Molecular epidemiology of β-lactamases in ceftriaxone-resistant Enterobacterales bloodstream infections in the mid-Atlantic United States.

Ceftriaxone-resistant Enterobacterales remain a public health threat; contemporary data investigating their molecular epidemiology are limited. Five hundred consecutive ceftriaxone-resistant (MIC ≥ 4 µg/mL) Enterobacterales bloodstream isolates were collected between 2018 and 2022 from three Maryland hospitals. Broth microdilution confirmed antibiotic susceptibilities.

Electronic evaluation of infection risk from room environment and prior room occupants: the transmission from room environment events (TREE) measure.

Over a 2-year period, we identified Transmission from Room Environment Events (TREE) across the Johns Hopkins Health System, where the subsequent room occupant developed the same organism with the same antimicrobial susceptibilities as the patient who had previously occupied that room. Overall, the TREE rate was 50/100,000 inpatient days.

Laboratory detection of carbapenemases among Gram-negative organisms.

SUMMARYThe carbapenems remain some of the most effective options available for treating patients with serious infections due to Gram-negative bacteria. Carbapenemases are enzymes that hydrolyze carbapenems and are the primary method driving carbapenem resistance globally. Detection of carbapenemases is required for patient management, the rapid implementation of infection prevention and control (IP&C) protocols, and for epidemiologic purposes.

Differential frequency of persister cells in clinically derived isolates of Pseudomonas aeruginosa after exposure to cefiderocol and ceftolozane/tazobactam.

Background: Bacterial persistence is a phenomenon whereby a subpopulation of bacteria survive high concentrations of an active antibiotic in the absence of phenotypic alterations. Persisters are associated with chronic and recurrent infections for pathogens including Pseudomonas aeruginosa. Understanding persister profiles of newer antibiotics such as cefiderocol and ceftolozane/tazobactam against P.

Clinical outcomes and emergence of resistance of infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam.

Few studies compare outcomes of patients with difficult-to-treat resistance (DTR) infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam. A multicenter prospective study was conducted of unique patients with DTR infections from 2018 to 2023 receiving >72 h of ceftolozane-tazobactam or ceftazidime-avibactam, with confirmation that the isolate was susceptible to the agent administered by broth microdilution. Inverse probability weighting (IPW) incorporating propensity scores was utilized to ensure balanced baseline characteristics.

Multicenter evaluation of activity of aztreonam in combination with avibactam, relebactam, and vaborbactam against metallo-β-lactamase-producing carbapenem-resistant gram-negative bacilli.

Treatment options for carbapenem-resistant gram-negative bacilli (CR-GNB), especially metallo-β-lactamase (MBL)-producing CR-GNB, are limited. Aztreonam (ATM) in combination with avibactam (AVI) has shown potential for treating MBL-producing carbapenem-resistant Enterobacterales (CREs) and . However, data on ATM in combination with other β-lactamase inhibitors (BLIs) are limited.

High Prevalence of Multistep Algorithms in Diagnostic Clostridioides difficile Laboratory Testing.

Context.—: Laboratory testing practices for diagnosis of Clostridioides difficile infection (CDI) have evolved in response to published guidelines, availability of highly sensitive nucleic acid amplification tests (NAATs), perceived problems with the specificity of NAATs, and CDI reporting requirements.

Objective.

Comparison of BD Phoenix and disk diffusion to broth microdilution for determining cefepime susceptibility among carbapenem-resistant Enterobacterales.

There are increasing reports of carbapenem-resistant Enterobacterales (CRE) that test as cefepime-susceptible (S) or susceptible-dose dependent (SDD). However, there are no data to compare the cefepime testing performance of BD Phoenix automated susceptibility system (BD Phoenix) and disk diffusion (DD) relative to reference broth microdilution (BMD) against carbapenemase-producing (CP-CRE) and non-producing (non-CP CRE) isolates. Cefepime susceptibility results were interpreted according to CLSI M100Ed32.

Assessing the impact of meropenem exposure on ceftolozane/tazobactam-resistance development in Pseudomonas aeruginosa using in vitro serial passage.

