Lyme disease medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Medical Therapy

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.

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.

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.[1][2]

Antibiotic Treatment Controversy

Further information: Lyme disease controversy

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)[3] advocates extended courses of antibiotics for chronic Lyme patients in light of evidence of persistent infection, while the Infectious Diseases Society of America[4] does not recognize chronic infection and recommends no treatment for persistent symptoms. Double-blind, placebo-controlled trials of long-term antibiotics for chronic Lyme have produced mixed results.

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).

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.[5]

Antibiotic Resistant Therapies

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.[6][7] Lyme arthritis which is antibiotic resistant may be treated with hydroxychloroquine or methotrexate.[8] Experimental data is consensual on the deleterious consequences of systemic corticosteroid therapy. Corticosteroids are not indicated in Lyme disease.[9]

Antibiotic refractory patients with neuropathic pain responded well to gabapentin monotherapy with residual pain after intravenous ceftriaxone treatment in a pilot study.[10] 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.[11]

Alternative Therapies

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.[12] Though there are no published data from clinical trials to support its use, preliminary results using a mouse model suggest its effectiveness against B. burgdorferi both in vitro and in vivo.[13] Anecdotal clinical research has shown potential for the antifungal azole medications such as 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.[14]

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;[15] no clinical trials of this treatment have been carried out, however.

Post-treatment Lyme Disease Syndrome

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).

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.

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 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:

  • Confirm your diagnosis. Make sure that Lyme disease is the only thing affecting your health.
  • Become well-informed. There is a lot of inaccurate information available, especially on the internet. Learn how to sort through this maze.
  • 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.
  • Maintain a healthy diet and get plenty of rest.
  • 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.

Antimicrobial Regimen

  • 1. Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines[16]
  • 1.1 Early neurologic disease
  • 1.1.1 Cranial nerve palsy (adult)
  • Preferred regimen (1): Amoxicillin 500 mg PO tid for 14 (14–21) days
  • Preferred regimen (2): Doxycycline 100 mg PO bid for 14 (14–21) days
  • Preferred regimen (3): Cefuroxime 500 mg PO bid for 14 (14–21) days
  • Alternative regimen (1): Azithromycin 500 mg PO qd for 7–10 days
  • Alternative regimen (2): Clarithromycin 500 mg PO bid for 14–21 days (not for pregnant)
  • Alternative regimen (3): Erythromycin 500 mg PO qid for 14–21 days
  • 1.1.2 Cranial nerve palsy (pediatric)
  • Preferred regimen (1): Amoxicillin 50 mg/kg/day PO tid (Maxmum, 500 mg/dose) for 14 (14–21) days
  • Preferred regimen (2): Doxycycline (for children aged ≥ 8 years) 4 mg/kg/day PO q12h (Maxmum, 100 mg/dose) for 14 (14–21) days
  • Preferred regimen (3): Cefuroxime 30 mg/kg/day PO q12h (Maxmum, 500 mg/dose) for 14 (14–21) days
  • Alternative regimen (1): Azithromycin 10 mg/kg/day PO (Maxmum, 500 mg/dose) for 7–10 days
  • Alternative regimen (2): Clarithromycin 7.5 mg/kg PO bid (Maxmum, 500 mg/dose) for 14–21 days
  • Alternative regimen (3): Erythromycin 12.5 mg/kg PO bid (Maxmum, 500 mg/dose) for 14–21 days
  • 1.1.3 Meningitis or radiculopathy (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
  • Note: for nonpregnant adult patients intolerant of β-lactam agents, Doxycycline 200–400 mg/day PO/IV q12h may be considered.
  • 1.1.4 Meningitis or radiculopathy (pediatric)
  • Preferred regimen: Ceftriaxone 50–75 mg/kg IV q24h (Maxmum, 2 g/day) for 14 (10–28) days
  • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6-8h (Maxmum, 6 g/day) for 14 (10–28) days
  • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h (Maxmum, 18–24 MU/day) for 14 (10–28) days
  • Note: for children ≥ 8 years of age intolerant of β-lactam agents, Doxycycline 4–8 mg/kg/day PO/IV q12h, max 200–400 mg/day may be considered
  • 1.2 Late neurologic disease
  • 1.2.1 Central or peripheral nervous system disease (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
  • 1.2.2 Central or peripheral nervous system disease (pediatric)
  • Preferred regimen: Ceftriaxone 50–75 mg/kg IV q24h (Maxmum, 2 g/day) for 14 (10–28) days.
  • Alternative regimen (1): Cefotaxime 150–200 mg/kg/day IV q6–8h (Maxmum, 6 g/day) for 14 (10–28) days
  • Alternative regimen (2): Penicillin G 200,000–400,000 U/kg/day IV q4h (Maxmum, 18–24 MU/day) for 14 (10–28) days
  • 2. American Academy of Neurology (AAN) Practice Parameter[17]
  • 2.1 Meningitis
  • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 days OR Cefotaxime 2 g IV q8h for 14 days OR Penicillin G 18–24 MU/day q4h for 14 days
  • Alternative regimen: Doxycycline 100–200 mg BID for 14 days
  • Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day; Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day; Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day; Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day
  • 2.2 Any neurologic syndrome with CSF pleocytosis
  • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 days OR Cefotaxime 2 g IV q8h for 14 days OR Penicillin G 18–24 MU/day IV q4h for 14 days
  • Alternative regimen: Doxycycline 100–200 mg BID for 14 days
  • Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g; Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day; Penicillin G 200,000–400,000 U/kg/day q4h, max 18–24 MU/day; Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day
  • 2.3 Peripheral nervous system disease (radiculopathy, diffuse neuropathy, mononeuropathy multiplex, cranial neuropathy; normal CSF)
  • Preferred regimen: Doxycycline 100–200 mg BID for 14 days
  • Alternative regimen: Ceftriaxone 2 g IV q24h for 14 days OR Cefotaxime 2 g IV q8h for 14 days OR Penicillin G 18–24 MU/day IV q4h for 14 days
  • Pediatric regimen: Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day; Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day; Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day; Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day; Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day
  • 2.4 Encephalomyelitis
  • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 days OR Cefotaxime 2 g IV q8h for 14 days OR Penicillin G 18–24 MU/day q4h for 14 days
  • Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day; Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day; Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day
  • 2.5 Encephalopathy
  • Preferred regimen: Ceftriaxone 2 g IV q24h for 14 days OR Cefotaxime 2 g IV q8h for 14 days OR Penicillin G 18–24 MU/day q4h for 14 days
  • Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day; Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day; Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day
  • 2.6 Post-treatment Lyme syndrome
  • Preferred regimen: symptomatic management
  • Note: Antibiotic therapy is not indicated.

