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New agents for the treatment of infections with Gram-negative bacteria: Restoring the miracle or false dawn?
Clin Microbiol Infect. 2017 Sep 08;:
Authors: Wright H, Bonomo RA, Paterson DL
Abstract
BACKGROUND: Antibiotic resistance in gram-negative resistance has developed without a commensurate response in the successful development of antibiotic agents, though recent progress has been made.
AIMS: This review aims to provide a summary of the existing evidence on efficacy, spectrum of activity and the development of resistance of new agents that have been licensed or completed advanced clinical trials that possess activity against resistant gram-negative organisms.
SOURCES: A review of the published literature via MEDLINE database was performed. Relevant clinical trials were identified with the aid of the clinicaltrials.gov registry. Further data was ascertained from review of abstracts from recent international meetings and pharmaceutical companies.
CONTENT: Data on the mechanism of action, microbiological spectrum, clinical efficacy and the development of resistance are reported for new agents that have activity against gram-negative organisms. This includes the beta-lactam/beta-lactamase inhibitor combinations ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/cilastatin/relebactam, meropenem/vaborbactam and aztreonam/avibactam; cefiderocol, a siderophore cephalosporin; plazomicin and eravacycline.
IMPLICATIONS: The development of new agents with activity against multi-drug resistant gram-negative pathogens has provided important therapeutic options for clinicians. Polymyxins appear to have been supplanted by new agents as first line therapy for KPC producers. Cefiderocol and ceftazidime/avibactam/aztreonam are promising options for metallo-beta-lactamase producers, and cefiderocol and ceftolozane/tazobactam for multiply resistant Pseudomonas aeruginosa, but definitive data showing clinical efficacy is as yet lacking. Reports of the development of resistance early after the release and use of new agents is of concern. Orally administered options and agents active effective against Acinetobacter baumannii are under-represented in clinical development.
PMID: 28893690 [PubMed - as supplied by publisher]