Saturday, May 28, 2011

4 Repost: Lyme Disease & Antibiotics: More Than Skin Deep

This is a repost from Thursday evening's Daily Kos.

Alexander Fleming discovered the first antibiotic, penicillin, in 1928. After the first clinical trials of antibiotics in the 1940s, they transformed medical care and dramatically reduced illness and death from infectious diseases.

I have to wonder if Alexander Fleming ever realized just how many purposes would be found for antibiotic use in the future - and if he would have ever predicted that their use would generate controversy.

A central controversy in treating people who have persisting symptoms of Lyme disease is whether or not they should receive more than three weeks of antibiotics to treat their condition.

And my question about this is why not treat them with longer courses of antibiotics if that is what is needed? Why is this such a big deal?

There are plenty of situations for which long term treatment with antibiotics is warranted. The most well known are tuberculosis (often treated for 9-12 months, sometimes longer) and Hansen's disease (leprosy, often treated for two years).

While I state upfront that overuse of antibiotics is not something I advocate - and use of antibiotics in general can lead to not only resistance but risk of acquiring secondary infections such as C. difficile - in a number of cases the benefit of taking antibiotics outweigh the risks.

That said, is there any hard and fast rule in the medical profession as to which conditions will be treated with antibiotics and for how long?

Let's look at a few conditions for which long term antibiotics have been used and studied.

For example: Acne.

What kind of treatment do patients with acne receive, and why do they need antibiotics in the first place? Let's take a look at that...

Antibiotic Use for Acne

Heather Brannon, MD, wrote that "Acne is caused by the effects of hormones on the pilosebaceous unit, consisting of a hair follicle, sebaceous gland, and a hair. The follicle becomes obstructed and an overgrowth of a normal skin bacteria, Propionibacterium acnes, causes destruction of the lining of the follicle. This process allows follicular material to enter the dermis, causing an inflammatory response." [1, 2]

Antibiotics work by several mechanisms. The most important is the decrease in the number of bacteria in and around the follicle. Antibiotics also work by reducing the irritating chemicals produced by white blood cells. Finally, antibiotics reduce the concentration of free fatty acids in the sebum, also reducing the inflammatory response.

Antibiotic Treatment For Acne

Tetracycline is the most widely prescribed antibiotic for acne, and 500 mg twice a day is used continued until a significant decrease in acne lesions is seen. The dose can then be decreased to 250 mg twice a day or discontinued.

Erythromycin varies with the type used, but it is typically prescribed as 250 - 500 mg twice a day.

Minocycline has been used effectively for decades as a treatment for acne. It is especially useful for pustular type acne. The usual starting dose is 50 to 100 mg twice a day.

Doxycycline is prescribed for 50 - 100 mg twice a day, and is often used for people who do not respond to or cannot tolerate erythromycin or tetracycline.[2]

So, you've got a good idea which dosages of what kind of antibiotics are used to treat acne.

Duration of Treatment For Acne and Risks

Some patients find they can improve their acne with oral antibiotics for 2-3 months to start, then decrease the dosage as they add a topical antibiotic for treatment. In some cases, oral antibiotic treatment must be extended for an additional 3 months or longer, depending on the patient's response to treatment.

Concern over the risk of long term antibiotic use for acne sparked some studies, which have mixed results:

  • A large study conducted by the British Journal of Dermatology studied 4274 acne patients and found that since 1991 an average of 51% of patients harbored colonies of resistant bacteria. Other studies have shown similar levels of antibiotic resistant acne bacteria. Interestingly, researchers are finding similar levels of resistance in both patients treated with antibiotics and those untreated as well, although those untreated have somewhat lower levels of resistance.[3]
  • There have been concerns that people who use antibiotics to treat their acne have a higher incidence of upper respiratory tract infections, however, followup studies have challenged that concern.[4]
  • A recent study has also shown that treating acne with antibiotics does not lead to antibiotic resistance: "Prolonged use of tetracycline antibiotics for the treatment of acne does not lead to increased antibiotic resistance, according to a study published online April 11 in the Archives of Dermatology." The study is specific to 3-4 months of tetracycline use, however, and other antibiotics like clindamycin and erythromycin show resistance after a couple months' use in patients.[5]

Clearly, more research is needed - but based on these studies, it at least looks like a draw, leaning somewhat towards "it depends on which antibiotic is used".