References

  1. ↑ Muellegger RR, Zoechling N, Soyer HP; et al. (1995). "No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment". Archives of dermatology. 131 (6): 678–82. PMID 7778919.
  2. ↑ Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L (1993). "Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection". J. Am. Acad. Dermatol. 28 (2 Pt 2): 312–4. PMID 8436647.
  3. ↑ "ILADS - Lyme Disease Educational Videos, Lyme Disease Conferences, and LymeTeam". Retrieved 2013-03-14.
  4. ↑ "IDSA : Index". Retrieved 2013-03-14.
  5. ↑ Oksi J, Nikoskelainen J, Hiekkanen H; et al. (2007). "Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study". Eur. J. Clin. Microbiol. Infect. Dis. 26 (8): 571–81. doi:10.1007/s10096-007-0340-2. PMID 17587070.
  6. ↑ Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK (1999). "Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis". Ann. Med. 31 (3): 225–32. PMID 10442678.
  7. ↑ Hartiala P, Hytönen J, Pelkonen J; et al. (2007). "Transcriptional response of human dendritic cells to Borrelia garinii--defective CD38 and CCR7 expression detected". J. Leukoc. Biol. 82 (1): 33–43. doi:10.1189/jlb.1106709. PMID 17440035.
  8. ↑ Massarotti EM (2002). "Lyme arthritis". Med. Clin. North Am. 86 (2): 297–309. PMID 11982303.
  9. ↑ Puéchal X (2007). "Non antibiotic treatments of Lyme borreliosis". Med Mal Infect. [Epub ahead of print]. doi:10.1016/j.medmal.2006.01.021. PMID 17376627.
  10. ↑ Weissenbacher S, Ring J, Hofmann H (2005). "Gabapentin for the symptomatic treatment of chronic neuropathic pain in patients with late-stage lyme borreliosis: a pilot study". Dermatology (Basel). 211 (2): 123–7. doi:10.1159/000086441. PMID 16088158.
  11. ↑ Blum D, Chtarto A, Tenenbaum L, Brotchi J, Levivier M (2004). "Clinical potential of minocycline for neurodegenerative disorders". Neurobiol. Dis. 17 (3): 359–66. doi:10.1016/j.nbd.2004.07.012. PMID 15571972.
  12. ↑ Taylor R, Simpson I (2005). "Review of treatment options for Lyme borreliosis". J Chemother. 17 Suppl 2: 3–16. PMID 16315580.
  13. ↑ Pavia C (2003). "Current and novel therapies for Lyme disease". Expert Opin Investig Drugs. 12 (6): 1003–16. PMID 12783604.
  14. ↑ Schardt FW (2004). "Clinical effects of fluconazole in patients with neuroborreliosis". Eur. J. Med. Res. 9 (7): 334–6. PMID 15337633.
  15. ↑ Lubke LL, Garon CF (1997). "The antimicrobial agent melittin exhibits powerful in vitro inhibitory effects on the Lyme disease spirochete". Clin. Infect. Dis. 25 Suppl 1: S48–51. PMID 9233664.
  16. ↑ Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, Peter J.; Bakken, Johan S.; Strle, Franc; Stanek, Gerold; Bockenstedt, Linda; Fish, Durland; Dumler, J. Stephen; Nadelman, Robert B. (2006-11-01). "The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 43 (9): 1089–1134. doi:10.1086/508667. ISSN 1537-6591. PMID 17029130.
  17. ↑ 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.

References

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