Video Blog: More problems with 2-week course of antibiotics for Lyme disease
There are physicians who continue to advise patients that 2 weeks of antibiotics is sufficient for treating Lyme disease (LD). [1,2] Their position has not changed despite the growing recognition that Lyme disease complications can occur after 2 weeks of antibiotic treatment. These difficulties include chronic neurologic LD,  Lyme encephalopathy, [4,5] Post Lyme disease,  and Post-Treatment Lyme Disease Syndrome (PTLDS). 
by Daniel J. Cameron, MD MPH
As early as 1990, Logigian and colleagues hypothesized that a two-week course of intravenous ceftriaxone would not successfully eradicate the Lyme bacterium. “The likely reason for relapse is failure to eradicate the spirochete completely with a two-week course of intravenous ceftriaxone therapy.” 
A recently published clinical trial from Slovenia offers insight into the problems with prescribing a two-week course of antibiotics. Researchers described the outcome of treating 77 patients with early European Lyme neuroborreliosis, sometimes referred to as Bannwarth’s Syndrome. 
The most frequent symptoms/signs were radicular pain, sleep disturbances, erythema migrans, headache, fatigue, malaise, paresthesias, and peripheral facial palsy. Meningeal signs and pareses were present in 19.5% and 7.8% respectively. One patient with radicular pain had a complete heart block and a lymphocytic pleocytosis by spinal fluid examination. 
Only 2 of their 77 patients were treated with more than two weeks of antibiotics:
- 72 patients were treated with ceftriaxone for two weeks;
- 2 patients were treated with ceftriaxone for three weeks;
- 2 patients were treated with doxycycline because of allergy to ceftriaxone;
- 1 patient was treated with doxycycline because of refusal of parenteral therapy.
Authors of the Slovenia trial identified several problems with the 2-week course of antibiotics.
1.) Antibiotics often had to be repeated. “Antibiotic therapy was repeated within 3 to 6 months in 20/77 (26%) patients because of unsatisfactory clinical response to the first treatment (3 patients), persistence of CSF cell count >10×106cells/L (8 patients), or both (9 patients),” according to Ogrinc. 
2.) Treatment failures were identified at the end of 6- or 12-month follow-up, despite retreatment. “Unfavorable long-term clinical outcome was observed in 9/74 patients (12%) and consisted of intense/annoying nonspecific symptoms, persistent PFP, or remaining pareses that influenced functioning,” Ogrinc points out. 
Unfavorable long-term clinical outcomes were defined as “partial improvement: partial regression of symptoms/signs, which still require substantial quantities of analgesics and/or significantly influence daily activities” or as “failure: persistence, intensification, or appearance of new symptoms/signs, and/or positive post-treatment CSF, skin, or blood cultures for Borrelia.” 
3.) Poor outcomes after 2 weeks of antibiotics occurred despite the relatively short duration of illness. The median duration of illness was 30 days for early European Lyme neuroborreliosis. Twelve of the 77 patients (15.6%) were ill for less than 2 months. 
Poor outcomes were also recently reported in a Netherlands’ study.  The 98 patients with persistent Lyme disease symptoms demonstrated only a slight improvement in their quality of life following a 2-week course of intravenous ceftriaxone. The physical-component summary score, which measures their quality of life, rose by only 3 points to 34.8. Their quality of life remained below that of cancer and heart attack patients.
Such findings are not limited to the European continent. A study in the U.S. found that despite a 3-week course of antibiotics, more than one-third of patients who presented with a erythema migrans rash were ill at 6-month follow-up.
“At 6 months, 36% of  patients reported new-onset fatigue, 20% widespread pain, and 45% neurocognitive difficulties,” according to Aucott, Johns Hopkins University School of Medicine. 
None of the patients described by Aucott were retreated as described in the Slovenia study. Instead, Aucott and colleagues concluded that their patients suffered from a Post-Treatment Lyme Disease Syndrome (PTLDS). Aucott noted, “Patients who developed PTLDS had significantly lower life functioning compared to those without PTLDS.” 
As doctors, we must develop better treatment regimens than the two- to three-week courses of antibiotics described in the Slovenian, Netherlands, and Aucott trials in order to avoid treatment failure. [7-9]
Dr. Daniel Cameron discusses in an All Things Lyme video blog the shortcomings of a recent study suggesting that 2 weeks of antibiotic therapy is effective in treating Lyme disease.
- Sanchez E, Vannier E, Wormser GP, Hu LT. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review. Jama, 315(16), 1767-1777 (2016).
- Wormser GP, Dattwyler RJ, Shapiro ED et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis, 43(9), 1089-1134 (2006).
- Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med, 323(21), 1438-1444 (1990).
- Logigian EL, Kaplan RF, Steere AC. Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis, 180(2), 377-383 (1999).
- Fallon BA, Keilp JG, Corbera KM et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology, 70(13), 992-1003 (2008).
- Krupp LB, Hyman LG, Grimson R et al. Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial. Neurology, 60(12), 1923-1930 (2003).
- Aucott JN, Rebman AW, Crowder LA, Kortte KB. Post-treatment Lyme disease syndrome symptomatology and the impact on life functioning: is there something here? Qual Life Res, 22(1), 75-84 (2013).
- Ogrinc K, Lusa L, Lotric-Furlan S et al. Course and Outcome of Early European Lyme Neuroborreliosis (Bannwarth’s Syndrome) – Clinical and Laboratory Findings. Clin Infect Dis, (2016).
- Berende A, ter Hofstede HJ, Vos FJ et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med, 374(13), 1209-1220 (2016).