Autor: Elena Bohannan
Email: bohannan@montana.campus.mci.net
Datum: 5.12.1997
Forum: sci.med.diseases.lyme
MANAGING LYME DISEASE
DIAGNOSTIC HINTS AND TREATMENT GUIDELINES
FOR LYME BORRELIOSIS
JOSEPH J. BURRASCANO, JR., M.D.
eleventh edition
copyright October, 1996
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TABLE OF CONTENTS
INTRODUCTION
BACKGROUND INFORMATION
DIAGNOSTIC HINTS
* ERYTHEMA MIGRANS
* DIAGNOSING LATE DISEASE
* DIAGNOSTIC CRITERIA
* SYMPTOM CHECKLIST
LYME DISEASE TREATMENT GUIDELINES
* GENERAL INFORMATION
* TREATMENT INFORMATION
* ANTIBIOTICS
* MONITORING OF THERAPY
* ANTIBIOTIC CHOICES
TREATMENT CATEGORIES
* PROPHYLAXIS
* FOR KNOWN TICK BITES
* EARLY LOCALIZED DISEASE
* DISSEMINATED DISEASE
1. early
2. late
ALTERNATE SCHEDULING OF ANTIBIOTIC TREATMENTS
1. pulse therapy
2. combination therapy
REFRACTORY DISEASE
o responsive to antibiotic therapy
o non-responsive to antibiotic therapy
ADJUNCTIVE THERAPY
SAFETY
NUTRITIONAL SUPPLEMENTS IN CHRONIC LYME DISEASE
LYME DISEASE REHABILITATION
REHAB THERAPY PRESCRIPTION
MANAGING YEAST INFECTIONS
PATIENT INSTRUCTIONS ON TICK BITE PREVENTION AND TICK REMOVAL
APPENDIX
* Rationale for treating tick bites
* Rationale for treatment recommendations
SUGGESTED READING
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INTRODUCTION
Welcome to the eleventh edition of the Guidelines. The entire document is
revised and edited to keep it current and to make it more readable. I have
built upon the format of last year's version to keep it familiar to my
regular readers.
In the introduction to my last edition, I mentioned how the diagnosis and
treatment of Lyme Disease had entered a new era, as simplistic approaches
were being replaced by more modern ones based on better knowledge, more
experience, and the application of common sense. This resulted in an
expansion of syndromes attributable to Lyme, and new treatment
recommendations regarding both drug and dose. Seronegativity, the existence
of chronic persistent infection, relapses and treatment failures had all
been confirmed. While none of this has changed, with this edition, better
diagnostic tests, a revised diagnostic scheme, an updated symptom list, new
applications of older antibiotics, and new approaches to symptom analysis
and management have all been added.
New developments include the commercial availability of reasonably
sensitive and very specific Bb antigen detection tests, such as direct
antigen assays and PCR. These are a definite plus in evaluating the
seronegative patient and those still ill or relapsing after therapy. SPECT
scanning of the brain, if done by knowledgeable radiologists using high
resolution equipment, will show characteristic abnormalities in Lyme
encephalopathy. This not only helps with the differential diagnosis, but if
done before and after acetazolamide, it will guide in the use of
vasodilators which may clear some cognitive symptoms. Tilt table testing is
another powerful tool which, just as in CFIDS, may suggest the need for
blood volume expansion and beta blockade to dramatically lessen fatigue and
increase stamina.
The concept of a "therapeutic alliance" between the caregiver and
patientmust be emphasized in managing Lyme. This means that the patient has
to work with and become part of the medical team, and must takeresponsibility
for complying with the recommendations given, maintaining the best possible
health status, reporting promptly any problems or new symptoms, and
especially in realizing that despite all our best efforts, success in
diagnosis and treatment is never assured. The medical team must make great
efforts to listen carefully to the patient and not be too quick to dismiss
seemingly bizarre or illogical complaints.
I hope you find the following reading helpful and interesting!
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BACKGROUND INFORMATION
Lyme is diagnosed clinically, as no currently available test, no matter the
source or type, is definitive in ruling in or ruling out infection with
Borrelia burgdorferi, or whether the infection is responsible for the
patient's symptoms. The entire clinical picture must be taken into account,
including a search for concurrent conditions and alternate diagnoses, and
other reasons for some of the presenting complaints. Often, much of the
diagnostic process in late, disseminated Lyme involves ruling out other
illnesses and defining the extent of damage that might require separate
evaluation and treatment.
B. burgdorferi contains beta lactamases, which, with some strains, may
confer resistance to cephalosporins and penicillins. This is apparently a
slowly acting enzyme system, and may be overcome by higher or more
continuous drug levels especially when maintained by continuous infusions
(cefotaxime) and by depot preparations (benzathine penicillin).
Nevertheless, some penicillin and cephalosporin treatment failures do occur
and have responded to sulbactam and vancomycin, which act on different cell
wall sites than penicillin.
There is now evidence that B. burgdorferi can remain viable within cells,
such as macrophages, lymphocytes, endothelial cells, neurons, and
fibroblasts, and evade the effects of antibiotics in vitro by sequestering
in these intracellular niches. In addition, Bb secretes a glycoprotein that
can encapsulate the organism, (an "S-layer"). This may impair immune
recognition and block antibiotic penetration. Because this glycoprotein
binds host IgM, it is possible that Borrelial antigens are hidden by host
protein, and in theory at least, this will interfere with immune
recognition, causing seronegativity, and affect spirochetal clearance.
There are multiple strains of Borrelia burgdorferi and they vary in their
antigen profile and antibiotic susceptibilities. In addition, L-forms exist
which do not contain cell walls, and thus cell wall antibiotics will not
affect them. Apparently, Bb can shift between the two forms during the
course of the infection and cause the varying serologic responses seen over
time, including seronegativity. Because of this, it may be necessary to
change antibiotic or even prescribe a combinations of agents.
Vegetative endocarditis has been associated with Borrelia burgdorferi, but
the vegetations may be too small to detect with echocardiography. Keep this
in mind when evaluating patients with murmurs, as this may explain why some
patients seem to continually relapse after even long courses of antibiotics.
Repeated treatment failures should alert the clinician to the possibility
of an otherwise inapparent immune deficiency, and a workup for this may be
advised.
There are three things that will predict treatment failure regardless of
which regimen is chosen: Non-compliance, alcohol use on a regular basis,
and failure of the patient to obtain proper rest. Advise them to take a
break when (or ideally before) the inevitable mid afternoon fatigue sets in.
As can be surmised from the above, treating Lyme is difficult. There is no
one best medication to use, for Bb strain variations result in differing
antibiotic susceptibilities, and individual patient variables affect how
specific medications are utilized. It is also impossible to know with
certainty whether parenteral therapy is indicated, or what duration of
treatment will be necessary to control the infection and prevent a relapse.
