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Thursday, December 4, 2008

Novel combinations of Lyme medications

It is hard to predict how patients will respond to antibiotic combinations. As I review records of patients that I have treated over several years, I have noted that Doxycyline in combination with Plaquenil had been very effective. I was using this before I became more "Lyme literate" and discovered that Burrascano and Donta claimed that Plaquenil was only effective with macrolides. I saw a patient yesterday who has had chronic Lyme disease. She presented mostly with fatigue, brain fog and muscle/joint pain. She was in the past diagnosed by a rheumatologist with a mixed connective tissue disorder. She had borderline auto-antibody immune indicators-low level RF and ANA. She was treated with prednisone and methotrexate with a poor response. Her condition devolved into what was called fibromyalgia before I began treating her. I have found that quinolones, particularly Cipro can be very effective for fibromyalgia symptoms. In this case I used Cipro in combination with Amoxicillin. She had a good response. She became 60% better. I then added Flagyl. She "loved" Flagyl. She felt much better. She was perhaps 80% better. This process transpired over about 18 months. She would try off antibiotics and relapses would occur.(Other antibiotics were used but this combo was the most effective consistently) Two months ago the Flagyl wasn't working as well. She was back down to the 60% better level. I tried something different: Amoxil- Cipro(250mg twice daily) and Plaquenil. The Flagyl was stopped. She returned for follow up. Plaquenil was magic. For the first time in decades- she was 100% better. Perhaps this relates to her tendency for autoimmune responses. Nonetheless, this is an example of how experimentation with atypical combinations of Lyme agents can pay off.


wildcat said...

hi my name is ana i need help my test came back through igenex positive for lyme but not through cdc i would like it if you can call me or email me @ my phone # is 1 503 746 7496 thanks ana i am very sick and need help

cehansen said...

Doc, did this patient have co-infections? I note you say this treatment transpired over 18 months. Were you just treating Lyme, per your post about treating Lyme before co's, or did you line this up to hit some co's as well?

I was particularly interested in the Cipro combo...isn't that a bartonella drug? Or did you use it for Lyme?
Have you seen a lot of tendon problems or troublesome side effects with the quinolones?

Lyme report: Montgomery County, MD said...

I do not call or email patients through this blog. It is for informational purposes. I am available for new patients. You can get my contact information through ILADS in Bethesda Maryland.

Lyme report: Montgomery County, MD said...

I have used Cipro for Lyme and found it to be effective. Original MIC studies show it to be effective. In the past Jemsek recommended this antibiotic. I believe- this is theoretical- that tendon ruptures occur when Cipro is given to patients with subclinical Lyme- or other infections of tendons etc. Starting with a low dose and telling patients to stop the medicine if they have any pain has worked well for me. None of my patients has had a tendon rupture. Quinolones do not appear to be more problematic then other antibiotics. Before Lyme, Cipro was frequently prescribed for 3-6 months for chronic prostatitis without concern. It seems that all these worries about antibiotic toxicity suddenly appear when the drugs are used for Lyme. Of course it would be dangerous to treat a disease which
"Doesn't exist" except in the minds of deluded doctors and patients.

It never occured to me that I might be treating a co-infection. I suspect a new co-infection will be uncovered soon- with any luck.

lymie said...

A Hungarian lyme doctor says he has much success in combining cipro with one of many other drugs (especially rocephin or doxycycline). No mention of flagyl, but this was several years ago (2002) before there was as much recognition of the need to treat for cyst forms. Don't know what his current thinking is, or whether he is still treating patients. And I don't know if these were chronic cases.

Not sure just which mix of pathogens he is treating with this protocol either. Might be differences geographically....Hungary different from the USA maybe... but there seems to be an unknown element or elements in treating tickborne diseases everywhere, plus patients can have a different mixes, known and unknown, even in the same geographic area.

Perhaps you have not seen enough patients treated with the cipro group of drugs to have come across the tendon problems yet, but they are real for some people.

jenbooks13 said...

Seems that if subclinical tendon "infection/invasion" of borrelia were the cause of cipro ruptures then other effective abx would also rupture the tendon, and they don't. There has to be some additional reason that has to do with quinolones themselves. Or you would be suggesting that cipro/levaquin etc are uniquely effective at killing borrelia in the tendons, which seems unlikely.

