Treating Lyme Disease: Antibiotics Are Usually Effective

This past summer likely heightened the U.S. population’s exposure to tick-borne infections. That is because tick populations are on the rise,[1] and outdoor activities typical of summer place humans in environments (including suburban yards/gardens) where ticks are plentiful.[2]

Lyme disease is the most common insect-borne illness, accounting for over half of all such disease.[3] It is caused by bacteria that infect humans via tick bites.[4] Each year approximately 476,000 persons in the U.S. are diagnosed and treated for Lyme disease.[5] Globally, an estimated 15% of the world’s population has antibodies against the bacteria that cause Lyme disease, indicating current or past infection.[6] Unsurprisingly, the infection is more common in rural than urban regions.[7]

Signs and symptoms of Lyme disease typically include fever, headache, fatigue and the sometimes distinctive “bull’s-eye” skin rash.[8],[9] Early (within one month of a tick bite) Lyme disease involves a rash in approximately 80% of cases.[10] Weeks to months after a tick bite, musculoskeletal involvement occurs in approximately 60% of cases, neurologic disease (for example, headaches, light sensitivity, sudden-onset facial paralysis and loss of sensation in one or more body segments)[11] in approximately 15% of cases and carditis (inflammation of the heart muscle) in approximately 1% of cases. Late disease (months to years after a tick bite) may yield intermittent or persistent inflammation of one or a few joints in 10% to 60% of untreated patients and ongoing neurologic disease (incidence not established).

Although Lyme disease was first recognized as a human tick-borne illness in the 1980s, it and several other tick-borne diseases remain topics of active pathophysiologic, diagnostic and treatment research.

Treatment of Lyme disease

Antibiotic therapy is the current mainstay treatment for acute Lyme disease. Preferred antibiotics to treat Lyme disease are doxycycline (ACTICLATE, DORYX, DORYX MPC, DOXY, MONODOX, ORACEA, VIBRAMYCIN), amoxicillin (AMOXIL, LAROTID) and cefuroxime axetil (available in generic only), with treatment durations ranging from 10 to 14 days, depending upon the antibiotic selected.[12]

The degree of effectiveness of these antibiotics to treat Lyme disease is uncertain. Additionally, the diagnosis of Lyme disease is challenging because good biomarkers for active infection have yet to be developed, and some signs and symptoms of Lyme disease overlap substantially with other illnesses like chronic fatigue syndrome and fibromyalgia.[13] In their 2020 report on tick-borne illness to the U.S. Congress, an expert working group noted that antibiotic treatment for Lyme disease is typical, but placebo-controlled trials have not confirmed their effectiveness.[14]

Experts have concluded that if the characteristic rash or other signs and symptoms are plausibly connected to a tick bite in a region where Lyme disease is prevalent, then a limited course of oral doxycycline, amoxicillin or cefuroxime axetil is generally successful.[15] These experts further caution that antibiotic courses should be taken early during the illness and not used if the only evidence of infection is a positive blood test for antibodies against the bacteria that cause Lyme disease. They also note that 10% to 20% of those treated may continue to suffer from Lyme disease if antibiotics are not properly initiated or completed.[16]

Regarding antibiotic treatment for patients with persistent symptoms of Lyme disease, a randomized, placebo-controlled trial published in the New England Journal of Medicine in 2016 found that a 12-week course of either oral doxycycline or a combination of the oral antibiotic clarithromycin (BIAXIN XL) and the oral antimalaria drug hydroxychloroquine (PLAQUENIL) following a two-week course of the intravenous antibiotic ceftriaxone (available in generic only) in such patients provided no additional benefit in terms of quality-of-life scores than a two-week course of ceftriaxone only.[17] Separately, the researchers for Cochrane (a non-industry, not-for-profit, health-focused scientific network) last updated their systematic review on antibiotic treatment of persistent neurologic complications of Lyme disease in 2016.[18] That review found only “low- to very low-quality clinical evidence” that antibiotics (including doxycycline and amoxicillin) ease brain and broader central nervous system complications that may result from Lyme disease.

The labels for doxycycline and amoxicillin do not list Lyme disease as an approved indication,[19],[20] though the label for cefuroxime axetil does.[21] Evidence presented in the cefuroxime axetil label of its effectiveness to treat early Lyme disease is from two clinical trials showing that at least 84% of those treated with either cefuroxime axetil or doxycycline experienced clinical improvement one to 12 months after a 20-day treatment, with slightly higher rates of apparent success for doxycycline.

Notable, but not usually disqualifying, adverse effects of doxycycline, amoxicillin and cefuroxime axetil include allergic reactions, which are rarely life-threatening; potential harm to the fetuses or babies of women using the drug (mainly for doxycycline); diarrhea, including the rare proliferation of the deadly bacteria C. difficile; the development of antibiotic-resistant bacteria; intracranial hypertension (high pressure on the brain; doxycycline only); for children, permanent (adult) tooth discoloration (doxycycline only); sunburn sensitivity (doxycycline only); and vaginitis (inflamed/infected vagina; cefuroxime only).

