Lyme disease medical therapy: Difference between revisions

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{{Lyme disease}}
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==Overview==
The mainstay of therapy for [[Lyme disease]] is [[antimicrobial]] therapy. [[Antimicrobial]] therapy may include [[doxycycline]], [[amoxicillin]], [[cephalosporin]]s, or [[macrolide]]s. The choice of [[antimicrobial]] therapy depends on the [[Lyme disease history and symptoms#Symptoms|stage of  Lyme disease]]. Individuals who remove attached [[ticks]] should be monitored closely for signs and symptoms of [[tick-borne diseases]] for up to 30 days.


==Medical Therapy==
==Medical Therapy==
===Lyme borreliosis (non-neuroborreliosis)===
'''Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for treatment of Lyme disease'''<ref name="pmid17029130">{{cite journal| author=Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS et al.| title=The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2006 | volume= 43 | issue= 9 | pages= 1089-134 | pmid=17029130 | doi=10.1086/508667 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17029130  }} </ref>
* '''1 Stage 1 - early localized Lyme disease'''
** 1.1 '''Erythema migrans'''
*** 1.1.1 '''Adult'''
**** Preferred regimen (1): [[Doxycycline]] 100 mg PO q12h for 10-21 days '''(avoid in [[pregnancy]])''' 
**** Preferred regimen (2): [[Amoxicillin]] 500 mg PO q8h for 14-21 days
**** Preferred regimen (3): [[Cefuroxime axetil]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[Azithromycin]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[Clarithromycin]] 500 mg PO q12h for 14–21 days '''(avoid in [[pregnancy]])'''
**** Alternative regimen (3): [[Erythromycin]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 '''Children < 8 years of age'''
***** Preferred regimen (1): [[Amoxicillin]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[Cefuroxime axetil]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[Azithromycin]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[Clarithromycin]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[Erythromycin]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 '''Children ≥ 8 years of age'''
***** Preferred regimen (1): [[Doxycycline]] 4 mg/kg/day PO q12h (maximum, 100 mg per dose)
***** Alternative regimen (1): [[Azithromycin]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[Clarithromycin]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[Erythromycin]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 2.1 '''When erythema migrans cannot be reliably distinguished from community-acquired bacterial [[cellulitis]]'''
*** 2.1.1 '''Adult'''
**** Preferred regimen (1): [[Amoxicillin-Clavulanate]] 500 mg PO q8h
*** 2.1.2  '''Pediatric'''
**** Preferred regimen (1):  [[Amoxicillin-Clavulanate]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


[[Antibiotics]] are the primary treatment for Lyme disease. [[Penicillin]] was first demonstrated by researchers to be useful against ''Borrellia'' in the 1950s; today the antibiotics of choice are [[doxycycline]], [[amoxicillin]] and [[ceftriaxone]]. [[Macrolide]] antibiotics are also used.
* 2 '''Stage 2 - early disseminated Lyme disease'''
 
** 2.1 '''Lyme carditis'''
Persons who remove attached ticks should be monitored closely for signs and symptoms of tick-borne diseases for up to 30 days. A three day course of [[doxycycline]] therapy may be considered for deer tick bites when the tick has been on the person for at least 12 hours. Patients should report any [[erythema migrans]] over the subsequent two to six weeks. If there should be suspicion of disease, then a course of [[doxycycline]] should be immediately given for ten days without awaiting serology tests which only yield positive results after an interval of one to two months.<!-- Advice given by Hosp. Trop. Med in 2004 to User:Davidruben-->
**: '''Note (1):''' A [[parenteral]] regimen is recommended at the start of therapy for patients who have been hospitalized for [[cardiac monitoring]]; oral regimen may be substituted to complete a course of therapy or to treat ambulatory patients.
 
**: '''Note (2)''': A temporary [[pacemaker]] may be required for patients with advanced [[heart block]].
In later stages, the bacteria disseminate throughout the body and may cross the [[blood-brain barrier]], making the infection more difficult to treat. Late  diagnosed Lyme is treated with oral or IV antibiotics, frequently [[ceftriaxone]], 2 grams per day, for a minimum of four weeks. [[Minocycline]] is also  indicated for neuroborreliosis for its ability to cross the blood-brain barrier.<ref>{{cite journal |author=Muellegger RR, Zoechling N, Soyer HP, ''et al'' |title=No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment |journal=Archives of dermatology |volume=131 |issue=6 |pages=678-82 |year=1995 |pmid=7778919 }}</ref><ref>{{cite journal |author=Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L |title=Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection |journal=J. Am. Acad. Dermatol. |volume=28 |issue=2 Pt 2 |pages=312-4 |year=1993 |pmid=8436647 }}</ref>
**: '''Note (3):''' Patients treated with [[Macrolide|macrolides]] should be closely observed to ensure resolution of the clinical manifest.
 