On another note--re: the Clongen bug. You seem to be in frequent contact with the lab, which is cool. I just had an idea (not a pleasant one, but anyway). There is news coming out next week that labs have id'd a unique microsporidia in c. elegans, which of course is the teeny worm that is researched in labs everywhere since it has a rudimentary nervous system etc. They've named it after the lab where it was just discovered and will now study it.

I've actually seen c. elegans once under the microscope and it's pretty (visited a lab that studies it).

Anyway, I then had the grossifying ;) thought that maybe the microfilarial worms in ticks are harboring these mystery bugs, and spewing them out as they spawn or die.

Can Clongen look at the tickborne microfilarial worms and see what they're harboring? Maybe Eva Sapi has the ability to do this in her lab. Maybe I will email her.

Yuck but maybe an important avenue of investigation. If it doesn't pan out it's a relief, but if it does, it's perhaps meaningful.

Thanks, if you think this is a worthwhile thought and wish to mention it to Clongen.

Michele said...

I know that Dr. B. used Cipro when treating a lot of chronic Lyme and he was successful. It is painful to think of all of the people, and we all know some, who are suffering with "fibromyalgia, chronic fatigue syndrome or other" and have been suffering for years because no one thought of Lyme disease. I guess my EM rashes and classic Lyme symptoms were both a blessing and a curse for me. The diagnosis could not be refuted but its a heck of a thing to get. We appreciate your efforts in providing individualized care to patients.

gale said...
This comment has been removed by the author.
jenbooks13 said...

Tyge, the news is embargoed until next week. At that point I can make a post here with some more details for you.

Seibertneurolyme said...

wildcat, -- flash discussion to help locate a doc.

Michele said...

Cipro tendon problems are real. I had been on Cipro a very short time before having serious pain, awake all night, with the tendons in my feet and hands. I had never had this before and there was no other change to explain it.

Shantih said...

My son's antibiotics have just been changed to Biaxin, Rifampin and Placquenil. An internet search states Biaxin and Rifampin shouldn't be taken in combination due to drug interactions. It's the weekend and I can't phone the doctor...any comments from anyone until I can? Thank you.

gale said...
This comment has been removed by the author.
jenbooks13 said...

Gale, email me at jenbooks13 at hotmail dot com.

Lyme report: Montgomery County, MD said...

Cipro may have exceptional penetration into certain soft tissue and joint related structures such as tendons. The ability of antibiotics to penetrate various tissues shows a great deal of variabiaity. The idea that the tendenopathy associated with quinolones has anything to do with occults infection within these tissues is strictly conjectural- thinking out loud- as it were. My observation is that 1) patients who have been other antibiotics tolerate quinolones better and 2) the tolerance to quinolones is better when a low dose is started and the dose is gradually increased. This theory is simply tossed out as a theoretical explanation of the anecdotal clinincal observation. It must be stressed that very little is known for certain about controversial issues related to therapy for these controversial disorders. There is no research. There is no scientific evidence. Unfortunately, doctors and patients must rely on anecdotal data and best guesses based on scientific principals. Please keep this in mind when various theories and ideas are discussed.

On the other hand, there is no scientific evidence to refute this hypothesis. Medical science simply reports that quinolone use is associated with tendon rupture. No explanation is offered.

Lyme report: Montgomery County, MD said...

Drug interactions: This is a potentially serious problem. It is important to research what the interactions might be. If for example, the blood level of one drug may be slightly decreased it may not be important. If the level of the other (Rifampin)- in this case is increased, then the treating physician should know to decrease the dose of this drug.

Patients with Lyme are frequently on a plethora of drugs and antibiotics. The risk of drug interactions must always be kept in mind. Much of this has to do with the enzymes which degrade and eliminate the drugs through the liver. Biaxin is a very effective drug but is notorious for drug interactions. It interacts with Rifampin and Diflucan and can affect cardiac conduction. It also interacts with Zocor which many patients take for high cholesterol. Zithromax is less effective but it is "cleaner"- with less drug to drug interactions.

There are computer programs which sort out drug interactions. It is very prudent for patients to get all their medications from the same pharmacy. Pharmacists routinely check for these interactions and much better versed in them than physicians.

jenbooks13 said...

