Ceftazidime/Avibactam, Meropenem/Vaborbactam, or Both? Clinical and Formulary Considerations.

  title={Ceftazidime/Avibactam, Meropenem/Vaborbactam, or Both? Clinical and Formulary Considerations.},
  author={Jason M Pogue and Robert A. Bonomo and Keith S. Kaye},
  journal={Clinical infectious diseases : an official publication of the Infectious Diseases Society of America},
  volume={68 3},
  • J. Pogue, R. Bonomo, K. Kaye
  • Published 18 July 2018
  • Biology, Medicine
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Ceftazidime/avibactam and meropenem/vaborbactam are changing the management of invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), leading to higher rates of clinical cure, decreased mortality, and decreased rates of acute kidney injury compared with colistin-based regimens. However, these 2 agents are not interchangeable with regard to management of CRE infections, and clinicians need to be aware of their differences. This review focuses on differences in the in vitro… 

Update on the role of ceftazidime-avibactam in the management of carbapenemase-producing Enterobacterales.

The current review focuses on the clinical experience in real life of ceftazidime-avibactam use in the treatment of carbapenemase-producing Enterobacterales.

Optimizing therapy in carbapenem-resistant Enterobacteriaceae infections.

CAZ-AVI and meropenem-vaborbactam seem destined to become the backbone of target therapy for high-risk patients with severe infections caused by susceptible CRE strains, however, empirical therapy should be based on risk factors to be defined in the near future, whereas the necessity of combinations with CAZ- AVI requires further studies.

Meropenem/vaborbactam: a next generation β-lactam β-lactamase inhibitor combination

It exhibited an almost complete coverage of KPC-CRE isolates from large surveillance studies and a low propensity for resistance selection, retaining activity also against strains producing KPC mutants resistant to ceftazidime-avibactam.

Meropenem-vaborbactam: a critical positioning for the management of infections by Carbapenem-resistant Enterobacteriaceae

Meropenem-vaborbactam is currently approved for the management of complicated urinary tract infections including acute pyelonephritis, complicated intraabdominal infections, and hospital-acquired pneumonia including ventilator-associated pneumonia.

Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Children.

A framework for antibiotic treatment of CRE infections in children is provided, highlighting relevant microbiologic considerations and summarizing available data related to the evaluation of FDA-approved antibiotics (as of September 2019) with CRE activity, including carbapenems, ceftazidime-avibactam, meropenem-vaborbactam and plazomicin.

Ceftazidime/Avibactam versus Polymyxin B in the Challenge of Carbapenem-Resistant Pseudomonas aeruginosa Infection

CAZ/AVI therapy was superior to polymyxin B therapy for patients with CRPA infection, and provided significant survival benefits, but further larger studies were needed to substantiate the findings.

Ceftazidime-avibactam: are we safe from class A carbapenemase producers' infections?

Detailed review data is provided on global ceftazidime-avibactam susceptibility, the mechanisms involved in resistance, and the molecular epidemiology of resistant isolates.

Synergistic Combination of AS101 and Azidothymidine against Clinical Isolates of Carbapenem-Resistant Klebsiella pneumoniae

The checkerboard analysis demonstrated the remarkable synergism between AS101 and AZT, with the observable decrease in the MIC value for two agents and the fractional inhibitory concentration (FIC) index ≤0.5 in all strains, suggesting the combination of AS 101 and azidothymidine could be a potential treatment option against CRKP for drug development.

Meropenem/vaborbactam activity in vitro: a new option for Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae treatment.

Meropenem/vaborbactam could be an important turning point in the treatment of KPC-producing K. pneumoniae infections, especially considering the emergence of ceftazidime/avibactam resistance.



Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia

There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections and across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics.

Clinical Outcomes, Drug Toxicity, and Emergence of Ceftazidime-Avibactam Resistance Among Patients Treated for Carbapenem-Resistant Enterobacteriaceae Infections.

  • R. ShieldsB. Potoski M. Nguyen
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2016
Thirty-seven carbapenem-resistant Enterobacteriaceae-infected patients treated with ceftazidime-avibactam showed clinical success and survival rates and resistance was detected in 30% (3/10) of microbiologic failures.

Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae

  • D. van DuinJ. Lok S. Evans
  • Medicine, Biology
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2018
Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections and require confirmation in a randomized controlled trial.

Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases.

Meropenem-Vaborbactam Resistance Selection, Resistance Prevention, and Molecular Mechanisms in Mutants of KPC-Producing Klebsiella pneumoniae

Data indicate that the selection of mutants with reduced sensitivity to meropenem-vaborbactam from KPC-producing Klebsiella pneumoniae strains is associated with previously described mechanisms involving porin mutations and the increase in the blaKPC gene copy number and not changes in the KPC enzyme and can be prevented by the drug concentrations achieved with optimal dosing of the combination.

Clinical outcomes after combination treatment with ceftazidime/avibactam and aztreonam for NDM-1/OXA-48/CTX-M-15-producing Klebsiella pneumoniae infection

Novel family of tetracycline-inactivating enzymes found in clinical Legionella pneumophila serogroup 1 isolates and Antimicrobial Susceptibility Testing of Legionnaires' disease.

First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate

Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the treatment of carbapenem-resistant Enterobacteriaceae, and inactivates class A serine carbAPenemases, including Klebsiella pneumoniae carbapentemase (KPC).

In Vitro Activity of Meropenem-Vaborbactam against Clinical Isolates of KPC-Positive Enterobacteriaceae

It is concluded that meropenem-vaborbactam demonstrates potent in vitro activity against a worldwide collection of clinical isolates of KPC-positive Enterobacteriaceae collected in 2014 and 2015.

In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases

Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility, and Klebsiella pneumoniae infections may select for carbapENem resistance.

Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an In Vitro Hollow-Fiber Model

In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2G of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of Enterobacteriaceae.