Chemical and microbiological stability of diluted ceftazidime in three different solutions under three storage temperatures over a 28 day period

BACKGROUND: Ceftazidime (CAZ) solutions are being used based on anecdotal reports for otitis externa complicated by multidrug-resistant Pseudomonas aeruginosa (MDR PA). The chemical and microbiological stability of these proposed compounded solutions have not been evaluated, and likely are affected by the diluent and storage duration or temperature. HYPOTHESIS/OBJECTIVES: Compounded CAZ solutions would show variable degradation dependent on diluent, time and temperature. The antimicrobial activity of the solutions would reflect changes in concentration and not alterations to the chemical compound. METHODS AND MATERIALS: Ceftazidime was compounded with 100 mL 0.9% sodium chloride (NA+CAZ), 118 mL Triz-EDTA Aqueous flush (TE+CAZ) and 125 mL Douxo Micellar Solution (MI+CAZ). Aliquots of the solutions were stored at 25ºC, 4ºC and -20ºC for 28 days. High-performance liquid chromatography was used to analyse CAZ recovery from compounded solutions at weekly intervals. A modified broth dilution technique was utilised to assess minimum inhibitory concentration (MIC) to monitor antimicrobial activity against a reference PA strain. RESULTS: Temperature, duration of storage and diluent each had independent effects on the chemical stability of CAZ. CAZ concentrations decreased over time as well as with increased temperature. NA+CAZ solutions exhibited the least degradation compared to the other solutions. The MIC for PA was most consistent for NA+CAZ solutions regardless of storage temperature and duration of storage. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemical and microbiological stability of compounded CAZ solutions varied by diluent, storage temperature and duration of storage. Dilution in NA resulted in the lowest variation in stability over 28 days when stored at refrigerated or frozen temperatures compared to other diluents.

Authors: S. E. Hoff, D. J. Berger, A. K. Viall, D. Schrunk and J. O. Noxon Title: Chemical and microbiological stability of diluted ceftazidime in three different solutions under three storage temperatures over a 28 day period Full source: Vet Dermatol, 2021,Vol Document type: Journal Article
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Abstract	Source
BACKGROUND: Ceftazidime (CAZ) solutions are being used based on anecdotal reports for otitis externa complicated by multidrug-resistant Pseudomonas aeruginosa (MDR PA). The chemical and microbiological stability of these proposed compounded solutions have not been evaluated, and likely are affected by the diluent and storage duration or temperature. HYPOTHESIS/OBJECTIVES: Compounded CAZ solutions would show variable degradation dependent on diluent, time and temperature. The antimicrobial activity of the solutions would reflect changes in concentration and not alterations to the chemical compound. METHODS AND MATERIALS: Ceftazidime was compounded with 100 mL 0.9% sodium chloride (NA+CAZ), 118 mL Triz-EDTA Aqueous flush (TE+CAZ) and 125 mL Douxo Micellar Solution (MI+CAZ). Aliquots of the solutions were stored at 25ºC, 4ºC and -20ºC for 28 days. High-performance liquid chromatography was used to analyse CAZ recovery from compounded solutions at weekly intervals. A modified broth dilution technique was utilised to assess minimum inhibitory concentration (MIC) to monitor antimicrobial activity against a reference PA strain. RESULTS: Temperature, duration of storage and diluent each had independent effects on the chemical stability of CAZ. CAZ concentrations decreased over time as well as with increased temperature. NA+CAZ solutions exhibited the least degradation compared to the other solutions. The MIC for PA was most consistent for NA+CAZ solutions regardless of storage temperature and duration of storage. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemical and microbiological stability of compounded CAZ solutions varied by diluent, storage temperature and duration of storage. Dilution in NA resulted in the lowest variation in stability over 28 days when stored at refrigerated or frozen temperatures compared to other diluents.