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Bioactivity of Ceftazidime and Fluconazole Included in Polymethyl Methacrylate Bone Cement for Use in Arthroplasty
J Martínez-Moreno1, V Merino2, A Nácher2
1Departamento de Farmacia y Tecnología Farmaceutica y Parasitología, Facultad de Farmacia, Valencia, Spain; Instituto de Reconocimiento Molecular y Desarrollo Tecnologico, Centro Mixto Universidad Politecnica de Valencia-Universidad de Valencia, Valencia, Spain; Servicio de Farmacia, Hospital Universitario Doctor Peset, Valencia, Spain.
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.
Insights
This study shows ceftazidime and fluconazole in bone cement effectively elute for prosthetic joint infection prophylaxis and treatment. Efficacy depends on microorganism sensitivity and drug release rates.
Area of Science:
- Orthopedics
- Infectious Diseases
- Materials Science
Background:
- Prosthetic joint infections (PJIs) commonly involve methicillin-resistant Staphylococcus aureus and gram-negative aerobic bacilli.
- While antibiotic-loaded bone cement efficacy is known, antifungal drug elution and bioactivity data are limited.
- This study investigates ceftazidime and fluconazole incorporation into bone cement for PJI management.
Purpose of the Study:
- To characterize the elution profile of ceftazidime and fluconazole from bone cement.
- To assess the bioactivity of these drugs when incorporated into polymethyl methacrylate for prophylaxis and treatment of bone infections.
- To evaluate the impact of drug concentration on elution and bioactivity.
Main Methods:
- Bone cement cylinders loaded with ceftazidime and fluconazole at prophylaxis (1:40) and treatment (4:40) ratios were prepared.
- Drug elution was quantified using a flow-through dissolution apparatus.
- Antibacterial properties were assessed via colony-forming unit counts and inhibition-halo tests, with simulated joint space concentrations.
Main Results:
- Elution ratios for ceftazidime and fluconazole were significantly higher for treatment proportions (453% and 648%, respectively) compared to prophylaxis.
- Simulated bioactivity indicated efficacy depends on microorganism sensitivity and increases post-drain removal.
- Pseudomonas aeruginosa biofilm formation was identified as a potential issue with ceftazidime use.
Conclusions:
- Ceftazidime and fluconazole can be incorporated into polymethyl methacrylate bone cement for PJI prevention and treatment.
- The effectiveness of these drugs is contingent upon the susceptibility of the infecting microorganism.
- Further research may optimize drug elution and antimicrobial activity in bone cement formulations.
