Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections
Issued Date
2022-09-01
Resource Type
ISSN
09248579
eISSN
18727913
Scopus ID
2-s2.0-85136560271
Pubmed ID
35787918
Journal Title
International Journal of Antimicrobial Agents
Volume
60
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Antimicrobial Agents Vol.60 No.3 (2022)
Suggested Citation
Kanj S.S., Bassetti M., Kiratisin P., Rodrigues C., Villegas M.V., Yu Y., van Duin D. Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections. International Journal of Antimicrobial Agents Vol.60 No.3 (2022). doi:10.1016/j.ijantimicag.2022.106633 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/87256
Title
Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections
Author's Affiliation
Siriraj Hospital
Sir Run Run Shaw Hospital
IRCCS San Martino Polyclinic Hospital
Universidad El Bosque
American University of Beirut Medical Center
Università degli Studi di Genova
P.D. Hinduja National Hospital and Medical Research Centre
UNC School of Medicine
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province
Sir Run Run Shaw Hospital
IRCCS San Martino Polyclinic Hospital
Universidad El Bosque
American University of Beirut Medical Center
Università degli Studi di Genova
P.D. Hinduja National Hospital and Medical Research Centre
UNC School of Medicine
Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province
Other Contributor(s)
Abstract
Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum β-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime–avibactam (CZA, a cephalosporin-β-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem–vaborbactam (MVB), ceftolozane–tazobactam (C/T) and imipenem–relebactam (I–R). Cefiderocol is a recent siderophore β-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many β-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I–R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new β-lactam–β-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel β-lactam approaches for treatment of MDR-GNB infections.