Real-Life Experience of Continuously Infused Ceftolozane/Tazobactam in Patients with Bronchiectasis and Multidrug-Resistant Pseudomonas aeruginosa Infection in the Outpatient Setting

Abstract

(1) Background: Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor with excellent activity against the multidrug-resistant (MDR) P. aeruginosa. Continuous infusion (CI) dosing allows the optimization of pharmacokinetic and pharmacodynamic (PK/PD) properties of β-lactam antibiotics and may support patients' treatment as outpatients. (2) Methods: Adult patients receiving their entire course of C/T as a CI in the outpatient setting were retrospectively included in the study. The primary outcome evaluated was clinical resolution. The secondary outcomes evaluated were PK/PD target attainment (ƒT > 4 × MIC) and microbiologic clearance at the end of treatment. Therapeutic drug monitoring to assess C/T concentration was performed. (3) Results: Three patients were enrolled in the study and received 9 g of C/T in CI every 24 h. One patient received an additional course of antimicrobial therapy due to disease exacerbation six months after initial treatment, accounting for four evaluated treatments. The primary outcome was achieved in 3/4 treatments and the secondary outcome was achieved in 4/4 and 3/3, respectively. In all patients, free ceftolozane concentrations were >10 times higher than the EUCAST breakpoint (4 mg/L). (4) Conclusions: Elastomeric infusion of C/T delivered in CI can be an effective and convenient way to treat acute diseases caused by MDR-P. aeruginosa, avoid hospital admission, and contribute to infection control strategies. Despite the small number of enrolled patients, clinical and microbiological results support this strategy.

Keywords: Pseudomonas aeruginosa; bronchiectasis; ceftolozane/tazobactam; continuous infusion; outpatient parenteral antimicrobial therapy; therapeutic drug monitoring.

Figure 1

Total ceftolozane serum concentrations. The green line represents the target concentration calculated as 4 times the highest recorded susceptible minimum inhibitory concentration (MIC) of 1 μg/mL divided by the protein binding ratio for ceftolozane (0.79). The pink line represents the highest target drug concentration for any susceptible pathogen within the EUCAST breakpoint of ≤4 mg/L divided by the protein binding ratio for ceftolozane.

Figure 2

Total tazobactam serum concentrations. The blue line represents the target concentration for tazobactam >0.5 mg/L divided by the protein binding ratio for tazobactam (0.7). TZB, tazobactam.