MODULE 3: ALLOPATHIC TREATMENT OF LYME DISEASE

Lesson 1:

General Considerations of Antibiotic Therapy
To antibiotic or not to antibiotic?
What to expect
Herxheimer reactions
Side effects of antibiotics
Strategies for success

Lesson 2: Antibiotic Therapy For Acute Lyme

Lesson 3: Antibiotic Therapy For Chronic Lyme

Lesson 4: Antibiotic Therapy for Co-infections

Lesson 5: Antibiotic Therapy in Pregnancy and Children

Lesson 6: Pros and Cons of IV and Injectable Medications

Lesson 7: Pulsing Medications

Lesson 8: Medication Interactions

Lesson 9: What To Do When Antibiotics Stop Working

LESSON 1: GENERAL CONSIDERATIONS OF ANTIBIOTIC THERAPY

To antibiotic or not to antibiotic?

• No right answer.
• Depends on the individual, their sensitivities, preferences, other factors.
• Mistake to be too black and white about it.
• Antibiotics do not come without side effects and associated issues, but for some have given them their life back.
• I still think a combination of antibiotics early in treatment, along with naturopathic support, then transitioning off to natural (multimodality) treatment as soon as possible, may be the optimal way.
• But again, no one right choice for everyone.
• Many people in long-term treatment finally go off antibiotics as could not get complete recovery and concern for side effects, but that initial burst may still have been helpful.
• DO not use antibiotics without some basic prophylactic naturopathic support.

Finding a doctor to prescribe

• ILADS and LDA will be best way to locate a Lyme-literate doctor.
  • www.ilads.org
  • www.lymediseaseassociation.org.
• Infectious disease docs often not willing.
• Some people work with LLMD/LLND long-distance then have local GP/primary care doc prescribe.

What to Expect in Antibiotic Therapy

Duration of Treatment

• Acute lyme = 2-4 weeks antibiotics (IDSA), up to 2 months (ILADS).
• Chronic lyme = long term – 6 months up to 2 years and beyond.
• Average treatment time: 12-24 months.
• Rare to resolve symptoms less than 12 months.
• Some continue antibiotic protocol indefinitely.
• ILADS protocol: treat for 2 monoths beyond resolution of symptoms.
• Sensible to continue herbal antimicrobial for a few months beyond ceasing antibiotics— address any remaining infection and prevent relapse.

Number of Medications

• Borrelia exists in 3 forms—spirochete, cell wall deficient, and cyst form.
• Morphs back and forth between forms to evade immune system and antimicrobial therapy.
• Each form of Borrelia is susceptible to different antibiotics.
• Therefore each of the three forms must be addressed for recovery to be possible.
• In some cases, natural treatments can be substituted for medications, but by and large, three antibiotics are required.
• Usually multiple choices within each category so can select based on sensitivity level, allergies, previous reactions etc.
• Then medications for co-infections.
• Then anti-fungals and any other medications for symptom management.

Dosage of Medications

• Bacteria and parasites in Lyme disease often require higher than typical doses of certain antibiotic and antiparasitic medications.
• Doxycycline – 100mg twice daily = bacteriostatic; needs 200mg twice daily to be bacteriocidal.

Feeling Worse Before Better aka Herxheimer Reactions

What is ‘Herxing’?

• Temporary worsening of symptoms, caused by the release of neurotoxins as pathogens are killed.
• It is the pathogens themselves that release the neurotoxins, but it becomes the task of the body to detoxify and excrete them.
• Is also an inflammatory cascade – increase in inflammatory cytokines such as TNF-alpha, IL-6 and IL-8.
• Herxing typically reflects a transient worsening of a person’s existing symptoms, or occasionally the onset of new symptoms.
• Spirochetes are renowned for their ability to trigger Herxes, but other co-infections can too – Babesia, Bartonella; even Candida.
• Being aware of what they are and understanding the process helps a lot.
• Some people want to feel Herxes so they know their treatment is working (although it’s possible to improve without them).

Is Herxing Specifically From Antibiotics?

• Herxing is not limited to pharmaceutical protocols.
• Antibiotics and natural treatment modalities can both cause Herxes.
• Egs – Rife therapy, HBOT, ozone therapy, herbs.
• Effectively, anything that kills off these bugs can trigger Herxes.

How Bad Will It Be?

• Patients experience depends greatly on their detoxification mechanisms - many people with chronic Lyme disease have compromised detoxification systems, which makes the Herxheimer reactions more profound.
• Different people have different levels of sensitivity.
• Some people will not experience Herxheimer reactions at all – others it will dictate the progression of their treatment.
• Methylation issues and other genetic predispositions play a role.
• KEY- to assist body in detoxification (see detoxification module).
• More sensitive patients will need to start very slowly in treatment to prevent overwhelming Herxes.

How Do You Know When To Keep Going and When To Back Off?

• In part depends on lifestyle factors – is the individual working, having to take care of kids, etc; do they have someone to take care of them at home?
• Eg – college student with summer off might want to treat more aggressively than a working single Mum; may be willing to withstand more Herx reactions. Working parent may need a slow and steady approach.
• Any life-threatening aspects to the Herxes - Some patients with motor neuron disease may have breathing or swallowing difficulties so a Herx reaction could be life threatening.
• Severe cardiac involvement is another questionable symptom.
• If a patient has major tachycardia or arrhythmia, pushing too much can be dangerous.
• Herxing is not a “badge of honor” where how much they can endure proves how tough they are.
• If Herxes get too severe, treatment will need to be slowed or even stopped for a period of time for the patient to stabilize.
• That can actually slow down treatment overall.
• So aggressive treatment is not always faster treatment.

Gauging How To Respond

Severe Herx:

• Feels unmanageable.
• 8/10 or above.
• Stop whatever caused the Herx ie the last medication, supplement, dosage change etc for a few days or until symptoms stabilize again.
• Restart at ¼ of previous dose, build dose more slowly.

