A molecular analysis of meropenem-vaborbactam non-susceptible KPC-producing .

We characterized the molecular determinants of meropenem-vaborbactam (MV) non-susceptibility among non-metallo-β-lactamase-producing KPC- (KPC-). Whole-genome sequencing was performed to identify mutations associated with MV non-susceptibility. Isolates with elevated MV MICs were found to have mutations encoding truncated or altered OmpK36 porins and increased copy numbers.

First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197.

Unlabelled: Resistance to ceftazidime-avibactam (CZA) due to carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively.

Difficult-to-treat (DTR) harboring Verona-Integron metallo-β-lactamase (): infection management and molecular analysis.

harboring Verona Integron-encoded metallo-β-lactamase enzymes (VIM-CRPA) have been associated with infection outbreaks in several parts of the world. In the US, however, VIM-CRPA remain rare. Starting in December 2018, we identified a cluster of cases in our institution.

Phage-antibiotic combinations against multidrug-resistant in static and dynamic biofilm models.

Biofilm-producing infections pose a severe threat to public health and are responsible for high morbidity and mortality. Phage-antibiotic combinations (PACs) are a promising strategy for combatting multidrug-resistant (MDR), extensively drug-resistant (XDR), and difficult-to-treat infections. Ten MDR/XDR strains and five .

Investigating and Treating a Corneal Ulcer Due to Extensively Drug-Resistant Pseudomonas aeruginosa.

Resistant Gram-negative bacteria are a growing concern in the United States, leading to significant morbidity and mortality. We identified a 72-year-old female patient who presented with unilateral vision loss. She was found to have a large corneal ulcer with hypopyon.

Identification of Genes and Characterization of Resistance Mechanisms to Colistin in Isolates from Colombian Hospitals.

We report the presence of the gene among 880 clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL).

Boronic Acid Transition State Inhibitors as Potent Inactivators of KPC and CTX-M β-Lactamases: Biochemical and Structural Analyses.

Design of novel β-lactamase inhibitors (BLIs) is one of the currently accepted strategies to combat the threat of cephalosporin and carbapenem resistance in Gram-negative bacteria. oronic cid ransition tate nhibitors (BATSIs) are competitive, reversible BLIs that offer promise as novel therapeutic agents. In this study, the activities of two α-amido-β-triazolylethaneboronic acid transition state inhibitors (S02030 and MB_076) targeting representative KPC (KPC-2) and CTX-M (CTX-M-96, a CTX-M-15-type extended-spectrum β-lactamase [ESBL]) β-lactamases were evaluated.

Imipenem/Relebactam Resistance in Clinical Isolates of Extensively Drug Resistant Pseudomonas aeruginosa: Inhibitor-Resistant β-Lactamases and Their Increasing Importance.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections are a major clinical challenge. Many isolates are carbapenem resistant, which severely limits treatment options; thus, novel therapeutic combinations, such as imipenem-relebactam (IMI/REL), ceftazidime-avibactam (CAZ/AVI), ceftolozane-tazobactam (TOL/TAZO), and meropenem-vaborbactam (MEM/VAB) were developed. Here, we studied two extensively drug-resistant (XDR) P.

Orthopedic Implant-Associated and Central Venous Catheter-Associated Infections Caused by spp. in the Veterans Affairs Healthcare System from 2000 to 2020.

A 72-year-old male developed a late-onset infection of an internal fixation device caused by Although often considered contaminants, bacteria from the genus may also be pathogens. We also summarize cases from the Veteran Health Administration (VHA) from which isolates were recovered and review the relevant literature. Using the national VHA database, we identified patients with cultures that grew spp.

Risk Factors for and Mechanisms of listin esistance Among nterobacterales: Getting at the CORE of the Issue.

Background: Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood.

Methods: A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, Michigan. Patients with CORE isolates from January 1, 2016, to March 31, 2017, were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls.

Molecular Analysis of Polymyxin Resistance among Carbapenemase-Producing in Colombia.

Polymyxin resistance in has been attributed to mutations in , , , and and to the presence of plasmid-mediated genes. Herein, we describe the molecular characteristics of 24 polymyxin- and carbapenem-resistant isolates recovered from six Colombian cities between 2009 and 2019. Minimum inhibitory concentrations (MICs) to polymyxin were confirmed by broth microdilution, and whole-genome sequencing was performed to determine sequence type, resistome, and mutations in the genes related to polymyxin resistance, as well the presence of .

Emergence of Resistance to Ceftazidime-Avibactam in a Pseudomonas aeruginosa Isolate Producing Derepressed in a Hollow-Fiber Infection Model.

