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Metallo-β-lactamase-mediated antimicrobial resistance and progress in inhibitor discovery

TRENDS IN MICROBIOLOGY (2023)

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Article Infectious Diseases

Progressive in vivo development of resistance to cefiderocol in Pseudomonas aeruginosa

Mustafa Sadek et al.

Summary: This study reports the development of cefiderocol resistance among sequential Pseudomonas aeruginosa clinical isolates, without exposure to the drug. The resistance was driven by multifactorial mechanisms, including mutational changes in iron transporter proteins associated with drug uptake and overexpression of certain genes.

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2023)

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Article Immunology

Evolution and Transmission of Cefiderocol-Resistant Acinetobacter baumannii During an Outbreak in the Burn Intensive Care Unit

Steven M. Smoke et al.

Summary: This study reports on the treatment outcomes of 11 critically ill burn patients using cefiderocol for carbapenem-resistant Acinetobacter baumannii infections. The clinical success rate was 36%, but was complicated by the emergence of treatment-resistant A. baumannii and its transmission among patients. The resistant strains harbored disrupted pirA and piuA genes, which were not disrupted in susceptible strains.

CLINICAL INFECTIOUS DISEASES (2023)

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Article Biochemistry & Molecular Biology

MeDBA: the Metalloenzyme Data Bank and Analysis platform

Jun-Lin Yu et al.

Summary: Metalloenzymes are the focus of research in chemistry, biology, and medicine due to their conservation of metal-coordination and ligand binding modes. The Metalloenzyme Data Bank and Analysis (MeDBA) is a versatile platform that provides comprehensive information, structural data, and analysis tools for metalloenzymes, facilitating further research in this field.

NUCLEIC ACIDS RESEARCH (2023)

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Article Microbiology

New Delhi Metallo-Beta-Lactamase Facilitates the Emergence of Cefiderocol Resistance in Enterobacter cloacae

Dennis Nurjadi et al.

Summary: This study found that the emergence of resistance to Cefiderocol in metallo-beta-lactamase-producing bacteria is facilitated by mutations in the CirA siderophore receptor, which are induced by the New Delhi metallo-beta-lactamase. However, inhibiting the metallo-beta-lactamase activity using dipicolinic acid can successfully prevent the development of Cefiderocol-resistant mutants. Therefore, caution should be taken when using Cefiderocol to treat infections caused by metallo-beta-lactamase-producing bacteria.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Immunology

Infectious Diseases Society of America Guidance on the Treatment of AmpC β-Lactamase-Producing Enterobacterales, Carbapenem-Resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia Infections

Pranita D. Tamma et al.

Summary: The Infectious Diseases Society of America (IDSA) has provided updated guidance on the treatment of antimicrobial-resistant infections, focusing on treating AmpC-producing Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Stenotrophomonas maltophilia infections. The guidance is based on clinical experience, expert opinion, and a review of available literature, as published data on optimal treatment options are limited. This document emphasizes treatment approaches for infections in the United States, considering differences in resistance epidemiology and the availability of specific anti-infectives internationally.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Cefiderocol for the Treatment of Infections Due to Metallo-B-lactamase-Producing Pathogens in the CREDIBLE-CR and APEKS-NP Phase 3 Randomized Studies

Jean-Francois Timsit et al.

Summary: The CREDIBLE-CR and APEKS-NP studies showed that cefiderocol treatment is effective against gram-negative bacteria producing metallo-B-lactamases, with favorable rates of clinical cure, microbiological eradication, and all-cause mortality compared to other treatment options.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Infectious Diseases

European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine)

Mical Paul et al.

Summary: These guidelines address the targeted antibiotic treatment of 3GCephRE and carbapenem-resistant Gram-negative bacteria, focusing on the effectiveness of individual antibiotics and on combination versus monotherapy. Most recommendations are based on low-certainty evidence.

CLINICAL MICROBIOLOGY AND INFECTION (2022)

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Review Biochemistry & Molecular Biology

Deciphering the evolution of metallo-β-lactamases: A journey from the test tube to the bacterial periplasm

Carolina Lopez et al.

