Long-term treatment with antibiotics and sensitivity

[deleder2k]

Has anyone read "Prolonged antibiotic therapy in PCR confirmed persistent Lyme disease" ?

Wolfgang Klemann, MD, PhD
Bernt-Dieter Huismans, MD, PhD
Stephan Heyl, MD, PhD
Abstract: We examined a sample of 90 individuals that had previously received a
course of appropriate antibiotics for Lyme disease without experiencing full
resolution of their symptoms and had evidence of persistent infection documented
by PCR analysis.


Mean duration of symptoms was 9.5 years (range 1 - 40 years). The treatment
was adapted to the individual case according to clinical response. Long term
antibiotic therapy was initiated and patients were treated continuously for at
least 6 months, in some cases several years of intermittent therapy was administered.


About 38,8% of the patients experienced full remission of symptoms while about
56,7% reported a significant improvement, 5,6% of patients were deemed
refractory to therapy. Therapeutic modalities are discussed in detail.
Key words: persistent Lyme disease, Borrelia PCR, long term antibiotic
treatment, lyme serology, Borrelia DNA


Key issues:
·
All study patients were Borrelia- DNA positive
·
Commonly reported symptoms included fatigue, muscolo- sceletal and
neuro-psychiatric complaints
·
Only about 42% of patients had a history of an erythema migrans
·
Serologic testing is fairly insensitive in late disseminated lyme disease
·
Antibiotic treatment must be tailored to the individual clinical response in
late disseminated lyme disease
·
The majority of patients benefited from long term antibiotic treatment
·
Recurrence of symptoms was common during treatment
·
Long term antibiotic therapy was generally well tolerated

While the study called "Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease" concluded completely different.. http://www.nejm.org/doi/full/10.1056/NEJM200107123450202

BACKGROUND

It is controversial whether prolonged antibiotic treatment is effective for patients in whom symptoms persist after the recommended antibiotic treatment for acute Lyme disease.



METHODS

We conducted two randomized trials: one in 78 patients who were seropositive for IgG antibodies to Borrelia burgdorferi at the time of enrollment and the other in 51 patients who were seronegative. The patients received either intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching intravenous and oral placebos. Each patient had well-documented, previously treated Lyme disease but had persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue. The primary outcome measures were improvement on the physical- and mental-health–component summary scales of the Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) — a scale measuring the health-related quality of life — on day 180 of the study.



RESULTS

After a planned interim analysis, the data and safety monitoring board recommended that the studies be discontinued because data from the first 107 patients indicated that it was highly unlikely that a significant difference in treatment efficacy between the groups would be observed with the planned full enrollment of 260 patients. Base-line assessments documented severe impairment in the patients' health-related quality of life. In intention-to-treat analyses, there were no significant differences in the outcomes with prolonged antibiotic treatment as compared with placebo among either the seropositive or the seronegative patients.



CONCLUSIONS

There is considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease. However, in these two trials, treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo.

How could two trials like this end up with a completely different result? I know they are different in design, but how could the studies end up with two completely different conclusions?

I am also wondering what the sensitivity is for Western Blot and Elisa.

CDC says:

You may have heard that the blood test for Lyme disease is correctly positive only 65% of the time or less. This is misleading information. As with serologic tests for other infectious diseases, the accuracy of the test depends upon the stage of disease. During the first few weeks of infection, such as when a patient has an erythema migrans rash, the test is expected to be negative.

Several weeks after infection, currently available ELISA, EIA and IFA tests and two-tier testing have very good sensitivity.

It says that 65% sensitivity is misleading, but how much is it? I've heard 95%, but that information was not from the CDC

 

[xrunner]

It's usually in the details.

I could not read the first paper but I noticed a couple of things:
1.treatment was tailored based on clinical response
2. treatment went on continuously for at least 6 months (I guess much longer than that)

The other trial concluded against "long-term" abx treatment but after only 3 months
which consisted of 30 days of iv ceftriaxone followed by 2 months of 200mg of doxycycline.

