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At least 10% of patients treated with antibiotic therapy for Lyme disease continue to suffer persisting symptoms. The reason for this is unknown, but one suspect is the continued survival of persisting forms of B. burgdorferi, the bacterium responsible for Lyme disease. In the test tube, Zhang and colleagues have grown one form of persisting bacteria known as biofilms, and used it to test various combinations of antibiotics. They also compared single continuous dosing versus pulse-dosing, which consists of repeated cycles of adding and removing antibiotics. They found that pulse-dosing was not effective for all antibiotics, and in fact reduced the activity of daptomycin against persisters. The best strategy they found against biofilm-like persisters was a single dose of a combination of daptomycin, doxycycline, and cefuroxime. They also showed that bacteriocidal drugs, which kill bacteria, are better used in pulse dosing than bacteriostatic drugs, which block bacterial replication but do not directly kill them. These promising in vitro data pave the way for animal model studies. If the findings prevail, they may suggest that future human trials are warranted.