Compatibility and stability of aztreonam and vancomycin hydrochloride

The physical compatibility and chemical stability of aztreonam and vancomycin hydrochloride when combined at clinically used high and low concentrations were studied. Admixtures consisting of aztreonam 4 mg/mL and vancomycin 1 mg/mL (as the hydrochloride salt) in 5% dextrose injection, aztreonam 4 mg/mL and vancomycin 1 mg/mL in 0.9% sodium chloride injection, aztreonam 40 mg/mL and vancomycin 10 mg/mL in 5% dextrose injection, and aztreonam 40 mg/mL and vancomycin 10 mg/mL in 0.9% sodium chloride injection were prepared in triplicate in polyvinyl chloride containers. Three containers of each type of admixture were stored at 4, 23, and 32°C. Samples were removed immediately and at various time points over 31 days. Compatibility was assessed by visual examination, with a turbidimeter, and with a particle sizer-counter. Stability was determined by stability- indicating high-performance liquid chromatography (HPLC). All the admixtures initially appeared clear to the unaided eye after the disappearance of a transient white swirl in the high-concentration admixtures (aztreonam 40 mg/mL and vancomycin 10 mg/mL). However, the high-concentration admixtures immediately developed unacceptable levels of a microcrystalline precipitate when viewed with a high-intensity fiber-optic light source. Easily visible gross turbidity and precipitation formed after various periods but often within 24 hours. HPLC showed aztreonam 4 mg/mL and vancomycin 1 mg/mL in 5% dextrose injection to be a stable combination for 7 days at 32 °C, 14 days at 23 °C, and 31 days at 4 °C. In 0.9% sodium chloride injection, the drugs in the low-concentration admixtures were stable for 7 days at 32 °C and for 31 days at 4 and 23 °C. Stability of the combination in the high- concentration admixtures was maintained for 3 days at 23 and 32 °C and for 14 days at 4 °C. Aztreonam and vancomycin hydrochloride were considerably less compatible and stable in the high-concentration admixtures than in the low-concentration ones.