Moderate Herx:

• Somewhat manageable.
• 5/10-7/10 severity.
• Reduce dose by ½ for a few days to a week.
• Build dose more gradually when reintroduced.

Mild Herx:

• Feels manageable.
• 1/10-5/10 severity.
• Soldier on knowing that the pathogens are being killed and good things are happening!

Check your Resources section for the Herx Handout that I give all my patients, including my top
suggestions for how to manage Herxes.
Much more also in the detoxification module.

Possibility of Side Effects

• With any medication there is the potential for side effects.
• General side effects, and ones specific to each medication (some have more than others).
• Often can be prevented with naturopathic support, and proactive preventive care.
• Much more on this in naturopathic treatment module.

General –

Liver and kidney stress:

• Multiple antibiotics for long durations can elevate liver enzymes and put stress on the kidneys.
• Liver and kidney function must be checked every month.
• Labs include a complete blood count and a comprehensive metabolic panel that includes BUN, creatinine, AST, ALT and GGTP.
• If liver enzymes become elevated or kidney function is affected, medications may have to be slowed down, doses lowered or ceased for a duration of time until levels normalize.

GI concerns:

• Some oral antibiotics cause gastrointestinal side effects.
• Gastritis - inflammation of the gastrointestinal tract.
• Imbalances in gut flora leading to Candida overgrowth.
• If diarrhea occurs, it may be a sign of yeast (Candida) overgrowth.
• Severe, ongoing diarrhea should be evaluated for C. difficile (both toxins A and B) as a cause of colitis.
• Any antibiotics can predispose a person to C. difficile, but ceftriaxone and clindamycin may create a higher risk.
• Signs of Candida overgrowth – gas, bloating, loose stool, white coating on tongue, vaginal irritation.
• Consider antifungals prophylactically.

Immune concerns:

• Antibiotics can lower white blood cell counts – often low already in chronic Lyme.
• Counter with immune support (see naturopathic module).
• Monitor with labs listed above – complete blood count will show WBC count.

Cardiac concerns:

• Medications such as telithromycin can prolong the QT interval and interfere with heart rhythm, so patients on this medication should have cardiac monitoring.
• Other macrolides such as azithromycin can too, but less common.
• Certain combinations of medications can make this worse so care must be taken with interactions.

Reproductive concerns:

• Women (and men!) also need to know that antibiotic therapy, especially the tetracycline family, may reduce the effectiveness of the oral contraceptive pill. Alternative birth control should be used while on antibiotic therapy.

Individual Side Effects –

• Each medication will have its own side effect profile.
• Be aware of that medication.

Examples:

• Doxycycline => sun sensitivity.
• Rifampin => yellowing of bodily fluids (not harmful).
• Flagyl => significant GI upset.

Differentiating a Herx Reaction From a Side Effect

• Can be hard to differentiate as can be overlap of symptoms.
• One of the reasons I like to start with herbs, as fewer actual side effects and any worsening is likely due to Herx.
• Clues that can help differentiate -

Timing:

• A medication reaction is usually quite immediate – within minutes to hours of taking the drug.
• A Herxheimer reaction often takes several days to appear (as the endotoxins build up gradually and reach a tipping point at which stage they make the person feel worse).

Symptom profile:

• A medication reaction often produces new symptoms, and/or shows up as allergy-type symptoms such as nausea, headaches and rashes.
• A Herxheimer reaction is typically representative of the symptoms the person usually experiences, just in a more severe way, so there may be more joint pain, more cognitive deficits, more night sweats – whatever the person’s usual symptoms are, but flared.

Strategies For Success

Recognize that what works for one might not work for another

• There is no one treatment that is going to work for everyone, or at least work the same way for everyone.
• Comparison can lead to frustration and despair – leads to emotional stress.
• Understand that there is some trial and error along the way.
• Patience is needed for the journey.
• Many factors which influence whether an antibiotic will be a good fit -
  • Medication allergies
  • Medication side effects
  • Pre-existing issues – eg someone with arrhythmia may have side effects from Zithromax (prolonged QT interval) where next person might not.
  • Ex: doxycycline – sun sensitivity. Mino – vestibular S/E, dizziness.
• Even within medication classes, two very slightly different drugs may give totally different side effects and clinical responses.
• For example, azithromycin and clarithromycin, both in the macrolide family.
• One person might tolerate one well, and the other not at all.
• Another patient might be the exact opposite.

Predicting which medications may work better for a patient—

• To some extent one medication or a combination of medications response can be predicted (level of sensitivity, prior treatment, co-infection picture etc), but sometimes it appears to have no rhyme or reason.
• There is no guarantee that what works for one person will work equally well for another.
• Treatment decisions have to be made one at a time, step-by-step, depending on the reaction to the last step, and adjusted along the way wherever necessary.
• Awareness and understanding of this can make the treatment journey much less frustrating.

Start gradually

• Always introduce one new medication every few days or longer, never more than one on the same day, so can gauge response.
• If not overly sensitive space by 1 week, if more sensitive may need up to a few weeks.
• If have side effects, profound Herxing, any adverse reactions, will know what the culprit is.
• Also allows the body to adjust.
• Realize that starting with more gentle meds is not wasting time; will save you time having to back track if treat too aggressively and Herx/ have negative side effects.

Ways to ease in if sensitive –

• Choose the more gentle meds – eg zithro and plaquenil are typically better tolerated than doxy and tinidazole. Omnicef is typically more gentle than Bicillin.
• Start with ¼ dose and build up gradually.
• Start with dosing every other day.
• Never start more than 1 medication at a time.
• Make sure have lots of detox support in place (see Detoxification Module).
• Be ok with taking other meds to help manage symptoms so can cope with Herxes – eg antidepressants, anti inflammatories etc.

