Calcium Sulphate as a Biodegradable Antibiotic Carrier Used in Osteomyelitis and Septic Arthritis Treatment

Razvan Ene1,2, Elisa Popescu1,2, Catalin Eduard Georgescu1,2, Monica Roman 1,2, Alexandru Lisias Dimitriu1,2.

1 Clinical Emergency Hospital Bucharest, Calea Floreasca no. 8, Bucharest, Romania, razvan77ene@yahoo.com

2 Carol Davila University of Medicine and Pharmacy, Blvd. Eroii Sanitari no. 8, Bucharest, Romania

Introduction Chronic osteomyelitis and septic arthritis remain challenging conditions associated with significant morbidity, recurrent infections, and substantial healthcare costs. Conventional management relies on surgical debridement combined with systemic antibiotics[1,2,3]; however, the use of polymethylmethacrylate (PMMA) antibiotic carriers is limited by non-resorbability, lack of bioactivity, and the frequent need for secondary removal procedures[4,5,6,7]. This study evaluates calcium sulphate as a biodegradable local antibiotic delivery system for the treatment of chronic bone and joint infections.

Experimental. Seventeen patients (10 males, 7 females; mean age 45 years) presenting with chronic osteomyelitis or septic arthritis were treated with surgical debridement, high-volume antiseptic lavage, and implantation of calcium sulphate beads impregnated with culture-specific antibiotics. Most cases (94.1%) had failed previous surgical and/or systemic antibiotic treatment. Patients were selected to minimize the risk of post-debridement bone fragility and fracture.

Results and Discussion. Out of the 17 patients 70.58% (12 cases) had postoperative infections and 29.41% (5 cases) had haematogenous non-surgical origin and 94.11% (16) of them had a history of surgery (such as local debridement involving the bone and soft tissue, arthroscopic lavage and synovectomy for knee osteoarthritis) and/or systemic treatment in order to eradicate the infection and only 5.88% (1) had no previous surgery (femoral osteomyelitis). All of the patients had 3 or 4 inflammation markers elevated before the surgery and their numbers dropped to normal values within 2-4 weeks. We encountered complications such as wound ooze, noted in 1(5.88%) patient that needed further intervention for wound closure, despite having no microorganism isolated from the wound ooze and no elevated inflammation markers and only 1 case of recurrence in a patient with a co-infection involving Acinetobacter baumannii Multi Drug Resistant and Pseudomonas aeruginosa, with the persistence of the former microorganism. All patients had improved functional scores within the 3,6 months follow-up visits.

Conclusions. The backbone of osteomyelitis treatment is surgical debridement. However, the other quintessential factors are identification of the causal organism and appropriate antibiotic therapy for adequate duration and relevant dead space management. In our case calcium sulphate beads impregnated with antibiotics proved to be an efficient antibiotic carrier.

References. 

[1] Thabit AK, Fatani DF, Bamakhrama MS, Barnawi OA, Basudan LO, Alhejaili SF. Antibiotic penetration into bone and joints: An updated review. Int J Infect Dis. 2019 Apr;81:128-136. doi: 10.1016/j.ijid.2019.02.005. Epub 2019 Feb 14. PMID: 30772469.

[2] Selvaratnam V, Roche A, Narayan B, Giotakis N, Mukhopadhaya S, Aniq H, Nayagam S. Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis. Strategies Trauma Limb Reconstr. 2023 Sep-Dec;18(3):148-154. doi: 10.5005/jp-journals-10080-1602. PMID: 38404569; PMCID: PMC10891352.

[3] Rădulescu M, Holban AM, Mogoantă L, Bălşeanu TA, Mogoșanu GD, Savu D, Popescu RC, Fufă O, Grumezescu AM, Bezirtzoglou E, Lazar V, Chifiriuc MC. Fabrication, Characterization, and Evaluation of Bionanocomposites Based on Natural Polymers and Antibiotics for Wound Healing Applications. Molecules. 2016 Jun 10;21(6):761. doi: 10.3390/molecules21060761. PMID: 27294905; PMCID: PMC6273619.

[4] Caplin JD, García AJ. Implantable antimicrobial biomaterials for local drug delivery in bone infection models. Acta Biomater. 2019 Jul 15;93:2-11. doi: 10.1016/j.actbio.2019.01.015. Epub 2019 Jan 14. PMID: 30654212; PMCID: PMC6615972.

[5] Selvaratnam V, Roche A, Narayan B, Giotakis N, Mukhopadhaya S, Aniq H, Nayagam S. Effectiveness of an Antibiotic-impregnated Bioabsorbable Carrier for the Treatment of Chronic Intramedullary and Diffuse Osteomyelitis. Strategies Trauma Limb Reconstr. 2023 Sep-Dec;18(3):148-154. doi: 10.5005/jp-journals-10080-1602. PMID: 38404569; PMCID: PMC10891352.

[6] Frazer RQ, Byron RT, Osborne PB, West KP. PMMA: an essential material in medicine and dentistry. J Long Term Eff Med Implants. 2005;15(6):629-39. doi: 10.1615/jlongtermeffmedimplants.v15.i6.60. PMID: 16393131.

[7] Lun DX, Li SY, Li NN, Mou LM, Li HQ, Zhu WP, Li HF, Hu YC. Limitations and modifications in the clinical application of calcium sulfate. Front Surg. 2024 Feb 29;11:1278421. doi: 10.3389/fsurg.2024.1278421. PMID: 38486794; PMCID: PMC10937423.