Antibiotic selection, route of administration, and duration of therapy for Lyme disease are guided by the patient’s clinical manifestations and stage of disease, as well as the presence of any concomitant medical conditions or allergies. Prompt treatment increases the likelihood of therapeutic success. Of great importance, doxycycline is contraindicated in patients younger than 8 years and in pregnant women. See the tables below.
Table 1. Clinical presentation and therapy for the stages of Lyme Disease (Open Table in a new window)
|Early localized||Erythema migrans||Oral||14-21 days|
|Early disseminated||Multiple erythema migrans||Oral||14-21 days|
|Isolated cranial nerve palsy||Oral||14-21 days|
|Meningitis||Intravenous or oral||14-21 days|
|-Hospitalized||Intravenous followed by oral||14-21 days|
|Borrelial lymphocytoma||Oral||14-21 days|
|Recurrent arthritis after oral therapy||Oral or intravenous||28 days or 14-28 days|
|Acrodermatitis chronica atrophicans||Oral||14-28 days|
Table 2. Adult and Pediatric treatment options, dosages, and routes of administration (Open Table in a new window)
|Treatment||Adult Dose||Pediatric Dose|
(patients =8 y)
|100 mg twice a day||
4 mg/kg (up to 100 mg)
twice a day
|Amoxicillin||500 mg three times a day||
50 mg/kg (up to 500 mg)
three times a day
|Cefuroxime axetil||500 mg twice a day||
30 mg/kg (up to 500 mg)
twice a day
|Intravenous therapy||Ceftriaxone||2 g once a day||
50-75 mg/kg (up to 2 g)
once a day
|Cefotaxime||2 g every 8 h||150-200 mg/kg (up to 2 g) every 8 h|
18-24 million U/d divided
every 4 h
(up to 2 g) every 8 h
In most patients with carditis, prompt institution of appropriate antibiotics is the only treatment needed. However, occasional patients with Lyme disease–related atrioventricular (AV) block may require hospitalization for temporary cardiac pacing. The indications for cardiac pacing are the same as for any other patient with varying degrees of heart block. Permanent pacing is very rarely needed.
Symptoms of arthritis may persist for a few weeks beyond adequate therapy. Repeat treatment usually is not necessary unless symptoms worsen or persist beyond 2 months.
Persistent arthritis after clearance of the infection is most likely related to autoimmunity and is more prevalent among individuals with HLA-DR2, HLA-DR3, or HLA-DR4 allotypes. These patients should be treated with nonsteroidal anti-inflammatory drugs (NSAIDs), plus hydroxychloroquine if necessary. As a last resort, such patients may need a synovectomy to eradicate the inflammatory arthritis in the involved joint.
Neurologic manifestations of Lyme disease in both adults and children respond well to penicillin, ceftriaxone, cefotaxime, and doxycycline. Although most studies of neuroborreliosis have used intravenous antibiotics, European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, or radiculitis, with intravenous regimens reserved for patients with parenchymal central nervous system (CNS) involvement, other severe neurologic symptomatology, or failure to respond to oral treatment. 
Borrelial lymphocytoma is sufficiently uncommon that no comparative trials address the ideal duration of treatment, route of administration of the antibiotic, or the choice of medication. Treatment is usually with 14-21 days of oral antibiotics. When symptoms of dissemination are noted, however, parenteral therapy sometimes is used.
Physicians should observe patients closely for possible Jarisch-Herxheimer reactions after the institution of therapy. This allergic/inflammatory response may manifest in the skin, mucous membranes, viscera, or nervous system.
In endemic areas, antibiotic prophylaxis may be appropriate for selected patients with a recognized tick bite (see Prevention). Prophylactic antibiotics are not routinely recommended, however, as tick bites rarely result in Lyme disease, and if infection does develop, early antibiotic treatment has excellent efficacy.
Several groups have published Lyme disease guidelines. The Infectious Diseases Society of America (IDSA) has released clinical practice guidelines for the assessment, treatment, and prevention of Lyme disease.  The American Academy of Neurology has established guidelines for the treatment of nervous system Lyme disease. 
The International Lyme and Associated Diseases Society (ILADS) issued updated recommendations for the management of Lyme disease in 2014.  The recommendations are all based on "very low quality evidence" and use patient preference as major portion of the support for the recommendations. In addition, the recommendations are limited to three specific aspects of Lyme disease. The differences between the IDSA and ILADS recommendations are outlined in the table below.
