - did you improve????
sorry if i seem foward - just nervious
Posted by CD57 (Member # 11749) on :
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