The persistence of Borrelia burgdorferi in the form of drug-tolerant bacteria may be one reason why some Lyme disease patients may continue to suffer symptoms despite antibiotic therapy. The authors determined which drug combinations were effective in eradicating persistent microcolonies of B. burgdorferi, and identified daptomycin, doxycycline and cefoperazone together as an effective way of eliminating bacteria. Even subculturing bacteria treated with this combination to fresh media did not result in bacterial growth, suggesting durable killing.