Stability of Two Reserve Antibiotics in Elastomeric Pumps: Ceftazidime-Avibactam and Ceftolozane-Tazobactam

Background/Objectives: Parenteral antibiotic therapy is indispensable in the treatment of several infections. The parenteral administration often leads to the need for prolonged hospitalization. Therefore, interest in outpatient parenteral antimicrobial therapy (OPAT) is growing. OPAT is typically administered in elastomeric devices, which release an infusion solution over a 24 h period and are meanwhile worn close to the body. This work aimed to evaluate the stability of the reserve antibiotics ceftazidime-avibactam and ceftolozane-tazobactam for OPAT use. Methods: Elastomeric pumps were prepared in triplicate at the dosages 3.75 and 7.5 g of ceftazidime-avibactam and 2.25, 4.5, and 9.0 g of ceftolozane-tazobactam in 240 mL 0.9% saline each. The pumps were first stored at 2-8 °C for 7 days and subsequently incubated for 48 h at 25 °C. To determine actual concentrations of ceftazidime, avibactam, ceftolozane, tazobactam, and pyridine, samples were taken at nine different time points during storage and incubation. High-performance liquid chromatography coupled to tandem mass spectrometry was used for quantification. Results: Although concentrations of ceftazidime and avibactam stayed above 90% during a 24 h incubation period at 25 °C, the pyridine limit of the European Pharmacopeia was already exceeded in the ceftazidime-avibactam pumps after the storage time at 2-8 °C. In the ceftolozane-tazobactam pumps, the ceftolozane concentration was stable for 24 h incubation, but tazobactam concentrations decreased below 90% within 12 h in the two higher dosages. Conclusions: Accordingly, stability cannot be guaranteed for both tested preparations and their use for OPAT should be thoroughly considered.