New chemotherapeutic approaches in the treatment of Lyme borreliosis.

1. It was demonstrated that while B. burgdorferi may be sensitive to relatively small concentrations of penicillin and ceftriaxone, the organism is killed slowly. This implies that, as in syphilis, prolonged blood levels of these drugs may be necessary in order to ensure cure. In contrast, the activity of tetracycline is more rapid in its action but is more dependent on drug concentration achieved. Unfortunately, the MIC and MBC for some strains are at or above the peak level achieved under optimal conditions. 2. Increasing the concentrations of penicillin or ceftriaxone above the MIC for the organism has little effect on the rate of killing. In contrast, the killing by tetracycline can be augmented by increasing concentrations of the drug. 3. Ceftriaxone is more active than penicillin, as measured by MIC, against the five strains of B. burgdorferi tested. 4. Ceftriaxone was efficacious in the treatment of Lyme borreliosis, which was recalcitrant to penicillin therapy. In a randomized trial comparing ceftriaxone to high-dose penicillin therapy, ceftriaxone was significantly more efficacious than penicillin in the treatment of the late complications of Lyme borreliosis.