Table 3. Comparison of Infectious Diseases Society of America (IDSA) and International Lyme and Associated Diseases Society (ILADS) recommendations for Lyme disease treatment (Open Table in a new window)
|Treatment of a tick bite without symptoms of Lyme disease||Doxycycline, 200 mg as a single dose||Doxycycline, 100 mg bid for 20 days|
|Erythema migrans||Doxycycline, amoxicillin, or cefuroxime for 14-21 days||Doxycycline, amoxicillin, or cefuroxime for 28-42 days or azithromycin for at least 21 days|
|“Persisting symptoms of Lyme disease”||No antibiotic therapy||Multiple agents (individually or in combination) are mentioned without specific doses or duration recommended|
Controversy regarding the treatment of Lyme disease abounds, including an antitrust investigation initiated in 2008 by the Connecticut Attorney General (CAG) into the development process for the 2006 IDSA Lyme disease treatment guidelines. The CAG claimed the process was tainted by suppression of scientific evidence and conflicts of interest. 
In April 2008, the CAG and the IDSA reached an agreement to end the investigation. In 2010, a review panel convened as part of that agreement concluded that “the IDSA’s 2006 Lyme disease guidelines were based on the highest-quality medical and scientific evidence available at the time and are supported by evidence that has been published in more recent years.” 
Treatment of Early Lyme Disease
Early localized Lyme disease refers to isolated erythema migrans and to an undifferentiated febrile illness. This stage occurs 1-30 days after the tick bite. In endemic areas, patients with erythema migrans and a recent history of possible or proven tick exposure can be treated empirically, without laboratory confirmation of the diagnosis. Serologic testing is appropriate for patients who present more than 3 weeks after tick exposure.
Doxycycline, amoxicillin, or cefuroxime axetil is recommended for the treatment of adult patients with early localized or early disseminated Lyme disease associated with erythema migrans, in the absence of specific neurologic manifestations or third-degree heart block. Antibiotics recommended for children include amoxicillin and cefuroxime axetil; in children 8 years and older, doxycycline may be used. Because of its cost, cefuroxime axetil is reserved for patients unable to take amoxicillin or doxycycline
Macrolides are alternative agents, but they are used only when the first-line agents are not tolerated or are contraindicated. Those macrolides that have been compared with other antimicrobials in clinical trials of Lyme disease have been found to be less effective. 
Treatment for 14 days is recommended (range, 10-21 d for doxycycline and 14-21 d for amoxicillin or cefuroxime axetil). Longer treatment was previously recommended, but several studies have shown similar efficacy between 10-day and longer courses (20-21 d). [55, 56] Erythema migrans typically shows improvement within a few days after the institution of appropriate antibiotic therapy.
Patients with other manifestations who are treated with oral formulations should be treated for 30 days because, with these manifestations, accurately pinpointing the date of infection is not always possible. This regimen may also be effective for neurologic disease.
Neurologic Lyme disease is effectively treated with a 2-week course of parenteral penicillin, ceftriaxone, or cefotaxime. [47, 57] Oral doxycycline is as efficacious as parenteral antibiotics in patients who have Lyme-associated meningitis, facial nerve palsy, or radiculitis. 
For pregnant women with erythema migrans, some physicians recommend parenteral therapy, although data on this are limited. Isolated reports exist of transplacental transmission from the mother to fetus. One European descriptive study showed good results of parenteral ceftriaxone in pregnant women with erythema migrans. 
Pregnant women who develop Lyme disease should not be treated with doxycycline or another tetracycline. Risks to the fetus include permanent discoloration of the teeth, enamel hypoplasia, and retardation of skeletal development.