Factor in co-infections early

• Get lab testing done, but realize not 100% reliable.
• Consider co-infection provocation first before starting any medications – the co-infections that show up will dictate the medications chosen (even the Lyme meds).
• Treating Lyme is like chess – you know where you want to end up, but have to plan the moves to get there.
• Decide first if treating Babesia or Bartonella, and if both, which is dominant.
• Then choose Borrelia meds that work well with the meds that address that co-infection.
• Eg – doxy and rifampin work well together for Bartonella so if Bartonella a big factor might choose doxy; if planning to treat Babesia may start with zithro because it partners with Mepron for babesia.
• These two more significant because less overlap with Borrelia treatment than others such as Ehrlichia, Rickettsia.
• Lyme and co-infection treatment like peeling layers of an onion- start with what seems to be the dominant infection.
• As time progresses and that co-infection reduces, may see a different pattern arise and need to work on a different co-infection at that point.
• Can treat Borrelia/Babesia together, and Borrelia/Bartonella together, but Bart/Babs meds don’t always play well together so hard to do all three.
• Can always treat secondary co-infections with herbs while treating primary one with antibiotics.
• Ehrlichia and Rickettsia tend to be treated more readily along with Borrelia.

Work Proactively on Minimizing Side Effects and Herxheimer Reactions

• Realize the importance of nutritional factors and lifestyle factors in healing.
• These are the things that are within control.
• Diet – gluten-free, sugar-free, dairy-free to reduce inflammation.
• Low sugar, low carb diet is key to preventing Candida.
• Fermented foods help keep intestinal flora intact.

Adopt a naturopathic approach:

• Include herbs and supplements to help the body offset side effects of medications.
• Basic examples – liver herbs, probiotics.
• Much more in naturopathic and detoxification modules.

Be active in detox:

• Minimize incoming toxins to reduce any undue stress on liver.
• Encourage patients to do a home-based detox therapy at home every day – outlined in detail in detoxification module.
• Be consistent with detox herbs and supplements.
• Be diligent with ordering monthly blood work.

LESSON 2: ANTIBIOTIC THERAPY FOR ACUTE LYME

Antibiotic Treatment For Acute Lyme

• Referring to first few weeks of infection.
• Diagnosis is made based on history of tick bite, EM rash and/ or flu-like illness following a tick exposure.
• Lab testing not reliable at this stage.
• If a person has had a known tick bite, it may be indicated to do prophylactic treatment even in the absence of the EM rash or symptoms.
• If treated early and aggressively enough, Lyme may be eradicated.

IDSA Protocol:

• No prophylactic treatment necessary for known tick bite, single 200mg dose may be offered to adults and children older than age 8 (within 72 hrs of bite).
• For symptomatic acute Lyme:
• Erythema migrans/ Lyme arthritis:
  • Doxycycline 100mg twice daily; or
  • Amoxicillin 500mg three times daily; or
  • Cefuroxime 500mg twice daily
    For 14 days (14-21 days)
• Early neurological Lyme/ lyme carditis:
  • Ceftriaxone 2 grams daily for 14 days (range 10-28 days)

ILADS Protocol:

• Amoxicillin, cefuroxime or doxycycline first-line agents for the treatment of EM.
• Azithromycin - acceptable, particularly in Europe, based on trials showing it to either outperform or be as effective as other first-line agents.
• Prophylactic protocol: four weeks of:
  • Doxycycline 200mg – twice daily
  • Tinidazole 500mg – twice daily
• Known acute Lyme Illness: 6-8 week treatment required:
  • Doxycycline is typically the medication of choice in early Lyme –
    • Strong activity against Borrelia
    • Ability to eliminate Ehrlichia and some of the other co-infections.

Dr. Richard Horowitz Protocol:
(presented at ILADS Conference, Toronto, 2011):

• First month:
  • Doxycycline 200mg – twice daily
  • Hydroxychloroquine (Plaquenil) – 200mg twice daily; or
  • Tinidazole 500mg – twice daily
• Second month:
  • Cefuroxime 500mg – twice daily.
  • Azithromycin 500mg – once daily; or
  • Clarithromycin 500mg –twice daily
  • Hydroxychloroquine (Plaquenil) - 200mg twice daily; or
  • Tinidazole - 500mg twice daily

My Protocol

• 2 months of:
  • Doxycycline 200mg – twice daily
  • Azithromycin 500mg – once daily
  • Cefuroxime 500mg – three times daily
  • Tinidazole 500mg – twice daily

After Acute Protocol

• If the person is not symptomatic at the end of the two-month protocol, it is still advised to follow with antimicrobial herbs for two more months.
• If no symptoms remain beyond that, Lyme disease has probably been eradicated.
• If symptoms persist, treatment would be continued per the regimens for chronic Lyme disease.

LESSON 3: ANTIBIOTIC THERAPY FOR CHRONIC LYME

Primary consideration:

• Borrelia can exist in 3 distinct forms:
  • Spirochete
  • Cell-wall deficient
  • Cyst form
• Need medication for all three forms, otherwise risk driving the bacteria into cyst form.
• Cyst forms – more dormant form, can feel better, but bacteria can survive and replicate in cyst form; then can convert back to spirochete or cell-wall deficient form later.

MEDICATION SUMMARY

COMMON DOSAGES

Medications For Spirochete Forms

• The medications used for these forms act by damaging the spirochete’s cell wall.
• The two main classes of medications are:
  • Penicillins and Cephalosporins
  • Eva Sapi of University of New Haven indicates that tinidazole (listed here under
    cyst-form medications below) may be an effective medication for all forms of
    Lyme disease including spirochete forms.

Penicillins

Amoxicillin:

• An oral form of penicillin.
• It is not considered the most effective antibiotic for Borrelia, but amoxicillin is still more effective than penicillin V.
• It can be safely used in pregnancy and breastfeeding, and is often given to children.
• High doses ranging from 3-6 grams per day must be taken to achieve benefit.
• To boost the effectiveness of amoxicillin:
  • Probenecid can be given simultaneously, at a dose of 500mg every 8 hours.
  • Another alternative is Augmentin XR, which is amoxicillin and clavulanate.
  • 1000mg can be given every 8 hours, up to 2000mg every 12 hours.
• Additional amoxicillin may still have to be given separately for full benefit.
• Contraindications:
  • Penicillin allergy.

