Monday, December 15, 2008

Rapid Rocephin Relapse

I have been treated a 30 something year old female for disseminated Lyme and neuroborreliosis for over a year. Most symptoms cleared up with oral meds. The cognitive issues stubbornly refused to budge. This patient interestingly also developed a tremor with features of Parkinson's disease. The Rocephin took a while, but after 8 weeks started showing some very positive effects. Memory, brain fog, word retrieval, cognitive processing speed and tremor all improved. Antibiotic therapy was interrupted because of an unrelated medical problem. She did OK for two weeks; during week 3 off Rocephin she experienced a precipitous decline. All the target symptoms mentioned above rapidly returned. She even developed joint pain which had been absent for months. What happened? I am sure this patient is tired of me thinking out loud every time I see her. Where there is no science, I have to logically figure out the process and make therapy decisions based on working hypotheses.

Obviously we restarted the Rocephin right away- but what else, and why?

I had tried Zithro with the Rocephin earlier in the course but after 6 days it was stopped because of side effects (nausea and vomiting- I think).

Why does the disease reactivate so quickly and so aggressively. It is like I whacked a hornet's nest with a baseball bat. As long as I was batting away the hornets stayed in their nest. As soon as I stopped whacking, they came out madder than Hell.

It can't be a Herx reaction. The meds were removed. A reverse Herx? Of course not.
The spriochetes couldn't have grown and spread that quickly. They are very slow replicators- it takes a long time for them to reproduce and invade new tissues.
Is it due to an inflammatory or autoimmune response? Maybe. It is known that Rocephin has some anti-inflammatory neuroprotective effects. Could removing it quickly cause rebound inflammation and/or autoimmunity? Interesting- doesn't pass the sniff test.

Let me put this phenomenon together with something I recently read. Intracellular bacteria cause minimal pathological effects. That's interesting. Perhaps when the Lyme bacteria convert into L-forms and disappear into the cellular cytoplasm they cause less overt disease/symptoms. This is the opposite of what many Lyme experts have claimed, but maybe they are wrong. Many antibiotics like Biaxin and Zithromax can kill Lyme in both the L-forms and the spirochete forms. One thing we know about Rocephin is that it only kills spirochetes forms, leaving L-forms (intracellular) unscathed.

A picture appeared in my mind. I could imagine Rocephin molecules zipping down the blood stream like speeding cars on the Autobahn. Any Lyme (spirochetes) in the way would be wiped off the road instantly. The Lyme germs would have to respond quickly if they were to survive. Quickly they converted into cysts and L-forms and slipped into cells. The Rocephin would clear the blood stream and its surrounding watershed of cell wall possessing spirochete forms. Lyme in its other forms was safe.

Where does this leave us? Autoimmunity? Rocephin doesn't destroy auto-antibodies. Could there be increased inflammation with cytokines and cellular destruction? This could only occur if Rocephin has a very potent immune suppressing effect like a steroid or immunomodulator like an anti TNF drug. There is nothing in the literature to suggest that Rocephin has such properties. If it had a potent immunomodulating effect then benefits after treatment should occur quickly. Usually, the benefits of Rocephin are not seen for several weeks.

Maybe the signs and symptoms associated with Lyme neroborreliosis are mediated almost entirely by intact- motile spirochetes. Rocephin is strictly clearing these forms from body fluids and tissues.

When you take away the Rocephin what happens? The L-forms and cyst forms (metaphorically) duck there heads out from their hiding places. They put a toe in the water to check the temperature. All clear. Party time for spirochetes. It is the rapid release of spirochetes into tissues and fluids which causes the immune response and clinical disease. That is my best hypothesis. Hopefully you followed the logical chain which got me there.

Wasn't there a study showing that Amoxicillin alone controlled symptoms in chronic Lyme? Yes. Perhaps it has always been about the spirochetes after all. The cysts and L-forms were just put there to make it impossible to kill the bastards (pardon my French).

Getting back to the patient. Not having the luxury of time as I put my thought together in this piece I made an executive decision: I started Rocephin and IV Flagyl. The Flagyl should help one mechanism of escape. Before I take her off Rocephin I will have to close the other door as well. If she couldn't take Zithromax, another anti-L-form therapy will be needed. The possibilites include Biaxin, Doxycyline, Minocycline and Cipro.

11 comments:

dogdoc said...

Makes sense... except, why would initial response take 8 weeks then? Wouldn't they "run away" quickly reducing clinical signs in that model?

If this was the case- can we use it clinically to enhance killing efficacy with Rocephin in brain and other cw antibiotics in rest of body? ie when we restart, we have a whole new population to hit. A percentage should die before being able to convert each time.

Also, could we "catch" them- ie have on cyst and l-form drug before Rocephin is started so nowhere to run? However, we do that too and it isn't a magic bullet either.

Mino if you are trying to get into cns in latter choice makes most sense.

jenbooks13 said...

The posting of cases is fascinating.

