Volunteer for NIAID-funded clinical studies related to Lyme disease on ClinicalTrials.gov.
Lyme disease is an infection caused by the bacterium Borrelia burgdorferi. In the majority of cases, it is successfully treated with oral antibiotics.
The term “chronic Lyme disease” (CLD) is very confusing, as it has been used to describe people with different illnesses. While the term is sometimes used to describe illness in patients with Lyme disease, in many occasions it has been used to describe symptoms in people who have no evidence of a current or past infection with B. burgdorferi (Infect Dis Clin N Am 22:341-60, 2008). In other cases, “CLD” is used in patients who have non-specific symptoms (like fatigue and pain) after treatment for Lyme disease, but who have no evidence of active infection with B. burgdorferi. Physicians sometimes describe these patients as having post-Lyme disease syndrome (PLDS).
Because of the confusion in how the term CLD is employed, experts in this field do not support its use (New Engl J Med 357:1422-30, 2008).
For early Lyme disease, a short course of oral antibiotics such as doxycycline or amoxicillin is curative in the majority of the cases. In more complicated cases, Lyme disease can usually be successfully treated with 3 to 4 weeks of antibiotic therapy.
In patients who have non-specific symptoms after being treated for Lyme disease, and no evidence of active infection (patients with PLDS), studies have shown that more antibiotic therapy is not helpful and can be dangerous.
These trials were designed to ensure that several key parameters were addressed.
The first clinical trial, which included two multicenter studies, provided no evidence that extended antibiotic treatment is beneficial (New Engl J Med 345:85-92, 2001). In those studies, physicians examined long-term antibiotic therapy in patients with a well-documented history of previous Lyme disease but who reported persistent pain, fatigue, impaired cognitive function, or unexplained numbness. Those symptoms are common among people reporting PLDS. Patients were treated with 30 days of an intravenous (IV) antibiotic followed by 60 days of an oral antibiotic.
These studies reinforced the evidence that patients reporting PLDS symptoms have a severe impairment in overall physical health and quality of life. However, results showed no benefit from prolonged antibiotic therapy when compared with placebo in treating those symptoms.
In another study, published in 2003, researchers examined the effect of 28 days of IV antibiotic compared with placebo in 55 patients reporting persistent, severe fatigue at least 6 months following treatment for laboratory-diagnosed Lyme disease. Patients were assessed for improvements in self-reported fatigue and cognitive function (Neurology 60:1923-30, 2003).
In that study, people receiving antibiotics did report a greater improvement in fatigue than those on placebo. However, no benefit to cognitive function was observed. In addition, six of the study individuals had serious adverse events associated with IV antibiotic use, four requiring hospitalization. Overall, the study authors concluded that additional antibiotic therapy for PLDS was not supported by the evidence.
More recently, a study supported by the National Institute of Neurological Disorders and Stroke again showed that long-term antibiotic use for Lyme disease is not an effective strategy for cognitive improvement (Neurology 70(13):992-1003, 2008). Researchers compared clinical improvement following 10 weeks of IV ceftriaxone versus IV placebo. The patients were treated for Lyme disease and presented with objective memory impairment tests. In a complicated statistical model, the ceftriaxone group showed a slightly greater improvement at 12 weeks, but at 24 weeks, both the ceftriaxone and the placebo groups had improved similarly from baseline. In addition, adverse affects attributed to IV ceftriaxone occurred in 26 percent of patients. The authors conclude that because of the limited duration of the cognitive improvement and the risks involved, 10 weeks of IV ceftriaxone was not an effective strategy for cognitive improvement in these patients and more durable and safer treatment strategies are still needed.
Carefully designed, placebo-controlled studies have failed to demonstrate that prolonged antibiotic therapy is beneficial. Although isolated success stories are always good to hear, such reports alone are not sufficient grounds to support a therapeutic approach.
A positive response to prolonged antibiotic therapy may be due to the placebo effect, which was reported as high as 40 percent in the studies described above.
Patients also risk negative and sometimes serious reactions to the antibiotics themselves. In the first studies described above, 25 percent of the patients in the treatment group experienced study-related adverse events (New Engl J Med 345:85-92, 2001). In the clinical trial looking at cognitive function, six patients experienced serious adverse events, four of whom required hospitalization (Neurology 60:1923-30, 2003). In the most recent trial for cognitive improvement, 26 percent of patients given IV therapy experienced adverse events compared with 7 percent for the IV placebo group (Neurology 70(13):992-1003, 2008).
In addition to personal safety concerns, unnecessary antibiotic use contributes to the serious, growing problem of antimicrobial resistance. Overuse of antibiotics has led to many bacteria developing resistance to the very drugs doctors once used to combat them.
back to top
Last Updated April 16, 2009
Last Reviewed April 16, 2009