Bicillin LA:

• Injection into the muscle, administered 2-3 times per week.
• Good compromise between oral and IV antibiotics.
• It comes in vials containing 1.2 million units.
• Most start with 1 vial injected in the gluteus muscle weekly, building up to three times weekly.
• It is a long-acting penicillin so it is easier to get sustained levels of this antibiotic, which gives greater benefit.
• Bicillin LA is significantly more effective than oral amoxicillin due to its good central nervous system penetration, which helps neurological symptoms.
• In particular, I find Bicillin LA to be very helpful in addressing the cognitive deficits that are so typical in Lyme disease, such as brain fog and memory loss.
• As an injectable, it bypasses the gastrointestinal tract so it does not contribute to gut issues to the same extent that oral antibiotics might.
• Contraindications:
  • Penicillin allergy.
  • Some patients find the injections themselves to be quite uncomfortable, and this can be partially offset by making sure the liquid is at room temperature before injecting (not straight out of the fridge) and by injecting it slowly, over a period of a few minutes.
  • Heating pads afterwards can help disperse the medication through the muscle tissue, minimizing aching in the area.
• Cautions:
  • Bicillin injections can produce significant and prolonged Herxes.
  • Some patients will notice a Herx reaction in the first few days while others experience it around day 25-30 of their Bicillin regimen.

Cephalosporins

Ceftriaxone

• 3rd generation cephalosporin that is given intravenously for the treatment of Lyme disease.
• Theoretically it can also be given intramuscularly, however that is not a practical long- term dosing method and is not widely used.
• IV ceftriaxone has historically been given in doses of two grams every day.
• More recently, better results have been seen with pulsed dosing of two grams twice daily, four days on with three days off each week.

Cefuroxime axetil

• 2nd generation oral cephalosporin
• The recommended dose is 1 gram twice daily.
• Cefuroxime can be used during pregnancy and breastfeeding, and can be given to children.
• In general, while 3rd generation cephalosporins are considered more effective than 1st and 2nd, cefuroxime has great benefit as it also has activity again Staph, so it is good for treating atypical EM rashes that may contain bacteria other than Borrelia.

Cefdinir

• 3rd generation oral cephalosporin.
• Often used now in place of cefuroxime.
• Generally well tolerated.
• Can be used in pregnancy.

Medications for Cell-wall Deficient Forms

Macrolides

Azithromycin

• Gentle and fairly well tolerated.
• Not among the most effective for Borrelia itself nor used as a first-line therapy, it has its place in Lyme treatment protocols.
• I choose it as a starting medication in patients who have high sensitivity levels to prescription medications, sometimes dosing it just three days per week.
• It is more effective for musculoskeletal symptoms such as joint and muscle pain than neurological symptoms.
• Some individuals who would not be able to tolerate doxycycline can handle azithromycin.
• Typical doses are 500-600mg daily given in a single dose. Azithromycin has a very long half-life so once daily dosing is possible.
• Frequently used in pregnancy.

Clarithromycin

• Somewhat more potent and more effective than azithromycin, clarithromycin also has greater tolerability issues.
• Many people experience some gastrointestinal side effects such as nausea, as well as a metallic taste in the mouth.
• Clarithromycin may cause more significant Candida overgrowth problems when compared with azithromycin, in part because it must be dosed more frequently due to its shorter half-life.
• pH considerations of zithro and clarithro:
  • Limited effectiveness of Azithryomycin and clarithromycin may relate to the acidic fluid pocket created around the Borrelia bacteria in the cell. This acidic fluid may inactivate these antibiotics.
  • Giving hydroxychloroquine (Plaquenil) or amantadine can raise the pH of the fluid and allow the two medications to work better.
  • Does not apply to telithromycin, which is not affected by the pH levels
• In spite of their limitations, azithromycin and clarithromycin still have a significant place in Lyme disease therapy especially when combined with other antibiotics. They are just not stand-alone medications.
• Mepron, a medication for Babesia, requires either azithromycin or clarithromycin for it to work effectively, so sometimes that dictates the inclusion of such medications in an individual’s protocol.
• Also, azithromycin and clarithromycin, having the same purpose as the tetracyclines such as doxycycline and minocycline (which is to target cell-wall deficient forms), tend to work well along with them.
• They act slightly differently as they work on slightly different ribosomes, but they fulfill the same goal and are often used concurrently for that reason.

Clindamycin

• Sometimes used for Borrelia and also Bartonella.
• Effective dose: 300mg two to three times daily.
• It can be effective as it penetrates the central nervous system and gets deep into other tissues to address deep-seated infection in the body.
• Caution:
  • Propensity to cause pseudomembranous colitis, which will cause unrelenting diarrhea.
  • Prevention is the key with high doses of mixed strain probiotics including Saccharomyces boulardii.

Telithromycin

• May be one of the most effective antibiotics against Borrelia, but not often used.
• It is dosed at 800mg once daily, and does not need amantadine or hydroxychloroquine to boost its efficacy.
• Cautions:
  • It has more serious side effects such as cardiac irregularities and liver enzyme elevation, so it requires close monitoring (EKG and liver enzymes every two weeks).
  • It also has numerous interactions with other medications due to its effect on liver enzyme systems that regulate the metabolism of certain drugs.
  • Telithromycin can provoke strong and prolonged Herxheimer reactions.
  • Given its toxicity and side effect profile, many Lyme-literate medical doctors in the United States will not prescribe telithromycin.

Tetracylines

Doxycycline

• Most widely used medication in Lyme disease treatment.
• It is used in acute Lyme but is equally effective in more chronic cases.
• Has broad-spectrum activity against Borrelia along with co-infections such as Bartonella, Ehrlichia and Mycoplasma.
• Has a broader spectrum of activity than minocycline when addressing Lyme with co- infections.
• Dosage: typically 200mg twice daily and as high as 600mg daily.
• Cautions:
  • It should not to be used during pregnancy or breastfeeding, or in children younger than eight years of age (it can cause irreversible tooth staining in kids).
  • Side effects include headaches, gastrointestinal disturbance and increased sun sensitivity.
  • It is best taken two hours away from metronidazole and tinidazole due to its ability to bind with them and impede absorption, and also two hours away from dairy products and minerals such as calcium and magnesium.