Therefore, begin with a regimen appropriate to the setting and modify it
over time based upon response. It cannot be determined in advance which of
the many complaints will improve with further antibiotics, and which will
be permanent. There is no test available that can quantify recovery or
response, and there is no test for cure. Therefore, it is vital that one
follow such measures as patient diaries that succinctly outline changes in
symptom severity over a course of therapy, temperature readings in late
afternoon, physical findings, notes from physical therapists, and cognitive
testing.
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DIAGNOSTIC HINTS
Because of the unreliability of Lyme tests, diagnosis must be made on
clinical grounds, with tests making up just one part of the process.
Consideration should also be given to tick exposure, rashes (even atypical
ones), evolution of typical symptoms in a previously asymptomatic
individual, and response to treatment- presence or absence of Jarisch
Herxheimer-like reactions, and improvement with therapy.
A great deal of effort must be made in ruling out other illnesses, for
often Lyme becomes a diagnosis of exclusion.
ERYTHEMA MIGRANS
Erythema migrans (EM) is diagnostic of Lyme Disease, but is present in
fewer than half with Lyme. Even if present, it may go unnoticed by the
patient. It is an erythematous, centrifugally expanding lesion that is
raised and warm. Sometimes there is mild stinging or pruritus. The EM rash
will begin four days to several weeks after the bite, and may be associated
with constitutional symptoms. Multiple lesions are present less than 10% of
the time, and represent disseminated disease. Some lesions have an atypical
appearance and skin biopsy specimens may be helpful. When an ulcerated or
vesicular center is seen, this may represent a mixed infection, involving
other organisms besides B. burgdorferi.
After a tick bite, serologic tests (ELISA. IFA, western blots, etc.) are
not expected to become positive until several weeks have passed. Therefore,
if EM is present, treatment must begin immediately. One should not wait for
results of Lyme tests, for they probably will not be reactive this early in
the illness and the chance to treat early disease should not be missed, for
this is when the success rate is the highest. Indeed, many knowledgeable
clinicians will not even order a Lyme test in this circumstance.
DIAGNOSING LATE DISEASE
When reactive, serologies indicate exposure only and do not directly
indicate whether the spirochete is now currently present. Because Lyme
serologies often give inconsistent results, test at more than one
laboratory using if possible different methods. I recommend ordering both
ELISAs and western blots. Be aware that in late disease there may be
repeatedly peaking IgM's and therefore a reactive IgM may not differentiate
early from late disease, but it does suggest an active infection. When late
cases of Lyme are seronegative, 36% will transiently become seropositive at
the completion of successful therapy.
Western blots are reported by showing which bands are reactive. 41KD bands
appear the earliest but cross react with T. pallidum and several other
spirochetes. The 18KD, 23-25KD (Osp C), 31KD (Osp A), 34KD (Osp B), 39KD,
83KD and the 93KD bands are the most specific but appear later or may not
appear at all. You need to see at least the 41KD and one of the specific
bands. 55KD, 60KD, 66KD, and 73KD are nonspecific and nondiagnostic.
Antigen detection tests including PCR are now available, and although they
are very specific, sensitivity remains poor, possibly less than 30%. This
is because Bb causes a deep tissue infection and is transiently found in
body humors. Therefore, multiple specimens are collected to increase yield,
just as is done in blood culturing for SBE, stools for O&P, etc. The
patient must be antibiotic free for at least six weeks before testing.
Antigen capture can be done on urine, CSF, and synovial fluid. PCR can be
done on blood (buffy coat is best), urine, CSF, any other body fluid
including breast milk, and on tissue biopsy specimens.
Spinal taps are not routinely recommended, as a negative tap does not rule
out Lyme. Antibodies to Bb can be detected in the CSF in just 20% of
patients with late disease. Therefore, spinal taps are only performed in
patients with pronounced neurological manifestations, if they are
seronegative, or are still significantly symptomatic after completion of
treatment. When done, the goal is to rule out other conditions, and to
determine if Bb antigens are present. It is especially important to look
for elevated protein and mononuclear cells, which would dictate the need
for more aggressive therapy, as well as the opening pressure, which can be
elevated and add to headaches, especially in children.
To aid the clinician, a workable set of diagnostic criteria were developed
with the input of dozens of front line physicians. The resultant document
has proven to be extremely useful not only to the clinician, but it also
can help clarify the diagnosis for third party payers and utilization
review committees. It is important to note that the CDC's published
reporting criteria are for surveillance only, not for diagnosis.
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LYME DISEASE DIAGNOSTIC CRITERIA AND RELATIVE VALUE
Tick exposure in an endemic region
Value=1
Historical facts and evolution of symptoms consistent with Lyme
Value=2
Systemic signs & symptoms consistent with Lyme (other potential
diagnoses
excluded):
* Single system, e.g., monoarthritis Value=1
* Two or more systems, e.g., monoarthritis and facial palsy Value=2
Erythema migrans, physician confirmed
Value=7
Acrodermatitis Chronica Atrophicans, biopsy confirmed
Value=7
Seropositivity
Value=3
Seroconversion on paired sera
Value=4
Tissue microscopy, silver stain
Value=3
Tissue microscopy, monoclonal immunofluorescence
Value=4
Culture positivity
Value=4
B. burgdorferi antigen recovery
Value=4
B. burgdorferi DNA/RNA recovery
Value=4
DIAGNOSIS
Lyme Borreliosis Highly Likely
Value=7 or above
Lyme Borreliosis Possible
Value=5-6
Lyme Borreliosis Unlikely
Value=4 or below
I suggest that when using these criteria, you state Lyme Borreliosis
is
"unlikely", "possible", or "highly likely" based upon the following
criteria"- then list the criteria.
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SYMPTOM CHECK LIST
This is not meant to be used as a diagnostic scheme, but is provided to
streamline the office interview. Note the format- complaints referable to
specific organ systems are clustered to better display multisystem
involvement.
NAME_______________________________________DATE__________________
RISK PROFILE (PLEASE CHECK)
* Tick infested area__ Frequent outdoor activities__ Hiking__ Fishing__
Camping__ Gardening__ Hunting__ Ticks noted on pets__
* Do you remember being bitten by a tick? No__ Yes__ when________
* Do you remember having the "bull's eye rash"? ..No__ Yes__
* Any other rash? No__ Yes__
Have you had any of the following? CIRCLE ALL YES ANSWERS
1.Unexplained fevers, sweats, chills, or flushing
2.Unexplained weight change--(loss or gain)
3.Fatigue, tiredness, poor stamina
4.Unexplained hair loss
5.Swollen glands: list areas_________________________________________
6.Sore throat
7.Testicular pain/pelvic pain
8.Unexplained menstrual irregularity
9.Unexplained milk production; breast pain
10.Irritable bladder or bladder dysfunction
11.Sexual dysfunction or loss of libido
12.Upset stomach
13.Change in bowel function--(constipation, diarrhea)
14.Chest pain or rib soreness
15.Shortness of breath, cough
16.Heart palpitations, pulse skips, heart block
17.Any history of a heart murmur or valve prolapse?
