Stability Studies of 16 Antibiotics for Continuous Infusion in Intensive Care Units and for Performing Outpatient Parenteral Antimicrobial Therapy

Abstract

The use of continuous infusion to improve the therapeutic efficacy of time-dependent antibiotics has been demonstrated. There is still a lack of data to safely perform these continuous infusions. The objectives in this study were to evaluate the stability by using stability-indicating methods (High-Performance Liquid Chromatography) of 16 antibiotics in concentrated solutions, especially for administration in intensive care units and solutions in elastomeric diffusers at 37 °C for outpatient parenteral antimicrobial therapy. The solutions were considered stable if the percentage of the drug was ≥90%, and the colour and clearness remained unchanged. In syringes, the stability data vary from 4 to 8 h (h) for meropenem in Dextrose 5% (D5W) and Normal Saline (NS), respectively, 6 h for cefotaxime, 12 h for cefoxitin, and 24 h for aztreonam, cefazolin, cefepime, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam in NS and D5W, and in water for injection for cloxacillin. A stability period of 48 h has been validated for vancomycin (D5W), aztreonam, and piperacillin/tazobactam. Cefoxitin, cefazolin, cefepime, cefotaxime, cloxacillin, and piperacillin are unstable for diffuser administration. In diffusers, stability times vary from 6 h for cefiderocol, 8 h for ceftazidime, 12 h for ceftazidime/avibactam and ceftolozane/tazobactam (NS), 24 h for temocillin (NS) and piperacillin/tazobactam (D5W), up to 48 h for aztreonam and vancomycin. Solutions stored at 37 °C are less stable and allow the administration of seven antibiotics using diffusers.

Keywords: antibiotic; continuous infusion; intensive care unit; outpatient parenteral antimicrobial therapy; stability.

Figure 1

Examples of chromatograms of piperacillin/tazobactam (300/37.5 µg/mL) (A); aztreonam (100 µg/mL) (B); cefotaxime (100 µg/mL) (C); and temocillin R and S (150 µg/mL) (D), obtained immediately after reconstitution in Normal Saline solution.