Minocycline

• Not used as widely as doxycycline in Lyme disease treatment.
• It is more lipid soluble than doxycycline so it may have greater benefit in neuroborreliosis (greater blood-brain barrier penetration).
• For this same reason it tends to have more vestibular side effects such as headache and dizziness.
• Sometimes used for its profound anti-inflammatory effects, which can be particularly helpful in reducing neurological symptoms.
• Dosing: 50mg twice daily up to 100 mg three times daily.
• Cautions:
  • It creates slightly less sun sensitivity and GI side effects as compared with doxycycline, but despite this, doxycycline remains the preferred choice.

Medications for Cyst Forms

Metronidazole (Flagyl)

• Dose: 500mg twice daily and can be pulsed 2 weeks on/ 2 weeks off.
• Alternatively can be given 3 consecutive days per week.
• Optimally it is dosed separately from doxycycline or minocycline by two hours.
• Can be used in children.
• Cautions:
  • Gastrointestinal side effects and tolerability issues.
  • Not safe in pregnancy - can cause birth defects.
  • Will heighten one’s sensitivity to alcohol and cause severe reactions.
    • Since herbal tinctures are often preserved with alcohol, more sensitive patients put their herbs in hot water to evaporate off the alcohol before drinking them.
    • For most patients the amount of alcohol in drop doses of herbs will not be enough to cause them problems.

Tinidazole

• Dose: 500mg twice daily, pulsed two weeks on/ two weeks off.
• Alternatively can be given 3 consecutive days per week.
• Comes with many of the same cautions as metronidazole, as it is in the same family of drugs:
  • It cannot be used in pregnancy
  • Does not combine well with alcohol
• Tinidazole seems to be much better tolerated and causes less GI upset than Flagyl.
• My first choice in cyst-form medications for Borrelia.
• Can provoke quite significant Herxes, usually lessen after first 2-3 cycles.
• Professor Eva Sapi studied metronidazole and tinidazole and found that the latter was much more effective in destroying colonies of Borrelia.
• May also have some activity against biofilm.

Plaquenil

• Essentially an anti-malaria drug, although it has multiple uses in medicine.
• In Lyme treatment we primarily use it to address cyst forms of Borrelia.
• Anti-inflammatory effects and immune modulating effects -
  • Widely used by rheumatologists for Rheumatoid Arthritis
  • Can lessen pain and inflammation in Lyme patients with severe musculoskeletal symptoms.
• It can shift the pH of the cell to make azithromycin and clarithromycin work better.
• Cautions:
  • Long-term use can cause retinal artery problems.
  • Patients are advised to get an eye exam before starting treatment and every three months thereafter.

Alinia

• Alinia has less of a track record in chronic Lyme disease treatment but in recent years has been used as a cyst-form medication. It may also be effective for Babesia, thus having double benefit.
• The dosage is 500mg twice daily.
• Alinia’s on-label use is intestinal parasitic infections such as Giardia and Cryptosporidium, and some patients do find that they have some diarrhea when starting Alinia.
• It is unclear whether that is medication sensitivity or a response to the die-off of existing intestinal parasites, although new research indicates that Lyme disease may in fact involve various parasitic infestations of not just the intestinal tract, but also other areas throughout the body.

LESSON 4: ANTIBIOTIC THERAPY FOR CO-INFECTIONS

Coinfections must be treated in addition to Borrelia, which include:

• Babesia
• Bartonella
• Ehrlichias
  • Human granulocytic Ehrlichia (HGE)
  • Human monocytic Ehrlichia (HME)
  • Rickettsia

Opportunistic/Co-existing infections:

• Mycoplasma pneumonia, other mycoplasma species
• Chlamydia pneumonia
• Viruses – Epstein-Barr, Cytomegalovirus, HHV6.
• Candida

• My opinion:
  • Untreated co-infections are one of the biggest hindrances to recovery.
• When the co-infections are bacterial in nature, it is easier to do this, as there may be crossover benefit between Lyme medications and medications that will be effective for the co-infection.
• Examples are doxycycline and minocycline, both of which are used for Borrelia, Mycoplasma and Ehrlichia.
• Babesia, on the other hand, is a tougher case because it is an intra-cellular parasite.
• The medications that are effective for Borrelia will not be effective for Babesia, since one is a bacterium and the other is a parasite.
• Babesia will require its own medication protocol, but can be treated at same time as Borrelia.

Medications For Babesia

• Most distinct regimen of all medications because of its identification as a protozoal parasitic infection.
• Usual treatment in past= clindamycin + quinine.
  • Abandoned due to unacceptable incidence of severe side effects.

Current Babesia Medications:

Mepron (Atovaquone)

• Atovaquone – 750 mg per 5mL.
• Nicknamed “liquid gold” because of its price.
• Has good track record in Babesia tx.
• Standard dosage: 1 teaspoon twice daily; some patients need up to 2 tsp twice daily.
• Must be taken with significant amount of fatty food for absorption (22g).

Side effects:

• Yellowish discoloration of vision and mild GI effects.

Considerations:

• Must be taken in combination with a macrolide (azithromycin, clarithromycin or telithromycin).
• Avoid: Should not take supplements containing CoQ10 or milk thistleà can reduce efficacy.
• If babesia is chronic, at least 4-6 months treatment required.
• Babesia duncani may be more aggressive and treatment resistant than Babesia microti.

Malarone

• Combination of atovaquone and proguanil.
• Contains only 1000mg atovaquone (compared to 1500 mg in 10 mL Mepron.
• Proguanil helps boost its effectiveness.
• Concurrent use of Bacrim DS or Septa may boost efficacy.
• Doesn’t need a macrolide along with it, so may be a better starting point for sensitive patients.

