RESEARCH ARTICLE Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin,

Although most Lyme disease patients can be cured with antibiotics doxycycline or amoxicil-lin using 2-4 week treatment durations, some patients suffer from persistent arthritis or post-treatment Lyme disease syndrome. Why these phenomena occur is unclear, but possibili-ties include host responses, antigenic debris, or B. burgdorferi organisms remaining despite antibiotic therapy. In vitro, B. burgdorferi developed increasing antibiotic tolerance as mor-phology changed from typical spirochetal form in log phase growth to variant round body and microcolony forms in stationary phase. B. burgdorferi appeared to have higher persister frequencies than E. coli as a control as measured by SYBR Green I/propidium iodide (PI) viability stain and microscope counting. To more effectively eradicate the different persister forms tolerant to doxycycline or amoxicillin, drug combinations were studied using previous-ly identified drugs from an FDA-approved drug library with high activity against such persist-ers. Using a SYBR Green/PI viability assay, daptomycin-containing drug combinations were the most effective. Of studied drugs, daptomycin was the common element in the most active regimens when combined with doxycycline plus either beta-lactams (cefopera