Although most
Lyme disease patients can be cured with
antibiotics doxycycline or
amoxicillin 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 possibilities include host responses, antigenic debris, or B. burgdorferi organisms remaining despite
antibiotic therapy. In vitro, B. burgdorferi developed increasing
antibiotic tolerance as morphology 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 previously identified drugs from an FDA-approved
drug library with high activity against such persisters. 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 (
cefoperazone or
carbenicillin) or an energy inhibitor (
clofazimine).
Daptomycin plus
doxycycline and
cefoperazone eradicated the most resistant microcolony form of B. burgdorferi persisters and did not yield viable spirochetes upon subculturing, suggesting durable killing that was not achieved by any other two or three
drug combinations. These findings may have implications for improved treatment of
Lyme disease, if persistent organisms or detritus are responsible for symptoms that do not resolve with conventional
therapy. Further studies are needed to validate whether such combination antimicrobial approaches are useful in animal models and human
infection.