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Background:Management of fungal osteomyelitis is prolonged and frequently unsuccessful. Antifungal-impregnated cement is sometimes used as adjunctive therapy.Objective:To examine the release of antifungals from biodegradable and nonbiodegradable cement carriers.Methods:In vitro methods were used to assess antifungal drug release and antifungal activity of impregnated cements commonly used as adjunctive treatment of osteomyelitis. Cements included thermoplastic, nonbioactive polymers (polymethylmethacrylate [PMMA]) or bioactive agents (hydroxyapatite [HAP], β-tricalcium phosphate [β-TCP]) and were formed into spheres (beads).Results:Amphotericin B provided consistent supernatant concentrations (release), between 1.75 and 2.0 ug/mL, over 110 days from all bone cements. Flucytosine and fluconazole were observed for 33–42 days before becoming undetectable from a nonbioactive sphere and 18–22 days from a bioactive sphere. Serum concentrations for micafungin, terbinafine, and anidulafungin impregnated into PMMA rapidly became undetectable, regardless of the matrix used. Investigational β-TCP spheres prolonged release for fluconazole and micafungin, but had no effect on amphotericin B. Serum calcium concentrations decreased 60–80% in all HAP-impregnated drug sphere supernatants. Only amphotericin B–impregnated PMMA impacted supernatant calcium, decreasing concentrations by 50–60%. The antifungal-impregnated beads did not appear to be toxic to osteoblasts during 72 hours of exposure in tissue culture medium.Conclusions:Elution characteristics of most antifungals from bone cement spheres are probably not optima) for treatment of deep-seated fungal infections if a similar phenomenon of antifungal release manifests in vivo. Ceramic nonabsorbable impregnated devices must be removed after their lifespan expires and may necessitate another surgical procedure that can increase surgical risk and cost. Bioactive osteoconductive materials may provide a surgical alternative to nonabsorbable matrices. However, there have been no controlled trials demonstrating improved therapeutic outcomes with local therapy and assessing whether biodegradable materials act as a new focus for infection.

OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay (ELISA) for amphotericin B in serum samples. Results are compared with those obtained by HPLC and bioassay. DESIGN: Comparison of results obtained by ELISA, HPLC, and bioassay. METHODS: We developed a new ELISA using a polyclonal rabbit antibody to measure serum amphotericin B concentrations. Blinded samples of amphotericin B in concentrations of 0.15–78 μg/mL were prepared in human serum and assayed simultaneously by the ELISA, HPLC, and bioassay. The results of each assay were derived from standard curves and evaluated by using the Table Curve 2D computer program. These data were compared by using correlation analysis with evaluation of Pearson's correlation coefficient by Student's t-est. RESULTS: ELISA and bioassay compared favorably at amphotericin B concentrations of 0.3–20 μg/mL with a correlation coefficient of r = 0.993, while ELISA and HPLC compared with a correlation coefficient of r = 0.944. The average coefficient of variation over the range 0.3–20.0 μg/mL was 28% ± 7% for HPLC, 26% ± 9% for ELISA, and 13% ± 4% for bioassay. Comparison of all three assays revealed the highest correlation with the ELISA assay (r = 0.998) for the range of concentrations (0.3–20 μg/mL) routinely achieved. Samples containing concentrations in excess of 20 μg/mL could be diluted. Desiccation for concentrations less than 0.3 μg/mL was not tested. CONCLUSIONS: The determination of serum amphotericin B concentrations by ELISA gave results similar to those obtained by a bioassay and HPLC technique. Although variability appears greater with ELISA, the ease of performing this assay expedites the evaluation of many samples. Finally, this assay may allow the determination of amphotericin B concentrations from lipid formulations without interference from coadministered antibacterials or azole antifungals.

OBJECTIVE:To report the first five cases of amphotericin B overdose with secondary cardiac complications in a pediatric population. Treatment is also presented.SETTING:Hospital.PATIENTS:Two infants and three children inpatients receiving amphotericin B.INTERVENTIONS AND RESULTS:Cardiac complications were observed in five pediatric patients who received between 4.6 and 40.8 mg/kg/d of amphotericin B. Cardiac arrest occurred in all patients, and four patients died. A detailed description of the cardiac event is provided for one patient who was on a cardiac monitor during the adverse reaction. Hydrocortisone prophylaxis and verapamil therapy were the primary therapies used in patient 1 (the only survivor). Evaluation of the literature provides substantial evidence for the use of hydrocortisone in prevention of cardiac arrhythmias.CONCLUSIONS:Amphotericin B overdose can be fatal in children and infants. The presentation in humans appears similar to that in dogs where cardiac arrhythmias occurred at doses of 5–15 mg/kg. Hydrocortisone may decrease the incidence of mortality associated with cardiac arrhythmias in children receiving amphotericin B overdoses. Animal studies are necessary to evaluate this observation and potential disadvantages of hydrocortisone usage.