Summary: Understanding the evolution of MBLs is crucial for understanding pathogenic bacteria's resistance to carbapenems. Current research mainly focuses on the in vitro environment, ignoring the physiological context inside bacteria. Recent efforts have been made to simulate the bacterial periplasm and explore the evolutionary traits of different clinical variants of MBLs while considering their solubility or membrane-bound state.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

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Article Infectious Diseases

Mechanisms of Reduced Susceptibility to Cefiderocol Among Isolates from the CREDIBLE-CR and APEKS-NP Clinical Trials

Patrice Nordmann et al.

Summary: The objective of this study is to characterize isolates with reduced susceptibility to cefiderocol in patients receiving cefiderocol for nosocomial pneumonia or carbapenem-resistant infections. The study found that although the minimum inhibitory concentration of some isolates increased by more than 4-fold, they remained susceptible to cefiderocol. Mutations related to enzyme activity and protein were identified in the isolates, which may contribute to the decreased susceptibility to cefiderocol.

MICROBIAL DRUG RESISTANCE (2022)

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Article Chemistry, Multidisciplinary

Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors

Jurgen Brem et al.

Summary: The discovery of a potent new class of MBL inhibitor, InCs, restores carbapenem activity against multidrug-resistant bacteria with low resistance frequency. In combination with meropenem, InCs show strong in vivo efficacy in mouse infection models.

NATURE CHEMISTRY (2022)

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Article Immunology

Rapid Development of Cefiderocol Resistance in Carbapenem-resistant Enterobacter cloacae During Therapy Is Associated With Heterogeneous Mutations in the Catecholate Siderophore Receptor cirA

Sabrina Klein et al.

Summary: This report presents a case of resistance development to cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, which encodes a siderophore receptor, contributing to phenotypic resistance to cefiderocol.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Microbiology

Klebsiella pneumoniae Mutants Resistant to Ceftazidime-Avibactam Plus Aztreonam, Imipenem-Relebactam, Meropenem-Vaborbactam, and Cefepime-Taniborbactam

Naphat Satapoomin et al.

Summary: The study reveals a variant of Klebsiella pneumoniae that exhibits resistance to multiple antibiotics, including ceftazidime-avibactam and meropenem-vaborbactam. Further mutations and enzyme production are required for resistance to other antibiotics.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Microbiology

Impact of Acquired Broad-Spectrum β-Lactamases on Susceptibility to Cefiderocol and Newly Developed β-Lactam/β-Lactamase Inhibitor Combinations in Escherichia coli and Pseudomonas aeruginosa

Laurent Poirel et al.

Summary: The study evaluated the susceptibility of broad-spectrum beta-lactamases to various antibiotics, and found that clavulanic-acid-inhibited extended-spectrum beta-lactamases significantly affected the susceptibility to ceftazidime-avibactam, ceftolozane-tazobactam, and cefiderocol.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Infectious Diseases

A novel Bacteroides metallo-β-lactamase (MBL) and its gene (crxA) in Bacteroides xylanisolvens revealed by genomic sequencing and functional analysis

Jozsef Soki et al.

Summary: Our study aimed to characterize the carbapenem resistance mechanism of an imipenem-resistant strain, Bacteroides xylanisolvens 14880 from Germany, and evaluate its prevalence. The strain displayed resistance to carbapenems, produced high specific imipenemase activity, and harbored a class B1 beta-lactamase gene, crxA, on a putative genomic island. The presence of crxA was specific to B. xylanisolvens with a carriage rate of 16.7%, suggesting a unique carbapenem resistance gene system in this Bacteroides species.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2022)

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Article Infectious Diseases

Characterization of GMB-1, a novel metallo-beta-lactamase (MBL) found in three different Enterobacterales species

Jennifer Schauer et al.

