Fluconazol neuroborelioza link do badan

F. W. Schardt

Clinical Effects of Fluconazole in Patients with Neuroborreliosis

Abstract

Eleven patients with neuro-borreliosis had been treated with 200 mg fluconazole daily for 25 days after an unsuccessful therapy with antibiotics. At the end of treatment eight patients had no borreliosis symptoms and remained free of relapse in a follow-up examination one year later. In the remaining four patients, symptoms were considerably improved. At the end oftherapy immune reactivity (lgl\/l+) disappeared in three patients. Since borrelia spp. are almost exclusively localised intracellular, they may depend on certain metabolites of their eucaryotic host cell.

Inhibition of P450 and other cytochromes by fluconazole may incapacitate Borrelia upon longterm exposure.

.,, ......  Fluconazole achieves high concentrations in many tissues as well as in CSF [20, 21,22, 23, 24, 26, 27, 28, 32, 33]. No previously published data exists on efficacy of fluconazole against Borrelia in vivo. In vitro investigations failed to reveal a direct antibacterial effect of fluconazole on Borrelia spp [34]. Concerning the mechanism of the therapeutic effect observed in our patients, we may speculate on a potential bacteriostatic impact of fluconazole due to its inhibitory action on cytochrome P450.

Since in vivo Borrelia spp. are almost exclusively localized intracellularly, they may depend on certain metabolites oftheir eucaryotic host cell for replication and long-term persistance [35]. Inhibition of P450 and other cytochromes may incapacitate

Borrelia spp. upon longterm exposure. This appears to correlate with the fact that in this study improvement/cure was observed in most cases only after 25 days of fluconazole treatment. Perhaps a longer therapy could have improved the results ..... ,,


http://www.neuroborreliose.net/downl.../neuroborreliosis.pdf.

Ocena in vitro wrażliwości na antybiotyki różnych form morfologicznych Borrelia burgdorferi Eva Sapi

Abstract

BACKGROUND:

Lyme disease is a tick-borne illness caused by the spirochete Borrelia burgdorferi. Although antibiotic therapy is usually effective early in the disease, relapse may occur when administration of antibiotics is discontinued. Studies have suggested that resistance and recurrence of Lyme disease might be due to formation of different morphological forms of B. burgdorferi, namely round bodies (cysts) and biofilm-like colonies. Better understanding of the effect of antibiotics on all morphological forms of B. burgdorferi is therefore crucial to provide effective therapy for Lyme disease.

METHODS:

Three morphological forms of B. burgdorferi (spirochetes, round bodies, and biofilm-like colonies) were generated using novel culture methods. Minimum inhibitory concentration and minimum bactericidal concentration of five antimicrobial agents (doxycycline, amoxicillin, tigecycline, metronidazole, and tinidazole) against spirochetal forms of B. burgdorferi were evaluated using the standard published microdilution technique. The susceptibility of spirochetal and round body forms to the antibiotics was then tested using fluorescent microscopy (BacLight™ viability staining) and dark field microscopy (direct cell counting), and these results were compared with the microdilution technique. Qualitative and quantitative effects of the antibiotics against biofilm-like colonies were assessed using fluorescent microscopy and dark field microscopy, respectively.

RESULTS:

Doxycycline reduced spirochetal structures ∼90% but increased the number of round body forms about twofold. Amoxicillin reduced spirochetal forms by ∼85%-90% and round body forms by ∼68%, while treatment with metronidazole led to reduction of spirochetal structures by ∼90% and round body forms by ∼80%. Tigecycline and tinidazole treatment reduced both spirochetal and round body forms by ∼80%-90%. When quantitative effects on biofilm-like colonies were evaluated, the five antibiotics reduced formation of these colonies by only 30%-55%. In terms of qualitative effects, only tinidazole reduced viable organisms by ∼90%. Following treatment with the other antibiotics, viable organisms were detected in 70%-85% of the biofilm-like colonies.

CONCLUSION:

Antibiotics have varying effects on the different morphological forms of B. burgdorferi. Persistence of viable organisms in round body forms and biofilm-like colonies may explain treatment failure and persistent symptoms following antibiotic therapy of Lyme disease.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132871/