Ceftolozane/Tazobactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination with Activity Against Multidrug-Resistant Gram-Negative Bacilli

  title={Ceftolozane/Tazobactam: A Novel Cephalosporin/$\beta$-Lactamase Inhibitor Combination with Activity Against Multidrug-Resistant Gram-Negative Bacilli},
  author={George G. Zhanel and Phillip Y. Chung and Heather J. Adam and Sheryl A. Zelenitsky and Andrew J. Denisuik and Frank Schweizer and Philippe R.S. Lagac{\'e}-Wiens and Ethan Rubinstein and Alfred S. Gin and Andrew J. Walkty and Daryl J. Hoban and Joseph P. 3rd Lynch and James A. Karlowsky},
Ceftolozane is a novel cephalosporin currently being developed with the β-lactamase inhibitor tazobactam for the treatment of complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), and ventilator-associated bacterial pneumonia (VABP. [] Key Result Ceftolozane demonstrates linear pharmacokinetics unaffected by the coadministration of tazobactam; specifically, it follows a two-compartmental model with linear elimination.

Cefiderocol: A Siderophore Cephalosporin with Activity Against Carbapenem-Resistant and Multidrug-Resistant Gram-Negative Bacilli

Cefiderocol is unique in that it enters the bacterial periplasmic space as a result of its siderophore-like property and has enhanced stability to β-lactamases, and its total activity against meropenem–non-susceptible and Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriales is comparable or superior to ceftazidime-avibactam.

Ceftolozane/Tazobactam: A Review in Complicated Intra-Abdominal and Urinary Tract Infections

Given its very good in vitro activity against extended-spectrum β-lactamase-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa isolates, ceftolozane/tazobactam provides a potential alternative to currently approved antibacterials for empirical treatment of cIAI and cUTI in adults.

Molecular Surveillance and Assessment of Ceftolozane/Tazobactam Resistance with Common β-Lactam Antibiotics and β-Lactamase Genes

Although c/t demonstrated strong activity against Enterobacteriaceae, the high percentage of isolates with intermediate susceptibility emphasizes the need for close monitoring and continued surveillance for c/T resistance among ESBLs.

A Review of Ceftolozane/Tazobactam for the Treatment of Infections Caused by Multidrug-Resistant Pathogens

This novel combination agent has a role in treating MDR infections, particularly P. aeruginosa, although its use should be reserved for patients without other treatment options to limit the risk of resistance.

What is the role of the new β-lactam/β-lactamase inhibitors ceftolozane/tazobactam and ceftazidime/avibactam?

The US FDA has recently approved the use of the anti-GNB antibiotics ceftolozane/tazobactam (TOL/TAZ) and ceftazidime/avibactsam (CAZ/AVI) and physicians now have two important weapons with which to manage infections by MDR bacteria, particularly in the case of complicated urinary tract infections ( cUTIs) and complicated intra-abdominal infections (cIAIs).

Ceftolozane/tazobactam for the treatment of complicated intra-abdominal and urinary tract infections: current perspectives and place in therapy

Ceftolozane–tazobactam (C/T) is a new combination of a cephalosporin with a β-lactamase inhibitor that shows excellent in vitro activity against a broad spectrum of Enterobacteriaceae and Pseudomonas aeruginosa.

A Dimer, but Not Monomer, of Tobramycin Potentiates Ceftolozane against Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa and Delays Resistance Development

It is reported that tobramycin homodimer, a nonribosomal aminoglycoside derivative, potentiates the activities of ceftolozane versus MDR/XDR P. aeruginosa in vitro and delays the emergence of resistance to ceftlozane-tazobactam in the wild-type PAO1 strain.

Profile of ceftolozane/tazobactam and its potential in the treatment of complicated intra-abdominal infections

A novel antipseudomonal cephalosporin in combination with an established Class A β-lactamase inhibitor, ceftolozane/tazobactam has been approved by the FDA for use in the treatment of complicated urinary tract infections and complicated intra-abdominal infections.

Ceftolozane/tazobactam (CXA 201) for the treatment of intra-abdominal infections

The place in the therapeutic armamentarium of ceftolozane/tazobactam is reviewed, with good activity against extended spectrum β-lactamase producing Enterobacteriaceae, and good anti-pseudomonal activity being stable against the most common resistance mechanisms driven by mutation in Pseudomonas aeruginosa.



Activity of a New Cephalosporin, CXA-101 (FR264205), against β-Lactam-Resistant Pseudomonas aeruginosa Mutants Selected In Vitro and after Antipseudomonal Treatment of Intensive Care Unit Patients

Clinical trials are needed to evaluate the usefulness of CXA-101 for the treatment of P. aeruginosa nosocomial infections, particularly those caused by multidrug-resistant isolates that emerge during antipseudomonal treatments.

Ceftaroline: a novel broad-spectrum cephalosporin with activity against meticillin-resistant Staphylococcus aureus.

Ceftaroline is a promising treatment for cSSSI and CAP, and has potential to be used as monotherapy for polymicrobial infections because of its broad-spectrum activity.

In Vivo Activities of Ceftolozane, a New Cephalosporin, with and without Tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, Including Strains with Extended-Spectrum β-Lactamases, in the Thighs of Neutropenic Mice

The T>MIC required for ceftolozane is less than with other cephalosporins and may be due to more rapid killing, and the 2:1 ratio of ceftlozane with tazobactam was the most potent combination studied.

Antimicrobial Activity of CXA-101, a Novel Cephalosporin Tested in Combination with Tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis Strains Having Various Resistance Phenotypes

A novel oxyimino-aminothiazolyl cephalosporin, CXA-201, and various comparators were susceptibility tested by broth microdilution methods against ceftazidime-resistant members of the family Enterobacteriaceae and Klebsiella pneumoniae carbapenemase and extended-spectrum β-lactamase strains.

Activity of a New Antipseudomonal Cephalosporin, CXA-101 (FR264205), against Carbapenem-Resistant and Multidrug-Resistant Pseudomonas aeruginosa Clinical Strains

CXA is highly active against carbapenem-resistant P. aeruginosa isolates, including MDR strains and Resistance was restricted to still-uncommon strains producing an acquired MBL or ESBL.

Chequerboard titration of cephalosporin CXA-101 (FR264205) and tazobactam versus beta-lactamase-producing Enterobacteriaceae.

The tazobactam concentrations needed to potentiate this cephalosporin against strains with extended-spectrum, AmpC and carbapenem-hydrolysing beta-lactamases were investigated and achieved concentration-dependent potentiation of CXA-101 versus ESBL producers and AmpC hyperproducers.

Antimicrobial Activity of Ceftolozane-Tazobactam Tested against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2011-2012)

Ceftolozane/tazobactam demonstrated high potency and broad-spectrum activity against many contemporary Enterobacteriaceae and P. aeruginosa isolates collected in U.S. medical centers.

Activity of cephalosporin CXA-101 (FR264205) against Pseudomonas aeruginosa and Burkholderia cepacia group strains and isolates.

Pan-β-Lactam Resistance Development in Pseudomonas aeruginosa Clinical Strains: Molecular Mechanisms, Penicillin-Binding Protein Profiles, and Binding Affinities

The results suggest that in addition to AmpC, efflux pumps, and OprD, the modification of PBP patterns appears to play a role in the in vivo emergence of PBLR strains, which still conserve certain susceptibility to the new antipseudomonal cephalosporin ceftolozane.