If in the future, bacteria involved in severe acne cases does become resistant to tetracycline use, there is evidence a bacteriophage of the bacteria causing it may be used in new treatment therapies.[6]

So What Does Acne Treatment Have To Do With Lyme Disease?

So here we are, after I've just given a detailed outline of how high antibiotic doses are to treat a bacterial infection that is skin deep for 3-4 months - sometimes longer - in order to help patients clear up their faces and have less irritated skin and less social ostracization.

In the transcript of an educational course on acne treatment, "Long-term Oral Antibiotics for Acne", dermatologists stated they have no problem giving their acne patients another 2 or 3 months worth of antibiotics to treat their acne if it isn't cleared up after the first 2-3 months of treatment.

And if patients have a flare up of symptoms, they advocate putting them back on antibiotics if they stopped taking them. They're pretty comfortable with using more antibiotics when they need to until patients symptoms improve.

Don't you think if patients who face ostracization for pimple-laiden skin can get more antibiotic treatment for an infection that is skin-deep, that Lyme disease patients should be able to get more antibiotic treatment for a bacterial infection which can move into major organs and the central nervous system in a few weeks after a tick bite?

Something is wrong here.

Other Conditions Using Longer Term Antibiotic Treatment

There are a number of other conditions for which long term antibiotics are used and they range anywhere from being inconvenient and irritating to being chronic and painful to live with. Research is ongoing in how antibiotics can be used to treat conditions which were once thought difficult to treat or never treated with antibiotics in the first place.

Rosacea

Rosacea is a skin condition that is treated with long-term antibiotics. One interesting thing about rosacea is that it has had an oral antibiotic specially formulated to treat it which has less risk of microbial resistance.[7]

Evidence has shown that long-term medical therapy increased the rate of remission in rosacea patients, and it should be noted that the specially formulated doxycycline used to treat rosacea now is used for months and years at a very low dose [8].

The Mayo Clinic states this about rosacea: "The duration of your treatment depends on the type and severity of your symptoms, but typically you'll notice an improvement within one to two months. Because symptoms may recur if you stop taking medications, long-term regular treatment is often necessary."[9]

Crohn's Disease

Antibiotics have been used to treat Crohn's disease, and a meta analysis concluded that long-term treatment with nitroimodazoles or clofazimine is effective in patients with Crohn's disease (median treatment length was 6 months; duration ranged from 3-24 months).[10]

Reactive Arthritis

Researchers from the University of South Florida College of Medicine found a combination of antibiotics can be an effective treatment for reactive arthritis caused by Chlamydia bacteria. Reactive arthritis symptoms usually last 3-12 months, although symptoms can return and develop into a long-term disease. In the past it was thought only a small percentage of people would experience chronic symptoms of reactive arthritis, but now more recent data suggests 30-50% of patients can develop a chronic form of the disease.[11]

Neurodegenerative & Inflammatory Disorders

Minocycline has used in other neurodegenerative and inflammatory disorders, such as multiple sclerosis, Parkinson's disease, Huntington's disease, rheumatoid arthritis and ALS for its non-antibiotic properties, and it and other antibiotics may be useful in long term treatment of such disorders.[12]

Questions To Consider

So those were just a few examples beyond acne, tuberculosis, and Hansen's disease of where more than a 2-3 week course of antibiotics has been recommended for various conditions which may be caused by a bacterial infection - and in the case of rosacea and other medical conditions - may not be. Antibiotics are used to treat rosacea and other conditions because of their anti-inflammatory properties.

With all this in mind, why don't the standard guidelines state conditions for individual doctor discretion in using long term courses of antibiotics to treat patients with persisting symptoms of Lyme disease?

What about designing Lyme disease treatment studies which are similar to those for Crohn's disease (longer term treatment) and reactive arthritis (using a combination of antibiotics to treat symptoms)?

What about adding the study and treatment of tickborne coinfections such as Babesia and Ehrlichiosis into treatment trials, since polymicrobial infection can have an effect on treatment outcome?