A few quick thoughts. Could there be a connection with glutamate and rocephin. If glutamate levels were rapidly altered by rocephin then on withdrawal perhaps it could cause severe symptoms. (I have thought this before and now I see the invisible angry eye of your colleague sickofit glowering upon me saying I have too much time and must defer to the expert in the trenches but no, I'm just posting what I think already and have thought for a while and a quick google of rocephin/glutamate for instance instantly turns this up:

http://www.google.com/search?hl=en&rlz=1B3GGGL_enUS177US226&q=ceftriaxone+glutamate&btnG=Search

I know of one patient bedridden and doing horribly on every abx approach. Her husband felt she was near death. She was put on microdoses of rocephin (if I recall, something like 75 mg a day?). And she slowly, steadily began to improve, and return to life, and within a few months was on a plane to visit her daughter. I don't believe she was by any means *well* but apparently she said, if this is all I ever get, I'll take it.

So there is a lot of mystery to rocephin and what it does in TBD. Also how do we know that an antibacterial only impacts bacteria? Perhaps it is also antiviral and we don't even know that. It seems to me viruses could proliferate rapidly when not suppressed.

dogdoc said...

I think doc was illuding to the glutamate activity when pointing out the effect took 8 weeks to start. If glutamate overexcitatory suppression was creating the effect and then rebound, it should have occurred right away.
Thats the first time I've heard of Rocephin being used in homeopathic doses.
I think you are very correct in that we assume we know the effects of the drugs that we are using and that we do not. Antibiotics have varied immune and nonantibacterial effects. When we see improvement, we do not know why that improvement is occurring.

lymie said...

TB is intracellular and does produce symptoms from that location. It has a long generation time also. Is more often latent than an actual case of disease. Maybe we should be looking at other intracellular pathogens to learn something about borrelia.

girl mark said...

I thought there were some conclusions drawn from Fallon's Columbia U study about the rapid relapse of some patients' neuro symptoms. If I recall correctly, it was still a relatively short course, and the same patients experienced permanent (?) improvement in their other non-neuro symptoms such as fatigue.

I think I recall that either in the study itself, or other analyses of it from the pundits (perhaps in Cure Unknown?), someone draws a conclusion that it's one of the antiinflammatory effect of the Rocephin that caused the rapid relapse- ie that with that length of treatment in those particular patients, it wasn't that it had eradicated the spirochetes in the CNS, but that the other side effects of the drugs had a positive effect of symptom relief.

Did your patient's joint pain return as rapidly as the cognitive dysfunction? Does that suggest anything?

jenbooks13 said...

Hi dogdoc, you're right there seems to be something lopsided about 8 weeks to improvement and fast relapse on removal. OTOH, if neurons were in an inflamed state because of chronic neurotoxicity, shifting glutamate expression might take just about that long for neurons to calm down un-inflame ;), and yet, sensitized as they are, relapse quickly.

One curious thing is that benzodiazapenes modulate some TBD symptoms and I still recall one guy who claimed he could head off a lyme-migraine with a little Valium.

Claire said...
This comment has been removed by the author.
Claire said...

Interesting post. The same thing happened to my daughter. She was on Rocephin for 6 weeks, had progress, went off due to a PICC line problem, and within 2/3 weeks had almost all of her symptoms back!

Dr. Burrascano has said that IV Rocephin suppresses Bartonella (or "BLO"), but does not eradicate it, he said in his experience, a quick relapse after IV Rocephin is due to Bartonella/BLO, since like you said, Borrelia burdorferi is slow growing.

Lyme report: Montgomery County, MD said...

The effects of Rocephin on glutamine are well known. The inflammed brain becomes sensitized to gluatmine. I have mentioned this in the past. The problem is that symptoms unrelated to brain-Lyme can also return in a rebound like manner. For example, in this patient joint pain also returned.

The Bartonella theory doesn't sell with me. Perhaps the unknown bacteria- a pseudomonas like organism my be the issue. I am not sold on this either. Patients taking 2 grams of Rocephin daily- for months, have had blood smears/stains with legions of motile bacteria unimpeded- no suppression there.

Bb like all spirochetes is slow growing. It takes about 24 hours (this number is open to debate) to replicate. For comparison's sake, Strep bacteria replicate in 20 minutes.

An army of new spirochetes is not appearing in 3 weeks.

Most patients, including this one, have been on many months of anti L-form/cyst form therapy before starting Rocephin.

The more you know- the more you realize you don't know anything.

A famous Greek philosopher said- I don't recall his name and I am paraphrasing: One of the most pathetic things about man is not only that he knows nothing(while believing he is well informed), but that he can't even begin to imagine the vast scope of his ignorance-
even when he does have the insight that he is woefully ignorant.

jenbooks13 said...

LOL that's some paraphrase.
Perhaps Socrates, who said his wisdom was limited to an awareness of his own ignorance.

I admit I am unwisely procrastinating now and must get to work already. Bad on me.

bugged said...

Why then is Rocephin the IV drug of choice for doctors when it comes to using IV antibiotics? Also, why was it thought that the L form, the hardest to treat, posed the greatest problem?