On cipro--please don't stop your speculations. They are really interesting for unlike 98% of doctors you have retained a scientific mind and curiosity. Even if ya use a lotta drugs! ;)

On drug combos, good point.

On your new post today, you may not be interested in this, but Martin Milner is an ND with a specialty in pulmonary medicine; anyway, he has pioneered a bleeding time test in the office. So you can probably test your patients for hypercoagulation ahead of time. If they do have it, then the question is what you want to use. You might want to use heparin; many naturopaths try to avoid drugs and use other effective fibrinolytics.

jenbooks13 said...

For tyge/gale--thanks for reminding me--might as well post it here. I am probably off base in this idea but perhaps it is worth pursuing. It occurred to me that if those with "refractory" TBI have microfilarial infections and the worms harbor a pathogen such as microsporidia or whatever this Clongen bug is, that they would of course relapse off abx, because they have not taken any drugs to kill the worms. I don't know a lot about drugs for worms but I do recall the occasional startling report of a lymie who would feel completely 100% better after taking a drug commonly prescribed for worms, the name of which I am forgetting. What if the worms happily went through their lifecycles, and each time they died off, they released more of the bacteria? The bacteria of course would be protected from abx penetration by the worms themselves, and the worms would not be killed by the abx. Well it's just a thought.

Discovery of microbe in roundworm provides animal model for 'emerging pathogen'
Press release from PLoS Biology

Microsporidia are single-celled parasites that are capable of causing infections in humans - primarily people with compromised immune systems, such as those infected with HIV or who have undergone organ transplants. An article in this week's issue of PLoS Biology documents a newly discovered species of microsporidia, which infects C. elegans, the round worm used as a model system by developmental biologists. The work, undertaken by a team of French and American scientists led by Professor Frederick Ausubel and Dr. Emily Troemel of Harvard Medical School, is a breakthrough for public health researchers who had been looking for a suitable laboratory model in which to study microsporidia.

"Microsporidia are classified as 'priority pathogens' by the National Institutes of Health, since they have been found in water supplies and because no drugs are available for treating the most common infections they cause in humans," said Emily Troemel, now an assistant professor of biology at UC San Diego. "The new species we discovered, which infects C. elegans, a small roundworm that is very easy to study in the lab, provides a powerful system in which to study these mysterious microbes, learn how animals respond to infection and develop new drugs to fight infections of microsporidia."

"The discovery is particularly exciting because it potentially offers a unique opportunity to identify new drugs for treating human microsporidian infections," said Professor Ausubel.

The researchers named the new species of microsporidia Nematocida parisii, or "nematode killer from Paris," because it was discovered in the intestines of roundworms found in Parisian compost pits. Authors Marie-Anne Félix and Antoine Barrière initially isolated the infected worms and sent them to Emily Troemel, then a postdoctoral fellow working in the Ausubel laboratory, to determine the nature of the pathogen. Since then, the scientists have found closely related naturally-occurring pathogens in Portugal and India, leading them to conclude that they are widespread natural parasites of C. elegans.

"C. elegans has been a 'lab rat' for scientists for decades. It has intestinal cells that look almost exactly like human intestinal cells, so we're able to tell what these parasites are doing to intestinal cells as they're invading and exiting the cells," said Troemel. "And because these worms are completely transparent, we can take intact worms, put them on a slide and see what's happening. We've already seen some interesting changes in the structure of intestinal cells during different time periods of infection."


Citation: Troemel ER, Felix MA, Whiteman NK, Barriere N, Ausubel FM (2008) Microsporidia are natural intracellular parasites of the nematode Caenorhabditis elegans. PLoS Biol 6(12): e309. doi:10.1371/journal.pbio.0060309

Michele said...

jenbooks13: Remind me. Do/did you ever even have Lymes disease or any of the associated diseases? You don't speak like someone who really has any intimate, personal knowledge of any of the diseases like a patient would; just someone who must have a lot of time on their hands, does research, thinks they are smarter than the docs and just a wanna be. Do you have chronic Lyme? Symptoms? Please keep reply's short so others can be heard. Wow that last one is long. Lets be considerate O.K. Thanks.

jenbooks13 said...