Dosage:

• 2 tablets twice daily of the 250/100mg strength.

Cost:

• Marginally less expensive than Mepron.

Absorption:

• Similar to Mepron, need high amounts of fatty food.
• Avoid: CoQ10 and milk thistle.

Lariam (Mefloquine)

• Used in malaria treatment and prophylaxis.
• Can be very effective on the neurological aspects of Babesia such as anxiety and depression.
• Not as widely used due to side effect profile.

Cautions:

• Can cause some neuropsychiatric side effects.
• On the milder end, vivid dreams or an exacerbation of depression or anxiety may occur.
• On the more serious end, hallucinations, suicidal ideation and even psychosis have been reported.
• Individuals with a history of bipolar disorder, schizophrenia or other serious mental illness would be poor candidates for mefloquine.
• My experience: can cause a worsening of psycho-emotional symptoms in accordance with Herx-type pattern.

Dosage:

• 250mg tablet 1X every 5-7 days.
• Can be taken along with atovaquone - typically use atovaquone for six to eight weeks to reduce the overall parasitic load before introducing mefloquine.

Coartem/Riamet

• Malarial medication - combination of artemether and lumefantrine – standard 20/120mg.
• Only dosed twice daily for 3 days of each month. 4 tablets per dose.
• I have done loading dose of 3 days per week for the first month.

Disadvantage:

• Other Babesia medications and macrolide or quinolone antibiotics must be stopped for those three days plus two to three days on each side, so that can create quite a disruption in the overall treatment protocol.

Alinia

• Mentioned earlier as a cyst form-medication for Borrelia.
• Dosage: 500mg twice daily.
• Often use in combination with Atovaquone (Mepron or Malarone).
• Can cause yellowing of body fluids.

Septra/ Bactrim

• Medication combination of trimethoprim and sulfamethoxazole.
• “Sulfa drugs”; beware of sulfa drug allergy.
• Good addition to strengthen protocol when Lyme and Babesia meds stabilized.

Considerations:

• Can be good choices in combination therapy with Borrelia and co-infections are present (especially babesia or bartonella).
• Significant Herx reactions can be expected, sometimes lasting several weeks.

Medications For Bartonella

Rifampin

• One of the primary medications used in treatment of Bartonella.
• Not particularly effective for Borrelia, but helpful in a combination therapy. 
  Considerations:
• Combines well with Doxycycline.
• Azithromycin and clarithromycin may increase its action and are commonly used along with it.
• Theoretically rifampin can be given with Mepron or Malarone, but it may reduce their efficacy.

Dosage:

• 300mg twice daily.

Side effects:

• Orange discoloration of urine, sweat and tears due to inherent color of medication, not liver problems.
• Can be liver toxic, liver enzymes must be monitored regularly.
• May cause hormone dysregulation - increases in Sex Hormone Binding Globulin (SHBG).
• People with hormone irregularities should be monitored closely or not use rifampin.

Levaquin

• Quinolone category of antibiotics (same family as Ciprofloxacin).

Dosage:

• 500-750 mg daily.

Cautions:

• Levaquin can be effective for Bartonella, but it is not my first choice due to its significant potential side effect of causing tendonitis, and even tendon rupture.
• Tendons are the connective tissues that connect bones to muscles, and tendonitis is the inflammation of these structures.
• Pain and swelling at the site are the primary signs, although in some cases rupture has occurred spontaneously, requiring surgical repair.
• Typically the larger tendons are affected first, such as the Achilles tendon behind the ankle, and tendons in the elbows and knees.
• Levaquin must be stopped at the first sign of tendon pain, although the risk of inflammation and even rupture may continue for several weeks or months.
• Preloading with magnesium may prevent issues, and high dose magnesium and vitamin C may be used to relieve pain and inflammation should it occur.

Septa/Bactrim

• Can add powerful boost to co-infection treatment protocol – similar as for Babesia.
• Not recommended with Rifampin as can increase liver toxicity.
• I use it when patient plateaued on Rifampin, or does not tolerate it well.

Medications For Ehrlichia/Anaplasma and Rickettsia

Doxycycline

• Given at similar doses to Borrelia.
• Higher doses over several months typically required for chronic cases: 400-600 mg/day.

Rifampin

• If treatment fails with doxycycline or in combination therapy, rifampin is next choice.
• Dosage: 300mg twice daily.

Medications For Mycoplasma

• Combination therapy using doxycycline or minocycline, hydroxychloroquine, and azithromycin.
• Rifampin or Septra can also be helpful.
• In cases that do not respond to these medications, a quinolone such as Levaquin or Ciprofloxacin may be used; however the cautions given above regarding tendon damage apply.

Medications For Viruses

• Many Lyme patients have high antibodies to the herpes family of viruses – Epstein-barr virus, cytomegalovirus, Human herpes virus 6, herpes simplex type 1 and 2, herpes zoster.
• Unclear the role that viruses play in illness.
• My opinion – not usually a primary factor in symptomatology (based on lack of response to anti-viral treatment) – other practitioners would disagree.
• I address viruses naturally – but can do trial of antiviral medication.
• Examples:
  • Acyclovir (Zovirax)
  • Valacylovir (Valtrex)
  • Valgancyclovir (Valcyte)
• Can add liver toxicity if on multiple antibiotics concurrently.

Medications For Candida

• More of a side effect than a co-infection.

Nystatin

• Anti-fungal medicine that targets intestinal yeast but is not absorbed through the gut into the blood stream.
• For this reason, it is a very safe and non-toxic medication as it does not put any stress on the liver.
• It is taken orally, goes on to kill yeast in the intestinal tract and is excreted through the bowels.
• Valuable as a preventative medication- can be taken along with any antibiotic regimen

Dosage:

• 500,000 units 3x/day
• Needs to be dose in this continual manner because it doesn’t build up in the system.

Fluconazole (Diflucan)

• Antifungal medication absorbed systemically.
• More effective for systemic symptoms like brain fog, vaginal yeast infections, itchy skin rashes.

