What are the treatment options for long-term Lyme disease (Lyme borreliosis)?

From the Guidelines

For patients with persistent symptoms following standard treatment of Lyme disease, additional antibiotic therapy is not recommended unless there is objective evidence of reinfection or treatment failure, as stated in the 2020 guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) 1. When considering treatment for long-term Lyme disease, it's essential to prioritize the most recent and highest quality evidence. The 2020 guidelines provide strong recommendations against additional antibiotic therapy for patients with persistent nonspecific symptoms such as fatigue, pain, or cognitive impairment following recommended treatment for Lyme disease, but who lack objective evidence of reinfection or treatment failure. Some key points to consider in the treatment of long-term Lyme disease include:

• The use of doxycycline, amoxicillin, or cefuroxime for 14-21 days is recommended for the treatment of early localized or early disseminated Lyme disease associated with erythema migrans, as stated in the 2006 guidelines by the Infectious Diseases Society of America (IDSA) 1.
• For patients with Lyme arthritis, a 28-day course of oral antibiotics such as doxycycline, amoxicillin, or cefuroxime axetil is recommended, with the option for re-treatment with another 4-week course of oral antibiotics or a 2-4 week course of intravenous ceftriaxone if symptoms persist, as stated in the 2006 guidelines by the IDSA 1.
• The 2020 guidelines also suggest a 2-4 week course of IV ceftriaxone for patients with Lyme arthritis who have no or minimal response to an initial course of oral antibiotic, although this is a weak recommendation based on low-quality evidence 1. It's crucial to work with healthcare providers experienced in treating persistent Lyme disease, as extended antibiotic use carries risks including gastrointestinal issues, allergic reactions, and antibiotic resistance. Treatment should be tailored to individual symptoms and may require adjustments based on response, with regular monitoring of liver function and other parameters essential during extended treatment courses.

From the FDA Drug Label

Doxycycline is indicated for the treatment of infections caused by the following microorganisms: ... Relapsing fever due to Borrelia recurrentis. The answer to the question about treatment for long term Lyme is not directly addressed in the label, as Lyme disease is not explicitly mentioned. However, Relapsing fever due to Borrelia recurrentis is mentioned, and while this is a different condition, it is caused by a similar type of bacteria (Borrelia).

• Key point: The label does not provide information on the treatment of long term Lyme disease.
• Clinical decision: The FDA drug label does not provide a clear answer to the question about treatment for long term Lyme disease, and therefore, no conclusion can be drawn from this label alone 2.

From the Research

Treatment Options for Long-Term Lyme Disease

• The primary treatment for Lyme disease is antimicrobial therapy, with oral agents such as doxycycline or amoxicillin being successful in more than 90% of patients 3.
• For severe acute and chronic infections, the parenteral agent ceftriaxone is the drug of choice due to its good penetration into the cerebrospinal fluid (CSF) and proven high efficacy in clinical trials 3.
• Several adjunct therapies are available, including hyperbaric oxygen therapy and immune system supplements, but clinical trials have yet to be conducted to assess their efficacy 3.

Antibiotic Treatment for Neurological Complications

• Various central nervous system-penetrant antibiotics, such as doxycycline, penicillin G, ceftriaxone, and cefotaxime, are efficacious in the treatment of European Lyme neuroborreliosis (LNB) 4.
• However, there is a lack of evidence on the efficacy of antibiotics for the treatment of LNB in the United States 4.
• A network meta-analysis found that oral amoxicillin, oral azithromycin, injectable ceftriaxone, and injectable cefotaxime were effective for treating Lyme disease, while cefuroxime and penicillin were safe for treating the disease 5.

Alternative Treatment Options

• A recent study identified piperacillin as a potential alternative treatment for Lyme disease, which specifically targets the Borrelia burgdorferi bacteria and eradicates it at low-nanomolar concentrations 6.
• Piperacillin was found to be effective in treating Lyme disease in mice at a 100-fold lower dose than doxycycline without affecting the murine microbiome 6.