Summary: The study aims to identify novel carbapenem resistance mechanisms and their potential to spread among clinical isolates. Through various tests, a new carbapenemase GMB-1 was identified in clinical isolates. Further studies confirmed its functional activity but showed reduced activity against certain drugs. The GMB-1 gene was found to be located on a genetic island on the chromosome, indicating the mobility and potential spread of carbapenemase genes in different species.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2022)

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Article Immunology

Carbapenemase-producing Pseudomonas aeruginosa -an emerging challenge

Fred C. Tenover et al.

Summary: The article discusses the clinical importance of carbapenem-resistant Pseudomonas aeruginosa (CR-PA) worldwide, including the resistance situation of the pathogen, transmission routes, different types of carbapenemases in various regions, and strategies for optimizing treatment.

EMERGING MICROBES & INFECTIONS (2022)

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Article Microbiology

Emergence of High-Level Cefiderocol Resistance in Carbapenem-Resistant Klebsiella pneumoniae from Bloodstream Infections in Patients with Hematologic Malignancies in China

Peng Lan et al.

Summary: Cefiderocol-resistant CRKP strains are emerging in Chinese patients with hematologic malignancies. The resistance is mediated by multiple factors including the deficiency of CirA, metallo- or serine-beta-lactamases, and can be further enhanced by NDM expression and CirA deficiency. This poses challenges to the clinical efficacy of cefiderocol in the future.

MICROBIOLOGY SPECTRUM (2022)

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Article Microbiology

Mutation of PA4292 in Pseudomonas aeruginosa Increases β-Lactam Resistance through Upregulating Pyocyanin Production

Xinrui Zhao et al.

Summary: Aztreonam/avibactam is an effective drug against Metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa, a pathogen causing highly lethal infections. This study discovered a novel gene mutation, PM292, that could lead to resistance to aztreonam/avibactam and beta-lactams. Additionally, the study found that overproduction of pyocyanin increased bacterial resistance to beta-lactams.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Microbiology

Biochemical Characterization of the Subclass B3 Metallo-β-Lactamase PJM-1 from Pseudoxanthomonas japonensis

Kageto Yamada et al.

Summary: In this study, the biochemical properties of a novel subclass B3 metallo-beta-lactamase (MBL) PJM-1 expressed in Pseudoxanthomonas japonensis, a commonly isolated environmental bacterium, were investigated. The bla(PJM-1) gene, comprising 906-bp, was found to be specific to P. japonensis and PJM-1 showed 81.8% amino acid identity with AIM-1. Recombinant expression and purification of PJM-1 were performed, revealing low catalytic activity against ceftazidime and cefepime, and strong inhibition by EDTA.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Infectious Diseases

Catecholate siderophore receptor CirA impacts cefiderocol susceptibility in Klebsiella pneumoniae

Peng Lan et al.

Summary: Cefiderocol, a cephalosporin antibiotic, exhibits expanded antimicrobial activity. CirA1 has higher iron-transporting ability than CirA198, leading to increased susceptibility to Cefiderocol.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2022)

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Article Microbiology

Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria

Abiu Sempere et al.

Summary: This retrospective study evaluated the efficacy of CZA/ATM in treating VIM-type-producing GNB infections in 24 patients. The results showed that CZA/ATM demonstrated synergistic activity in most patients and could be considered as an alternative therapy for such infections.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

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Article Infectious Diseases

Cefiderocol resistance genomics in sequential chronic Pseudomonas aeruginosa isolates from cystic fibrosis patients

Carla López-Causapé et al.

CLINICAL MICROBIOLOGY AND INFECTION (2022)

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Article Immunology

Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase-Producing Enterobacterales

Marco Falcone et al.

Summary: This study aimed to compare the outcomes of patients with MBL-producing Enterobacterales bloodstream infections treated with CAZ-AVI + ATM or other active antibiotics. The results showed that CAZ-AVI + ATM was associated with lower 30-day mortality, lower clinical failure at day 14, and shorter length of stay.

CLINICAL INFECTIOUS DISEASES (2021)

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Article Infectious Diseases

An updated phylogeny of the metallo-β-lactamases

Fanny Berglund et al.