Ceftazidime (CAZ)-avibactam (AVI) is a β-lactam/β-lactamase inhibitor combination with activity against type A and type C β-lactamases. Resistance emergence has been seen, with multiple mechanisms accounting for the resistance. We performed four experiments in the dynamic hollow-fiber infection model, delineating the linkage between drug exposure and both the rate of bacterial kill and resistance emergence by all mechanisms.

Predicting β-lactam resistance using whole genome sequencing in Klebsiella pneumoniae: the challenge of β-lactamase inhibitors.

Although multiple antimicrobial resistance (AMR) determinants can confer the same in vitro antimicrobial susceptibility testing (AST) phenotype, their differing effect on optimal therapeutic choices is uncertain. Using a large population-based collection of clinical strains spanning a 3.5-year period, we applied WGS to detect inhibitor resistant (IR), extended-spectrum β-lactamase (ESBL), and carbapenem resistant (CR) β-lactamase (bla) genes and compared the genotype to the AST phenotype in select isolates.

Monitoring Ceftazidime-Avibactam and Aztreonam Concentrations in the Treatment of a Bloodstream Infection Caused by a Multidrug-Resistant Enterobacter sp. Carrying Both Klebsiella pneumoniae Carbapenemase-4 and New Delhi Metallo-β-Lactamase-1.

In an infection with an Enterobacter sp. isolate producing Klebsiella pneumoniae Carbapenemase-4 and New Delhi Metallo-β-Lactamase-1 in the United States, recognition of the molecular basis of carbapenem resistance allowed for successful treatment by combining ceftazidime-avibactam and aztreonam. Antimicrobial synergy testing and therapeutic drug monitoring assessed treatment adequacy.

Identification of four patients with colistin-resistant Escherichia coli containing the mobile colistin resistance mcr-1 gene from a single health system in Michigan.

Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632).

Nacubactam Enhances Meropenem Activity against Carbapenem-Resistant Klebsiella pneumoniae Producing KPC.

Carbapenem-resistant (CRE) are resistant to most antibiotics, making CRE infections extremely difficult to treat with available agents. carbapenemases (KPC-2 and KPC-3) are predominant carbapenemases in CRE in the United States. Nacubactam is a bridged diazabicyclooctane (DBO) β-lactamase inhibitor that inactivates class A and C β-lactamases and exhibits intrinsic antibiotic and β-lactam "enhancer" activity against In this study, we examined a collection of meropenem-resistant isolates carrying or ; meropenem-nacubactam restored susceptibility.

Know your enemy: managing resistant Gram-negative infections.

Report from the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2018), Madrid, Spain, 21-24 April 2018 Gram-negative bacteria such as Klebsiella, Acinetobacter and Pseudomonas cause some of the most serious infections and are increasingly resistant to multiple drugs and in some cases, to all available antibiotics. Management of infections caused by these organisms is a global challenge that has serious implications for every hospital and department and therefore every delegate attending ECCMID 2018.

Emergence of Resistance to Colistin During the Treatment of Bloodstream Infection Caused by Carbapenemase-Producing .

We report the emergence of colistin resistance in carbapenemase (KPC)-producing after 8 days of colistin-based therapy, resulting in relapse of bloodstream infection and death. Disruption of the gene by insertion of a mobile genetic element was found to be the mechanism, which was replicated in vitro after exposure to subinhibitory concentrations of colistin and meropenem.

Evaluation of Sensititre Broth Microdilution Plate for determining the susceptibility of carbapenem-resistant Klebsiella pneumoniae to polymyxins.

Colistin and polymyxin B MICs were determined for 106 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates using Sensititre Research Use Only GNX2F plates (Thermo Fisher) and compared to CLSI broth macrodilution (BMD) as the reference method. For colistin, EUCAST breakpoints were applied and testing of isolates with very major (VM) errors was repeated in duplicate by both methods to determine a majority result. Essential agreement (MIC ± one dilution) of GNX2F with the reference method was 97.

Molecular characterisation of carbapenem-resistant Enterobacter cloacae complex in Colombia: bla and the 'changing landscape'.

Objectives: The aim of this study was to examine the population structure of representative carbapenem-resistant Enterobacter cloacae complex (CR-Ecl) isolates from eight different Colombian regions and to characterise their associated β-lactamases.

Methods: A total of 28 CR-Ecl isolates collected in Colombia between 2009-2013 through the Colombian Nosocomial Network were included in this study. Antimicrobial susceptibility testing was performed by the broth microdilution method.