"Chronic Lyme Disease"
What is "chronic Lyme disease"?
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 individuals who have no evidence of a current or past infection with B. burgdorferi. (Infect Dis Clin N Am 2008; 22:341-60). 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 Eng. J. Med. 2008; 357:1422-30).
How is Lyme disease treated?
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 three to four 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.
Has NIAID looked at the potential benefits of long-term antibiotic therapy on PLDS?
Yes. In an effort to address the confusion regarding appropriate therapy, NIAID has funded three placebo-controlled clinical trials on the efficacy of prolonged antibiotic therapy for the treatment of PLDS. The published results were subjected to rigorous statistical, editorial and scientific peer review.
These trials were designed to ensure that several key parameters were addressed:
- The susceptibility of Borrelia burgdorferi to the antibiotics used
- The ability of the antibiotics used to both cross the blood-brain barrier and access the central nervous system and to persist at effective levels throughout the course of therapy
- The ability of the antibiotics used to kill bacteria living both outside and inside mammalian cells
- The safety and welfare of patients enrolled in the trials
The first clinical trial, which included two multicenter studies, provided no evidence that extended antibiotic treatment is beneficial (New Eng. 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 individuals 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, individuals 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 therefore 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 2008; 70(13):992-1003). Researchers compared clinical improvement following 10 weeks of IV ceftriaxone vs. 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.
If long-term antibiotic therapy is not effective why do some individuals report improved symptoms following such treatment?
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.
I thought antibiotics were safe. If so, what is the harm in prescribing them?
All medications may have side effects, including antibiotics. Because few antibiotics are highly specific, they not only destroy "bad" bacteria but also kill many of the beneficial bacteria that inhabit the body. These good bacteria play a critical role in maintaining general health and preventing disease-causing organisms from establishing a foothold. Serious, potentially fatal antibiotic-associated infections remain a major concern in hospitals, and thus antibiotic use is monitored carefully. Intravenous antibiotics, such as those sometimes promoted for treating symptoms attributed to CLD, require lines and catheters that present an avenue for dangerous secondary infections to take hold.
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 (Neurology 60:1923-30, 2003), six patients experienced serious adverse events, four of whom required hospitalization. In the most recent trial for cognitive improvement (Neurology 70(13):992-1003, 2008) 26 percent of patients given IV therapy experienced adverse events compared with seven percent for the IV placebo group.
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.
Related Links
Learn About Lyme Disease - Centers for Disease Control and Prevention