*** 2.1.1 '''Adult'''
===Antibiotic Treatment Controversy===
**** Parenteral regimen
{{see|Lyme disease controversy}}
***** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 (14–21) days
 
***** Alternative regimen (1): [[Cefotaxime]] 2 g IV q8h for 14 (14–21) days
With little research conducted specifically on treatment for late/chronic Lyme disease, particularly lyme encephalopathy, treatment remains controversial. Currently there are two sets of peer-reviewed published guidelines in the United States; the International Lyme and Associated Diseases Society (ILADS)<ref name="urlILADS - Lyme Disease Educational Videos, Lyme Disease Conferences, and LymeTeam">{{cite web |url=http://www.ilads.org |title=ILADS - Lyme Disease Educational Videos, Lyme Disease Conferences, and LymeTeam |format= |work= |accessdate=2013-03-14}}</ref> advocates extended courses of antibiotics for chronic Lyme patients in light of evidence of [[Lyme disease microbiology|persistent infection]], while the Infectious Diseases Society of America<ref name="urlIDSA : Index">{{cite web |url=http://www.idsociety.org/ |title=IDSA : Index |format= |work= |accessdate=2013-03-14}}</ref> does not recognize chronic infection and recommends no treatment for persistent symptoms. [[Double-blind]], [[placebo|placebo-controlled]] trials of long-term antibiotics for chronic Lyme have produced mixed results.
***** Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 14 (14–21) days '''(patients with normal [[renal function]])'''
 
**** Oral regimen
A controversial new guideline developed by the American Academy of Neurology, finds conventionally recommended courses of antibiotics are highly effective for treating nervous system Lyme disease. They find no compelling evidence that prolonged treatment with antibiotics has any benefit in treating symptoms that persist following standard therapy. The guideline is endorsed by the Infectious Diseases Society of America (IDSA). However, these guidelines refer mostly to early acute lyme neuroborreliosis, as there is a paucity of studies on late lyme encephalopathy and parenchymal CNS disease. The guideline leader was John J. Halperin and was co-written by Gary Worsmer and Eugene Shapiro, neither of whom are neurologists. Halperin, Worsmer and Shapiro were all co-authors of the IDSA Lyme guidelines released in 2006 by the Journal of Clinical Infectious Diseases. There is significant disagreement with this guideline (www.ilads.org).
***** Preferred regimen (1): [[Amoxicillin]] 500 mg PO q8h for 14 (14–21) days
 
***** Preferred regimen (2): [[Doxycycline]] 100 mg PO q12h for 14 (14–21) days '''(avoid in [[pregnancy]])'''
The latest double blind, randomized, [[placebo]]-controlled multicenter clincal study, done in Finland, results indicated that oral adjunct antibiotics were not justified in the treatment of patients with disseminated Lyme borreliosis who initially received intravenous antibiotics for 3 weeks. The researchers noted the clinical outcome of said patients should not be evaluated at the completion of intravenous antibiotic treatment but rather 6-12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies did not seem to provide any useful information for further care of the patient.<ref>{{cite journal |author=Oksi J, Nikoskelainen J, Hiekkanen H, ''et al'' |title=Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study |journal=Eur. J. Clin. Microbiol. Infect. Dis. |volume=26 |issue=8 |pages=571-81 |year=2007 |pmid=17587070 |doi=10.1007/s10096-007-0340-2}}</ref>
***** Preferred regimen (3): [[Cefuroxime]] 500 mg PO q12h for 14 (14–21) days
 
***** Alternative regimen (1): [[Azithromycin]] 500 mg PO q6h for 7–10 days  
===Antibiotic Resistant Therapies===
***** Alternative regimen (2): [[Clarithromycin]] 500 mg PO q12h for 14–21 days '''(avoid in [[pregnancy]])'''
Antibiotic treatment is the central pillar in the management of Lyme disease. In the late stages of borreliosis, symptoms may persist despite extensive and repeated antibiotic treatment.<ref>{{cite journal |author=Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK |title=Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis |journal=Ann. Med. |volume=31 |issue=3 |pages=225-32 |year=1999 |pmid=10442678 }}</ref><ref>{{cite journal |author=Hartiala P, Hytönen J, Pelkonen J, ''et al'' |title=Transcriptional response of human dendritic cells to Borrelia garinii--defective CD38 and CCR7 expression detected |journal=J. Leukoc. Biol. |volume=82 |issue=1 |pages=33-43 |year=2007 |pmid=17440035 |doi=10.1189/jlb.1106709}}</ref> Lyme arthritis which is antibiotic resistant may be treated with [[hydroxychloroquine]] or [[methotrexate]].<ref>{{cite journal |author=Massarotti EM |title=Lyme arthritis |journal=Med. Clin. North Am. |volume=86 |issue=2 |pages=297-309 |year=2002 |pmid=11982303 }}</ref> Experimental data is consensual on the deleterious consequences of systemic [[corticosteroid]] therapy. Corticosteroids are not indicated in Lyme disease.<ref>{{cite journal |author=Puéchal X |title=Non antibiotic treatments of Lyme borreliosis. |journal= Med Mal Infect |volume=[Epub ahead of print] |issue= |pages= |year=2007 |pmid=17376627 |doi=10.1016/j.medmal.2006.01.021}}</ref>
***** Alternative regimen (3): [[Erythromycin]] 500 mg PO q6h for 14–21 days
 