In patients without neurologic disease, Lyme arthritis can usually be treated successfully with oral antibiotics, with an extended treatment time of 28 days. Recommended regimens for adult patients are as follows  :
Doxycycline, 100 mg twice daily
Amoxicillin, 500 mg three times daily
Cefuroxime axetil, 500 mg twice daily per day
Recommended regimens for pediatric patients are as follows  :
Amoxicillin, 50 mg/kg/day in three divided doses (maximum of 500 mg/dose)
Cefuroxime axetil, 30 mg/kg/day in two divided doses (maximum of 500 mg/dose)
Doxycycline, 4 mg/kg/day in two divided doses (maximum of 100 mg/dose), if the patient is 8 years of age or older
Patients with mild residual joint swelling after a recommended course of oral antibiotic therapy can be re-treated with another 4-week course of oral antibiotics. Patients whose arthritis fails to improve or worsens can be re-treated with a 2- to 4-week course of intravenous ceftriaxone. IDSA guidelines suggest that clinicians consider waiting several months before starting a second round of antibiotics, as joint inflammation tends to resolve slowly even when the infection has been eliminated. 
In patients with persistent arthritis despite intravenous therapy, polymerase chain reaction (PCR) of synovial fluid (and synovial tissue, if available) can be done. PCR results may remain positive for several weeks after the eradication of Borrelia burgdorferi; nevertheless, if PCR is positive for B burgdorferi DNA, the patient can be treated with oral antibiotic therapy for another month. 
If PCR is negative, the patient should be given symptomatic treatment with nonsteroidal anti-inflammatory drugs NSAIDs). If necessary, NSAID treatment can be supplemented with oral hydroxychloroquine, 20 mg twice daily. [20, 43] Consultation with a rheumatologist is recommended in these cases.
Eventual resolution of chronic Lyme arthritis can be expected in all patients. However, patients who continue to have significant pain or limitation of function after 3-6 months of symptomatic therapy can be considered for arthroscopic synovectomy. [20, 43]
Intra-articular corticosteroids should not be given before antibiotic treatment, as they may promote persistent Lyme arthritis. Intra-articular corticosteroids are rarely indicated after antibiotic treatment. 
The patient with myocarditis generally is not very ill, and significant muscle dysfunction is unusual. Pericarditis with tamponade, while rare, has been reported.
Patients with atrioventricular (AV) heart block and/or myopericarditis associated with early Lyme disease may be treated with either oral or parenteral antibiotic therapy for 14 days (range, 14-21 days). Hospitalization and continuous monitoring are advisable for patients with any of the following  :
Associated symptoms (eg, syncope, dyspnea, or chest pain)
Second-degree or third-degree AV block
First-degree heart block with prolongation of the PR interval to more than 30 milliseconds (the degree of block may fluctuate and worsen very rapidly in such patients)
For patients with advanced heart block, a temporary pacemaker may be required; consultation with a cardiologist is recommended. Use of the pacemaker may be discontinued when the advanced heart block has resolved. An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis.
Although facial palsies may resolve without treatment, oral antibiotic therapy may prevent further sequelae. Encephalitis/encephalopathy should be treated with intravenous antibiotic therapy for 28 days.
The use of ceftriaxone in early Lyme disease is recommended for adult patients with acute meningitis or radiculopathy. Possible satisfactory alternatives include parenteral therapy with cefotaxime or penicillin G. For patients who are intolerant of β-lactam antibiotics, increasing evidence indicates that oral doxycycline (200-400 mg/d in two divided doses orally for 10-28 d) may be adequate. [60, 61, 62] With any regimen, neurologic symptoms may take 6 months to reach maximum improvement.
Patients with Lyme meningitis may need to be admitted not only for pain control but also for administration of intravenous antibiotics. If diagnostic uncertainty exists regarding the etiology of the meningitis, the antibiotic coverage may need to be extended for other more serious bacterial pathogens until the precise etiology is clarified.
Adult patients with late neurologic disease affecting the central or peripheral nervous system should be treated with intravenous medication. Response to treatment is usually slow and may be incomplete. Retreatment is not recommended unless relapse is shown by reliable objective measures.
Conjunctivitis and photophobia in stage 1 Lyme disease require no therapy. Bell palsy in stage 2 Lyme disease is self-limited, but patients require supportive therapy to prevent the complications of exposure keratitis. Keratitis and episcleritis benefit from topical corticosteroids, usually a short course of prednisolone acetate 1% or fluorometholone 0.1%.
A treatment regimen for severe neuro-ophthalmic disease (involving the optic nerve) or posterior segment disease (eg, pars planitis, vitreitis) has not been established. Oral corticosteroids without concomitant antibiotics should not be used.