18.Joint pain or swelling: list
joints_________________________________________________
19.Stiffness of the joints, neck, or back
20.Muscle pain or cramps
21.Twitching of the face or other muscles
22.Headache
23.Neck creaks and cracks, neck stiffness, neck pain
24.Tingling, numbness, burning or stabbing sensations, shooting pains
25.Facial paralysis (Bell's Palsy)
26.Eyes/Vision: double, blurry, increased floaters, light sensitivity
27.Ears/Hearing: buzzing, ringing, ear pain, sound sensitivity
28.Increased motion sickness, vertigo, poor balance
29.Lightheadedness, wooziness
30.Tremor
31.Confusion, difficulty in thinking
32.Difficulty with concentration, reading
33.Forgetfulness, poor short term memory
34.Disorientation: getting lost, going to wrong places
35.Difficulty with speech or writing
36.Mood swings, irritability, depression
37.Disturbed sleep-too much, too little, early awakening
38.Exaggerated symptoms or worse hangover from alcohol
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LYME DISEASE TREATMENT GUIDELINES
GENERAL INFORMATION
After a tick bite, Bb undergoes rapid hematogenous dissemination, and for
example, can be found within the central nervous system as soon as twelve
hours after entering the bloodstream. This is why even early infections
require full dose antibiotic therapy with an agent able to penetrate all
tissues in adequate concentrations to be bactericidal to the organism.
It has been shown that the longer a patient had been ill with Lyme prior to
first definitive therapy, the longer the duration of treatment must be, and
the need for more aggressive treatment increases.
As the spirochete has a very long generation time (12 to 24 hours in vitro
and possibly much longer in living systems) and may have periods of
dormancy, during which time antibiotics will not kill the organism,
treatment has to be continued for a long period of time to eradicate all
the active symptoms and prevent a relapse, especially in late infections.
If treatment is discontinued before all symptoms of active infection have
cleared, the patient will remain ill and possibly relapse further. In
general, early disseminated Lyme is treated for four to six weeks, and late
Lyme usually requires a minimum of four to six months of continuous
treatment. All patients respond differently and therapy must be
individualized. It is not uncommon for a patient who has been ill for many
years to require open ended treatment regimens; indeed, some patients will
require ongoing maintenance therapy to remain well.
It has been observed that symptom will flare in cycles every four weeks. It
is thought that this represents the organism's cell cycle, with the growth
phase occurring once per month. As antibiotics will only kill bacteria
during their growth phase, therapy is designed to bracket at least one
whole generation cycle. This is why the minimum treatment duration should
be at least four weeks. If the antibiotics are working, over time these
flares will lessen in severity and duration. The very occurrence of ongoing
monthly cycles indicates that living organisms are still present and that
antibiotics should be continued.
With treatment, it is common for symptoms to flare at the fourth week, then
every four weeks until the Borrelia are no longer active. This presumably
represents recurrent Herxheimer-like reactions as Bb enters its vulnerable
growth state. For unknown reasons, the worst occurs at the fourth week of
treatment. In those with long-standing highly symptomatic disease who are
on I.V. therapy, it can be very severe, similar to a serum sickness
reaction, and be associated with transient leucopenia and/or elevations in
liver enzymes. If this happens, decrease the dose temporarily, or interrupt
treatment for several days, then resume with a lower dose. If you are able
to continue therapy and get the patients through this rough time, and
continue I.V. medications, then they dramatically improve. Those whose
treatment is stopped and not restarted at this point usually will need
retreatment in the future due to ongoing or recurrent symptoms. Those
patients on I.V. therapy who have a strong reaction at the fourth week will
need to continue parenteral antibiotics for several months, for when this
monthly reaction finally lessens in severity, then oral or IM medications
can be substituted. Indeed, it is just this observation that guides the
clinician in determining the endpoint of I.V. treatment. In general, I.V.
therapy is given until there is a clear positive response, then treatment
is changed to IM or po until free of signs of active infection for 4-8
weeks. Some patients, however, will not respond to IM or po treatment and
I.V. therapy will have to be used throughout.
All patients must keep a carefully detailed daily diary of their symptoms
to help us judge the effects of treatment, the presence of the classic four
week cycle, and treatment endpoint. Remember- there currently is no test
for cure, so clinical follow-up assumes a major role in Lyme Disease care.
TREATMENT INFORMATION
There is no universally effective antibiotic for treating Lyme Disease. The
choice of medication used and the dosage prescribed will vary for different
people based on multiple factors. These include age, weight,
gastrointestinal function, blood levels achieved, and patient tolerance.
Doses found to be effective clinically are often higher than those
recommended in older texts. This is due to deep tissue penetration by Bb,
it's presence in the CNS including the eye, within tendons, and because
very few of the many strains of this organism now known to exist have been
studied for antibiotic susceptibility. In addition, all animal studies to
date have only addressed early disease in models which behave differently
than human hosts. For the background and rationale for the following
recommendations, please refer to the suggested reading list and the
appendix at the end of this document.
ANTIBIOTICS
There are four types of antibiotics in general use for Lyme treatment. The
tetracyclines, including doxycycline and minocycline, are bacteriostatic at
doses commonly prescribed, and unless high blood levels are attained,
treatment failures in early and late disease are common. However, these
high doses are difficult to tolerate. Tetracycline may be effective in a
subgroup of patients with chronic Lyme if dosed high enough (1500 to 2000
mg daily). Doxycycline can be very effective but only if adequate blood
levels are achieved either by high oral doses (300 to 600 mg daily) or by
parenteral administration.
Penicillins are bactericidal. As would be expected in managing an infection
with a gram negative organism such as B. burgdorferi, amoxicillin has been
shown to be more effective than oral penicillin V. Because of its short
half life and need for high levels, amoxicillin is usually administered
along with probenecid, and blood levels are extremely variable and should
be tested.
Cephalosporins are useful but must be of advanced generation: first
generation drugs are not effective, and second generation drugs are
comparable to amoxicillin and doxycycline both in-vitro and in-vivo. Third
generation agents are currently the most effective of the cephalosporins
because of their very low MBC's (0.06 for ceftriaxone) and because of
excellent tissue penetration. Also, cephalosporins have been shown to be
effective in penicillin and tetracycline failures. Cefuroxime axetil
(Ceftin), a second generation agent, is also effective against staph and
thus is useful in treating atypical erythema migrans that may represent a
mixed infection, containing some of the more common skin pathogens in
addition to Bb. Because this agent is difficult to tolerate due to G.I.
side effects and is costly, it is not used as first line drug.
When choosing a third generation cephalosporin, there are several points to
remember: cefotaxime (Claforan) and ceftriaxone (Rocephin) both have
demonstrated activity in-vitro, in-vivo, and in clinical studies.
Ceftriaxone is administered once daily (an advantage for home therapy), but
has 95% biliary excretion and can crystallize in the biliary tree with
resultant colic and possible cholecystitis. GI excretion results in a large
impact on gut flora. Biliary and superinfection problems with ceftriaxone
can be lessened if this drug is given in interrupted courses, such as five
days in a row each week. Cefotaxime, which must be given at least every
twelve, and preferably every eight hours, is less convenient, but as it has
only 5% biliary excretion, it never causes biliary concretions, and may
have less impact on gut flora. Very preliminary information suggests that
cefotaxime can be even more efficacious if given as a continuous infusion,
rather than in interrupted doses.
