Ceftriaxone Pulse Dose for Post-Treatment Lyme Disease

1. Age 18 to 75 at the time of consent
2. Ability and willingness to sign informed consent
3. Available for the study period
4. Must have met the definition of a prior well-defined or probable Lyme disease infection, AND meet the definition of PTLDS
5. Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit
6. Have a level of fatigue that interferes with their ability to function in their job, schooling, or other social/personal activities (FSS score of 4 or higher)
7. Subjects will need to have been off of antibiotics (those standard antibiotics used to target Lyme disease to include doxycycline, amoxicillin, cefuroxime, azithromycin, ceftriaxone or penicillin) for at least 6 weeks prior to study enrollment and be willing to remain off of any outside antibiotics during the duration of the treatment component of the study.

Exclusion Criteria:

1. Female: pregnant or lactating
2. Women who intend to become pregnant during the treatment study period (approximately 45 days)
3. Patients with a diagnosis of Lyme disease based on only a positive Lyme IgM immunoblot
4. A history of cephalosporin allergy or significant intolerance
5. Lyme related symptoms that have been present for greater than 10 years

6. Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus.

   Note: Subjects who have well controlled HIV, who are on ART with a CD4 count greater than 200 will be allowed to participate.

7. Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition (to include any finding of increased suicide risk as identified by a rating of moderate or high risk on the CSSRS assessment), which in the opinion of the investigator prevents the subject from participating in the study
8. Known concurrent rheumatologic or similar disease thought to interfere with study participation or confound results at the discretion of the investigator. These may include but are not limited to rheumatoid arthritis, systemic lupus erythematous, Sjogren's syndrome, scleroderma, psoriasis, fibromyalgia, chronic fatigue syndrome/myalgic encephalomyelitis, or obstructive sleep apnea
9. Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous treatment with a cephalosporin antibiotic, or severe allergic reaction to penicillins (e.g. anaphylaxis or severe rash with Stevens Johnson syndrome or similar)
10. Planned travel during the study period that would interfere with the ability to complete all study visits (this can be a temporary exclusion with plan to schedule enrollment during a window of time during which they could attend their study visits)
11. Significant screening physical examination abnormalities or chronic medical condition that in the opinion of the investigator may impact subject safety
12. 12. Participation (active or follow-up phase) or planned participation in another vaccine, drug, or medical device in the 4 weeks prior to this trial, within 5 times the elimination half-life, whichever is longer, or during the trial
13. Prior history of Clostridium difficile infection
14. Currently taking warfarin (Coumadin)
15. Unable to comply with study requirements
16. Clinician discretion