Summary: The objective was to expand the phylogeny of MBLs, revealing distinct monophyletic groups within subclasses B1 and B3 and identifying new variants of zinc binding sites. Based on the results, it is recommended to refine the nomenclature of MBLs into phylogenetic groups that accurately describe their characteristics.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Infectious Diseases

Cefiderocol versus high-dose, extended-infusion meropenem for the treatment of Gram-negative nosocomial pneumonia (APEKS-NP): a randomised, double-blind, phase 3, non-inferiority trial

Richard G. Wunderink et al.

Summary: Cefiderocol was found to be non-inferior to high-dose, extended-infusion meropenem in terms of all-cause mortality on day 14 in patients with Gram-negative nosocomial pneumonia, with similar tolerability. This suggests that cefiderocol is a potential option for the treatment of patients with nosocomial pneumonia, including those caused by multidrug-resistant Gram-negative bacteria.

LANCET INFECTIOUS DISEASES (2021)

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Review Biochemistry & Molecular Biology

Molecular Evolution of Transition Metal Bioavailability at the Host-Pathogen Interface

Giuliano T. Antelo et al.

Summary: The molecular evolution of the adaptive response at the host-pathogen interface, known as an 'arms race,' involves strategies employed by the innate immune system to starve microbes of metals, countered by pathogens maintaining access to metal ions. Recent exploration of how evolution repurposes host and pathogen proteins to perform new functions is discussed, with a focus on metalloproteins restricting bacterial access to transition metals. Coevolution with bacterial metal acquisition systems and the evolution of metallo-?-lactamases in the context of host-imposed nutritional immunity are also examined.

TRENDS IN MICROBIOLOGY (2021)

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Editorial Material Immunology

Evolution of Cefiderocol Non-Susceptibility in Pseudomonas aeruginosa in a Patient Without Previous Exposure to the Antibiotic

Ana Paula Streling et al.

Summary: A study reported the emergence of non-susceptibility to cefiderocol in a subpopulation of Pseudomonas aeruginosa recovered from a patient without prior exposure to the antibiotic. Whole genome sequencing revealed mutations in major iron transport pathways linked to cefiderocol uptake, highlighting the importance of susceptibility testing before therapy with siderophore cephalosporins.

CLINICAL INFECTIOUS DISEASES (2021)

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Review Infectious Diseases

Systematic review on estimated rates of nephrotoxicity and neurotoxicity in patients treated with polymyxins

Florian Wagenlehner et al.

Summary: Polymyxin treatment is associated with a higher risk of nephrotoxicity compared to non-polymyxin-based regimens. The nephrotoxicity rate is higher in patients receiving polymyxins, while there is no significant difference in neurotoxicity between polymyxin and non-polymyxin treatments.

CLINICAL MICROBIOLOGY AND INFECTION (2021)

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Article Microbiology

Colistin Heteroresistance Is Largely Undetected among Carbapenem-Resistant Enterobacterales in the United States

Victor Band et al.

Summary: The study revealed varying levels of colistin heteroresistance among highly drug-resistant carbapenem-resistant Enterobacterales (CRE), with most heteroresistant isolates being misclassified as colistin susceptible by clinical diagnostic testing. The findings from the 2015 study suggest a high frequency of colistin heteroresistance in CRE.

MBIO (2021)

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Article Pharmacology & Pharmacy

AncPhore: A versatile tool for anchor pharmacophore steered drug discovery with applications in discovery of new inhibitors targeting metallo-β-lactamases and indoleamine/tryptophan 2,3-dioxygenases

Qingqing Dai et al.

Summary: AncPhore is a versatile tool for drug discovery that improves prediction ability on different types of target proteins by analyzing pharmacophore features and using anchor pharmacophores. It has the potential to efficiently identify new inhibitors for various protein targets.

