- ILADS Guideliness
Guidelines for the management of
Lyme disease (PDF)
November 1st, 2006
Joseph J. Burrascano Jr, MD:
Diagnostic Hints and Treatment
Guidelines for Lyme and Other Tick Borne Illnesses
October, 2008 NEW UPDATES
National Guideline Clearinghouse:
Summary of ILADS Treatment Guidelines for Lyme Disease
disease can become persistent, recurrent, and refractory even in the
face of antibiotic therapy, evaluation and treatment must be prompt and
Prompt Use of
Although no well
designed studies have been carried out, the available data support the
prompt use of antibiotics to prevent chronic Lyme disease. Antibiotic
therapy may need to be initiated upon suspicion of the diagnosis, even
without definitive proof. Neither the optimal antibiotic dose nor the
duration of therapy has been standardized, but limited data suggest a
benefit from increased dosages and longer treatment, comparable to the
data on tuberculosis and leprosy which are caused by similarly
In acute Lyme
disease, the choice of antibiotics should be tailored to the individual
and take into account the severity of the disease as well as the
patient’s age, ability to tolerate side effects, clinical features,
allergy profile, comorbidities, prior exposure, epidemiologic setting,
persistent and refractory Lyme disease treatment is more likely to
include intravenous and/or intramuscular antibiotics. The choices depend
in part on the patient’s response to antibiotic therapy and on the
success of antibiotics in treating other Lyme disease patients.
starts with oral antibiotics, and some experts recommend high dosages.
The choice of antibiotic therapy is guided by weighing the greater
activity of intravenous antibiotics in the central nervous system
against the lower cost and easy administration of oral antibiotics for
For many Lyme
disease patients, there is no clear advantage of parenteral therapy.
Along with cost considerations and pressure to treat patients with Lyme
disease with the least intervention, there is growing interest in the
use of oral therapy.
therapies for Lyme disease may include (in alphabetical order): oral
amoxicillin, azithromycin, cefuroxime, clarithromycin, doxycycline, and
tetracycline. These antibiotics have similar favorable results in
comparative trials of early Lyme disease.
It is common
practice to consider intravenous antibiotics upon failure of oral
medications in patients with persistent, recurrent, or refractory Lyme
disease, and as the first line of therapy for certain conditions, (i.e.,
encephalitis, meningitis, optic neuritis, joint effusions, and heart
intravenous antibiotic should be selected on the basis of in vitro
sensitivity testing or clinical experience. Intravenous antibiotics are
also justified by concern for penetration into the central nervous
ceftriaxone, cefotaxime, and penicillin were the only intravenous
antibiotics routinely studied for use in Lyme disease. Intravenous
imipenem, azithromycin, and doxycycline have an adequate antispirochetal
spectrum of activity and may represent suitable alternative therapies.
However, the latter two drugs are often considered for intravenous use
only if they are not tolerated orally.
benzathine penicillin (1.2 to 2.4 million units per week) is sometimes
effective in patients who do not respond to oral and intravenous
antibiotics. If intramuscular benzathine penicillin is used, long-term
therapy may be necessary due to the low serum concentration of this form
of penicillin. Benzathine penicillin has mainly been used in patients
who have had multiple relapses while receiving oral or intravenous
antibiotic therapy or who are intolerant of oral or intravenous
therapy with two or more antibiotics is now increasingly used for
refractory Lyme disease and has also been given as initial therapy for
some chronic presentations.
This approach is
already used for another tick-borne illness, babesiosis. Oral
amoxicillin, cefuroxime, or (more recently) cefdinir combined with a
macrolide (azithromycin or clarithromycin) are examples of combination
regimens that have proven successful in clinical practice, although
controlled clinical trials are lacking in persistent, recurrent, and
refractory Lyme disease.
therapy in patients with Lyme disease raises the risk of adverse events.
This risk must be weighed against the improved response to combination
therapy in Lyme disease patients failing single agents.
increasingly use the sequence of an intravenous antibiotic followed by
an oral or intramuscular antibiotic. In two recent case series that
employed combination therapy and sequential therapy, most patients were
successfully treated. A logical and attractive sequence would be to use
intravenous therapy first (e.g., intravenous ceftriaxone), at least
until disease progression is arrested and then follow with oral therapy
for persistent and recurrent Lyme disease.
clinicians recommend that certain drugs used for Lyme disease be given
at higher daily doses: for example, 3,000–6,000 mg of amoxicillin,
300–400 mg doxycycline, and 500–600 mg of azithromycin. Some clinicians
prescribe antibiotics using blood levels to guide higher doses. Close
monitoring of complete blood counts and chemistries are also required
with this approach.
doses, there may be an increase in adverse events in general and
gastrointestinal problems in particular. Acidophilus has reportedly
reduced the incidence of Clostridium difficile colitis and non-C.
difficile antibiotic-related diarrhea.
effects of antibiotics, however, were less common than previous
estimates. In a recent clinical trial of chronic Lyme disease, the
overall serious adverse event rate was 3% after three months of
antibiotics, including 1 month of intravenous antibiotics. Clinicians
who have experience with higher dose antibiotic therapy must balance the
benefit of higher drug levels achieved with this therapy against the
modest risk of gastrointestinal and other side effects.
