Bioactivity of Ceftazidime and Fluconazole Included in Polymethyl Methacrylate Bone Cement for Use in Arthroplasty

Background

The microorganisms that most frequently cause prosthetic joint infection are methicillin-resistant Staphylococcus aureus and gram-negative aerobic bacillus. Studies have documented the efficacy of mixing antibiotics with polymethyl methacrylate, but that of antifungal drugs has not received much attention. The objective of this in vitro study was to characterize the elution profile and bioactivity of ceftazidime and fluconazole when incorporated into bone cement in proportions intended for prophylaxis and treatment of bone infections.

Methods

Antibiotic-loaded bone cement cylinders in a proportion of 1:40 and 4:40 (ratio of grams of antibiotic to grams of cement) were assayed. Drug delivery was investigated in a flow-through dissolution apparatus (SotaxCE7). To assess bioactivity, antibiotic concentrations were simulated in the joint space of 1000 patients. Antibacterial properties were evaluated by counting colony forming units and the inhibition-halo test.

Results

The ratio of released ceftazidime and fluconazole was 453% and 648%, respectively, higher when used for treatment proportions than prophylaxis proportions. A bioactivity simulation exercise showed that the efficacy of ceftazidime/fluconazole determined as the amount of drug is released at the active site in the first 3 days after surgery would depend on the sensitivity of the microorganism and would increase substantially after drain removal. The microbiology study showed that biofilm formation by Pseudomonas aeruginosa could be a problem when ceftazidime was used in treatment or prophylaxis proportions.

Conclusion

Our in vitro findings suggest that ceftazidime and fluconazole can be added into polymethyl methacrylate for the prevention/treatment of infections associated to joint surgery. Their efficacy depends on the sensitivity of the microorganism causing the infection.