*** 2.1.2 '''Pediatric'''
Antibiotic refractory patients with neuropathic pain responded well to [[gabapentin]] monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.<ref>{{cite journal |author=Weissenbacher S, Ring J, Hofmann H |title=Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study |journal=Dermatology (Basel) |volume=211 |issue=2 |pages=123-7 |year=2005 |pmid=16088158 |doi=10.1159/000086441}}</ref> The immunomodulating, neuroprotective and anti-inflammatory potential of [[minocycline]] may be helpful in late/chronic Lyme disease with neurological or other inflammatory manifestations. Minocycline is used in other [[neurodegenerative]] and [[inflammatory]] disorders such as [[multiple sclerosis]], [[Parkinsons]], [[Huntingtons disease]], [[rheumatoid arthritis]] (RA) and [[ALS]].<ref>{{cite journal |author=Blum D, Chtarto A, Tenenbaum L, Brotchi J, Levivier M |title=Clinical potential of minocycline for neurodegenerative disorders |journal=Neurobiol. Dis. |volume=17 |issue=3 |pages=359-66 |year=2004 |pmid=15571972 |doi=10.1016/j.nbd.2004.07.012}}</ref>
**** Parenteral regimen
 
***** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
===Alternative Therapies===
***** Alternative regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
A number of other alternative therapies have been suggested, though clinical trials have not been conducted. For example, the use of [[hyperbaric oxygen therapy]] (which is used conventionally to treat a number of other conditions), as an adjunct to antibiotics for Lyme has been discussed.<ref name="Taylor">{{cite journal | author = Taylor R, Simpson I | title = Review of treatment options for Lyme borreliosis. | journal = J Chemother | volume = 17 Suppl 2 | issue = | pages = 3-16 | year = 2005 | pmid = 16315580}}</ref> Though there are no published data from clinical trials to support its use, preliminary results using a [[murine|mouse]] model suggest its effectiveness against ''B. burgdorferi'' both [[in vitro]] and [[in vivo]].<ref name=Pavia>{{cite journal | author = Pavia C | title = Current and novel therapies for Lyme disease. | journal = Expert Opin Investig Drugs | volume = 12 | issue = 6 | pages = 1003-16 | year = 2003 | pmid = 12783604}}</ref> Anecdotal clinical research has shown potential for the antifungal [[azole]] medications such as [[Fluconazole|diflucan]] in the treatment of Lyme, but has yet to be repeated in a controlled study or postulated a developed hypothetical model for its use.<ref>{{cite journal |author=Schardt FW |title=Clinical effects of fluconazole in patients with neuroborreliosis |journal=Eur. J. Med. Res. |volume=9 |issue=7 |pages=334-6 |year=2004 |pmid=15337633 }}</ref>
***** Alternative regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) '''(patients with normal [[renal function]])'''
 
**** Oral regimen
[[Alternative medicine]] approaches include bee venom because it contains the peptide [[melittin]], which has been shown to exert inhibitory effects on Lyme bacteria [[in vitro]];<ref>{{cite journal |author=Lubke LL, Garon CF |title=The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on the Lyme disease spirochete |journal=Clin. Infect. Dis. |volume=25 Suppl 1 |issue= |pages=S48-51 |year=1997 |pmid=9233664 }}</ref> no clinical trials of this treatment have been carried out, however.
***** Preferred regimen (1):  [[Amoxicillin]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
 
***** Preferred regimen (2): [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
===Post-treatment Lyme Disease Syndrome===
***** Preferred regimen (3): [[Cefuroxime]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2-4 week course of antibiotics will have lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months. Although often called “chronic Lyme disease,” this condition is properly known as “Post-treatment Lyme disease Syndrome” (PTLDS).
***** Alternative regimen (1):  [[Azithromycin]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
 