Erythromycin has been shown to be almost ineffective when used alone. The
advanced macrolides (they are classified as azalides) such as azithromycin
and clarithromycin can be difficult to tolerate due to poor GI tolerance at
the high doses needed, and their excessive tendency to promote yeast
overgrowth. As they have impressively low MBCs and do concentrate in
tissues and penetrate cells, they theoretically should be ideal agents.
However, initial clinical results were disappointing. It has been suggested
that when Bb is within a cell, it is held within a vacuole and bathed in
fluid of low pH, and this acidity may inactivate these azalides. Therefore,
they are administered concurrently with hydroxychloroquine or amantadine,
which raise vacuolar pH, rendering these agents much more effective.
Biliary and superinfection problems with ceftriaxone can be lessened if
this drug is given in interrupted courses, such as five days in a row each
week It is not known whether this same technique will make erythromycin a
more effective antibiotic in Lyme.
Other agents with demonstrated in-vitro efficacy have been used
successfully in treating Lyme patients and are listed further below.
MONITORING THERAPY
Drug levels are done until the most acceptable dose is achieved and then at
any time major changes in the treatment regimen occur. With parenteral
therapy, CBC and chem/liver panels are done at least every two weeks and
during symptom flares, with urinalysis and prothrombin time monitored monthly.
ANTIBIOTIC CHOICES
ORAL THERAPY: Always check blood levels when using agents marked with an *,
and adjust dose to achieve a peak level in the mid-teens and a trough
greater than five. Because of this, the doses listed below may have to be
raised.
*Amoxicillin- Adults: 1g q8h plus probenecid 500mg q8h; doses up to 6 grams
daily are often needed
* Pregnancy: 1g q6h and adjust.
* Children: 50 mg/kg/day divided into q8h doses.
*Doxycycline- Adults: 100 mg tid with food; doses of up to 600 mg daily are
often needed, as doxycycline is only effective at high blood levels. Not
for children or in pregnancy. If levels are too low at tolerated doses,
give parenterally.
*Cefuroxime axetil- Oral alternative that may be effective in amoxicillin
and doxycycline failures. Useful in EM rashes co-infected with common skin
pathogens.
* Adults and pregnancy: 1g q12h and adjust.
* Children: 125 to 500 mg q12h based on weight.
Tetracycline- Adults only, and not in pregnancy. 500 mg tid to qid
Erythromycin- Poor response and not recommended.
Azithromycin- Adults: 500 to 1200 mg/d. Adolescents: 250 to 500 mg/d add
hydroxychloroquine, 200-400 mg/d, or amantadine 100-200 mg/d. Cannot be
used in pregnancy or in younger children.
Clarithromycin- Adults: 250 to 500 mg q6h plus hydroxychloroquine, 200-400
mg/d, or amantadine 100-200 mg/d. Cannot be used in pregnancy or in younger
children.
Augmentin- Cannot exceed three tablets daily due to the clavulanate, thus
is given with amoxicillin.
Chloramphenicol- Not recommended as not proven and potentially toxic.
PARENTERAL THERAPY
Ceftriaxone- Risk of biliary sludging can be minimized with intermittent
breaks in therapy (ie: infuse five days in a row per week).
* Adults and pregnancy: 2g q24h. for large body habitus or more severe
illness, dose up to 4g daily
* Children: 75 mg/kg/day up to 2g/day
Cefotaxime- Comparable efficacy to ceftriaxone; no biliary complications.
* Adults and pregnancy: 2g q8h; may dose as high as 12g daily. Consider
continuous infusion.
* children: 90 to 180 mg/kg/day dosed q6h (preferred) or q8h, not to
exceed 12 g daily.
*Doxycycline- Requires central line as is caustic.
* Surprisingly effective, probably because blood levels are higher when
given parenterally.
* Always measure blood levels.
* Adults: 400 mg q24h and adjust based on levels.
* Cannot be used in pregnancy or in younger children.
Penicillin G- IV penicillin G is minimally effective and not recommended.
Benzathine penicillin- Surprisingly effective IM alternative to oral
therapy. May need to begin at lower doses as strong, prolonged (6 or more
week) Herxheimer-like reactions have been observed.
* Adults: 1.2 million U once to twice weekly.
* Adolescents: 300,000 to 1.2 million U weekly.
* Should not be used in pregnancy.
Poorly studied but anecdotally effective
Vancomycin- observed to be one of the best drugs in treating Lyme, but
potential toxicity limits its use. It is a perfect candidate for pulse
therapy to minimize these concerns. Use standard doses and confirm levels.
Imipenim- similar in efficacy to cefotaxime, but may work when
cephalosporins have failed. Must be given q6 to q8 hours.
Cefuroxime- useful but not demonstrably better than ceftriaxone or cefotaxime.
Ampicillin IV- more effective than penicillin G. Must be given q6 hours.
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TREATMENT CATEGORIES
PROPHYLAXIS of high risk groups- education and preventive measures.
Antibiotics are not given.
TICK BITES - Embedded Deer Tick With No Signs or Symptoms of Lyme (see
appendix):
Decide to treat based on the type of tick, whether it came from an endemic
area and percent infected, how it was removed, and length of attachment
(nymphs: at least one day; adults: anecdotally, as little as four hours).
The risk of transmission is greater if the tick is engorged, or of it was
removed improperly allowing the tick's contents to spill into the bite
wound. High risk bites are treated as follows:
1) Adults: Oral therapy for 21 days.
2) Pregnancy: Amoxicillin 1000 mg q6h for 6 weeks.
Alternative: Cefuroxime axetil 1000 mg q12h for 6 weeks.
3) Young Children: Oral therapy for 21 days.
EARLY LOCALIZED ­ Single erythema migrans with no constitutional
symptoms:
1) Adults: oral therapy for 6 weeks.
2) Pregnancy: 1st and 2nd trimesters: I.V. X 21 days then oral X 6
weeks 3rd trimester: Amoxicillin 1000 mg q6h X 6 weeks.
3) Children: oral therapy for 6 weeks.
DISSEMINATED DISEASE - Multiple lesions, constitutional symptoms,
lymphadenopathy, or any other manifestations of dissemination.
EARLY DISSEMINATED: Milder symptoms present for less than one year and not
complicated by immune deficiency or prior steroid treatment:
1) Adults: oral therapy until no active disease for 4 weeks (4-6
months typical)
2) Pregnancy: As in localized disease, but duration as above. Some
experienced clinicians treat throughout pregnancy.
3) Children: Oral therapy with duration based upon clinical response.
PARENTERAL ALTERNATIVES for more ill patients and those unresponsive to or
intolerant of oral medications:
1) Adults and children: I.V. therapy for 6 weeks or until clearly
improved. Follow with oral therapy or IM benzathine penicillin until
no active disease for 8 weeks. I.V. may have to be resumed if oral or
IM therapy fails.