The best approach for these patients might be a trial of antibiotic therapy, in which patients receive 2-3 weeks of intravenous penicillin or ceftriaxone. If patients respond to treatment, the trial is successful, ocular Lyme disease is diagnosed, and no further therapy is needed. Recurrences of Lyme uveitis, once adequate intravenous therapy has been given, can be treated with judicious corticosteroids.
Acrodermatitis Chronica Atrophicans
Acrodermatitis chronica atrophicans is usually treated with 1-month course of oral antibiotics, usually a beta-lactam or doxycycline. One study showed fewer relapses with 30 days compared with 20 or fewer days of therapy. In the same study, 30 days of oral antibiotics were more effective than 15 days of intravenous ceftriaxone (2 g/d).  It is important to ensure that no neurologic manifestations are present before embarking on oral therapy.
Post-Treatment Lyme Disease Syndrome
Despite appropriate antibiotic treatment, patients with Lyme disease may experience lingering symptoms similar to fibromyalgia (eg, fatigue, pain, joint and muscle aches). This condition has been termed chronic Lyme disease or, more precisely, post-treatment Lyme disease syndrome (PTLDS). 
These symptoms have not been shown in any controlled trials to be responsive to antibiotic therapy.  A study by Klempner et al failed to show a benefit of treatment with 2 g of intravenous ceftriaxone daily for 30 days, followed by oral doxycycline at 200 mg/d for 60 days.  Long-term IV ceftriaxone therapy can result in the formation of biliary sludge, which can lead to biliary colic.
Extended antibiotic therapy, sometimes for longer than 6 months, has been advocated for PTLDS. This not only can cause great harm to patients but also has resulted in one or more deaths. 
The existence of PTLDS has been called into question as a result of a lack of direct evidence of persistent infection. [67, 68] Hassett and colleagues reported that rates of psychiatric comorbidity and other psychological factors (eg, depression, anxiety, tendency to catastrophize pain) were higher in patients with “chronic Lyme disease” (defined as symptomatic patients with previously treated Lyme disease and patients whose symptoms were attributed to Lyme disease without good evidence for Lyme disease) than in other patients commonly seen in Lyme disease referral centers, and that those factors were related to poor functional outcomes. 
Co-infection with other tick-borne illnesses occur in roughly 10-15% of patients with Lyme disease and should be considered in patients with a poor response to conventional antimicrobial therapy or atypical clinical presentations (eg, high fever, leukopenia). Co-transmitted infective organisms can include the following:
Prevention of tick-borne disease can be divided into personal and environmental measures. Clinicians in endemic areas should provide patient education on personal measures for tick avoidance and management of tick exposure (see Patient Education).
Environmental prevention involves clearing underbrush and spraying acaricides in the spring around property sites. These measures prevent both mice and ticks from encroaching on properties. Studies involving the treatment of wild deer and mice have not been conclusive in reducing tick-borne diseases in humans.
In patients in endemic areas who present with an attached tick, prompt removal can reduce the likelihood of contracting Lyme disease. Transmission of infection is unlikely if the duration of tick attachment is less than 24 hours, but is very likely for ticks attached for longer than 72 hours.
Removal of a tick is ideally accomplished using fine-tipped forceps and wearing gloves. Grasp the tick as close to the skin surface as possible, including the mouth parts, and pull upward with steady, even traction. (See the image below). Do not twist or jerk the tick because this may cause the mouth parts to break off and remain in the skin; however, note that the mouth parts themselves are not infectious. Wear gloves to avoid possible infection.
The use of forceps and gloves represents an optimal method of removal. However, removal of the tick should not be delayed in order to obtain forceps and it is extremely unlikely that one can become infected by touching an engorged tick even if the tick is carrying Borrelia (which most of them are not, even in endemic areas).
Using lidocaine (subcutaneously or topically) may actually irritate the tick and prompt it to regurgitate its stomach contents. Once the tick is removed, wash the bite area with soap and water or with an antiseptic to destroy any contaminating microorganisms.
For more information, see Tick Removal.