What You Can Do

To mitigate the expanding risk of tick-borne illness, cover your skin when you are gardening, hiking or otherwise in grassy, brushy, leafy regions where ticks may be present. Soon after exposure to such environments, remove any ticks from your clothing or skin. Regions in the U.S. that are of particular concern are the northeastern states from the Virginias to Maine, as well as Minnesota and Wisconsin.[22]

If you suspect Lyme disease, meet with your doctor to obtain proper diagnosis and treatment. Note that Lyme disease can be difficult to diagnose and may be complicated by other co-occurring infections (including other tick-borne illnesses)[23] or non-infection illnesses,[24] though most cases respond well to oral antibiotics.

If you do begin antibiotics for early Lyme disease, be aware that up to 15% of treated patients may experience a worsening of symptoms during the first day of treatment in response to the clearance of dying bacteria.[25] More importantly, be sure to watch for certain adverse effects that may result from antibiotic use. Contact your doctor immediately if you experience problems, but otherwise fully complete your prescribed multiday course unless certain adverse effects require you and your doctor to discontinue that regimen earlier.
 

References

[1] Tick-Borne Disease Working Group. 2020 Report to Congress. U.S. Department of Health and Human Services. Office of the Assistant Secretary for Health. https://www.hhs.gov/sites/default/files/tbdwg-2020-report_to-ongress-final.pdf. Accessed August 8, 2022.

[2] Hu L. Diagnosis of Lyme disease. UpToDate. May 24, 2021.

[3] Tick-Borne Disease Working Group. 2020 Report to Congress. U.S. Department of Health and Human Services. Office of the Assistant Secretary for Health. https://www.hhs.gov/sites/default/files/tbdwg-2020-report_to-ongress-final.pdf. Accessed August 8, 2022.

[4] Centers for Disease Control and Prevention. January 19, 2022. Lyme disease. https://www.cdc.gov/Lyme/. Accessed August 8, 2022.

[5] Centers for Disease Control and Prevention. Why is CDC concerned about Lyme disease? January 13, 2021. https://www.cdc.gov/Lyme/why-is-cdc-concerned-about-Lyme-disease.html. Accessed August 8, 2022.

[6] Dong Y, Zhou G, Cao W, et al. Global seroprevalence and sociodemographic characteristics of Borrelia burgdorferi sensu lato in human populations: a systematic review and meta-analysis. BMJ Glob Health. 2022;7(6):e007744.

[7] Ibid.

[8] Centers for Disease Control and Prevention. Lyme disease. January 19, 2022. https://www.cdc.gov/Lyme/. Accessed August 8, 2022.

[9] Centers for Disease Control and Prevention. Signs and symptoms of untreated Lyme disease. January 15, 2021. https://www.cdc.gov/Lyme/signs_symptoms/index.html. Accessed August 8, 2022.

[10] Hu L. Diagnosis of Lyme disease. UpToDate. May 24, 2021.

[11] Halperin JJ. Nervous system Lyme disease. UpToDate. June 18, 2021.

[12] Hu L, Shapiro ED. Treatment of Lyme disease. UpToDate. May 24, 2021.

[13] Tick-Borne Disease Working Group. 2020 Report to Congress. U.S. Department of Health and Human Services. Office of the Assistant Secretary for Health. https://www.hhs.gov/sites/default/files/tbdwg-2020-report_to-ongress-final.pdf. Accessed August 8, 2022.

[14] Ibid.

[15] Hu L, Shapiro ED. Treatment of Lyme disease. UpToDate. May 24, 2021.

[16] Tick-Borne Disease Working Group. 2020 Report to Congress. U.S. Department of Health and Human Services. Office of the Assistant Secretary for Health. https://www.hhs.gov/sites/default/files/tbdwg-2020-report_to-ongress-final.pdf. Accessed August 8, 2022.

[17] Berende A, ter Hofstede HJ, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016;374(13):1209-1220.

[18] Cadavid D, Auwaerter PG, Rumbaugh J, Gelderblom H. Antibiotics for the neurological complications of Lyme disease. Cochrane Database Syst Rev. 2016;12(12):CD006978.

[19] Almirall. Label: doxycycline (ACTICLAT). March 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/205931s005,208253s003lbl.pdf. Accessed August 8, 2022.

[20] Direct Rx. Label: amoxicillin (AMOXIL). January 2020. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=375cdfd0-7996-5a42-e054-00144ff88e88&type=display. Accessed August 8, 2022.

[21] Aurobindo Pharma. Label: cefuroxime axetil (generic only). October 2021. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=faef39e9-d793-4191-a728-310f6fab759d&type=display. Accessed August 8, 2022.

[22] Centers for Disease Control and Prevention. Why is CDC concerned about Lyme disease? January 13, 2021. https://www.cdc.gov/Lyme/why-is-cdc-concerned-about-Lyme-disease.html. Accessed August 8, 2022.

[23] Hu L, Shapiro ED. Treatment of Lyme disease. UpToDate. May 24, 2021.

[24] Ibid.

[25] Ibid.