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

Author:

Venuti Francesco1,Gaviraghi Alberto1,De Nicolò Amedeo2ORCID,Stroffolini Giacomo3ORCID,Longo Bianca Maria1,Di Vincenzo Alessia2,Ranzani Fabio Antonino1,Quaranta Matilde1,Romano Francesca1,Catellani Eleonora4,Marchiaro Carlotta4,Cinnirella Giacoma4,D’Avolio Antonio2ORCID,Bonora Stefano1,Calcagno Andrea1ORCID

Affiliation:

1. Unit of Infectious Diseases, Department of Medical Sciences, University of Torino at the Amedeo di Savoia Hospital, ASL Città di Torino, Corso Svizzera 164, 10149 Torino, Italy

2. Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy

3. Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, 37024 Verona, Italy

4. ASL Città di Torino, Amedeo di Savoia Hospital, Corso Svizzera 164, 10149 Torino, Italy

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.

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology

Reference40 articles.

1. Ceftazidime/Avibactam and Ceftolozane/Tazobactam: Second-generation β-Lactam/β-Lactamase Inhibitor Combinations;Bonomo;Clin. Infect. Dis.,2016

2. Ceftolozane-Tazobactam for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections: A Multicenter Study;Gallagher;Open Forum Infect. Dis.,2018

3. Ceftolozane-Tazobactam Activity against Pseudomonas aeruginosa Clinical Isolates from U.S. Hospitals: Report from the PACTS Antimicrobial Surveillance Program, 2012 to 2015;Shortridge;Antimicrob. Agents Chemother.,2017

4. Zerbaxa® (Ceftolozane and Tazobactam) (2023, May 10). US Prescribing information. Merck Sharp & Dohme LLC, Available online: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/206829s011s012lbl.pdf.

5. Zerbaxa® (Ceftolozane and Tazobactam) (2023, May 10). EMA Summary of Product Characteristics. Merck Sharp & Dohme B.V. Available online: https://www.ema.europa.eu/en/documents/product-information/zerbaxa-epar-product-information_en.pdf.

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