<em>In vitro</em> study of new combinations for local antibiotic therapy with calcium sulphate - Near constant release of ceftriaxone offers new treatment options

<p class="p p-first" id="__p2">Introduction: Local application of antibiotics provides high concentrations at the site of interest, with minimal systemic toxicity. Carrier materials might help manage dead space. Calcium sulphate (CaSO₄) has a dissolution time that only slightly exceeds the usually recommended duration of systemic antibiotic treatments. This <em>in vitro</em> study evaluates compatibility, release kinetics and antibacterial activity of new combinations of antibiotics with CaSO₄ as carrier material.</p><p id="__p3">Methods: CaSO₄ pellets added with 8% w/w antibiotic powder were exposed once in phosphate-buffered saline (PBS) solution and once in bovine plasma, in an elution experiment run over 6 weeks at 37 °C. Antibiotic elution was examined at various time points. Concentration was measured by liquid chromatography with tandem mass spectrometry. Antimicrobial activity was checked with an agar diffusion test.</p><p id="__p4">Results: Piperacillin-tazobactam, ceftazidime, cefepime, and meropenem showed fast reduction of concentration and activity. Flucloxacillin and cefuroxime remained present in relevant concentrations for 4 weeks. Ciprofloxacin, levofloxacin and clindamycin lasted for 6 weeks, but also at cell toxic concentrations. Ceftriaxone showed a near-constant release with only a small reduction of concentration from 130 to 75 mg/l. Elution profiles from PBS and plasma were comparable.</p><p class="p p-last" id="__p5">Conclusion: CaSO₄ provides new possibilities in the local treatment of bone and joint infections. Ceftriaxone appears to be of particular interest in combination with CaSO₄. Release persists at clinically promising concentrations, and appears to have a depot-like slow release from CaSO₄, with only a small reduction in activity and concentration over 6 weeks. To the best of our knowledge, such a particular persistent release never was described before, for any antibiotic in combination with a carrier material for local application.</p>