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ABSTRACT
Introduction
Ceftolozane-tazobactam is a combination of a new cephalosporin, with activity similar to that of ceftazidime, and a known inhibitor of beta-lactamases. This compound shows excellent activity against most gram-negative organisms causative of hospital-acquired pneumonia (HAP) or ventilator-acquired pneumonia (VAP), including extended spectrum beta-lactamase (ESBL)-producing Enterobacterales and multidrug-resistant (MDR) Pseudomonas aeruginosa.
Areas covered
This article reviews the spectrum of activity, the main pharmacokinetic and pharmacodynamic characteristics and the clinical efficacy and safety of ceftolozane-tazobactam in the treatment of HAP/VAP in adult patients.
Expert opinion
The results of a randomized clinical trial have demonstrated an efficacy and safety profile of ceftolozane-tazobactam similar to that of its comparator for the treatment of patients with HAP/VAP. Several retrospective studies have shown good efficacy of the drug for the treatment of respiratory infections caused by MDR P. aeruginosa. The use of this drug may be incorporated as a new therapeutic option for the treatment of patients with HAP/VAP in a carbapenem-saving setting or as a therapeutic alternative with a better safety profile than other therapeutic options in patients with infections caused by MDR P. aeruginosa.
| Drug name | Ceftolozane + tazobactam |
| Phase (for indication under discussion) | III |
| Indication (specific to discussion) | Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) |
| Pharmacology description/mechanism of action | Combination of a new oxyimino-cephalosporin (ceftolozane) and a β-lactamase inhibitor (tazobactam). Ceftolozane presents bactericidal activity by binding to penicillin binding proteins and inhibiting the bacterial cell wall biosynthesis. Tazobactam forms covalent bond with β-lactamase enzymes protecting ceftolozane against hydrolysis. It improves the activity of ceftolozane inhibiting some class A β-lactamases including ESBLs and a number of class C β-lactamases. |
| Route of administration | Intravenous |
| Chemical structure |  |
| Pivotal trials | [55] |
Article highlights
Ceftolozane-tazobactam is a combination drug comprising a novel cephalosporin ceftolozane and the β-lactamase inhibitor tazobactam.
This antibiotic is active against extended spectrum beta-lactamases producing Enterobacterales and against drug-resistant P. aeruginosa.
It has a good efficacy and safety profile for the treatment of hospital acquired pneumonia in a randomized clinical trial.
There is quite clinical experience, in retrospective studies, showing good efficacy of the drug in the treatment of respiratory infections caused by multidrug-resistant P. aeruginosa.
This box summarizes key points contained in the article.
Box 1. Drug summary box
Table
Declaration of Interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer Disclosures
One reviewer declares that they serve as an advisory board member for Merck & Co. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.