Yes, I unfortunately walked in a garden in coastal Connecticut on June 6, 2000 and exactly two weeks later had a five inch bullseye on the back of my knee, a stiff neck and a low grade fever. Classic signs. Had sky high elisa, positive western blots from Stonybrook etc. Did antibiotics (oral, two weeks, and then four weeks) and only got sicker. Some of it was herxheimer and some of it was drug toxicity as I am very sensitive to drugs and always have been. Horrible fungal issues, horrible diarrhea, stuffed up ears (fungus) bla bla bla. Had a terrible case of lyme/babesia and was afraid I would be in a wheelchair or die because I was so ill. Then I assembled bit by bit, my alternative med protocol which has not cured me but got me back on my feet. I fought for my life with every bit of strength and grit and intelligence I could muster, no matter what, and I know the whole territory very well. I also am very well educated and have a lot of friends who are practicing doctors. Sorry if my posts bug you, I don't intend them that way.

Michele said...

jenbooks: Seems as though they "bug" no pun intended a lot of people. You and I have similiar Lyme stories it is just that I act as a patient and am both a patient and a doc (MD) and like to hear from the docs with the expertise in the trenches seeing about 100 patients/day not reading books all day. They are the ones with the knowledge base They have the expertise. Not you. Repeat that. You don't ask questions. You answer everyone's. You critique the LymeMD and how he may have treated a patient or a diagnosis. You think of yourself as brighter, more up to date than the docs yet you are not. You the worst kind of patient, the Monday morning quarterback. We see in hindsight pretty well. Be humble if it is in you. If you want to talk to another patient please say "hey ----, I had that. If you want to know what I did about it see ___________ give the link. Just look at the space you take up. Who could have the time. Well, I have patients to see.

Michele said...

Worse of all jenbooks, you have said things in the past, Monday morning quarterbacking Lymemd, that really made him feel bad. Please rethink your role here.

jenbooks13 said...

Commentary is commentary and it's the essence of the blogosphere and what brings it alive. All of it can only render his blog *more* interesting.

jenbooks13 said...

I want to add, sickofit, that suggesting first that I was not a lyme patient at all, and then by stating that I'm the "worst kind of lyme patient", seems like an attempt to invalidate the content of my posts by invalidating me.

What he's doing (putting himself out there very nakedly so to speak) is *quite* interesting but people will have opinions about it.

I absolutely agree there is nothing to substitute for extensive, hands-on clinical experience. I don't have that and would never venture to suggest or fathom which combo of drugs patients should be on, for instance. However, how and when does a patient decide to trust that "in the trenches" doc--without questioning and self-education? What if that in the trenches doc is a busy rheumatologist diagnosing a lyme patient incorrectly and prescribing steroids? Who gets the invisible halo of authority and why? It brings to mind the advice of Ronald Reagan in regards to treaties with Russia, "Trust, but verify."

*And* sometimes cures come out of the commonplace, so to speak. Consider the "work" of ordinary citizen John Franzius on cancer and radio waves which attracted the notice of University of Pittsburgh Medical Center, MD Anderson Cancer Center in Houston and Rice University initially and is now being seriously researched.

Thus openness to ideas, from any quarter, is a good modus operandi.

Lyme report: Montgomery County, MD said...

I have seen no evidence here to connect microsproridium to TBD.

It is a parasite which lives inside cells. It mostly causes GI symptoms. And infection generally only occurs in immunosuppressed patients.

Lyme does impact the immune system, but not to the level of HIV or anti TNF drugs used by rheumatologists.

I have not used albendazole. Other LLMDs have used it for Babesia- I thought. Perhaps they are treating something else.

No nematode has been associated with TBD either- at this time.

jenbooks13 said...

Thanks for the feedback. Please post when Clongen ID's the bug and agrees to let you post about it. It will be interesting.

Burgdorfer found six bugs in the tick gut in the 80's, including microfilarial worms. Eva Sapi also found microfilarial worms in recent work but has not published that part, I don't believe.

Whether they are meaningful who knows. I've wondered about reports of people getting sick every four weeks or so. Reminds me of parasite life cycles.

gale said...

As I was the one who brought up the microxporidia-thing I have to say- write here that I agree with you now and that it was probably a wrong hypothesis by some pathologists.- Sorry