Ceftolozane/tazobactam for difficult-to-treat Pseudomonas aeruginosa infections: A systematic review of its efficacy and safety for off-label indications.

Abstract

Ceftolozane/tazobactam (C/T) is a novel β-lactam/β-lactamase inhibitor combination targeting Enterobacteriaceae and Pseudomonas aeruginosa (PA). It is approved in adult patients for complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) as well as for nosocomial pneumonia. It displays excellent activity against PA, even multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The aim of this systematic review (PROSPERO protocol no. CRD42019117350) was to summarise the available evidence from observational studies regarding the efficacy and safety of off-label use of C/T when administered to treat MDR- or XDR-PA infections. The MEDLINE and Embase databases were screened from inception up to 30 June 2019. Studies were deemed eligible if they described real-life use of C/T in the case of MDR- or XDR-PA infections for non-approved indications. Exclusion criteria were cIAIs, cUTIs, pneumonia (unless occurring in a paediatric population) and infections by non-MDR/XDR-PA. Thirty articles fulfilled the inclusion criteria. In total, 130 cases of MDR- or XDR-PA infections treated with C/T in 128 patients were described. The most relevant off-label uses were skin and soft-tissue infection (49/30; 37.7%), bone and joint infection (42/130; 32.3%) and bloodstream infection (23/130; 17.7%). Five cases involved paediatric patients. The overall clinical success rate was 76.2%. The most common adverse event was hypokalaemia (4.2%, in 48 evaluable cases). C/T may be a useful therapeutic option for difficult-to-treat infections by PA even outside the framework of approved indications. Further studies are necessary to better define new indications for the drug.

• Authors: Alberto Enrico Maraolo, Maria Mazzitelli, Enrico Maria Trecarichi, Antonio Riccardo Buonomo, Carlo Torti, Ivan Gentile
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 55 Issue 3 Pg. 105891 (Mar 2020) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 31923569 (Publication Type: Journal Article, Systematic Review)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• ceftolozane, tazobactam drug combination
• Tazobactam

Topics

• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Cephalosporins (pharmacology, therapeutic use)
• Drug Resistance, Multiple, Bacterial (drug effects)
• Enterobacteriaceae (drug effects)
• Enterobacteriaceae Infections (drug therapy)
• Humans
• Intraabdominal Infections (drug therapy)
• Observational Studies as Topic
• Pseudomonas Infections (drug therapy)
• Pseudomonas aeruginosa (drug effects)
• Soft Tissue Infections (drug therapy)
• Tazobactam (pharmacology, therapeutic use)
• Urinary Tract Infections (drug therapy)