Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survive in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated the different modes of degeneration of Borrelia burgdorferi suspensions during a 96-h exposure to various antibiotics. By dark-field microscopy and ultrastructural investigations, increasing blebbing and the gradual formation of granular and cystic structures could be followed during the exposure time. Although antibiotic concentrations at the MIC at which 90% of organisms are inhibited after 72 h were 80% or even greater, motile organisms were still present after incubation with penicillin and doxycycline but not after incubation with ceftriaxone. By transmission electron microscopy, intact spirochetal parts, mostly situated in cysts, were seen up to 96 h after exposure with all three antibiotics tested. According to experiences from studies with other spirochetes it is suggested that encysted borreliae, granules, and the remaining blebs might be responsible for the ongoing antigenic stimulus leading to complaints of chronic Lyme borreliosis.Borrelia burgdorferi, the pathogenic agent of Lyme borreliosis, has been recognized as a bacterium that is susceptible to antibiotics. The long-term persistence of these bacteria in tissues, despite adequate treatment of infected patients, has been indicated to be responsible for late complications and a chronic course of disease (17,26,28). The withdrawal of borreliae, or parts of them, into privileged or secluded sites, where they are further inaccessible to antibiotics, raises the question of whether antibiotics themselves can be made responsible for transforming the organism into a persistent, viable, or nonviable but antigenically potent form.Immobilization of bacteria has been seen as a result of incubation with antibiotics in vitro (21). By light microscopy, Preac-Mursic et al. (29) observed blebs, spherical structures, and granules in B. burgdorferi cultures during incubation with antibiotics. In ultrastrucutral studies the action of penicillin on cultures of Borrelia hermsii has been investigated (3).Penicillin, doxycycline, and ceftriaxone are the most preferred antibiotics for treating Lyme borreliosis. Although certain differences in the actions of these antimicrobial agents have been evaluated, they seem to be equally effective (34).Culture experiments were carried out to investigate the actions of these antibiotics on the motility, morphology, and survival of B. burgdorferi during exposure to antibiotic solutions. The course and mode of degeneration of these spirochetes were recorded on a videomicroscope and were photographed with an electron microscope. MATERIALS AND METHODSCulture experiments. Three strains of B. burgdorferi sensu lato, B31 (ATCC 35219) and two isolates from erythema migrans lesions on the skin of patients in Vienna, isolates hig...

The reliability of various in vitro techniques to identify Borrelia burgdorferi infection is still unsatisfactory. Using a high-power resolution videomicroscope and staining with the borrelia genus-specific monoclonal flagellar antibody H9724, we identified borrelial structures in skin biopsies of erythema chronicum migrans (from which borrelia later was cultured), of acrodermatitis chronica atrophicans, and of morphea. In addition to typical borreliae, we noted stained structures of varying shapes identical to borreliae found in a "borrelia-injected skin" model; identical to agar-embedded borreliae; and identical to cultured borreliae following exposure to hyperimmune sera and/or antibiotics. We conclude that the H9724-reactive structures represent various forms of B. burgdorferi rather than staining artifacts. These "atypical" forms of B. burgdorferi may represent in vivo morphologic variants of this bacterium.

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