Antibiotics for Lyme Disease: Can They Help Persistent Symptoms?
Antibiotics are the standard treatment for Lyme disease.
Most patients recover, but persistent symptoms can remain.
A study examined whether previously untreated patients benefited.
Antibiotics remain the standard treatment for Lyme disease, particularly when the infection is recognized early. Common first-line antibiotics include doxycycline, amoxicillin, and cefuroxime axetil. Most patients improve with appropriate treatment, although recovery can be gradual and some continue to experience persistent symptoms despite recommended therapy.
One study published in the European Journal of Internal Medicine examined whether patients with long-standing, non-specific symptoms who had never previously been treated for Lyme disease might also benefit from a four-week course of antibiotics.
The study, entitled Antibiotic treatment in patients that present with solely non-specific symptoms and positive serology at a Lyme centre, evaluated 97 previously untreated patients who had positive Borrelia IgG serology and persistent subjective symptoms.
Which antibiotics are used to treat Lyme disease?
Recommended antibiotic therapy depends on the stage and clinical manifestations of Lyme disease. For early localized infection, commonly prescribed oral antibiotics include doxycycline, amoxicillin, and cefuroxime axetil. Azithromycin may be considered in selected patients who cannot take these medications. Intravenous ceftriaxone is generally reserved for certain neurologic or cardiac manifestations of Lyme disease.
Most treatment recommendations are based on patients with objective manifestations such as erythema migrans, facial palsy, Lyme arthritis, or Lyme carditis. Less evidence is available for patients who present primarily with persistent, non-specific symptoms.
Who was included in the study?
The Dutch investigators evaluated 97 patients who had never received antibiotic treatment for Lyme disease but had positive IgG serology and persistent subjective symptoms.
These non-specific symptoms included:
- Myalgia and arthralgia
- Fatigue, lethargy, and loss of energy
- Sleep disturbances
- Headache
- Inflammatory symptoms including fever, sore throat, and night sweats
- Cognitive complaints
- Sensory symptoms
- Digestive symptoms
- Dizziness or lightheadedness
- Shortness of breath or palpitations
- Mood disturbances
The investigators wanted to determine whether these previously untreated patients benefited from antibiotics commonly used to treat Lyme disease and whether certain clinical features predicted treatment response.
Study results
Nearly half of the patients experienced either a clear or intermediate response to antibiotic treatment.
Most participants were adults, more than 70% were men, and symptoms had been present for an average of approximately two years before treatment.
Patients received either doxycycline or amoxicillin. Most completed a four-week course of therapy.
Interestingly, patients whose symptoms suggested an inflammatory illness appeared more likely to benefit from doxycycline than patients without inflammatory features.
[bctt tweet=”Can antibiotics help Lyme disease patients who have persistent fatigue, sleep problems, or cognitive symptoms? A Dutch observational study suggests some previously untreated patients may benefit.” username=”DrDanielCameron”]
The investigators also reported that patients with inflammatory symptoms and those whose immunoblot contained the p58 antigen appeared more likely to improve following treatment.
Among all participants:
- 15.5% experienced a clear response.
- 26.8% experienced an intermediate response.
- Approximately one-half experienced no meaningful improvement.
Authors’ conclusions
The investigators concluded that antibiotics may benefit some previously untreated patients who have persistent non-specific symptoms together with positive Borrelia serology.
However, they emphasized that many improvements were only partial and that randomized controlled trials are needed to determine whether these findings can be confirmed.
The authors also noted an important alternative explanation: some patients may have improved because antibiotic therapy treated another bacterial infection rather than active Borrelia burgdorferi infection.
As they explained, inflammatory symptoms could reflect illnesses other than Lyme borreliosis that also respond to antibiotics.
How should these findings be interpreted?
This observational study adds an important perspective because it evaluated patients who had never previously received antibiotic treatment for Lyme disease. That differs from many randomized clinical trials, which primarily enrolled patients who remained symptomatic despite earlier antibiotic therapy.
