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Carbapenem resistance, an emerging global health problem, compromises the treatment of infections caused by nosocomial pathogens. Preclinical and clinical trials demonstrate that a new generation of carbapenemases inhibitors, together with the recently approved avibactam, relebactam and vaborbactam, would address this resistance. Our review summarizes the latest developments related to carbapenemase inhibitors synthesized to date, as well as their spectrum of activity and their current stage of development. A particular focus will be on β-lactam/β-lactamase inhibitor combinations that could potentially be used to treat infections caused by carbapenemase-producer pathogens. These new combinations mark a critical step forward the fight against antimicrobial resistance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365662 | PMC |
http://dx.doi.org/10.14740/jocmr4764 | DOI Listing |
Microbiol Spectr
September 2025
Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, Zhejiang, People's Republic of China.
is an emerging opportunistic pathogen with high genetic diversity. The emergence and prevalence of carbapenem-resistant poses a major health threat due to its intrinsic resistance to multiple antibiotics, which severely restricts the selection and treatment of antibiotics for infection. This study presents the first documented case in China of a bloodstream infection caused by and strain (designated S96) co-producing , , and .
View Article and Find Full Text PDFPathogens
August 2025
Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
Class D β-lactamases (DBLs) represent a major threat to antibiotic efficacy by hydrolyzing β-lactam drugs, including last-resort carbapenems, thereby driving antimicrobial resistance in Gram-negative bacteria. The enzymes share a structurally conserved two-domain α/β architecture with seven active-site motifs and three flexible extended loops (the P-loop, Ω-loop, and newly designated B-loop) that surround the active site. While each of these loops is known to influence enzyme function, their coordinated roles have not been fully elucidated.
View Article and Find Full Text PDFPathogens
August 2025
School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus.
Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam.
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July 2025
Department of Clinical Microbiology, Dr Andrija Štampar Teaching Institute of Public Health Zagreb, 10000 Zagreb, Croatia.
Background/objectives: is a frequent causative agent of urinary and wound infections in both community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESCs) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpCs). Recently, carbapenem-resistant isolates of emerged due to the production of carbapenemases, mostly belonging to Ambler classes B and D.
View Article and Find Full Text PDFPathogens
July 2025
Institute of Biological Sciences, Faculty of Exact and Natural Sciences, University of Siedlce, 14 Bolesława Prusa Str., 08-110 Siedlce, Poland.
Infections caused by are increasing worldwide. We evaluated the antibiotic resistance profile, biofilm production, and the frequency of 12 genes encoding carbapenemases and 13 virulence factors in 90 isolates from patients of three hospitals in various regions of Poland. Antibiotic resistance survey was performed using the disc-diffusion method, genes encoding resistance to carbapenems and virulence factors were detected with PCR, and biofilm formation was tested using microtiter plates.
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