STUDY DESIGN: A rabbit model was used to assess the penetration into the nucleus pulposus of 3 commonly used antifungal medications: amphotericin B, amphotericin B lipid complex, and fluconazole. OBJECTIVES: The purpose of this study was to quantitate the penetration of antifungal medications into the normal rabbit nucleus pulposus. SUMMARY OF BACKGROUND DATA: Fungal infections of the spine are rarely, if ever, treated with medical management alone. Although antibiotic penetration into the nucleus pulposus has been studied extensively, no previous studies have attempted to quantitate the penetration of antifungals into the nucleus pulposus. METHODS: Twenty-four rabbits were given 2 doses of 1 of the antifungal medications studied. One hour after completion of the second dose, the animal was killed and the thoracolumbar spine was excised en bloc. Specimens of nucleus pulposus and serum were obtained and sent to an outside laboratory for analysis. Gas chromatography was used to determine the fluconazole tissue levels, and a bioassay was used to measure amphotericin B tissue levels. RESULTS: Three animals in the amphotericin B group died either after the first or second dose of medication was administered. Although amphotericin B and amphotericin B lipid complex did not show adequate penetration into the nucleus pulposus in 12 out of 12 animals, fluconazole reached therapeutic tissue levels in 5 out of 7 animals. CONCLUSIONS: Fluconazole showed superior penetration into the nucleus pulposus in an uninfected rabbit model when compared to amphotericin B and amphotericin B lipid complex. These findings were found to be statistically significant (P = 0.021), and they suggest that fluconazole may be a better choice for empiric therapy of fungal spine infections while cultures and sensitivities are pending.
STUDY DESIGN: A rabbit model was used to assess the penetration into the nucleus pulposus of 3 commonly used antifungal medications: amphotericin B, amphotericin B lipid complex, and fluconazole. OBJECTIVES: The purpose of this study was to quantitate the penetration of antifungal medications into the normal rabbit nucleus pulposus. SUMMARY OF BACKGROUND DATA: Fungal infections of the spine are rarely, if ever, treated with medical management alone. Although antibiotic penetration into the nucleus pulposus has been studied extensively, no previous studies have attempted to quantitate the penetration of antifungals into the nucleus pulposus. METHODS: Twenty-four rabbits were given 2 doses of 1 of the antifungal medications studied. One hour after completion of the second dose, the animal was killed and the thoracolumbar spine was excised en bloc. Specimens of nucleus pulposus and serum were obtained and sent to an outside laboratory for analysis. Gas chromatography was used to determine the fluconazole tissue levels, and a bioassay was used to measure amphotericin B tissue levels. RESULTS: Three animals in the amphotericin B group died either after the first or second dose of medication was administered. Although amphotericin B and amphotericin B lipid complex did not show adequate penetration into the nucleus pulposus in 12 out of 12 animals, fluconazole reached therapeutic tissue levels in 5 out of 7 animals. CONCLUSIONS:Fluconazole showed superior penetration into the nucleus pulposus in an uninfected rabbit model when compared to amphotericin B and amphotericin B lipid complex. These findings were found to be statistically significant (P = 0.021), and they suggest that fluconazole may be a better choice for empiric therapy of fungal spine infections while cultures and sensitivities are pending.
Authors: Maria N Gamaletsou; Dimitrios P Kontoyiannis; Nikolaos V Sipsas; Brad Moriyama; Elizabeth Alexander; Emmanuel Roilides; Barry Brause; Thomas J Walsh Journal: Clin Infect Dis Date: 2012-08-21 Impact factor: 9.079