Research into Prolonged Treatment for Lyme Disease
To help answer questions about the treatment of Lyme disease, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), funded four placebo-controlled clinical studies that evaluated the effectiveness of prolonged antibiotic treatment on patients with persistent symptoms following standard recommended treatment regimens. The published results were subjected to rigorous statistical and scientific peer review.
The studies examined:
- The susceptibility of B. burgdorferi to the antibiotics used
- The ability of the antibiotics to remain at effective levels throughout the course of therapy, to cross the blood-brain barrier, and to access the central nervous system
- The ability of the antibiotics to kill bacteria living both outside and inside mammalian cells
- The safety and welfare of patients enrolled in the trials
In the first two clinical studies, researchers examined the benefits of prolonged antibiotic therapy as compared to placebo in a total of 129 patients with previously treated Lyme disease.1 These patients reported persistent pain, fatigue, impaired cognitive function, or otherwise unexplained numbness. Patients were treated with 30 days of IV antibiotics followed by 60 days of an oral antibiotics. Patients who received antibiotics did not improve more than patients who received placebo.
In another study, researchers examined the effects of 28 days of IV antibiotics as compared to placebo in 55 patients.2 Patients had reported persistent, severe fatigue for at least 6 months following treatment for well-documented Lyme disease. Patients were assessed for improvements in self-reported fatigue and cognitive function. Those receiving antibiotics reported greater improvement in fatigue than those on placebo. However, no benefit to cognitive function was observed. Six of 55 patients had serious adverse events associated with the study and 4 required hospitalization, 3 for IV line infections, and 1 for severe allergic reaction. The authors concluded that despite improvement in fatigue, given the lack of improvement in cognitive function and the risk of serious complications, additional antibiotic therapy for PTLDS could not be recommended.
More recently, a study supported by the National Institute of Neurological Disorders and Stroke also showed that prolonged antibiotic use for Lyme disease is not an effective strategy for cognitive improvement.3 Researchers compared clinical improvement after 10 weeks of IV ceftriaxone versus IV placebo. All patients had been treated previously for Lyme disease and presented with objective memory impairment. The ceftriaxone group showed a slightly greater improvement at 12 weeks, but at 24 weeks, both groups had made similar gains. Any improvements noted disappeared after therapy was discontinued. Problems such as blood clots, allergic reactions, and gall bladder removal were attributed to IV ceftriaxone use in 26% of patients. The authors concluded that because the cognitive improvement was brief and the risks involved were high, a 10-week course of IV ceftriaxone was not an effective strategy for improving cognitive abilities.
- Berende A, ter Hofstede HJ, Donders AR, van Middendorp H, Kessels RP, Adang EM, Vos FJ, Evers AW, Kullberg BJ. Persistent Lyme empiric antibiotic study Europe (PLEASE)--design of a randomized controlled trial of prolonged antibiotic treatment in patients with persistent symptoms attributed to Lyme borreliosis. BMC Infect Dis. 2014 Oct 16;14:543
- Klempner MS, Hu LT, Evans J, Schmid CH, Johnson GM, Trevino RP, Norton D, Levy L, Wall D, McCall J, Kosinski M, Weinstein A. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. New Eng. J. Med. 345:85-92, 2001.
- Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, Dattwyler R, Chandler B. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology. 2003 Jun 24;60(12):1923-30.
- Fallon BA, Keilp JG, Corbera KM, Petkova E, Britton CB, Dwyer E, Slavov I, Cheng J, Dobkin J, Nelson DR, Sackeim HA. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008 Mar 25;70(13):992-1003. Epub 2007 Oct 10.
Dangers of long-term treatment for Lyme disease
- De Wilde M, Speeckaert M, Callens R, Van Biesen W. Ceftriaxone-induced immune hemolytic anemia as a life-threatening complication of antibiotic treatment of 'chronic Lyme disease'. Acta Clin Belg. 2016 May 12:1-5. [Epub ahead of print]
- Ettestad PJ, Campbell GL, Welbel SF, et al. Biliary complications in the treatment of unsubstantiated Lyme disease. J Infect Dis. 1995;171:356–361.
- Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis. 2010;51:369–370.
- Lantos PM, Shapiro ED, Auwaerter PG, Baker PJ, Halperin JJ, McSweegan E, Wormser GP. Unorthodox alternative therapies marketed to treat Lyme disease. Clin Infect Dis. 2015 Jun 15;60(12):1776-82.
- Marks CM, Nawn JE, Caplow JA. Antibiotic treatment for chronic Lyme disease-Say no to the DRESS. JAMA Intern Med. 2016 Dec 1;176(12):1745-1746.
- Patel R, Grogg KL, Edwards WD, Wright AJ, Schwenk NM. Death from inappropriate therapy for Lyme disease. Clin Infect Dis. 2000;31(4):1107-9.
- Page last reviewed: March 4, 2015
- Page last updated: January 19, 2017
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