Background: Osteomyelitis is a challenging condition caused by infection and inflammation of the bone, presenting a significant economic burden to healthcare systems. Calcium sulfate/hydroxyapatite (CaS/HA) is a bone void filler composed of 60% calcium sulfate and 40% hydroxyapatite. This case series aimed to report the efficacy and infection-related outcomes of CaS/HA combined with Gentamicin (CaS/HA-G) in treating osteomyelitis. Methods: Patients aged 18 and older diagnosed with osteomyelitis requiring surgical intervention and treated with CaS/HA-G during their procedure were included in the study, with a median (Q1–Q3) = 10 (7–16)-month follow-up period of time. Data collected included demographic, surgical, and outcome information. Infection eradication was determined by the normalization of the C-reactive protein, erythrocyte sedimentation rate levels, or the absence of clinical infection symptoms. Results: The case series involved 21 patients (twelve male, nine female) with a mean (SD) age of 54.8 (16.6) years. Vancomycin or/and Tobramycin were used as an additional antibiotic in 17 patients. At the last follow-up, 20 out of 21 patients (95.2%) had eradicated the infection, with a median (Q1–Q3) eradication time of 128 (71.8–233.5) days. Conclusions: In conclusion, this study demonstrates that CaS/HA-G is effective in controlling osseous infection in osteomyelitis while acting as an absorbable bone void filler.
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