***** Alternative regimen (2): [[Clarithromycin]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
The exact cause of PTLDS is not yet known. Most medical experts believe that lingering symptoms are due to residual damage to the tissues and the immune system that occurred during the infection. Similar complications and auto-immune responses are known to occur following other infectious diseases.
***** Alternative regimen (3):  [[Erythromycin]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
 
** 2.2 '''Borrelial lymphocytoma'''
In contrast, a few health care providers tell patients that these symptoms reflect persistent infection with Borrelia burgdorferi. However, there is no credible scientific evidence that PTLDS is caused by persistent infection. More importantly, studies have shown that patients treated with prolonged courses of antibiotics do not do better than patients treated with placebo.
*** The same regimens used to treat patients with [[erythema migrans]] ([[Lyme disease medical therapy#Medical Therapy|see above]])
 
The good news is that patients with PTLDS almost always get better with time; the bad news is that it can take months or even years to feel completely well. If you have been treated for Lyme disease and still feel unwell, see your doctor to discuss how to relieve your suffering. Doctors may want to treat you in ways similar to patients who have [[fibromyalgia]] or [[chronic fatigue syndrome]]. This does not mean that your doctor is dismissing your pain or saying that you have these conditions instead. It simply means that the doctor is trying to help you cope with your symptoms using the tools available.
 
You may be tempted to try treatments that are unproven or non-standard in order to feel better. Unfortunately, many fraudulent products claiming to treat “chronic Lyme disease” are available on the internet or through some providers. These products have not been shown to help and can be toxic and even deadly.


It is normal to feel overwhelmed by your ongoing symptoms. Some things that may help you manage your PTLDS include:
* 3 '''Stage 3 - Late disseminated Lyme Disease'''
*Confirm your diagnosis. Make sure that Lyme disease is the only thing affecting your health.
** 3.1 '''Lyme arthritis'''
*** 3.1.1 '''Adult'''
**** Preferred regimen (1): [[Doxycycline]] 100 mg PO q12h for 28 days '''(avoid in [[pregnancy]])'''
**** Preferred regimen (2): [[Amoxicillin]] 500 mg PO q8h for 28 days
**** Preferred regimen (3): [[Cefuroxime axetil]] 500 mg PO q12h for 28 days
*** 3.1.2 '''Pediatric'''
**** Preferred regimen (1):  [[Amoxicillin]] 50 mg/kg/day PO q8h for 28 days   (maximum, 500 mg per dose)
**** Preferred regimen (1): [[Cefuroxime axetil]] 30 mg/kg/day PO q12h for 28 days (maximum, 500 mg per dose)
**** Preferred regimen (1): [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 28 days  (maximum, 100 mg per dose)
**:'''Note:''' Patients with persistent or recurrent [[joint swelling]] after a recommended course of oral [[antibiotic]] therapy are suggested re-treatment with another 4-week course of oral [[antibiotics]] or with a 2–4 week course of [[ceftriaxone]].
** 3.2 '''Patients with arthritis and objective evidence of neurologic disease'''
*** 3.2.1 '''Adult'''
**** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 2–4 weeks
**** Alternative regimen (1): [[Cefotaxime]] 2 g IV q8h for 2–4 weeks
**** Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 2-4 weeks '''(patients with normal [[renal function]])'''
*** 3.2.2 '''Pediatric'''
**** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg IV q24h for 2–4 weeks (maximum, 2 g)
**** Preferred regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h for 2–4 weeks (maximum, 6 g per day)
**** Alternative regimen (1): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h for 14 for 2–4 weeks (maximum, 18–24 million U per day) '''(patients with normal [[renal function]])'''
** 3.3 '''Acrodermatitis chronica atrophicans'''
*** Preferred regimen (1): [[Doxycycline]] 100 mg PO q12h for 21 days '''(avoid in [[pregnancy]])'''
*** Preferred regimen (2): [[Amoxicillin]] 500 mg PO q8h for 21 days
*** Preferred regimen (3): [[Cefuroxime axetil]] 500 mg PO q12h for 21 days


*Become well-informed. There is a lot of inaccurate information available, especially on the internet. Learn how to sort through this maze.
* 4. '''Post–Lyme Disease Syndromes'''
** Preferred regimen: Further [[antibiotic]] therapy for [[Lyme disease]] should not be given unless there are objective findings of active disease (including physical findings, abnormalities on [[Cerebrospinal fluid|cerebrospinal]] or [[synovial fluid]] analysis, or changes on formal [[Neuropsychological assessment|neuropsychologic testing]])