Considerations:

• Systemic absorption makes this drug more toxic—can add to liver stress
• If systemic yeast is suspected:
  • One option is to take a 30-day course of fluconazole before long-term antibiotics are commenced, switching then to Nystatin along with antibiotics.
  • Other patients take fluconazole just two to three days per week.

Summary of Dosages

LESSON 5: ANTIBIOTIC THERAPY DURING PREGNANCY AND BREASTFEEDING; ANTIBIOTIC
THERAPY FOR CHILDREN

• Lyme Disease Foundation, Hartford CT – started registry in early 80s over 11 years.
• Showed that women who took adequate amounts of antibiotics during pregnancy showed a very low, in fact almost zero, transmission rate to their baby.
• ILADS 2011: Dr. Charles Ray Jones -
  • Women with active Lyme disease who do not take antibiotics have a 50% chance of passing the infection to their child.
  • Women who take one antibiotic during pregnancy have a 25% chance of passing  Lyme disease to their child.
  • Women who take two antibiotics during pregnancy have less than a 5% chance of passing Lyme disease on to their child.

Risks of not treating:

• In a published review of 95 cases of pregnant women with Lyme disease who were treated with antibiotics – 66 of them parenterally (IV or IM injection), 19 of them with oral antibiotics and 10 women with no treatment.
• 60% of untreated women had adverse outcomes compared with 12% and 31% of treated mothers (parenteral and oral, respectively).
• Loss of the pregnancy and cavernous hemeangioma were the most common adverse outcomes (Lakos & Solymosi, 2010).

Considerations:

• Medications given are deemed safe in pregnancy. Category B - not known to cause birth defects or pregnancy complications.
  • Examples – amoxicillin, penicillin, bicillin, cefuroxime, ceftriaxone, azithromycin.
• Some docs use Mepron – category C.
• Certain medications are not appropriate – minocycline, doxycycline, Bactrim, trimethoprim, Cipro, Levaquin, diflucan, rifampin, Biaxin, flagyl.
• Although taking antibiotics during pregnancy is not ideal, it is a far better choice than risking the transmission of Lyme disease to a baby, which could then impact his or her entire life.
• Since Borrelia spirochetes have been detected in breast milk by PCR testing, the antibiotic regimens above should be continued during this time also, or breast-feeding avoided.

Optimal Medications in pregnancy:
Source: Dr. Joseph Burrascano and Dr. Charles Ray Jones

• Amoxicillin – 1 gram four times daily; or
• Bicillin LA – 1 injection three times weekly; or
• Cefuroxime – 1 gram every 12 hours; and
• Azithromycin – 500mg daily.

Antibiotic Therapy For Children

• Watch for illness after tick bite – fully evaluate for Lyme and co-infections and treat.
• Children sometimes present with predominantly neurological and/or neuropsychiatric symptoms.
• Children can be treated with antibiotic therapy – med choices and dosages will be adjusted for them.
• Tetracyclines are not used in children eight years and younger, because of their ability to cause permanent discoloration of the teeth.
• Safe/effective meds for children:
  • Amoxicillin – 50mg/ kg/ day divided into doses every 8 hours. Max daily dose 1500mg.
  • Cefuroxime – 125mg-500mg every 12 hours based on weight. Max daily dose 1000mg.
  • Azithromycin – 250-500mg daily depending on their weight. Max daily dose 500mg.
  • Tinidazole -125-250mg daily depending on their weight. May be pulsed two days per week.
  • Plaquenil can be given 100mg twice daily, especially if auto-immune/ joint pain.

• Kids older than 8:
  • Doxycycline 4mg/kg/day divided into 2 doses. Max daily dose 200mg.
  • Bicillin LA can be used in kids over 8 depending on size of buttocks; use ¾ in needle. 1.2 mill units weekly.

• Meds for Co-infections:
  • Mepron – ½ - 1 tspn daily.
  • Rifampin – 10-20mg/kg up to 600mg daily.
  • Levaquin or Avalox not used in children as more risk of tendon issues.
  • Bactrim – good in combination with zithro.
• Higher doses may be indicated in older children/ adolescents.

LESSON 6: PROS AND CONS OF INTRAVENOUS AND INJECTABLE ANTIBIOTICS

IV Therapy

IV Therapy may be beneficial in following conditions:

• Illness duration longer than one year.
• Major neurological involvement.
• Lack of response to oral/ intramuscular medications.
• GI function compromised to point where oral medications are either not getting properly absorbed or causing excessive GI side effects.

Pros of IV therapy:

• Medications can be given in higher doses than oral to achieve higher blood levels.
• Medications given via IV bypass the gastrointestinal tract => fewer GI side effects.
• Many of the medications given orally can be given via IV including doxycycline, azithromycin and metronidazole.

Cons of IV therapy:

• Having a PICC line or a central line can be very disruptive to activities of daily living.
  • It requires daily maintenance, and risks of infection are always present.
• IV therapy may continue over several months, not just a few weeks.
  • The minimum duration recommended for chronic Lyme is 14 weeks, however if the patient is showing improvement but is still symptomatic, even longer times may be required.
• IV ceftriaxone does not cover all phases of Borrelia nor does it address co-infections, so oral/ IM medications must still be administered for those.
  • Very few patients do all of their three or four mediations via IV.
• IV ceftriaxone can cause biliary sludging and put the individual at risk of having to have their gall bladder surgically removed.
  • Interestingly, Dr. Burrascano believes that the gall bladder might be a reservoir of infection and has observed that his patients who do not have a gall bladder fare slightly better overall.
  • Any surgery can be stressful for a Lyme patient, as it involves chemicals, anesthesia, heightened risk of infection, adrenal and immune stress.
• IV ceftriaxone still clears through the liver and may still cause imbalances in the intestinal flora. Preventive measures to keep gut flora balanced must be undertaken.

Intra-muscular administration

• If IV is not available or indicated, an alternative is Bicillin LA via IM.