2) Pregnancy: IV then oral therapy as above.
LATE DISSEMINATED: present greater than one year, more severely ill
patients, and those with prior significant steroid therapy or any other
cause of impaired immunity:
1) Adults and pregnancy: extended I.V. therapy (6 to 10 or more
weeks), then oral or IM, if effective, to same endpoint.
2) Children: IV therapy for 6 or more weeks, then oral or IM follow up
as above.
ALTERNATE SCHEDULING OF ANTIBIOTIC TREATMENT
PULSE THERAPY
Pulse therapy consists of administering antibiotics (usually parenteral
ones) two to three days in a row per week. This allows for several advantages:
* Dosages are doubled (ie: cefotaxime, 12 g daily), increasing efficacy
* More toxic medications can be used with increased safety (ie:
vancomycin)
* May be effective when conventional, daily regimens have failed.
* IV access may be easier or more tolerable
* More agreeable lifestyle for the patient
Note that this type of treatment is expected to continue for a minimum of
ten weeks, and often must continue beyond twenty weeks. The efficacy of
this regimen is based on the fact that it takes 48 to 72 hours of
continuous bactericidal antibiotic levels to kill the spirochete, yet it
will take longer than the four to five days between pulses for the
spirochetes to recover. As with all Lyme treatments, specific dosing and
scheduling must be tailored to the individual patient's clinical picture
based upon the treating physician's best clinical judgment.
COMBINATION THERAPY
This consists of using two or more dissimilar antibiotics simultaneously
for antibiotic synergism and to better compensate for differing killing
profiles and sites of action of the individual medications. A typical
combination is the use of a cell wall agent plus a protein inhibitor (ie:
amoxicillin plus clarithromycin). Note that GI intolerance and yeast
superinfections are the biggest drawbacks to this type of treatment.
However, these complications can often be prevented or easily treated, and
the clinically observed benefits of this type of regimen clearly have
outweighed these problems in selected patients.
REFRACTORY DISEASE
PERSISTENT SIGNS AND SYMPTOMS THAT RESPOND TO ANTIBIOTIC THERAPY
Patients in this group improve on antibiotics yet relapse repeatedly when
medications are discontinued. Some patients in this category have been
proven, in peer reviewed medical literature, to have persistent infection.
The treating physician may decide on chronic therapy in order to avoid
clinical deterioration. Recommend you confirm blood levels, and study
immune competence. This includes T- and B- cell function and counts,
Natural Killer cell functional assays, complement levels, neutrophil
function, and vaccine responsiveness.
Options for treatment:
- Longer duration, including open ended maintenance therapy
- Increased dose
- Different drug
- Change method of administration (oral to IV)
- Combination or pulse therapy
- Synovetomy
- Search for and treat concurrent illnesses
- Supportive therapy as needed
PERSISTENT SIGNS AND SYMPTOMS NOT RESPONSIVE TO ANTIBIOTICS
- Reconsider the diagnosis, and perform specific Bb antigen tests after
antibiotic free for 6 to 12 weeks
- Search for and treat concurrent illnesses
- Supportive therapy based on symptoms
- NSAIDS and hydroxychloroquine
- Antidepressants, analgesics, muscle relaxants, and amantadine
- Synovectomy
- Psychiatric/psychometric evaluation and treatment if indicated
- Long­term follow­up
- Consider retreatment if condition changes
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ADJUNCTIVE THERAPY
RECOMMENDED IN ALL LYME PATIENTS:
- daily yogurt and acidophilus preparations
- multivitamins and B complex 50 mg daily
- Physical therapy, rehabilitation, and a graded exercise program
PRESCRIBE AS NEEDED, especially in more severe cases:
- vitamin and nutritional supplements as listed below
- Psychosocial evaluation and possibly refer for counseling
- NSAIDS and remittive agents
- antidepressants, analgesics, muscle relaxants, and amantadine
- Immune globulins and other immunotherapy if indicated
- Sinequan (DAW) in low doses (5 to 50 mg daily) reportedly improves T-cell
function
CONTRAINDICATED:
- alcohol use
- excessive caffeine intake
- any avoidable stresses
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SAFETY
Nearly a decade of experience in treating thousands of patients with Lyme
has proven that therapy as described above, although intense, is generally
well tolerated. The most common adverse reaction seen is allergy to
probenecid. In addition, yeast superinfections are seen, but these are
generally easily recognized and managed. The induction of Clostridium
difficile toxin production is seen most commonly with ceftriaxone, but can
occur with any of the antibiotic regimens mentioned in this document.
However, regular use of the lactobacillus preparations seems to be helpful
in controlling yeast and antibiotic related colitis, as the number of cases
of C. difficile in Lyme patients is low when these guidelines are
followed.
When using PICC lines (peripherally inserted central catheters), if ANY
line problems arise, it is recommended that the line be pulled for patient
safety. Salvage attempts (urokinase, repairing holes) are often ineffective
and may not be safe.
Please advise all patients who take the tetracyclines of skin and eye
sensitivity to sunlight and the proper precautions. When doxycycline is
given parenterally, do not freeze the solution prior to use!
Years of experience with chronic antibiotic therapy in other conditions,
including rheumatic fever, acne, recurrent otitis, recurrent cystitis,
COPD, bronchiectasis, and others have not revealed any consistent dire
consequences as a result of such medication use. Indeed, the very real
consequences of untreated, chronic persistent infection by B. burgdorferi
can be far worse than the potential consequences of this treatment.
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NUTRITIONAL SUPPLEMENTS IN CHRONIC LYME DISEASE
Studies on patients with chronic Lyme Disease and in those with the Chronic
Fatigue Syndrome have demonstrated that some of the late symptoms are
related to cellular damage and deficiencies in certain essential nutrients.
Double blinded, placebo controlled studies, and in one case direct assay of
biopsy specimens have proven the value of the supplements listed.
ESSENTIAL FATTY ACIDS:
Studies show that when EFAs are taken regularly, statistically significant
improvements in fatigue, aches, weakness, vertigo, dizziness, memory,
concentration and depression are likely. There are two broad classes: GLA
and EPA, derived respectively from plant and fish oils. The plant sources
are many, so choose one from the list below.
Plant Oils:
* evening primrose oil
* black currant seed oil
* borage oil
Fish oil: "MAX EPA" (or any similar preparation containing 1,000 mg of
EPA)
RECOMMENDATION: four plant oil capsules and two to four EPA capsules daily,
taken with the largest meal of the day. Benefit begins within severaldays,
but further improvement continues to occur over time. Continue for three to
four months.
CO-Q 10 (ubiquinone):
This is a vitamin B- like compound essential to every living cell.
Deficiencies have been related to poor function of the heart, limitations
of stamina, and poor resistance to infections. Tissue biopsy studies have
resulted in the recommendation that a patient with chronic Lyme should take
between 200 and 300 mg daily, in two or three equal doses. For proper
function, a one month course of iron and vitamin C is required. I recommend
one Feosol Capsule and at least 500 mg of vitamin C taken together daily.
