So, let me talk a little bit about treatment, you have heard a little bit about antibiotic therapy for Lyme Disease. The range of antibiotics that are useful for this disease continues to expand and the usefulness of different combinations also continues to expand and basically it is the principles of antibiotic therapy. This is something that probably is useful. Generally, oral antibiotics are useful for musculoskeletal Lyme Disease or disease which is primarily musculoskeletal. In contrast, intravenous antibiotics are more useful for patients with neurologic Lyme Disease and, as you have heard, prolonged treatment may be necessary to treat Chronic Lyme Disease, and also it is important to rotate therapies in order to avoid getting resistant bugs that may not respond any more to treatment that you have been using for some time.
In terms of oral antibiotics, there is mono therapy and also combination therapy.
With intravenous antibiotics, there are daily intravenous regimens, and also staggered regimens that are becoming more popular now.
And finally there is a third approach, which is using intramuscular Penicillin which is kind of the old way to treat Lyme Disease which you know fell out of favour because intravenous therapy was less painful but the fact is that intramuscular Penicillin is coming back into style because it is very hard to get intravenous therapy in some places and also the intramuscular Penicillin seems to work for neurologic Lyme Disease.
So in terms of oral mono therapy: Doxycycline and Minocycline and also Tetracycline have been the primary means of treating this disease. These drugs have very good tissue penetration and they also cover Borrelia and Erhlichia. Interestingly, both of these drugs have anti-inflammatory properties which is why they are also used in patients with rheumatoid arthritis because in addition to their antibiotic therapy they also decrease inflammation from joint disease so that is another useful aspect in Lyme. Unfortunately, they can also cause significant photo - sensitivity and intestinal upset and that has limited their use. In San Francisco, when I have patients on high dose Doxycycline, they often come in with what I call Doxy Knuckles and that is because everybody in California loves to drive cars so they are out driving their car and they get this rash along their knuckles where their hands are on the steering wheel so, yeah, that is a very typical give away.
Other mono therapy agents, Amoxycillin and Augmentin are less effective in general against Chronic Lyme Disease but they do have less side effects and are more tolerable and also they are cheaper than other agents so they are also used especially with children.
Now, combination therapy has evolved over the last few years. The principle of combinations is generally to use a macrolide such as Clarithromycin or Azithromycin combined with something like a Cephalosporin such as Ceftriaxin and more recently Omnicef. The idea being that these are really synergistic antibiotics, the Cephalosporin gets into the cell and kills the bugs in the cell whereas the macrolide works outside the cell and can kill the bugs when they come outside the cell. In particular, Omnicef with Biaxin or Zithromax has become a very, very effective treatment for Chronic Lyme Disease and this should probably be the treatment of choice for patients who have primarily musculoskeletal disease except for the fact that they are relatively expensive and that’s limited their use over Doxycycline.
Another combination that you heard about this morning, is the combination, again, of a macrolide plus Metronidazole or Flagyl. As you heard Flagyl kills the spore forms of Borrelia and again the reason for using this combination is that Flagyl gets into cells and can kill the bugs in the cells but it has no activity outside the cells so you need something else to go with it such as a macrolide to kill the bugs when they come out of the cyst form and get outside the cell. There are some side effects such as GI upset and neuropathy from Flagyl, and Flagyl interestingly can give these prolonged Herxheimer reactions that can be very difficult for patients. You are not just getting a Herxheimer reaction (I haven’t talked about that much) but you are not just getting it for a few days you are getting it for weeks and you have to sort of deal with that and say look, this shows that the drug is working, and you have to bear with it, and often after patients go through that, their symptoms improve.
Intravenous antibiotics are listed on this slide. Ceftriaxone or Rocephin is still the standard intravenous therapy for neurologic Lyme Disease. It’s convenient, its once daily dosing, it gets very good CNS penetration and the question was asked before well maybe why would this cure cysts? Well, you are getting such high levels in the central nervous system that you may be actually affecting the cysts even though the drug doesn’t directly cure them and also the cysts can’t stay in the cyst form forever so when they transform into another form the Ceftriaxone may be killing them. It does have a gall bladder toxicity which has been a problem but not an insurmountable problem.
An alternative intravenous treatment is Cefotaxime or Claforan and this is less convenient, it has to be dosed twice a day at least and it can cause the same kind of liver toxicity interestingly although people think that it doesn’t.
Intravenous Doxycyline is extremely effective against neurologic Lyme Disease but unfortunately it has a prolonged infusion time about four hours a day and it also tends to cause more of the sun sensitivity than the oral Doxycycline so side effects have been a problem.
And more recently, intravenous Azithromycin or Zithromax has also been used. It is also convenient with once daily dosing but we have limited experience of that at the present time.
Adjunctive Therapy – there are some other medications which are helpful for the symptoms of Lyme Disease and I think it is important to treat the symptoms of this disease because patients come in with a symptoms list that Dr Donta showed you and they are very, very unhappy and very miserable with that, and while you are waiting for the antibiotics to work I think it is important to try to control those symptoms to make people more functional and a little happier.
So, one thing that has been very useful is the older anti-depressants such as Amitriptyline and Nortriptyline which are interesting because for a depression they are used in the doses of about 100mg but Lyme Disease patients tend to be exquisitely sensitive to these drugs. I went to a conference up in Northern California and there were a bunch of Lyme patients there who were talking about their Elavil and how they would sort of grind the Elavil up into these little pieces and sprinkle some on their tongue and then they would be knocked out for another whole night and so there is this exquisite sensitivity to these drugs that is very useful for improving sleep and also for pain control because it helps with neuropathy.
Another group of drugs that is very useful is the Cox-2 Inhibitors, the longer acting anti-inflammatories such as Celebrex, Mobic, Vioxx (NB Vioxx and Vioxx Acute were withdrawn on the 1st October 2004 due to increased risk of confirmed thrombic events) and others. These are also good for controlling musculoskeletal pain mostly because they are long acting so you don’t have to keep popping an ibruprofen every five minutes but you can take one of these and it works for a whole day and also there is less intestinal problems with them.
Now, you have heard a little bit about vitamins and minerals, supplements, and I am not going to get into that. These probably do have their place in treating the disease but I think at this point they are pretty much unproven and some of them are fairly expensive and we can talk about that later.
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