In ongoing discussions of the use of long term antibiotic treatment for persisting symptoms of Lyme disease, only the same three clinical studies keep getting cited (Klempner, Krupp) which show low to no effective reduction of symptoms in patients using antibiotic treatment for Lyme disease after treatment is stopped.

These studies have their criticisms and are limited in what they could measure in terms of outcome and could not provide evidence of persistent infection one way or another.

Clearly more research is needed in this area - and with large random controlled studies.

If some researchers have proposed that the reason some Lyme disease patients experience persisting symptoms in what is labeled "Post-Lyme Disease Syndrome" due to inflammation from cytokines/a hyperactive immune response - why not use antibiotics for their anti-inflammatory properties?

So far, in my research, I've seen support for both Borrelia burgdorferi leading to persistent infection in patients - as well as inflammation being related to persistent symptoms in Post-Lyme Disease Syndrome.

Wouldn't treating these conditions with longer term antibiotics hit two birds with one stone?

If the reason for not treating persisting symptoms with longer courses of antibiotics is due to the concern for antibiotic resistance - which is a serious concern when one thinks of MRSA and VRSA - what about all these other conditions?

And surely some conditions merit antibiotic use with far more intensity and duration early on in order to prevent resistance and have a more favorable outcome for patients?

The bottom line:

The consequences of insufficient treatment for Lyme is not merely a painful memory of a prom photo with breakouts - it's people who have lost their ability to have careers and families and life fulfillment - and maybe even life, itself.

There's a reason Lyme patients feel that the people who have knee-jerk reactions to more than a month of abx are sentencing us to diminished lives, not just a lousy photograph in the scrapbooks of our lives.

Lyme disease bacteria can disseminate to different organs and into the central nervous system and brain shortly after infection. IT IS MORE THAN SKIN DEEP.


References:
1. Pathophysiology of Acne vulgaris: http://www.aafp.org/afp/20001015/1823.html
2. http://dermatology.about.com/cs/antibiotics/a/acneabx.htm
3. Coates P, Vyakrnam S, Eady EA, Jones CE, Cove JH, Cunliffe WJ. "Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study." The British Journal of Dermatology. 2002 May;146(5):840-8.
4. Antibiotic treatment of acne may be associated with upper respiratory tract infections.
http://www.ncbi.nlm.nih.gov/pubmed/16172310
5. http://www.medscape.com/viewarticle/740768
6. Farrar MD, Howson KM, Bojar RA, et al. (June 2007). "Genome sequence and analysis of a Propionibacterium acnes bacteriophage". Journal of Bacteriology 189 (11): 4161–7. doi:10.1128/JB.00106-07. PMC 1913406.PMID 17400737
7. http://www.rosacea.org/patients/faq.php#antibiotics
8. http://www.medscape.com/viewarticle/554690_4
9. http://www.mayoclinic.com/health/rosacea/DS00308/DSECTION=treatments-and-drugs
10. Long-Term Antibiotic Treatment for Crohn's Disease: Systematic Review and Meta-Analysis of Placebo-Controlled Trials
http://cid.oxfordjournals.org/content/50/4/473.full
11. "Combination Antibiotics as a Treatment for Chronic Chlamydia-Induced Reactive Arthritis." J. D. Carter, L. R. Espinoza, R. D. Inman, K. B. Sneed, L. R. Ricca, F. B. Vasey, J. Valeriano, J. A. Stanich, C. Oszust, H. C. Gerard, and A. P. Hudson. Arthritis & Rheumatism; Published Online: April 29, 2010 (DOI: 10.1002/art.27394); Print Issue Date: May 2010.
12. Blum D, Chtarto A, Tenenbaum L, Brotchi J, Levivier M (2004). "Clinical potential of minocycline for neurodegenerative disorders". Neurobiol. Dis. 17 (3): 359–366. doi:10.1016/j.nbd.2004.07.012. PMID 15571972.