Having being treated for three years on and off I know that, for the purpose of treating a disseminated Lyme, 30 days of ceftriaxone are nothing whilst 200mg daily of doxycycline are ineffective (in my case it worked at 400mg).

For results I think you need more effective treatment protocols, eg. combinations of abx based on individual response, also considering possible co-infections, and a longer treatment plan which seems what they did in the positive study.

 

[Aerose91]

It seems treatments that are successful are so far and few in between. Who are the doctors who are giving the correct and successful doses of antibiotics and seeing some people have complete recovery?

My current doctor is against all antibiotic therapy which makes me nervous. Even though I know they are toxic for you in the cases of late stage Lyme it seems not only necessary, but imperative.

 

[Valentijn]

It says that 65% sensitivity is misleading, but how much is it? I've heard 95%, but that information was not from the CDC

Funny how they don't cite to anything regarding their own statements, or even provide an actual number. Just ... "It's not 65%". They're also referring to the sensitivity of two combined tests, instead of one. I'm not sure how they'd be calculating that, exactly.

 

[deleder2k]

It seems treatments that are successful are so far and few in between. Who are the doctors who are giving the correct and successful doses of antibiotics and seeing some people have complete recovery?

My current doctor is against all antibiotic therapy which makes me nervous. Even though I know they are toxic for you in the cases of late stage Lyme it seems not only necessary, but imperative.

If your current doctor is against all antibiotic therapy I would go see another doctor.

 

[Jonathan Edwards]

Has anyone read "Prolonged antibiotic therapy in PCR confirmed persistent Lyme disease" ?

While the study called "Two Controlled Trials of Antibiotic Treatment in Patients with Persistent Symptoms and a History of Lyme Disease" concluded completely different.. http://www.nejm.org/doi/full/10.1056/NEJM200107123450202

How could two trials like this end up with a completely different result? I know they are different in design, but how could the studies end up with two completely different conclusions?

I have not looked at the papers in detail but are the results in fact different? Maybe in the controlled trial the percentage improvement was the same - but the same in the placebo group too? Probably not, but if the first study is not blinded and controlled the results are effectively meaningless - just like PACE. Judging by the way it is written and the bad arithmetic (about 38.8 + about 56.7 + about 5.6 = about 101.1) I would not have much confidence in it anyway.

I am also wondering what the sensitivity is for Western Blot and Elisa.

CDC says:
It says that 65% sensitivity is misleading, but how much is it? I've heard 95%, but that information was not from the CDC

I think you have to consider these figures in terms of sensitivity to predict that you already know that the patient has definite clinical Lyme disease. If the history does not provide definitive diagnostic evidence (which will be the case for nearly all ME/CFS sufferers) I doubt the figures are helpful. Unless there is some other way of proving infection at a late stage, and I think the whole point is that there isn't, then there is no way of working out how sensitive an antibody test is.

 

[Aerose91]

If your current doctor is against all antibiotic therapy I would go see another doctor.

Are abx something that should be done asap or is it more important to get the toxicity down first? I.e. PC therapy and methylation. I don't know if the clock is ticking on the effectiveness of antibiotic therapy.

 

[justy]

Are abx something that should be done asap or is it more important to get the toxicity down first? I.e. PC therapy and methylation. I don't know if the clock is ticking on the effectiveness of antibiotic therapy.

Havent you had a positive Lyme test? I thought I saw you had. In which case then It would seem appropriate to treat that as soon as possible. I think most people with Lyme have at least 1co infection - they are difficult to test for.

Dr Horowitz is taking patients and Dr Jemsek -I believe he is in Washington and from what I have read he has very good success rates, but treats very aggressively. Dr H looks at biotoxin illness as well as bacterial load. There is a lot of good info out there onm the Lyme forums etc - I am meeting a lot of people misdiagnosed with M.E when they really had Lyme undiagnosed and many are improving or getting better with various treatments - oral and IV abx, Herbals, homeopathy, Rife etc.

 

[deleder2k]

Are abx something that should be done asap or is it more important to get the toxicity down first? I.e. PC therapy and methylation. I don't know if the clock is ticking on the effectiveness of antibiotic therapy.