ACTA PHARMACEUTICA SINICA B (2021)

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Article Chemistry, Medicinal

Selection of QPX7831, an Orally Bioavailable Prodrug of Boronic Acid β-Lactamase Inhibitor QPX7728

K. Raja Reddy et al.

Summary: Efforts were made to identify an oral prodrug of beta-lactamase inhibitor clinical candidate QPX7728, and compound 5-Na (QPX7831 Sodium) emerged with optimal properties across all key attributes after synthesizing 17 prodrugs and investigating their key properties.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Microbiology

Epidemiology of Carbapenem Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Program, 2012 to 2017

Krystyna M. Kazmierczak et al.

Summary: The study estimated the incidence of carbapenem-resistant Enterobacterales globally and found that the resistance mechanisms varied by region, with KPC-type, metallo-beta-lactamases, and OXA-48-like beta-lactamases being the main contributors. The overall percentage of meropenem-nonsusceptible Enterobacterales increased from 2012 to 2017, with different carbapenemase types showing increasing proportions in different regions.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

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Article Infectious Diseases

Activity of cefepime/zidebactam (WCK 5222) against 'problem' antibiotic-resistant Gram-negative bacteria sent to a national reference laboratory

Shazad Mushtaq et al.

Summary: The study demonstrated that cefepime/zidebactam showed universal susceptibility against multidrug-resistant Enterobacterales, inhibited most Enterobacterales with MBLs, and had enhanced activity against isolates highly resistant to cefepime and zidebactam alone. Additionally, cefepime/zidebactam exhibited good inhibitory effects on Pseudomonas aeruginosa and Acinetobacter baumannii, with the potential to overcome critical resistances in both gram-negative bacteria.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Immunology

Meropenem-Vaborbactam as Salvage Therapy for Ceftazidime-Avibactam-, Cefiderocol-Resistant ST-512 Klebsiella pneumoniae-Producing KPC-31, a D179Y Variant of KPC-3

Giusy Tiseo et al.

Summary: A 68-year-old man had recurrent bacteremia caused by a K. pneumoniae strain producing the KPC-3 variant enzyme, resistant to ceftazidime-avibactam but susceptible to meropenem after treatment.

OPEN FORUM INFECTIOUS DISEASES (2021)

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Article Microbiology

Contribution of PER-Type and NDM-Type β-Lactamases to Cefiderocol Resistance in Acinetobacter baumannii

Laurent Poirel et al.

Summary: The study found that PER-like beta-lactamases and NDM-like beta-lactamases significantly contributed to reduced susceptibility to Cefiderocol (FDC). The combination of FDC with avibactam exhibited excellent activity against multidrug-resistant isolates coproducing OXA-23 and PER-type beta-lactamases.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2021)

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Review Chemistry, Multidisciplinary

Metallo-β-lactamases in the Age of Multidrug Resistance: From Structure and Mechanism to Evolution, Dissemination, and Inhibitor Design

Guillermo Bahr et al.

Summary: Antimicrobial resistance is a major problem in current practical medicine, with the spread of genes coding for resistance determinants among bacteria challenging the use of antibiotics. Metallo-beta-lactamases play a central role in antibiotic resistance, with their diverse characteristics explored in the chemical, biochemical, and microbiological aspects.

CHEMICAL REVIEWS (2021)

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Letter Infectious Diseases

No in vitro activity of cefiderocol against OXA-427-producing Enterobacterales

Ann-Sophie Jacob et al.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Infectious Diseases

Activity of plazomicin against carbapenem-intermediate or -resistant Escherichia coli isolates from the United States and international sites in relation to clonal background, resistance genes, co-resistance, and region

Brian D. Johnston et al.

Summary: Plazomicin shows high overall utility against carbapenem-intermediate or -resistant E. coli, but this varies with region and multiple bacterial characteristics. Even among comparator-intermediate or -resistant isolates, the plazomicin-susceptible fraction remains relatively high, except for amikacin.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Infectious Diseases

Investigation of mechanisms responsible for decreased susceptibility of aztreonam/avibactam activity in clinical isolates of Enterobacterales collected in Europe, Asia and Latin America in 2019

Rodrigo E. Mendes et al.

