β-lactam
Mechanisms of ResistanceStructural Insights into the Inhibition of the Extended-Spectrum β-Lactamase PER-2 by AvibactamThe diazabicyclooctane (DBO) avibactam (AVI) reversibly inactivates most serine-β-lactamases.
Mechanisms of ResistanceNacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPCCarbapenem-resistant Enterobacteriaceae (CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents. Klebsiella pneumoniae carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged...
Editor's Pick Mechanisms of Action: Physiological EffectsBedaquiline Eliminates Bactericidal Activity of β-Lactams against Mycobacterium abscessusThe β-lactams imipenem and cefoxitin are used for the treatment of Mycobacterium abscessus lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of M. abscessus with the antimycobacterial ATP...
Chemistry; BiosynthesisNegative Impact of Carbapenem Methylation on the Reactivity of β-Lactams for Cysteine Acylation as Revealed by Quantum Calculations and Kinetic AnalysesThe Enterococcus faecium l,d-transpeptidase (Ldtfm) mediates resistance to most β-lactam antibiotics in this bacterium by replacing classical peptidoglycan polymerases. The catalytic Cys of Ldtfm is rapidly acylated by β-lactams belonging to the carbapenem class but not by penams or cephems.
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Experimental TherapeuticsEfficacy of Human-Simulated Epithelial Lining Fluid Exposure of Meropenem-Nacubactam Combination against Class A Serine β-Lactamase-Producing Enterobacteriaceae in the Neutropenic Murine Lung Infection ModelNacubactam is a novel, broad-spectrum, β-lactamase inhibitor that is currently under development as combination therapy with meropenem. This study evaluated the efficacy of human-simulated epithelial lining fluid (ELF) exposures of meropenem, nacubactam, and the combination of meropenem and nacubactam against class A serine carbapenemase-producing ...
Mechanisms of ResistanceAmpI Functions as an Iron Exporter To Alleviate β-Lactam-Mediated Reactive Oxygen Species Stress in Stenotrophomonas maltophiliaStenotrophomonas maltophilia is an organism with a remarkable capacity for drug resistance with several antibiotic resistance determinants in its genome. S. maltophilia genome codes for L1 and L2, responsible for intrinsic β-lactam resistance.
Clinical TherapeuticsAdjuvant β-Lactam Therapy Combined with Vancomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: Does β-Lactam Class Matter?We analyzed the impact of vancomycin (VAN) combined with adjuvant β-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95...
MinireviewPast and Present Perspectives on β-Lactamasesβ-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years ago. These well-studied enzymes, currently numbering almost 2,800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally occurring β-lactams.
Mechanisms of ResistanceCharacterization of the AmpC β-Lactamase from Burkholderia multivoransBurkholderia multivorans is a member of the Burkholderia cepacia complex, a group of >20 related species of nosocomial pathogens that commonly infect individuals suffering from cystic fibrosis. β-Lactam antibiotics are recommended as therapy for infections due to B.
- Mechanisms of ResistanceInactivation of the Pseudomonas-Derived Cephalosporinase-3 (PDC-3) by Relebactam