Background Cytotoxic preparations centralisation helped to secure the circuit of chemotherapy but also brought new constraints for caregivers especially when cytotoxic preparation unit in the pharmacy is closed. As ANSM agency recommended and considering physicochemical stability studies, we chose, in our University hospital, to prepare in advance and store intrathecal preparations. However and even if there is an infectious risk, microbiological stability of cytotoxic preparations has not been studied yet.
Purpose Therefore we decided to investigate microbiological stability of usual intrathecal preparations produced in our service.
Materials and methods Three intrathecal preparations were studied: methotrexate Mylan® 25 mg/ml, aracytine Pfizer® 20 mg/ml and hydrocortisone Upjohn® 50 mg/ml. They were prepared under sterile isolator and kept in double pack between 2 and 8°C for 0 to 4 days. First, according to European Pharmacopoeia, we studied growth of 6 microbial strains (Clostridium sporogenes, Pseudomonas aeruginosa, Staphylococcus aureus, Aspergillus niger, Bacillus subtilis, Candida albicans) in tryptic soy and thioglycolate resazurin medium alone and supplemented with intrathecal preparation. Second, sterility of the preparations was tested by direct inoculation of intrathecal preparation aged from 0 to 4 days in medium. All tests were repeated 3 times.
Results The 6 strains were able to grow in culture broth alone and with hydrocortisone intrathecal preparation. Bacterial growth was also possible when methotrexate or aracytine was added to the medium but only if diluted up to 1/50 for methotrexate and up to * for aracytine. Sterility tests showed no bacterial or fungal culture in our preparations stored up to 4 days prior inoculation.
Conclusions This study ensures us that our process provides sterile intrathecal methotrexate, hydrocortisone and aracytine preparation. Sterility was controlled after storage for up to 4 days after manufacture in a double pack at 2 to 8°C and as physicochemical stability was demonstrated by previous works, we are now able to provide intrathecal preparations manufactured as recommended even when service is closed. It could be interested to extend this work to others cytotoxic preparations needed in case of emergency.
No conflict of interest.
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