Background: Patients infected with difficult-to-treat Pseudomonas aeruginosa are likely to receive meropenem (MEM) empirically before escalation to ceftolozane/tazobactam (C/T). We assessed whether pre-exposure to MEM affected C/T resistance development on C/T exposure.

Materials And Methods: Nine clinical P.

Status check: next-generation sequencing for infectious-disease diagnostics.

Next-generation sequencing (NGS) applications for the diagnostics of infectious diseases has demonstrated great potential with three distinct approaches: whole-genome sequencing (WGS), targeted NGS (tNGS), and metagenomic NGS (mNGS, also known as clinical metagenomics). These approaches provide several advantages over traditional microbiologic methods, though challenges still exist.

Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M Extended-Spectrum β-Lactamase-Producing Enterobacterales Bloodstream Infections?

Background: Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Patient outcomes from non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown.

Methods: A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018-2022 was conducted.

A diagnostic stewardship approach to prevent unnecessary testing of an enteric bacterial molecular panel.

Testing for enteric bacterial pathogens in patients hospitalized for more than 3 days is almost always inappropriate. Our study validates the utility of the 3-day rule and the use of clinical decision support tools to decrease unnecessary testing of enteropathogenic bacteria other than . Overriding the restriction was very low yield.

Priorities and Progress in Diagnostic Research by the Antibacterial Resistance Leadership Group.

The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms.

Updating breakpoints in the United States: a summary from the ASM Clinical Microbiology Open 2022.

Accurate antimicrobial susceptibility testing (AST) and reporting are essential for guiding appropriate therapy for patients and direction for public health prevention and control actions. A critical feature of AST reporting is the interpretation of AST results using clinical breakpoints for reporting as susceptible, susceptible-dose dependent, intermediate, or resistant. Breakpoints are subject to continuous adjustment and updating to best reflect current clinical data.

Guiding antimicrobial stewardship through thoughtful antimicrobial susceptibility testing and reporting strategies: an updated approach in 2023.

Antimicrobial susceptibility test and report guidelines are an important tool for antimicrobial stewardship programs. Since 1972, Tables 1 within the Clinical and Laboratory Standards Institute (CLSI) M100 document have provided a general framework upon which clinical microbiologists and antimicrobial stewardship teams can build algorithms for susceptibility testing and reporting that meet the specific needs of their institution. Many changes were made to Tables 1 in M100-Ed33 to modernize the content to reflect the landscape of current clinical practice, including the growing armamentarium of antimicrobial agents, the emergence of new mechanisms of antimicrobial resistance, the increasing prevalence of infections caused by multidrug-resistant organisms, and updated consensus recommendations for first-choice and alternative agents for treatment.

Cefepime in vivo activity against carbapenem-resistant Enterobacterales that test as cefepime susceptible or susceptible-dose dependent in vitro: implications for clinical microbiology laboratory and clinicians.

Background: Carbapenem-resistant Enterobacterales (CRE) are a public health concern. Among these isolates, there are reports of isolates that test as cefepime susceptible or susceptible-dose dependent (SDD) in vitro despite presence of a carbapenemase. This study aimed to evaluate the pharmacokinetic/pharmacodynamic profile of cefepime against carbapenemase-producing (CP-CRE) and non-producing (non-CP-CRE) isolates with a range of cefepime MICs.

An NDM-Producing Clinical Isolate Exhibiting Resistance to Cefiderocol and the Combination of Ceftazidime-Avibactam and Aztreonam: Another Step Toward Pan-β-Lactam Resistance.

Background: Cefiderocol and ceftazidime-avibactam plus aztreonam (CZA-ATM) are preferred treatment regimens for New Delhi metallo-β-lactamase (NDM)-producing infections.

Methods: We report the case of a US patient who traveled to India to receive a renal transplant. He subsequently experienced pyelonephritis by an NDM-producing Broth microdilution and the broth disk elution method indicated resistance to all β-lactams, including cefiderocol and CZA-ATM.