Ceftolozane and tazobactam for the treatment of hospital acquired pneumonia

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:

• P. aeruginosa
• VAP
• pneumonia
• sepsis
• VAT

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.

Additional information

Funding

This paper was not funded.