*Track your symptoms. It can be helpful to keep a diary of your symptoms, sleep patterns, diet, and exercise to see how these influence your well being.
===Lyme neuroborreliosis===
* 1. '''Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines'''<ref name="pmid17029130">{{cite journal| author=Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS et al.| title=The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. | journal=Clin Infect Dis | year= 2006 | volume= 43 | issue= 9 | pages= 1089-134 | pmid=17029130 | doi=10.1086/508667 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17029130  }} </ref>
** 1.1 '''Early neurologic disease (Stage 2 - early disseminated Lyme disease)'''
*** 1.1.1 '''Cranial nerve palsy'''
**** 1.1.1.1 '''Adult'''
***** Preferred regimen (1): [[Amoxicillin]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[Doxycycline]] 100 mg PO q12h for 14 (14–21) days '''(avoid in pregnancy)'''
***** Preferred regimen (3): [[Cefuroxime]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[Azithromycin]] 500 mg PO q6h for 7–10 days
***** Alternative regimen (2): [[Clarithromycin]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3): [[Erythromycin]] 500 mg PO q6h for 14–21 days
**** 1.1.1.2. '''Pediatric'''
***** Preferred regimen (1): [[Amoxicillin]] 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg/dose)
***** Preferred regimen (2): [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg/dose) 
***** Preferred regimen (3): [[Cefuroxime]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg/dose)
***** Alternative regimen (1): [[Azithromycin]] 10 mg/kg/day PO q6h for 7–10 days (maximum, 500 mg/day)
***** Alternative regimen (2): [[Clarithromycin]] 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg/dose)
***** Alternative regimen (3): [[Erythromycin]] 12.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg/dose)
*** 1.1.2 '''Meningitis or radiculopathy'''
**** 1.1.2.1 '''Adult'''
***** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 (10–28) days
***** Alternative regimen (1): [[Cefotaxime]] 2 g IV q6-8h for 14 (10–28) days
***** Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 14 (10–28) days '''(patients with normal [[renal function]])'''
***:'''Note:''' For adult patients intolerant of [[Beta-lactam antibiotic|β-lactam agents]], [[doxycycline]] '''(avoid in [[pregnancy]])''' 200–400 mg/day PO/IV q12h may be considered.
**** 1.1.2.2 '''Pediatric'''
***** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
***** Alternative regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6-8h for 14 (10–28) days  (maximum, 6 g/day) 
***** Alternative regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
***:'''Note:''' For children intolerant of [[Beta-lactam antibiotic|β-lactam agents]], [[doxycycline]] '''(children aged ≥ 8 years)''' 4–8 mg/kg/day PO/IV q12h (maximum, 200–400 mg/day may be considered)
** 1.2 '''Late neurologic disease (Stage 3 - late disseminated Lyme disease)'''
*** 1.2.1 '''Central or peripheral nervous system disease'''
**** 1.2.1.1 '''Adult'''
***** Preferred regimen: [[Ceftriaxone]] 2 g IV q24h for 14 (10–28) days
***** Alternative regimen (1): [[Cefotaxime]] 2 g IV q8h for 14 (10–28) days
***** Alternative regimen (2): [[Penicillin G]] 18–24 MU/day IV q4h for 14 (10–28) days '''(patients with normal [[renal function]])'''
**** 1.2.1.2 '''Pediatric'''
***** Preferred regimen: [[Ceftriaxone]] 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
***** Alternative regimen (1): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h for 14 (10–28) days  (maximum, 6 g/day)
***** Alternative regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''


*Maintain a healthy diet and get plenty of rest.
* 2 '''American Academy of Neurology (AAN) Practice Parameter'''<ref>{{Cite journal| doi = 10.1212/01.wnl.0000265517.66976.28| issn = 1526-632X| volume = 69| issue = 1| pages = 91–102| last1 = Halperin| first1 = J. J.| last2 = Shapiro| first2 = E. D.| last3 = Logigian| first3 = E.| last4 = Belman| first4 = A. L.| last5 = Dotevall| first5 = L.| last6 = Wormser| first6 = G. P.| last7 = Krupp| first7 = L.| last8 = Gronseth| first8 = G.| last9 = Bever| first9 = C. T.| last10 = Quality Standards Subcommittee of the American Academy of Neurology| title = Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology| journal = Neurology| date = 2007-07-03| pmid = 17522387}}</ref>
 