Because of the
disappointing long-term outcome with shorter courses of antibiotics, the
practice of stopping antibiotics to allow for a delayed recovery is no
longer recommended for patients with persistent, recurrent, and
refractory Lyme disease. Reports show failure rates of 30–62% within 3
years of short-course treatment using antibiotics thought to be
effective for Lyme disease. Conversely for neurologic complications of
Lyme disease, doubling the length of intravenous ceftriaxone treatment
from 2 to 4 weeks improved the success rate from 66 to 80%.
The management of
chronic Lyme disease must be individualized, since patients will vary
according to severity of presentation and response to previous
factors (i.e., coinfections, previous treatment failures, frequent
relapses, neurologic involvement, or previous use of corticosteroids) or
evidence of unusually severe Lyme disease should lead to the initiation
of prolonged and/or intravenous antibiotic treatment. Physicians should
always assess the patient’s response to treatment before deciding on
appropriate duration of therapy (i.e., weeks versus months).
The importance of
establishing the diagnosis of Lyme disease is heightened in light of
increasing concern about antibiotic overuse. After an appropriate
history, physical examination, and laboratory testing are completed,
empiric antimicrobial therapy should be initiated on the basis of
clinical clues, the severity of the patient’s acute illness, underlying
disease, and the likelihood of B. burgdorferi infection. The
International Lyme and Associated Diseases Society (ILADS) working group
recommends that empiric treatment be considered routine for patients
with a likely diagnosis of Lyme disease.
disease is more resistant to treatment and more likely to produce a
relapse. Although persistent Lyme disease may resolve without additional
therapy, many experts believe that this condition should be treated with
repeated and prolonged antibiotics. Physicians should extend the
duration of antibiotics to prevent or delay recurrent and refractory
antibiotic treatment, Lyme disease has a propensity for relapse and
requires careful follow-up for years. The data suggest that failure to
eradicate the organism may be the reason for a recurrence of symptoms.
Early and aggressive treatment with antibiotics is indicated for
recurrent Lyme disease. The ultimate impact from retreating each episode
of recurrent Lyme disease is currently unclear.
disease is a devastating condition that usually affects patients with
persistent symptomatology and long-term disability. Prompt and
aggressive institution of antibiotic therapy may be essential to prevent
refractory disease. Increasing evidence shows that antibiotics have a
beneficial effect on the course of refractory Lyme disease even in cases
where the patient is intolerant of antibiotics or when a previous
regimen has failed. Several months of therapy are often required to
produce clear evidence of improvement. During this time, symptomatic
treatment may be combined with antibiotic treatment.
fail to respond or their conditions deteriorate after initiation of
empiric therapy, a number of possibilities should be considered other
than Jarisch-Herxheimer reaction. These include adverse events that
limit treatment, allergic history to medication, inappropriate or
inadequate dosing regimen, compliance problems, incorrect medication,
immune sequelae, and sequestering of the organism (e.g., in the central
nervous system). An alternative diagnosis or coinfection should also be
may be a potential role for symptomatic treatment in chronic Lyme
disease, this approach has little support due to the strong possibility
of persistent infection. Owing to the potential hazard of
immunosuppression and the poor outcome in one study, steroid therapy is
not recommended. Surgical synovectomy is associated with significant
morbidity and does not address neurologic presentations; it should be
reserved for knee pain failing antibiotic treatment. Intra-articular
steroid injection may be useful as a temporizing procedure in patients
with persistent knee pain but this runs the risk of masking persistent
therapy (particularly anti-inflammatory medications, tricyclic
antidepressants, selective serotonin re-uptake inhibitors, and
hydroxychloroquine) may be useful in concert with antibiotics and in
individuals failing antibiotics.
therapy (HBOT) is under study but is not recommended for routine
therapeutic use. Other treatments, including cholestyramine (CSM),
antifungal therapy, and antiviral agents require further study.
are becoming more interested in alternative therapies (e.g., traditional
Chinese medicine, anti-oxidants, hyperthermia, bee venom, naturopathy
and homeopathy), physicians should be prepared to address questions
regarding these topics.
The outcome of
treating fibromyalgia secondary to Lyme disease with nonantibiotic
regimens has been poor. The most encouraging clinical trial showed
success in only one of 15 patients and only modest improvement in 6 of
15 individuals with fibromyalgia despite 2 years of treatment.
therapy has been much more effective than supportive therapy in
symptomatic patients with fibromyalgia secondary to Lyme disease.
treatment alone without antibiotics raises the risk of conversion to
refractory chronic Lyme disease and/or exacerbation of an undiagnosed
persistent infection and is not recommended. Increasingly, clinicians do
not feel comfortable treating fibromyalgia in Lyme disease without
of patients with Lyme disease have recommended that antibiotics be
discontinued after 30 days of treatment. Complicating the decision to
stop antibiotics is the fact that some patients present with disease
recurrence after the resolution of their initial Lyme disease symptoms.