Pros:

• Bicillin LA is very effective medication.
• Only given every 72 hours.
• Good central nervous system penetration – crosses BBB better than orals.
• Relieves some of the burden on the gastrointestinal system.
• Rochephin can also be given IM but not practical for long-term administration as daily injection.

Cons:

• Still only addresses spirochete form of Borrelia.
• Not a stand-alone therapy.
• Injections can be uncomfortable.
• Penicillin allergy is a contraindication – although I have had many patients who recall having a rash with penicillin as a child who can tolerate Bicillin as an adult. We never try it if any respiratory involvement (breathing difficulty, closing of airways), but if simple rash, can try ¼ dose Bicillin with Benadryl on hand.

LESSON 7: PULSING ANTIBIOTICS

Some medication protocols involve pulsing antibiotics rather than daily use.

Advantages of pulse therapy:

• Can get higher doses of medications – often doubled – for greater efficacy.
• Breaks between pulses allow body recovery time, and reduce overall toxicity of medications.
• May break through plateau’s in daily dosing regimens.
• Can be less costly than daily regimens.
• Can help introduce medications in highly sensitive patients and reduce overall Herxheimer effects.
• Can reduce GI side effects if medications not given every day.

Examples of medications given in a pulsed fashion:

• Tinidazole/metronidazole – given either 2 weeks on/ 2 weeks off. Or 3 days on/ 4 days off.
• Rocephin – dosing used to be 2 grams every day; now often given 2 grams twice daily, 4-5 days per week.
• Artemisinin – 200mg three or four times daily, 4 days on/ 3 days off.
• Bicillin LA – given every 72 hours (because of long-acting nature of the medication).

I have seen some doctors space out medications throughout the week; this is a form of pulsing,
but is more geared to lowering total medication load in sensitive patients.

• Example: azithromycin Mon-Wed-Fri; minocycline Tues-Thurs; tinidazole Sat-Sun.

LESSON 8: MEDICATION INTERACTIONS

Medication Interactions With Food

General:

• Avoid grapefruit juice as interacts with many different medications.
• Can affect the cytochrome p450 enzyme systems in the body.
• Less of the drug is metabolized prior to absorption into the circulation which increases the amount of the drug in the blood => higher therapeutic and/or toxic effects in the body.
• Grapefruit seed extract and grapefruit essential oil are both ok.

Doxycycline:

• Do not eat dairy within 2 hours of taking.

Mepron and Malarone:

• Take with fatty food to enhance absorption – approximately 22grams is ideal.
• See Nutrition With Mepron Guide in resources section.

Alinia:

• Absorption enhanced by food.

Coartem:

• Absorption enhanced by food.

Medication Interactions With Herbs/Supplements:

General:

• Separate probiotics from all antibiotics and antifungals by 2 hours.

Doxycycline/minocycline:

• Do not take minerals within 2 hours of taking.

Malarone and Mepron:

• Do not take milk thistle or CoQ10.

Medication Interactions With Other Medications:

Rifampin:

• Interacts with several medications.
• May reduce efficacy of –
  • Tinidazole
  • Metronidazole
  • Mepron
  • Malarone
  • Doxycycline

Rifampin + Bactrim – can lead to side effects involving the liver.

• Not advised to take together.

Plaquenil + Tinidazole/Metronidazole – may increase risk of nerve damage.

Azithromycin/clarithromycin + Levaquin/Cipro – increase risk of irregular heart rhythm.

Doxycycline and minocycline:

• Separate from tinidazole by 2 hours.
• May reduce efficacy of penicillin medications.

Coartem/Riamet:

• Do not take on same days as macrolides (azithromycin, clarithromycin) – can cause irregular heart rhythm.
• Do not take with Cipro or Levaquin – can lead to irregular heart rhythm.

LESSON 9: WHAT TO DO WHEN ANTIBIOTICS STOP WORKING

If antibiotic therapy is not bringing desired results, or improvements but then plateau, consider
the following:

Rotation of Medications

• Obvious first option is to change medication protocol.
• Dr. Burrascano suggests rotating medications every 6 weeks.
• I will continue medication so long as it’s still having a positive effect – but will rotate meds once plateau occurs.

Higher Dosing

• Some people need higher doses of certain medications than even the standard Lyme dosing.
  • Example:
    • Dr. Horowitz feels optimal dose of Mepron is 10mL twice daily, not 5mL twice daily.
• Risk/benefit ratio must be evaluated with regular testing for liver/kidney stress.

Look for Interactions

• Make sure nothing is interacting in an adverse way.
• See section on interactions for foods, herbs, supplements and other medications.
• Example:
  • Rifampin reduces efficacy of several medications – may need to dose those higher to get same therapeutic effect.

Look for missed co-infections

• Untreated co-infections can get in the way of Lyme treatment.
• Co-infections, especially Babesia and Bartonella, need distinct treatment regimens, due to little overlap with Borrelia meds.

Biofilm

• Make sure the patient is taking agents to break down biofilm.
• These include lumbrokinase, nattokinase, serrapeptase, stevia, EDTA.
• Take away from antibiotics and on empty stomach.

Consider Pulse Regimens

• May allow for higher doses of medications on “on” days.
• Then give system a break on “off” days.
• Sometimes changing way medications are given can be enough to shift a plateau, or have a more beneficial effect.

Add More Naturopathic Support

• If antibiotics give limited benefit, can add herbal antimicrobials to boost overall effect.
• Combination of antimicrobial types is good.
• If treating primary co-infection with medications, option to treat secondary co-infection with herbs along the way.
• Also can add ozone therapy, high dose vitamin C, and other modalities at the same time as antibiotic therapy.

Reevaluate Use of Antibiotics

• If antibiotics are really not helping, then can reevaluate plan and consider switching to all natural treatment.
• Best to take a multi-modality approach in this case – combination of herbs, supplements, immune support; and possibly include a frequency-based therapy such as Rife; and/or oxygen-based therapy, such as HBOT or ozone.
• See more in last modality on living with Lyme over the long haul.