Because this study was not randomized and did not include a placebo group, its findings cannot establish that antibiotics were responsible for symptom improvement. Nevertheless, the results suggest that selected previously untreated patients with positive Lyme serology and inflammatory features may warrant further investigation in future randomized clinical trials.
Studies evaluating antibiotic treatment for persistent symptoms
Several randomized clinical trials have examined whether additional antibiotic therapy benefits patients with persistent symptoms following treatment for Lyme disease. Their findings have varied depending on the patient population studied, treatment regimen, and outcome measures.
The NIH-sponsored Klempner trial found no overall improvement in quality-of-life measures after prolonged antibiotic therapy. However, participants had been ill for an average of nearly five years and had already received multiple previous courses of antibiotics before enrollment, making the results difficult to generalize to all patients with persistent symptoms.
The STOP-LD trial by Krupp and colleagues reported significant improvement in fatigue following intravenous ceftriaxone, although other primary outcomes were not significantly improved.
The Fallon trial later found short-term improvement in cognitive function after intravenous ceftriaxone. While cognitive benefits were not sustained after treatment ended, some secondary outcomes, including physical functioning and pain among patients with greater baseline impairment, improved during follow-up.
More recently, the Dutch PLEASE trial evaluated longer-term antibiotic therapy after all participants first received two weeks of intravenous ceftriaxone. The investigators found that prolonged oral antibiotic therapy was not superior to shorter treatment on the primary outcome, although participants in all treatment groups demonstrated meaningful improvement over time.
A subsequent biostatistical review by DeLong and colleagues argued that several of the NIH retreatment trials may have been underpowered to detect clinically meaningful differences and concluded that the positive findings observed in some studies warrant additional investigation rather than definitive conclusions regarding treatment effectiveness.
What do current studies suggest?
Taken together, the available evidence indicates that most patients diagnosed and treated early for Lyme disease recover with recommended antibiotic therapy. However, a subset of patients continues to experience persistent symptoms after treatment.
Modern reviews suggest that no single mechanism explains these ongoing symptoms. Proposed explanations include post-infectious immune changes, persistent inflammation, tissue injury from the original infection, and, in some cases, persistent infection. Additional research is needed to better identify which patients may benefit from additional treatment strategies.
Editor’s Note
The Dutch observational study has several important limitations. Because it was not a randomized, placebo-controlled trial, improvements cannot be attributed with certainty to antibiotic therapy. Some patients may have improved because treatment addressed another bacterial infection rather than active Lyme disease.
Nevertheless, the study evaluated a unique group of patients who had never previously received antibiotic therapy despite positive Lyme serology and persistent symptoms. The findings support further randomized studies to determine whether selected previously untreated patients may benefit from antibiotic treatment.
Frequently Asked Questions
Do antibiotics cure Lyme disease?
Most patients diagnosed and treated early recover with recommended antibiotic therapy. Recovery may take weeks or months, and some patients continue to experience persistent symptoms despite appropriate treatment.
What antibiotics are commonly used for Lyme disease?
Doxycycline, amoxicillin, and cefuroxime axetil are commonly prescribed oral antibiotics. Intravenous ceftriaxone is reserved for selected neurologic or cardiac manifestations.
Does amoxicillin treat Lyme disease?
Yes. Amoxicillin is one of the recommended first-line oral antibiotics for many patients with early Lyme disease, particularly children and adults who cannot take doxycycline.
Does doxycycline work for persistent Lyme symptoms?
Doxycycline is highly effective for treating early Lyme disease. Whether additional antibiotic treatment benefits patients with persistent symptoms remains an area of ongoing research, with studies reporting mixed results.
Clinical Takeaway
Antibiotics remain the standard treatment for Lyme disease and are highly effective for most patients when treatment is started promptly. This Dutch observational study suggests that some previously untreated patients with persistent non-specific symptoms and positive Lyme serology may also improve with antibiotic therapy, particularly those with inflammatory features.