Summary: The study identified a small number of Enterobacterales isolates exhibiting resistance to aztreonam/avibactam, with altered PBP3 and beta-lactamases being the main resistance mechanisms in Escherichia coli, while Klebsiella pneumoniae showed multiple resistance mechanisms. Further investigations are needed to clarify resistance mechanisms in Enterobacter cloacae.

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY (2021)

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Article Critical Care Medicine

Clinical Outcome of Patients on Ceftazidime-avibactam and Combination Therapy in Carbapenem-resistant Enterobacteriaceae

Vasant Nagvekar et al.

Summary: CRE infections have a significant impact on mortality and healthcare costs. The study evaluated the clinical response and patient outcomes with CZA treatment for CRE infections in Indian ICUs. Results suggest that CZA may be a viable option for patients with CRE infections, with an overall cure rate of 77.5%.

INDIAN JOURNAL OF CRITICAL CARE MEDICINE (2021)

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Article Immunology

Infectious Diseases Society of America Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa)

Pranita D. Tamma et al.

Summary: This guidance document provides recommendations for the treatment of antimicrobial-resistant infections caused by ESBL-E, CRE, and DTR-P. aeruginosa, with a focus on the United States. It discusses empiric treatment selection, duration of therapy, and other management considerations for both adults and children. The current version of the guidance is valid as of September 17, 2020, and will be updated periodically.

CLINICAL INFECTIOUS DISEASES (2021)

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Review Microbiology

Epidemiology of beta-Lactamase-Producing Pathogens

Karen Bush et al.

CLINICAL MICROBIOLOGY REVIEWS (2020)

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Article Chemistry, Medicinal

Discovery of Taniborbactam (VNRX-5133): A Broad-Spectrum Serine- and Metallo-β-lactamase Inhibitor for Carbapenem-Resistant Bacterial Infections

Bin Liu et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Review Chemistry, Medicinal

Principles and current strategies targeting metallo-β-lactamase mediated antibacterial resistance

Yu-Hang Yan et al.

MEDICINAL RESEARCH REVIEWS (2020)

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Article Chemistry, Medicinal

Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-β-lactamases

Scott J. Hecker et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Article Microbiology

Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-β-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance

Jun-ichi Wachino et al.

MBIO (2020)

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Article Microbiology

Antibiotic Susceptibility of NDM-Producing Enterobacterales Collected in the United States in 2017 and 2018

Joseph D. Lutgring et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Microbiology

In Vitro Pharmacodynamics of Fosfomycin against Carbapenem-Resistant Enterobacter cloacae and Klebsiella aerogenes

Tze-Peng Lim et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Microbiology

Metallo-beta-Lactamases: Structure, Function, Epidemiology, Treatment Options, and the Development Pipeline

Sara E. Boyd et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Biology

Comprehensive exploration of the translocation, stability and substrate recognition requirements in VIM-2 lactamase

John Z. Chen et al.

ELIFE (2020)

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Article Infectious Diseases

In vitro activity of ceftazidime-avibactam against Gram-negative isolates collected in 18 European countries, 2015-2017

Gregory G. Stone et al.

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS (2020)

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Article Microbiology

In Vitro Activity of Cefiderocol, a Siderophore Cephalosporin, against Multidrug-Resistant Gram-Negative Bacteria

Shazad Mushtaq et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Microbiology

Cefiderocol Resistance in Acinetobacter baumannii: Roles of β-Lactamases, Siderophore Receptors, and Penicillin Binding Protein 3

Saquib Malik et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Article Microbiology

Struggle To Survive: the Choir of Target Alteration, Hydrolyzing Enzyme, and Plasmid Expression as a Novel Aztreonam-Avibactam Resistance Mechanism

Ke Ma et al.

MSYSTEMS (2020)

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Article Infectious Diseases

In vitro activity of the siderophore cephalosporin, cefiderocol, against molecularly characterized, carbapenem-non-susceptible Gram-negative bacteria from Europe

Christopher Longshaw et al.

JAC-ANTIMICROBIAL RESISTANCE (2020)

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Article Immunology

Efficacy of Ceftazidime-Avibactam Salvage Therapy in Patients With Infections Caused by Klebsiella pneumoniae Carbapenemase-producing K-pneumoniae

Mario Tumbarello et al.