** 2.1 '''Meningitis'''
*Share your feelings. If your family and friends can't provide the support you need, talk with a counselor who can help you find ways of managing your life during this difficult time. As with any illness, Lyme disease can affect you and your loved ones. It doesn't mean that your symptoms are not real. It means that you are a human being who needs extra support in a time of need.
*** 2.1.1 '''Adult'''
**** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days
**** Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days
**** Preferred regimen (3): [[Penicillin G]] 18–24 MU/day q4h for 14 days '''(patients with normal [[renal function]])'''
**** Alternative regimen (1): [[Doxycycline]] 100–200 mg q12h for 14 days '''(avoid in [[pregnancy]])'''
*** 2.1.2 '''Pediatric'''
**** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
**** Preferred regimen (2): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
**** Preferred regimen (3): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
**** Alternative regimen (1): [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4–8 mg/kg/day q12h (maximum 200 mg/day)
** 2.2 '''Any neurologic syndrome with CSF pleocytosis'''
*** 2.2.1 '''Adult'''
**** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days
**** Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days
**** Preferred regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days '''(patients with normal [[renal function]])'''
**** Alternative regimen (1): [[Doxycycline]] 100–200 mg q12h for 14 days '''(avoid in [[pregnancy]])'''
*** 2.2.2 '''Pediatric'''
**** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
**** Preferred regimen (2): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
**** Preferred regimen (2): [[Penicillin G]] 200,000–400,000 U/kg/day q4h (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
**** Alternative regimen (1): [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4–8 mg/kg/day q12h (maximum 200 mg/day)
** 2.3 '''Peripheral nervous system disease (radiculopathy, diffuse neuropathy, mononeuropathy multiplex, cranial neuropathy; normal CSF)'''
*** 2.3.1 '''Adult'''
**** Preferred regimen (1): [[Doxycycline]] 100–200 mg q12h for 14 days '''(avoid in [[pregnancy]])'''
**** Alternative regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days
**** Alternative regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days
**** Alternative regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days '''(patients with normal [[renal function]])'''
*** 2.3.2 '''Pediatric'''
**** Preferred regimen (1):  [[Doxycycline]] '''(for children aged ≥ 8 years)''' 4–8 mg/kg/day q12h (maximum 200 mg/day)
**** Alternative regimen (1): [[Ceftriaxone]] 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
**** Alternative regimen (2): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
**** Alternative regimen (3): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
** 2.4 '''Encephalomyelitis'''
*** 2.4.1 '''Adult'''
**** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days
**** Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 
**** Preferred regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days '''(patients with normal [[renal function]])'''
*** 2.4.2 '''Pediatric'''
**** Preferred regimen (1): [[Ceftriaxone]] 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
**** Preferred regimen (2): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
**** Preferred regimen (3): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
** 2.5 '''Encephalopathy'''
*** 2.5.1 '''Adult'''
**** Preferred regimen (1): [[Ceftriaxone]] 2 g IV q24h for 14 days
**** Preferred regimen (2): [[Cefotaxime]] 2 g IV q8h for 14 days 
**** Preferred regimen (3): [[Penicillin G]] 18–24 MU/day IV q4h for 14 days '''(patients with normal [[renal function]])'''
*** 2.5.2 '''Pediatric'''
**** Preferred regimen (1):  [[Ceftriaxone]] 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
**** Preferred regimen (2): [[Cefotaxime]] 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
**** Preferred regimen (3): [[Penicillin G]] 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) '''(patients with normal [[renal function]])'''
** 2.6 '''Post-treatment Lyme syndrome'''
*** Preferred regimen: [[symptomatic]] management
**: '''Note:''' [[Antibiotic]] therapy is not indicated
===Follow-up===
*Approximately 10 to 20% of patients treated for [[Lyme disease]] with a recommended 2-4 week course of [[Antibiotic|antibiotics]] will develop [[Lyme disease natural history, complications and prognosis|post-treatment Lyme disease syndrome (PTLDS)]]. Patients report lingering symptoms of [[fatigue]], [[pain]], or [[Joint aches|joint]] and [[muscle aches]]. In some cases, these can last for more than 6 months.
*The majority of patients with [[Lyme disease natural history, complications and prognosis|post-treatment Lyme disease syndrome]] gradually improve over months/years of the primary [[infection]].


==References==
==References==
{{reflist|2}}
{{reflist|2}}


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Anmol Pitliya, M.B.B.S. M.D.[2]

Overview

The mainstay of therapy for Lyme disease is antimicrobial therapy. Antimicrobial therapy may include doxycycline, amoxicillin, cephalosporins, or macrolides. The choice of antimicrobial therapy depends on the stage of Lyme disease. Individuals who remove attached ticks should be monitored closely for signs and symptoms of tick-borne diseases for up to 30 days.