Although randomized trials of retreatment have produced mixed results, differences in study populations and trial design make interpretation challenging. Additional high-quality research is needed to identify which patients, if any, are most likely to benefit from additional antibiotic treatment.
Current evidence supports individualized clinical evaluation while recognizing both the established benefits of early antibiotic treatment and the remaining uncertainties surrounding persistent Lyme disease symptoms.
Related Articles
Learn more about diagnosis, treatment, and recovery from Lyme disease:
Lyme disease treatment
How Lyme disease is diagnosed
Lyme disease recovery
Post-treatment Lyme disease syndrome (PTLDS)
Persistent Lyme disease overview
References
- Nijman G, van Kooten B, Vermeeren YM, van Hees BC, Zomer TP. Antibiotic treatment in patients that present with solely non-specific symptoms and positive serology at a Lyme centre. Eur J Intern Med. 2020;74:67-72.
- Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.
- Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003;60(12):1923-1930.
- Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
- Berende A, ter Hofstede HJM, Vos FJ, et al. Randomized trial of longer-term therapy for symptoms attributed to Lyme disease. N Engl J Med. 2016;374:1209-1220.
- DeLong AK, Blossom B, Maloney EL, Phillips SE. Antibiotic retreatment of Lyme disease in patients with persistent symptoms: a biostatistical review of randomized, placebo-controlled clinical trials. Contemp Clin Trials. 2012;33(6):1132-1142.
- Adkison H, Embers ME. Lyme disease and the pursuit of a clinical cure. Front Med (Lausanne). 2023;10:1183344.
- Cameron DJ. Generalizability in two clinical trials of Lyme disease. Epidemiol Perspect Innov. 2006;3:12.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
I had Lyme disease 15 years ago & was treated with doxycycline for 10 days. For the last 5 years I have had inconsistent joint aching, tiredness, irritability, dizziness etc. I recently had about 25 blood tests to determine cause of my problem including a test for Lyme (of course it was negative). All tests were negative.
I believe that I may still have Lyme. The doctor put me on hydroxychloroquine (1/2 of 200 mg) & meloxicam. After 6 weeks I had a allergic reaction to hydrox though it was helping joint issues. I take meloxicam as needed which also helps. There is no diagnosis & doctor does not believe I still may have Lyme.
What further testing can be done? I do not think doctors in Florida are knowledgeable about Lyme disease.
I advise my patients that there is at least 20% of individuals with Lyme disease who are treated for 10 days are sick on long term followup. I advise my patients that they should see a doctor using clinical judgment if the tests are negative.
I wonder how Lyme can turn into autoimmune presentation and how it can muddy the whole picture? One can have both chronic infections and autoimmune condition (as a result of these infections); the result is lots of inflammation and when using antibiotics–even more inflammation; can one stay on low doses of antibiotics for a long period of time, rotate and use anti-inflammatory medicine with steroids? I believe many of us have incompetent immune system–not enough fighter wbc-lymphocytes and not enough suppressive wbc–to control the inflammation…
I still find antibiotics important in my practice. I sometimes find a treatment that has been overlooked. We don’t have very many other options for the immune system. I typically advise consultations with specialists to rule out other illnesses.
I have had Lymes since August, 2016. I have had one treatment session of medicine through an IV line because I had a pick line in my arm for 28 days. I am still sick with nausea, inflammation, headaches and all the symptoms of lymes. I feel really bad. I have been taking antiobiotics off and on for that period of time. I am still sick. I would like to know what your suggestions are on what you think I should do.
I cannot make specific suggestions without seeing you.
Are there any other treatments besides Doxy? I just cannot take that
There are a range of other antibiotic treatments to consider that are easier to tolerate i.e., amoxicillin, Ceftin, Zithromax, Biaxin, Malarone depending on your situation.