is a common cause of pulmonary and invasive mold infections among immunocompromised hosts. Mortality in immunocompromised hosts with invasive infections (IAI) has been reported to be as high as 80%. Therefore, appropriate therapy is essential in treating IAI.
View Article and Find Full Text PDFBackground: Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.
View Article and Find Full Text PDFThis study reports the activity of cefiderocol against Enterobacterales, , and spp. isolates collected from the United States and Europe, including Israel and Turkey, from 2020 to 2021. Among Enterobacterales, 2.
View Article and Find Full Text PDFWe evaluated the activities of aztreonam/avibactam and recently approved β-lactamase inhibitor combinations (BLICs) to compare the antimicrobial susceptibility patterns of Enterobacterales and isolated from intensive care unit (ICU) and non-ICU patients. Clinical isolates (1/patient) were consecutively collected from 72 United States medical centres in 2020-2022 and susceptibility tested by broth microdilution. The results for 5421 isolates from ICU patients were analysed and compared to those for 20,649 isolates from non-ICU patients.
View Article and Find Full Text PDFWe subjected seven . isolates to a 10-day serial passaging against five antipseudomonal agents to evaluate resistance levels post-exposure and putative resistance mechanisms in terminal mutants were analyzed by whole-genome sequencing analysis. Meropenem (mean, 38-fold increase), cefepime (14.
View Article and Find Full Text PDFBackground: Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved β-lactamase inhibitor combinations (BLICs).
Objectives: To evaluate a large collection of CRE isolates, including those non-susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam.
Methods: Overall, 24 580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC).
A total of 35,360 Enterobacterales isolates were consecutively collected from 75 US medical centers in 2018-2022. Among these isolates, 2612 (7.4%) were categorized as multidrug-resistant (MDR).
View Article and Find Full Text PDFBackground: Aztreonam/avibactam is under development to treat infections caused by Gram-negative bacteria. We evaluated the activities of aztreonam/avibactam and comparators against a global collection of carbapenem-resistant Enterobacterales (CRE), including ceftazidime/avibactam-resistant isolates.
Methods: Isolates were consecutively collected (24 924; 1/patient) from 69 medical centres in 36 countries during 2019-21.
Open Forum Infect Dis
February 2023
Background: The Clinical and Laboratory Standards Institute (CLSI) lowered the Enterobacterales-susceptible/-resistant breakpoints for amikacin in 2023 from ≤16/≥64 mg/L to ≤4/≥16 mg/L and the breakpoints for gentamicin and tobramycin from ≤4/≥16 mg/L to ≤2/≥8 mg/L. Because aminoglycosides are frequently used to treat infections caused by multidrug-resistant (MDR) and carbapenem-resistant Enterobacterales (CRE), we evaluated the impact of these changes on the susceptibility rates (%S) of Enterobacterales collected from US medical centers.
Methods: A total of 9809 Enterobacterales isolates were consecutively collected (1/patient) from 37 US medical centers in 2017-2021 and susceptibility was tested by broth microdilution.
Background: As the frequency of metallo-β-lactamase (MBL)-producing Enterobacterales is increasing worldwide, effective antimicrobials to treat the infections caused by these organisms are urgently needed.
Methods: The activity of aztreonam-avibactam and comparators were evaluated against 27 834 Enterobacterales isolates collected from 74 US medical centers in 2019-2021. Isolates were susceptibility tested by broth microdilution.
The Pseudomonas aeruginosa LasR-LasI (LasR-I) quorum sensing system regulates secreted proteases that can be exploited by cheaters, such as quorum sensing receptor-defective () mutants. mutants emerge in populations growing on casein as a sole source of carbon and energy. These mutants are exploitative cheaters because they avoid the substantial cost of engaging in quorum sensing.
View Article and Find Full Text PDFrapidly colonizes surfaces using swarming motility. Surface contact induces the surface-sensing regulon, including lateral flagellar genes, spurring dramatic shifts in physiology and behavior. The bacterium can also adopt a sessile, surface-associated lifestyle and form robust biofilms.
View Article and Find Full Text PDFThe marine bacterium and human pathogen rapidly colonizes surfaces by using swarming motility and forming robust biofilms. Entering one of the two colonization programs, swarming motility or sessility, involves differential regulation of many genes, resulting in a dramatic shift in physiology and behavior. has evolved complex regulation to control these two processes that have opposing outcomes.
View Article and Find Full Text PDFVibrio fischeri uses the AinS/AinR pheromone-signaling system to control bioluminescence and other symbiotic colonization factors. The Ain system is thought to initiate cell-cell signaling at moderate cell densities and to prime the LuxI/LuxR signaling system. Here we compared and analyzed the ain locus from two V.
View Article and Find Full Text PDFUnlabelled: The squid light organ symbiont Vibrio fischeri controls bioluminescence using two acyl-homoserine lactone pheromone-signaling (PS) systems. The first of these systems to be activated during host colonization, AinS/AinR, produces and responds to N-octanoyl homoserine lactone (C(8)-AHL). We screened activity of a P(ainS)-lacZ transcriptional reporter in a transposon mutant library and found three mutants with decreased reporter activity, low C(8)-AHL output, and other traits consistent with low ainS expression.
View Article and Find Full Text PDFTwo distinct but interrelated pheromone-signaling systems, LuxI/LuxR and AinS/AinR, positively control bioluminescence in Vibrio fischeri. Although each system generates an acyl-homoserine lactone (AHL) signal, the protein sequences of LuxI/LuxR and AinS/AinR are unrelated. AinS and LuxI generate the pheromones N-octanoyl-AHL (C8-AHL) and N-3-oxo-hexanoyl-AHL (3OC6-AHL), respectively.
View Article and Find Full Text PDFBioluminescence in Vibrio fischeri ES114 is activated by autoinducer pheromones, and this regulation serves as a model for bacterial cell-cell signaling. As in other bacteria, pheromone concentration increases with cell density; however, pheromone synthesis and perception are also modulated in response to environmental stimuli. Previous studies suggested that expression of the pheromone-dependent bioluminescence activator LuxR is regulated in response to glucose by cyclic AMP (cAMP) receptor protein (CRP) (P.
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