Medical Therapy

Lyme borreliosis (non-neuroborreliosis)

Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for treatment of Lyme disease[1]

  • 1 Stage 1 - early localized Lyme disease
    • 1.1 Erythema migrans
      • 1.1.1 Adult
      • 1.1.2 Pediatric
        • 1.1.2.1 Children < 8 years of age
          • Preferred regimen (1): Amoxicillin 50 mg/kg PO per day q8h (maximum, 500 mg per dose)
          • Preferred regimen (2): Cefuroxime axetil 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
          • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h (maximum, 500 mg per day)
          • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
          • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
        • 1.1.2.2 Children ≥ 8 years of age
          • Preferred regimen (1): Doxycycline 4 mg/kg/day PO q12h (maximum, 100 mg per dose)
          • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h (maximum, 500 mg per day)
          • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
          • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
    • 2.1 When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
  • 2 Stage 2 - early disseminated Lyme disease
    • 2.1 Lyme carditis
      Note (1): A parenteral regimen is recommended at the start of therapy for patients who have been hospitalized for cardiac monitoring; oral regimen may be substituted to complete a course of therapy or to treat ambulatory patients.
      Note (2): A temporary pacemaker may be required for patients with advanced heart block.
      Note (3): Patients treated with macrolides should be closely observed to ensure resolution of the clinical manifest.
      • 2.1.1 Adult
        • Parenteral regimen
          • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 (14–21) days
          • Alternative regimen (1): Cefotaxime 2 g IV q8h for 14 (14–21) days
          • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (14–21) days (patients with normal renal function)
        • Oral regimen
          • Preferred regimen (1): Amoxicillin 500 mg PO q8h for 14 (14–21) days
          • Preferred regimen (2): Doxycycline 100 mg PO q12h for 14 (14–21) days (avoid in pregnancy)
          • Preferred regimen (3): Cefuroxime 500 mg PO q12h for 14 (14–21) days
          • Alternative regimen (1): Azithromycin 500 mg PO q6h for 7–10 days
          • Alternative regimen (2): Clarithromycin 500 mg PO q12h for 14–21 days (avoid in pregnancy)
          • Alternative regimen (3): Erythromycin 500 mg PO q6h for 14–21 days
      • 2.1.2 Pediatric
        • Parenteral regimen
          • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
          • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
          • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) (patients with normal renal function)
        • Oral regimen
          • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg per dose)
          • Preferred regimen (2): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
          • Preferred regimen (3): Cefuroxime 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg per dose)
          • Alternative regimen (1): Azithromycin 10 mg/kg PO q6h 7–10 days (maximum, 500 mg per day)
          • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg per dose)
          • Alternative regimen (3):  Erythromycin 12.5 mg/kg PO q6h for 14–21 days (maximum,500 mg per dose)
    • 2.2 Borrelial lymphocytoma
  • 3 Stage 3 - Late disseminated Lyme Disease
    • 3.1 Lyme arthritis
      • 3.1.1 Adult
      • 3.1.2 Pediatric
        • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 28 days  (maximum, 500 mg per dose)
        • Preferred regimen (1): Cefuroxime axetil 30 mg/kg/day PO q12h for 28 days (maximum, 500 mg per dose)
        • Preferred regimen (1): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 28 days  (maximum, 100 mg per dose)
      Note: Patients with persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy are suggested re-treatment with another 4-week course of oral antibiotics or with a 2–4 week course of ceftriaxone.
    • 3.2 Patients with arthritis and objective evidence of neurologic disease
      • 3.2.1 Adult
        • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 2–4 weeks
        • Alternative regimen (1): Cefotaxime 2 g IV q8h for 2–4 weeks
        • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 2-4 weeks (patients with normal renal function)
      • 3.2.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 2–4 weeks (maximum, 2 g)
        • Preferred regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 2–4 weeks (maximum, 6 g per day)
        • Alternative regimen (1): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 for 2–4 weeks (maximum, 18–24 million U per day) (patients with normal renal function)
    • 3.3 Acrodermatitis chronica atrophicans