Routine prophylaxis after a recognized tick bite is not recommended. A guideline from the Infectious Disease Society of America recommends prophylactic antibiotic therapy for adults and children older than 8 years, using a single 200-mg dose of doxycycline (in children, 4 mg/kg up to a maximum dose of 200 mg) only if all of the following criteria are met  :
The attached tick can be reliably recognized as a nymphal or adult Ixodes scapularis
The tick has been attached for at least 36 hours, as determined by the degree of engorgement of the tick or certainty about the time of exposure to the tick
Prophylaxis can be started within 72 hours of the time the tick was removed
The local rate of infection of these ticks with Borrelia burgdorferi is at least 20% (unlikely outside of select areas in New England, the mid-Atlantic States, Minnesota, and Wisconsin)
Doxycycline treatment is not contraindicated
The species of tick is important because non-Ixodes ticks (and other insects), although they can contain the organism, are highly unlikely to cause disease. The one clinically relevant exception may be bites by Amblyomma americanum in the central and southern midwestern United States, but few data exist on treating these tick bites prophylactically.
Doxycycline is relatively contraindicated in children younger than 8 years and in pregnant women. Amoxicillin should not be substituted for doxycycline in persons for whom doxycycline prophylaxis is contraindicated, for the following reasons  :
The absence of data on an effective short-course regimen for prophylaxis
The likely need for a multiday regimen (and its associated adverse effects)
The excellent efficacy of antibiotic treatment of Lyme disease if infection develops
The extremely low risk that a person with a recognized bite will develop a serious complication of Lyme disease
Even in areas where about 15-30% of ticks are infected with Borrelia burgdorferi, tick bites rarely result in Lyme disease. Nevertheless, appropriate prophylaxis can significantly reduce that risk.  In a 2010 meta-analysis of trials in which patients with no clinical evidence of Lyme disease were randomly allocated to treatment or placebo groups within 72 hours after an Ixodes tick bite, the risk of Lyme disease in the control group was 2.2% compared with 0.2% in the antibiotic-treated group. 
In December 1998, the FDA approved a vaccine (LYMErix Lyme disease vaccine [recombinant OspA]) directed against the outer surface protein A of B burgdorferi, after trials indicated efficacy. In 2002, this vaccine was pulled off the market by the manufacturer because of poor demand.  Patients who received this vaccine are no longer protected against Lyme disease, because the vaccine’s effect was not long lasting.
In most patients with erythema migrans, no consultation is needed. However, consultation with appropriate specialists (eg, rheumatologist, neurologist, cardiologist) may be indicated to ensure that other diseases are not the cause of unusual presenting symptoms in a patient with a positive Lyme titer.
Difficulties can arise in choosing the appropriate antibiotic treatment regimen, especially in children or potentially pregnant women. An infectious disease consult is helpful in these situations. 
Consultation with a rheumatologist may be helpful in the evaluation and treatment of patients with persistent arthritis despite conventional antimicrobial therapy and those who present with fibromyalgia occurring after treated Lyme disease.
Consultation with a neurologist is recommended in patients with persistent or chronic manifestations of Lyme disease, such as chronic fatigue syndrome. In addition, in patients with acrodermatitis chronica atrophicans, neurologic disease is not uncommon and its presence alters the treatment plan; therefore, consultation is appropriate if neurologic signs or symptoms are present.
Consultation with a cardiologist may be indicated in patients with coexisting cardiac disease.
Follow-up monitoring until all signs and symptoms have completely resolved is indicated for all patients with Lyme disease. In early Lyme disease, lack of prompt resolution should lead the physician to question the original diagnosis. Later manifestations tend to resolve much more slowly than early ones. Follow-up monitoring by the primary care physician or an appropriate specialist is indicated for patients with extracutaneous manifestations.
Patients with Lyme disease whose specific symptoms of Lyme disease (not symptoms of fibromyalgia or chronic fatigue) do not improve may need retreatment. Patients who plateau in their improvement may also need retreatment. Given the cost and convenience, a 30-day course of oral antibiotic therapy may be indicated before repeating intravenous therapy.
Repeat serologic testing is not indicated, because IgM titers may persist with treatment, and changes in IgG titers do not reflect the efficacy of treatment. That is, the standard serologic tests, with initial positive results, may remain positive for long periods and should not be used as a test of cure. Data suggest that C6-peptide may return negative results after treatment with antibiotics.
Follow-up may be of particular importance in patients with the chronic sequelae of the controversial post-Lyme disease syndrome. These patients’ condition may be refractory to conventional therapies.
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