Improvement in stamina and general well being do not begin for several
weeks. The body will manufacture its own Co-Q 10 when the original
infection is controlled, but only if stimulated by aggressive exercise.
Therefore, use this supplement until the patient is feeling well and is
exercising regularly.
VITAMIN B
Studies in the 1950s demonstrated the need for supplemental vitamin B in
infections with other Borrelia. This enhances clearing of neurological
symptoms. I recommend one 50 mg B-complex capsule daily.
MULTI-VITAMIN
I recommend at least one therapeutic strength multivitamin daily, taken at
bedtime. My current favorite that is generally available is Centrum Silver.
MAGNESIUM (optional)
Magnesium supplementation is often very helpful for the tremors, twitches,
cramps, muscle soreness, arrhythmias and weakness. It may also help in
energy level and cognition. Unexplained hyperreflexia is an indicator of Mg
deficiency. The best source is magnesium chloride ("Slo-Mag", four a day)
or magnesium oxide (Mag-Ox, 400 mg once daily). DO NOT rely on "cal-mag",
calcium plus magnesium combination tablets as they are not well absorbed.
In some extreme cases, I.M. or I.V. magnesium may be necessary.
All of these products are available without a prescription from health food
stores and some pharmacies.
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LYME DISEASE REHABILITATION
Those with long-standing Lyme end up in poor physical condition. Even with
successful treatment of the Lyme infection, they will not return to normal
unless they take an active role in personal rehabilitation.
In late stage disease, many negative effects to the body are occurring:
muscles atrophy, and to some degree, the heart muscle also suffers, as do
the joints, tendons, nerves, etc. The per cent fat content of the body as a
whole rises, the cholesterol rises, and the balance between HDL and LDL
becomes less favorable. In at least 80% of the patients, significant weight
gain occurs.
Because of the extreme fatigue and body pain, many Lyme sufferers end up
spending inordinate amounts of time in bed, and get far less exercise than
they had before they became ill. This begins a debilitating downward spiral
that can be very difficult to reverse.
As a result, Lyme patients are stiff, weak, tired, have poor stamina, and
are at increased risk for cardiovascular disease and diabetes. Antibiotic
treatment alone cannot correct these effects. Therefore, it is necessary to
prescribe physical therapy, the extent of which depends on an individual
patients' condition, followed by a graded exercise program.
The earliest phase involves multiple modalities (massage, heat, TENS, MENS,
ultrasound, etc.) and aggressive range of motion exercises supervised by a
physical therapist. The goal is to relieve discomfort and to promote better
sleep and flexibility. This then evolves into stretching and mild muscular
toning which can lessen joint pain and increase mobility and stamina.
Finally, the program must expand to include muscular conditioning and
strengthening, ideally under the supervision of a credentialed exercise
physiologist. "Body sculpture" classes are ideal. Aerobics are not
recommended until the patient has fully recovered.
This is the time for the very best of health habits. I recommend light, low
fat food, with high quality nutritional value, minimal amounts of starch
and other simple carbohydrates, absolute abstention from alcohol,
elimination of caffeine, and if applicable, a serious commitment to weight
loss. Consider recommending books that outline "arthritis diets", as they
can help some patients.
Cessation of smoking is extremely important and must be addressed immediately.
As written orders for physical therapy are required to initiate the
program, an example of the format of a typical prescription for Lyme
rehabilitation follows.
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LYME REHAB-PHYSICAL THERAPY PRESCRIPTION
NAME_____________________________________________________________
D.O.B._____________________________ DATE________________________
Please enroll this patient in a program of therapy to rehabilitate him/her
from the effects of Lyme Disease. If necessary, begin with classic physical
therapy, then progress when appropriate to a whole body conditioning
program. Such therapy must be graded, carefully individualized, and be
performed on a one-on-one basis, at least initially, to ensure the maximal
amount of supervision and guidance.
THERAPEUTIC GOALS (to be achieved in order as the patient's ability allows):
PHYSICAL THERAPY:
1. Relieve pain and muscle spasms utilizing multiple modalities as
available and as indicated: massage, heat, ultrasound, TENS, "micro
amp", etc.
2. Increase mobility while protecting damaged and weakened joints,
tendons, and ligaments, to increase range of motion and relieve
stiffness.
EXERCISE Begin with a private trainer for careful direction and education.
PATIENT EDUCATION AND MANAGEMENT (to be done during the initial one-on-one
sessions and reinforced at all visits thereafter):
1. Instruct patients on correct exercise technique, including proper
warm-up, breathing, joint protection, proper body positioning during
the exercise, and how to cool-down and stretch afterwards.
2. Please work one muscle group at a time and perform extensive and
extended stretches to each muscle group immediately after each one is
exercised, before moving on to the next muscle group.
3. A careful interview should be performed at the start of each session
to make apparent the effects, both good and bad, from the prior
visit's therapy, and adjust therapy accordingly.
PROGRAM:
1. Improve strength and reverse the poor conditioning that results from
Lyme, through a whole-body exercise program ("stretch and tone", or
"body sculpture" classes). This consists of light calisthenics and
weight lifting, using small weights and many repetitions.
2. Exercise no more often than every other day
3. Each session should last one hour. If the patient is unable to
continue for the whole hour, then modify the program to decrease the
intensity to allow him/her to do so.
4. This is what is required to achieve wellness and is the main focus of
rehab. Simply placing the patient on a treadmill or an exercise bike
is not acceptable, nor is a simple walking program.
5. Aerobic exercises are not allowed, not even low impact variety, until
the patient has recovered.
Please feel free to contact my office if you would like to discuss this
client's situation in more detail.
PHYSICIAN'S SIGNATURE____________________________________________
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MANAGING YEAST INFECTIONS
Many patients with Lyme Disease develop an overgrowth of yeast. Therefore,
it is recommended that on a daily basis the patient eat a full container of
yogurt that contains active cultures, and take acidophilus, two after each
meal. Here are some suggestions on how to control yeast:
MOUTH: A tongue with a beige coating, bad breath, and dysgeusia are signs
of thrush. The patient must brush the tongue whenever they brush their
teeth, and use antiseptic mouthwashes then. Because the effectiveness of a
mouthwash is related to how long it is in contact with the germs, it should
be kept in the mouth while brushing.
Since yeast germs feed on sugars, have patients avoid simple carbohydrates,
starches, fruits, and juices for at least two weeks, or until the problem
is gone.
Prescription medications may be necessary. Mycelex troches and Nystatin
liquid are not recommended for they contain large amounts of simple sugars.
Nystatin powder is used, mixed with water, to be swished and swallowed qid
(pc and hs). Systemic antifungals (Diflucan, Nizoral) may be necessary.
The most effective (and drastic) treatment, employed as a last resort,
consists of using "Dakin's Solution" as a mouth rinse. This is a mixture of
household liquid bleach (Clorox), one teaspoon in four ounces of water. A
small amount is held in the mouth while brushing, then spit out, and
repeated until the mouth has cleared. This may be necessary every few weeks..