Lyme neuroborreliosis

  • 1. Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines[1]
    • 1.1 Early neurologic disease (Stage 2 - early disseminated Lyme disease)
      • 1.1.1 Cranial nerve palsy
        • 1.1.1.1 Adult
          • Preferred regimen (1): Amoxicillin 500 mg PO q8h for 14 (14–21) days
          • Preferred regimen (2): Doxycycline 100 mg PO q12h for 14 (14–21) days (avoid in pregnancy)
          • Preferred regimen (3): Cefuroxime 500 mg PO q12h for 14 (14–21) days
          • Alternative regimen (1): Azithromycin 500 mg PO q6h for 7–10 days
          • Alternative regimen (2): Clarithromycin 500 mg PO q12h for 14–21 days
          • Alternative regimen (3): Erythromycin 500 mg PO q6h for 14–21 days
        • 1.1.1.2. Pediatric
          • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h for 14 (14–21) days (maximum, 500 mg/dose)
          • Preferred regimen (2): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg/dose)
          • Preferred regimen (3): Cefuroxime 30 mg/kg/day PO q12h for 14 (14–21) days (maximum, 500 mg/dose)
          • Alternative regimen (1): Azithromycin 10 mg/kg/day PO q6h for 7–10 days (maximum, 500 mg/day)
          • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg/dose)
          • Alternative regimen (3): Erythromycin 12.5 mg/kg PO q12h for 14–21 days (maximum, 500 mg/dose)
      • 1.1.2 Meningitis or radiculopathy
        • 1.1.2.1 Adult
          • Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 (10–28) days
          • Alternative regimen (1): Cefotaxime 2 g IV q6-8h for 14 (10–28) days
          • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (10–28) days (patients with normal renal function)
        Note: For adult patients intolerant of β-lactam agents, doxycycline (avoid in pregnancy) 200–400 mg/day PO/IV q12h may be considered.
        • 1.1.2.2 Pediatric
          • Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
          • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6-8h for 14 (10–28) days (maximum, 6 g/day)
          • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) (patients with normal renal function)
        Note: For children intolerant of β-lactam agents, doxycycline (children aged ≥ 8 years) 4–8 mg/kg/day PO/IV q12h (maximum, 200–400 mg/day may be considered)
    • 1.2 Late neurologic disease (Stage 3 - late disseminated Lyme disease)
      • 1.2.1 Central or peripheral nervous system disease
        • 1.2.1.1 Adult
          • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 (10–28) days
          • Alternative regimen (1): Cefotaxime 2 g IV q8h for 14 (10–28) days
          • Alternative regimen (2): Penicillin G 18–24 MU/day IV q4h for 14 (10–28) days (patients with normal renal function)
        • 1.2.1.2 Pediatric
          • Preferred regimen: Ceftriaxone 50–75 mg/kg IV q24h for 14 (10–28) days (maximum, 2 g/day)
          • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h for 14 (10–28) days (maximum, 6 g/day)
          • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h for 14 (10–28) days (maximum, 18–24 MU/day) (patients with normal renal function)
  • 2 American Academy of Neurology (AAN) Practice Parameter[2]
    • 2.1 Meningitis
      • 2.1.1 Adult
      • 2.1.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
        • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
        • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
        • Alternative regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
    • 2.2 Any neurologic syndrome with CSF pleocytosis
      • 2.2.1 Adult
      • 2.2.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
        • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
        • Preferred regimen (2): Penicillin G 200,000–400,000 U/kg/day q4h (maximum, 18–24 MU/day) (patients with normal renal function)
        • Alternative regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
    • 2.3 Peripheral nervous system disease (radiculopathy, diffuse neuropathy, mononeuropathy multiplex, cranial neuropathy; normal CSF)
      • 2.3.1 Adult
      • 2.3.2 Pediatric
        • Preferred regimen (1): Doxycycline (for children aged ≥ 8 years) 4–8 mg/kg/day q12h (maximum 200 mg/day)
        • Alternative regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
        • Alternative regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
        • Alternative regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
    • 2.4 Encephalomyelitis
      • 2.4.1 Adult
      • 2.4.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
        • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
        • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
    • 2.5 Encephalopathy
      • 2.5.1 Adult
      • 2.5.2 Pediatric
        • Preferred regimen (1): Ceftriaxone 50–75 mg/kg/day IV q24h (maximum, 2 g/day)
        • Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6–8h (maximum, 6 g/day)
        • Preferred regimen (3): Penicillin G 200,000–400,000 U/kg/day IV q4h (maximum, 18–24 MU/day) (patients with normal renal function)
    • 2.6 Post-treatment Lyme syndrome
      Note: Antibiotic therapy is not indicated

Follow-up

References

  1. 1.0 1.1 Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS; et al. (2006). "The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America". Clin Infect Dis. 43 (9): 1089–134. doi:10.1086/508667. PMID 17029130.
  2. Halperin, J. J.; Shapiro, E. D.; Logigian, E.; Belman, A. L.; Dotevall, L.; Wormser, G. P.; Krupp, L.; Gronseth, G.; Bever, C. T.; Quality Standards Subcommittee of the American Academy of Neurology (2007-07-03). "Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology". Neurology. 69 (1): 91–102. doi:10.1212/01.wnl.0000265517.66976.28. ISSN 1526-632X. PMID 17522387.