I really don't know. I just meant that if you have GP that refuses all antibiotic treatment for diseases you definitely get it for (like pneumonia), I would see another doctor.

 

[Aerose91]

Havent you had a positive Lyme test? I thought I saw you had. In which case then It would seem appropriate to treat that as soon as possible. I think most people with Lyme have at least 1co infection - they are difficult to test for.

Dr Horowitz is taking patients and Dr Jemsek -I believe he is in Washington and from what I have read he has very good success rates, but treats very aggressively. Dr H looks at biotoxin illness as well as bacterial load. There is a lot of good info out there onm the Lyme forums etc - I am meeting a lot of people misdiagnosed with M.E when they really had Lyme undiagnosed and many are improving or getting better with various treatments - oral and IV abx, Herbals, homeopathy, Rife etc.

I had one band pop up for Lyme under LabCorp, then did a more aggressive test (Stoneybrook) and that came back negative. Another quest test came back negative then most recently a quest test popped for 2 bands (39 and 41). I haven't been able to afford the IgeniX test so that's all I'm working from. I really have no idea what to think. However I am working with a couple doctors right now, one is really well versed in methylation and the other is Dr Enlander- he does do IV antibiotics.

 

[Dufresne]

How is it we're reading this first study and talking about the sensitivity of serological testing? This Zecklab in Germany is apparently confirming infection by PCR of skin biopsies. It's in the title of the study. And this was published in 2011.

http://www.grin.com/en/e-book/16617...firmed-persistent-lyme-disease#preview_footer

I must be having a bad brain day and missing something. Why is this not replicated or proven false four years later? Why haven't we heard about this?

I did a search over at Lymenet for "Zecklab" and came up with nothing.

Does anybody know this lab's reputation?

 

[msf]

'Unless there is some other way of proving infection at a late stage, and I think the whole point is that there isn't, then there is no way of working out how sensitive an antibody test is.'

I think Prof. Edward's point is a very important one, but there are two sides to it. First of all, this isn't entirely true, as there are new methods (controversial, of course) for confirming Lyme . But if you accept that is currently no way of proving that someone is infected with Lyme, then this has implications for both sides. It means that it is impossible to have total confidence in any claims that a new test is more reliable than an old test, but conversely, it means that it is also impossible to have total confidence that the opposite is the case.

This means that patients should be wary of both those who claim that the new tests are reliable, and of those that claim that the old tests are infallible. This absence of certainty means that there will continue to be patients (and doctors) who are willing to entertain the idea that the old tests might be fallible, and who, moreover, are willing to undergo treatment for Lyme after testing positive on these new tests.

I hope that this it is soon no longer necessary for patients to make these judgments themselves, but I am sure that the process of proving Lyme infection by culture will be just as controversial as the process of proving it by antibody tests has been.

I think it would be more helpful for patients if doctors and researchers were more honest about the limits of their current tests/knowledge, but the adversarial, competitive nature of modern medicine and research means that this is unlikely to happen.

 

[optimist]

(about 38.8 + about 56.7 + about 5.6 = about 101.1)

YES! When having been raised by a mom who when she's certain, is always 110% certain, 101.1% seem a bit low.

 

[Daffodil]

why isn't everyone getting the LTT ELISPOT Borrelia test instead of guessing with Igenex etc.?

 

[heapsreal]

Is sinusitis a common symptom with lyme?
I ask this as i feel alot better on abx for sinusitis and this stops the post nasal drip and severe frontal sinus headaches. I often wonder if it could be lyme. Or sinusitis is just another cfs/me co-infection due to a crappy immune system??

 

[cigana]

Is sinusitis a common symptom with lyme?
I ask this as i feel alot better on abx for sinusitis and this stops the post nasal drip and severe frontal sinus headaches. I often wonder if it could be lyme. Or sinusitis is just another cfs/me co-infection due to a crappy immune system??

Yes it is common with Lyme but the problem is, so is everything else! It's almost impossible to distinguish....
The good news is though at least you understand it might be bacteria related since it responds to abx in you.
Of course sinus problems are classic with mold, so imo you should seriously look into the possibility of current or previous exposure to damp in your living/work environment.