Other resources:
- Acne vulgaris: http://en.wikipedia.org/wiki/Acne_vulgaris
- CDC Antibiotic Resistance FAQ: http://www.cdc.gov/ghttp://www.cdc.gov/getsmart/antibiotic-use/anitbiotic-resistance-faqs.html
- Klempner MS, Hu LT, Evans J, et al. (July 2001). "Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease". N. Engl. J. Med. 345 (2): 85–92. doi:10.1056/NEJM200107123450202. PMID 11450676. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=11450676&promo=ONFLNS19.
- Kaplan RF, Trevino RP, Johnson GM, et al. (June 2003). "Cognitive function in post-treatment Lyme disease: do additional antibiotics help?". Neurology 60 (12): 1916–22. PMID 12821733. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=12821733.
- Krupp LB, Hyman LG, Grimson R, et al. (24 June 2003). "Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial". Neurology 60 (12): 1923–30. doi:10.1212/01.WNL.0000071227.23769.9E. PMID 12821734. http://www.neurology.org/cgi/content/abstract/60/12/1923.
- B. A. Fallon, MD, J. G. Keilp, PhD, K. M. Corbera, MD, E. Petkova, PhD, C. B. Britton, MD, E. Dwyer, MD, I. Slavov, PhD, J. Cheng, MD, PhD, J. Dobkin, MD, D. R. Nelson, PhD and
H. A. Sackeim, PhD. "A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy." Neurology March 25, 2008 vol. 70 no. 13 992-1003 http://www.neurology.org/content/70/13/992.short
http://www.medscape.org/viewarticle/588328

4 comments:

  1. Another thoughtful article. Thanks Camp Other!
    I do wish that you had mentioned that most of our antibiotic resistance comes from all the meat we consume. Riddled with an average of 5-8 types of antibiotics. And when tested also has most forms of antibiotic resistant bacteria. The animals are fed cocktails of antibiotics and we humans are consuming it all. Even 'organic' non-medicated meat has these problems because they start with parents who have been medicated. This is what is causing our food chain to disintegrate. Why is it OK to give antibiotics to animals that are not sick and not to humans that are sick? This is unacceptable. -Jess

    ReplyDelete
  2. Jess,

    Thanks for reading, and for your comment.

    Yes, antibiotic treatment of livestock is a major contributor to antibiotic resistance, and it was mentioned in comments on the original post of this article to the Daily Kos. I have also posted about antibiotic resistant bacteria in meat in the Friday Four column in the past, though it's not something I've written about extensively.

    Denmark hasn't used antibiotics in its livestock for some time now and other countries in the EU are following. It is only a matter of time before the US follows suit - petitions to stop the use of antibiotics in US livestock have been around for some time, the danger of overusing antibiotics known for some time - and this must change now.

    "Why is it OK to give antibiotics to animals that are not sick and not to humans that are sick?" Very good question.

    ReplyDelete
  3. More info about long term antibiotics in ALS.

    Here's an interesting link to a Phase III double-blind study of ceftriaxone on patients with ALS.

    It's a Phase III study, so they've already determined that ceftriaxtone is safe for ALS patients for at least 20 weeks. Now, at Phase III, enrollees are getting either 12 months of ceftriaxtone or placebo.

    Frequently Asked Questions (pdf file) re: this study from the Northeast ALS Consortium.

    And, there is the use of long-term antibiotics in the treatment of Chlamydophila Pneumoniae (formerly known as Chlamydia Pneumoniae).

    When you read the extensive material at http://www.cpnhelp.org/, you quickly see the similarities between the protocols of Lyme knowledgeable practitioners and those for C. Pneumoniae.

    Just passing this along.

    ReplyDelete
  4. Rick L,

    Hi. Welcome to CO blog!

    Thank you for stopping by and commenting on the study of the use of antibiotics with ALS. I will have to take some time out to read the study and see what the outcome is. Interesting.

    Some conditions need long term antibiotic treatment. I would hope we find a new medical treatment that is lower risk and effective, but until we do, if antibiotic treatment benefits outweigh the risk and improve the quality of life for people, access to the option is important. Sometimes there aren't other tools in the toolkit, or if they're lower risk, they're lower benefit, too.

    In terms of CP treatment, are there any particular treatment guidelines documents you can point me to? Do you have issues with diagnosis and testing for CP, as one does for Lyme disease?

    Everyone is more familiar with their own condition that that of others, but I think we have much we can learn from each other and help each other out.

    ReplyDelete

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