After using an antiseptic to clean the mouth, it is necessary to
immediately eat yogurt or liquid acidophilus, or chew an acidophilus
capsule to replenish the beneficial flora in the mouth. Because the germ
count after such a cleaning will be artificially reduced, and because yeast
germs are opportunists, they would be the first to come back. By having the
yogurt or acidophilus then, a more normal oral flora will result and thrush
will be better controlled.
INTESTINAL TRACT: An overgrowth of yeast here will ferment dietary sugars
and starches, forming acids, gas, and alcohols. Symptoms include gas,
heartburn and/or pain in the stomach area, and because of the alcohol,
there can be headaches, dizziness, lightheadedness, and wooziness. To clear
intestinal yeast, first the tongue and mouth must be cleared so yeast does
not reenter the system with every swallow. Avoid excessive sweets,
starches, fruits and juices for two weeks or longer to starve the germs.
Systemic antifungals usually are needed.
VAGINAL: An occasional vaginal yeast infection can be controlled with
products such as Monistat cream or suppositories. If it is a recurrent or
ongoing problem, then it often reflects a simultaneous intestinal
infection, reinfecting the genital area with every bowel movement.
Therefore this is treated as above, and preparations such as Monistat
should be used concurrently for two weeks.
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PATIENT INSTRUCTIONS
BITE PREVENTION AND TICK REMOVAL
HOW TO PROTECT YOURSELF FROM TICK BITES
PROPERTY Remove wood piles, rock walls, and bird feeders as these attract
tick-carrying small animals and can increase the risk of acquiring Lyme.
INSECTICIDES: Property should be treated with a product called "Damminix".
This consists of cardboard tubes containing cotton balls that have been
dipped in insecticide. These tubes are placed around the property in the
wooded areas and below shrubs. Mice, which are a key link in the
propagation of Lyme disease, find the cotton and bring it back to their
burrows to be used as nesting material, with the result being a big
decrease in the number of ticks in the area. Unfortunately, after two years
tick populations may rise again as other small animals that do not gather
cotton become hosts to the ticks. Therefore, Damminix alone is not
recommended. Use this product in conjunction with liquid or granular
insecticides.
LIQUID & GRANULAR PESTICIDES: Products meant for widespread application
include Dursban, Tempo, and sevin. They are available as a liquid
concentrate and as granules. If liquid insecticides are used, application
should be by fogging, not by coarse sprays. Apply these products in a strip
a few feet wide at the perimeter of the lawn at any areas adjacent to woods
and underbrush. Also treat any ornamental shrubs near the house that may
serve as a habitat for small animals. The best time to apply these products
is in late Spring and early Fall.
CLOTHING When wearing long pants, tuck the cuffs into the socks so any
ticks that get on shoes or socks will crawl on the outside of the pants and
be less likely to bite. Also, light colored clothing should be worn so the
ticks will be easier to spot. Smooth materials such as windbreakers are
harder for ticks to grab onto and are preferable to knits, etc.
Tick repellents that contain "permethrin" (Permanone, Permakill) are meant
to be sprayed onto clothing. Spray the clothes before they're put on, and
let them dry first. Do not apply this chemical directly to the skin.
Ticks are very intolerant of being dried out. After being outdoors in an
infested area, place clothes in the dryer for a few minutes to kill any
ticks that may still be present.
SKIN Insect repellents that contain "DEET" are somewhat effective when
applied to the arms, legs, and around the neck. Do not use any repellent
over wide areas of the body as they can be absorbed causing toxicity. Also,
it is inadvisable to use a product that contains more than 50% DEET, and
25% concentrations are preferred. Use repellents cautiously on small
children, as they are more susceptible to their toxic effects. Be aware
that this repellent evaporates quickly and must be reapplied frequently.
Check carefully for ticks not only when home but frequently while still
outside!
HOW TO REMOVE AN ATTACHED TICK
Using a tweezer (not fingers!), grasp the tick as close to the skin as
possible and pull straight out. Then apply an antiseptic. Do not try to
irritate them with heat or chemicals, or grasp them by the body, as this
may cause the tick to inject more germs into your skin. Tape the tick to a
card and record the date and location of the bite. Remember, the sooner the
tick is removed, the less likely an infection will result.
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APPENDIX
RATIONALE FOR TREATING TICK BITES
The Medical Advisory Committee of the Lyme Disease Foundation now
recommends antibiotic prophylactic treatment upon a known tick bite for:
1. People at higher health risk bitten by an unknown type of tick or tick
capable of transmitting Borrelia burgdorferi, e.g., pregnant women, babies
and young children, people with serious health problems, and those who are
immunodeficient.
2. Persons bitten in an area endemic for Lyme Borreliosis by an
unidentified tick or tick capable of transmitting B. burgdorferi.
3. Persons bitten by a tick capable of transmitting B. burgdorferi, where
the tick is engorged, or the attachment duration of the tick is greater
than four hours, and/or the tick was improperly removed. This means when
the tick is squeezed between the fingers, irritated with toxic chemicals in
an effort to get it to back out, or disrupted in such a way that it's
contents were allowed to contact the bite wound. Such practices increase
the risk of disease transmission.
4. A patient, when bitten by a known tick, clearly requests oral
prophylaxis and understands the risks. This is a case­by­case
decision.
The physician cannot rely on a laboratory test or clinical finding at the
time of the bite to definitely rule in or rule out Lyme Disease infection,
so must use clinical judgment as to whether to use antibiotic prophylaxis.
Testing the tick itself for the presence of the spirochete, even with PCR
technology, is not reliable enough to guide your decision to treat, as
false positives and false negatives occur.
An established infection by B. burgdorferi can have serious,
long­standing or permanent, and painful medical consequences, and be
expensive to treat. Since the likelihood of harm arising from
prophylactically applied spirochetal antibiotics is low, and since
treatment is inexpensive and painless, it follows that the risk benefit
ratio favors tick bite prophylaxis.
It is the Medical Advisory Committee's recommendation that antibiotic
prophylactic treatment for tick bite in many circumstances is not only
justified but warranted. The ultimate decision for treatment on tick bite
should be determined jointly between the physician and patient.
RATIONALE FOR TREATMENT RECOMMENDATIONS:
When I began treating Lyme Borreliosis (LB) in the mid 1980s, I recognized
that in disseminated disease, the then recommended ten to fourteen day
courses of antibiotics would either result in only a lessening of the
illness, or an initial good outcome followed by a relapse of symptoms.
These patients would then respond again to a repeat course of antibiotics.
Published studies by Steere and others (1) had, at that time, defined
success as the elimination of the "major" symptoms of Lyme (arthritis,
carditis, and Bell's Palsy) even though they usually resolve over time
without treatment. These same studies go on to report the persistence of
"minor symptoms" of Lyme even after antibiotic therapy, and the authors
call it the "post Lyme syndrome".