CLINICAL INFECTIOUS DISEASES (2019)

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Article Chemistry, Medicinal

Profiling interactions of vaborbactam with metallo-β-lactamases

Gareth W. Langley et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2019)

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Article Chemistry, Medicinal

H2depda: An acyclic adjuvant potentiates meropenem activity in vitro against metallo-β-lactamase-producing enterobacterales

Xiu-Fang Shi et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Public, Environmental & Occupational Health

Mortality related to Verona Integron-encoded Metallo--lactamase-positive Pseudomonas aeruginosa: assessment by a novel clinical tool

Marjolein C. Persoon et al.

ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL (2019)

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Article Chemistry, Medicinal

Heteroaryl Phosphonates as Noncovalent Inhibitors of Both Serine- and Metallocarbapenemases

Orville A. Pemberton et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Chemistry, Medicinal

SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model

Simon Leiris et al.

ACS INFECTIOUS DISEASES (2019)

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Article Public, Environmental & Occupational Health

Risk factors and epidemiologic predictors of blood stream infections with New Delhi Metallo-b-lactamase (NDM-1) producing Enterobacteriaceae

B. M. Snyder et al.

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Dipicolinic Acid Derivatives as Inhibitors of New Delhi Metallo-β-lactamase-1

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NMR-filtered virtual screening leads to non-metal chelating metallo-β-lactamase inhibitors

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In Vitro Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015

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Multiyear, Multinational Survey of the Incidence and Global Distribution of Metallo-β-Lactamase-Producing Enterobacteriaceae and Pseudomonas aeruginosa

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Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against Pseudomonas aeruginosa

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Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases

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Interaction of Avibactam with Class B Metallo-β-Lactamases

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Susceptibility of contemporary isolates to fosfomycin: a systematic review of the literature

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Membrane anchoring stabilizes and favors secretion of New Delhi metallo-β-lactamase

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Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees

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Cross-class metallo-β-lactamase inhibition by bisthiazolidines reveals multiple binding modes

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In Vitro Activity of Aztreonam-Avibactam against a Global Collection of Gram-Negative Pathogens from 2012 and 2013

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Characterization of Escherichia coli NDM isolates with decreased susceptibility to aztreonam/avibactam: role of a novel insertion in PBP3

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Zinc Chelation by a Small-Molecule Adjuvant Potentiates Meropenem Activity in Vivo against NDM-1-Producing Klebsiella pneumoniae

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X-ray crystallographic analysis of IMP-1 metallo-β-lactamase complexed with a 3-aminophthalic acid derivative, structure-based drug design, and synthesis of 3,6-disubstituted phthalic acid derivative inhibitors

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Aspergillomarasmine A overcomes metallo-β-lactamase antibiotic resistance

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Rhodanine hydrolysis leads to potent thioenolate mediated metallo-β-lactamase inhibition

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An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening

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The ABCD's of β-lactamase nomenclature

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Crystal Structure of Serratia fonticola Sfh-I: Activation of the Nucleophile in Mono-Zinc Metallo-β-Lactamases

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Crystal structure of New Delhi metallo-β-lactamase reveals molecular basis for antibiotic resistance

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Secretion of GOB Metallo-β-Lactamase in Escherichia coli Depends Strictly on the Cooperation between the Cytoplasmic DnaK Chaperone System and the Sec Machinery: Completion of Folding and Zn(II) Ion Acquisition Occur in the Bacterial Periplasm

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Structural insights into the design of inhibitors for the L1 metallo-β-lactamase from Stenotrophomonas maltophilia

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The influence of metallo-β-lactamase production on mortality in nosocomial Pseudomonas aeruginosa infections

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A metallo-β-lactamase enzyme in action:: Crystal structures of the monozinc carbapenemase CphA and its complex with biapenem

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MUSCLE: multiple sequence alignment with high accuracy and high throughput

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Analysis of the context dependent sequence requirements of active site residues in the metallo-β-lactamase IMP-1

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