This is consistent with incomplete antibiotic therapy. Although the
optimal time to discontinue antibiotics is unknown, it appears to be
dependent on the extent of symptomatology, the patient’s previous
response to antibiotics, and the overall response to therapy (see
Rather than an
arbitrary 30-day treatment course, the patient’s clinical response
should guide duration of therapy. Patients must therefore be carefully
evaluated for persistent infection before a decision is made to withhold
The decision to
discontinue antibiotics should be made in consultation with the patient
and should take into account such factors as the frequency and duration
of persistent infection, frequency of recurrence, probability of
refractory Lyme disease, gains with antibiotics, the importance to the
patient of discontinuing antibiotics, and potential for careful
approach would be to continue therapy for Lyme disease until the Lyme
spirochete is eradicated. Unfortunately there is currently no test
available to determine this point. Therefore, the clinician must rely on
the factors outlined above to decide on the length of antibiotic therapy
for chronic Lyme disease.
compelling evidence that Lyme disease can result in serious and
potentially refractory illness. Use of alternative antibiotics to treat
early Lyme disease with erythema migrans is generally not indicated
unless coinfection is suspected.
The ILADS Working
Group believes that the risk of alternative antibiotics is acceptable in
selected Lyme disease patients presenting with chronic Lyme disease.
Alternative antibiotics include less commonly used oral antibiotics (cefixime,
cefdinir, metronidazole) and intravenous antibiotics (imipenem,
azithromycin). The role of alternative antibiotics in low-risk patients
is less certain and there is less consensus among the guideline
developers as to whether the potential benefits outweigh the risks.
polymicrobial infection in Lyme disease is a rapidly changing area of
clinical practice. Uncomplicated Lyme disease may be managed without
addressing coinfection by means of standard oral or parenteral
antibiotic therapy. Some but not all experts recommend therapy for
subclinical or chronic coinfection with Ehrlichia, Babesia, or
Bartonella on the basis of their belief that responses are more prompt
with this approach.
duration, and type of treatment for coinfections have not been defined.
Published reports of coinfection are limited to a small number of
patients treated in open-label, nonrandomized studies. Doxycycline has
been indicated for Ehrlichia. A recently published randomized trial
determined that treatment of severe Babesia microti with the combination
of atovaquone and azithromycin was as effective as the use of standard
oral therapy with clindamycin and quinine.
The decision to
use alternative antibiotics should be based on the individual case,
including a careful assessment of the patient’s risk factors and
personal preferences. Patients managed in this way must be carefully
selected and considered reliable for follow-up. Further controlled
studies are needed to address the optimal antimicrobial agents for
coinfections and the optimal duration of therapy.
Evidence-based guidelines for the management of Lyme disease. Expert
Rev Antiinfect Ther 2004;2(1 Suppl):S1-13. [66 references]
DEVELOPER(S): International Lyme and Associated Diseases Society —
Disease Specific Society
FUNDING: International Lyme and Associated Diseases Society
COMMITTEE: The ILADS Working Group
GROUP THAT AUTHORED THE GUIDELINE: Working Group Members:
Daniel Cameron, MD, MPH, Internal Medicine and Epidemiology, Mt. Kisco,
New York; Andrea Gaito, MD, Rheumatology, Basking Ridge, New Jersey;
Nick Harris, PhD, Immunology, Pal Alto, California; Gregory Bach, DO,
Family and Integrative Medicine, Colmar, Pennsylvania; Sabra Bellovin,
MD, Family Practice, Portsmouth, Virginia; Kenneth Bock, MD, Family
Practice, Rhineback, New York; Steven Bock, MD, Family Practice,
Rhineback, New York; Joseph Burrascano, MD, Internal Medicine, East
Hampton, New York; Constance Dickey, RN, Registered Nurse, Hampden,
Maine; Richard Horowitz, MD, Internal Medicine, Hyde Park, New York;
Steven Phillips, MD, Internal Medicine, Ridgefield, Connecticut;
Laurence Meer-Scherrer, MD, Internal Medicine, Flamatt, Switzerland;
Bernard Raxlen, MD; Psychiatry, Greenwich, Connecticut; Virginia Sherr,
MD, Psychiatry, Holland, Pennsylvania; Harold Smith, MD, Emergency
Medicine, Danville, Pennsylvania; Pat Smith, President, Lyme Disease
Association, Inc., Jackson, New Jersey; Raphael Stricker, MD, Hematology
and Immunotherapy, San Francisco, California
DISCLOSURES/CONFLICTS OF INTEREST: Not stated
STATUS: This is the current release of the guideline.