In 1987 I participated in a study in which twenty six patients with active
disseminated LB, who were culture positive for Borrelia burgdorferi (Bb),
were treated with ceftriaxone I.V. for fourteen days, using either two or
four grams a day. Although culture negative at the immediate end of
therapy, all patients became culture positive again within several weeks,
which corresponded to the time when their symptoms recurred. I concluded
then that the persistence of symptoms after this type of therapy in fact
represented ongoing infection. The results of this study were presented in
1989 at the national meeting of the Lyme Borreliosis Foundation.
Upon the advice of colleagues who for years have been involved in seminal
LB research (2), I then studied the effects of lengthened duration of
treatment. I found a direct correlation between treatment duration and the
ultimate outcome of patients' symptoms. Using amoxicillin 3g/day plus
probenecid 1.5g/day in divided doses, the per cent success was tabulated
for therapies lasting for from one through six months. Success here is
defined as the elimination of all LB symptoms, both major and minor,
without a relapse by three months after completion of treatment.
The data clearly demonstrated a direct relationship between duration and
success, starting at 17% for one month of therapy, and reaching a plateau
at 67% at five months duration. These data were also presented at the 1989
meeting mentioned above.
Next, using ceftriaxone, results of therapy were tabulated based on
duration. Even with 45 days of continuous antibiotic, none of the patients
returned to or maintained their well, pre-Lyme state. However, if oral
medications were continued after ceftriaxone, to the endpoint of being free
of signs and symptoms of active disease, then relapses did not occur.
Again, the average duration of antibiotic treatment necessary to achieve
this was at least four months.
Further culture studies involving 74 patients confirmed that the patients
had to be free of signs and symptoms of active Borreliosis before
antibiotics were discontinued in order to be both culture negative, and not
experience a relapse during three months of follow up.
There are now a growing number of published reports utilizing various forms
of Bb antigen detection that demonstrate the persistence of infection in
antibiotically treated patients (3,4,5,6,7,8), confirming my earlier work.
Even Steere has proposed this as a mechanism for chronic arthritis in
Lyme (9).
Although syphilis perhaps is not a synonymous spirochetosis to Lyme,
similar findings of organism persistence despite presumed adequate (short
course) therapy has been reported in those who later became immune
deficient (10).
Indeed, Wassermann in 1936 recommended a minimum of twenty
six weeks of treatment for established infection, based upon
generation-time studies.
I have recently participated in an NIH study utilizing the antigen
detection method of Dorward et al (11). In testing over 130 patients with
Chronic Persistent LB, in whom symptoms of active disease continued despite
even prolonged treatment (indeed, some would describe as excessive the
treatment given to several participants), Bb could be recovered from blood,
CSF, urine, and tears. Indeed, many of these patients had received months
to years of aggressive, often parenteral therapy for LB. For example, one
had received continual antibiotics for three years, while another was
treated for 18 months with repeated courses of parenteral therapy. As a
matter of record, neither one was a patient of mine.
These examples clearly indicate what researchers have recognized as the
ability of Bb to evade host defenses (1,12,13,14,15) even in the presence
of antibiotics (5,6,7,8).
I do not now recommend treatment forever, but I point out the above results
to be able to make several points:
1. There has never been a study in the history of this illness that even in
the simplest way proves that currently recognized short-course (two to four
week) therapy results in a bacteriologic cure.
2. There has never been a consensus in patients still symptomatic after
short treatment courses as to what constitutes the post Lyme syndrome, how
Bb induces it, and what perpetuates it if bacteriologic cure is indeed
presumed.
3. Patients must be kept on therapy until free of active symptoms or they
either will never recover fully, or suffer a relapse.
4. Extended durations of antibiotic therapy clearly have helped literally
thousands of patients who were not helped by short courses of treatment.
5. Finally, we have to recognize that in some patients, LB may not be
curable in a strict bacteriologic sense.
Until sensitive and specific antigen detection tests become widely
available, treatment of LB will remain difficult, controversial, and the
subject of much discussion.
J.J. Burrascano, Jr., M.D.
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SUGGESTED READING
1. Steere, A.C. Lyme Disease. N Engl J Med 1989; 321:586-96
2. MacDonald, A.B., Berger, B.W., Schwann, T.G. Clinical implications of
delayed growth of the Lyme Borreliosis spirochete, Borrelia
burgdorferi.
Acta Tropica 1991; 48:89-94
3. Cimmino, M.A., Azzolini, A., Tobia, F., Pesce, C.M. Spirochetes in the
spleen of a patient with chronic Lyme Disease. Am J Clin Pathol 1989;
91:95-97
4. Berger, B.W., Johnson, R.C., Schwann, T.G. Clinical and microbiologic
findings in six patients with erythema migrans of Lyme Disease. Am J Acad
Dermatol 1989; 21:1188-91
5. Kirsch, M. etal. Fatal adult respiratory distress syndrome in a patient
with Lyme Disease. JAMA 1989; 259:2737-39
6. Pfister, H.W., Preac-Mursic, V., Wilske, B. Latent Lyme
neuroborreliosis: Presence of Borrelia burgdorferi in the CSF without
concurrent inflammatory signs. Neurology 1989; 39:1118-20
7. Preac-Mursic, V., Weber, K., Pfister, H.W., Wilske, B. Survival of
Borrelia burgdorferi in antibiotically treated patients with Lyme
Borreliosis. Infection 1989; 17(6):355-359
8. Hassler, D., Riedel, K., Zorn, J., Preac-Mursic, V. Pulsed high dose
cefotaxime therapy in refractory Lyme Borreliosis. Lancet 1991; 338:13
9. Steere, A.C., Dwyer, E., Winchester, R. Association of chronic Lyme
arthritis with HLA-DR4 and HLA-DR2 alleles. NEJM 1990; 323:219-23
10. Musher, D.M. Syphilis, Neurosyphilis, Penicillin, and AIDS. J Infect
Dis 1991; 163:1201-1206
11. Dorward, D.W., Schwan, T.G., Garon, C.F. Immune capture and detection
of Borrelia burgdorferi antigens in urine, blood, or tissues from infected
ticks, mice, dogs, and humans. J Clin Microbiol 1991; 29(6):1162-70
12. Asbrink, E., Hovmark, A. Successful cultivation of spirochetes from
skin lesions of patients with erythema chronicum migrans Afzelius and
acrodermatitis Chronica atrophicans. Acta Pathol Microb Immunol Scand
1985; Sect B, 93:161-163
13. Pachner, A.R., Itano, A. Borrelia burgdorferi infection of the brain:
Characterization of the organism and response to antibiotics and immune
sera in the mouse model. Neurology 1990; 40:1535-40
14. MacDonald, A.B. Gestational Lyme Borreliosis. Implications for the
fetus. IN Rheumatic Disease Clinics of North America 1989;
15(4):657-677
15. Logigian, E.L., Kapan, R.F., Steere, A.C. Chronic neurologic
manifestations of Lyme Disease. N Engl J Med 1990; 323:1438-44
16. LaVoie, P.E. Lyme Disease. IN Conn's Current Therapy 1991 pp
101-105
17. Liegner, K.B. Lyme Disease: the Sensible Pursuit of Answers. J Clin
Microbiol 1993; 31(8): 1961-63
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