ABSTRACT
Introduction
Patients admitted to hospitals are at risk of developing nosocomial infections. These types of infections typically occur in immune-compromised patients. Furthermore, nosocomial infections are frequently caused by resistant organisms, including nonfermenting gram-negative bacilli such as Pseudomonas aeruginosa.
Areas covered
P. aeruginosa is a hazardous pathogen. It can resist numerous antibiotics, due to several resistance mechanisms. It is associated with serious illnesses, particularly hospital-acquired infections including ventilator-associated pneumonia. In the past, only a limited number of anti-pseudomonal drugs were available. However, several therapeutic advancements have been made, in recent years, to target P. aeruginosa, including the development of the new cephalosporin: ceftolozane-tazobactam.
Expert opinion
Ceftolozane-tazobactam is a combination of a novel semi-synthetic fifth-generation cephalosporin with a well-established beta-lactamase inhibitor. From a structural perspective, ceftolozane-tazobactam has attested increased stability to AmpC β-lactamases. Additionally, ceftolozane-tazobactam is less affected by changes in efflux pumps and porin permeability due to an enhanced affinity to certain penicillin-binding proteins (PBPs). This enables the molecule to overcome the most common anti-drug resistant mechanisms of bacteria. According to previous clinical trials conducted, ceftolozane-tazobactam must be considered when treating patients with confirmed or suspected P. aeruginosa respiratory tract infections, either nosocomial pneumonia or ventilator-associated pneumonia.
KEYWORDS:
Article highlights
Ceftolozane-tazobactam is a combination of a novel semi-synthetic fifth-generation cephalosporin with a well-established beta-lactamase inhibitor.
Ceftolozane is an oxyimino-aminothiazolyl cephalosporin developed by the addition of amino groups to the 4-position of a 3-amino-2-methylpyrazole cephalosporin, thus improving the minimum inhibitory concentration (MIC) values against AmpC β-lactamases
Ceftolozane-tazobactam is typically compared to other antimicrobial agents including meropenem, ceftazidime-avibactam, cefepime, piperacillin-tazobactam, or colistin.
Upon inspection of resistant isolates, the susceptibility rate of MDR P. aeruginosa to ceftolozane-tazobactam was 86.6%, whereas in XDR isolates the susceptibility rate was 71.%.
Ceftolozane-tazobactam must be considered when treating patients with confirmed or suspected P. aeruginosa infection from respiratory tract infections – either nosocomial pneumonia or ventilator-associated pneumonia.
In patients with increased risk of carrying multi-drug resistant strains of P. aeruginosa ceftolozane-tazobactam should also be considered as a treatment option
Acknowledgments
Chloe Carpenter for English editing.
Declaration of interest
I Martín-Loeches has received fees from MSD for advisory boards and lectures. 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
A reviewer on this manuscript has received speakers’ fees and provided consultancy for MSD. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.