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Author: search.filters.author.MUNITA SEPULVEDA, JOSE MANUELEnd date: 409

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    Comparative evaluation of the activity of novel β-lactam antibiotics against difficult-to-treat
    <i>Pseudomonas aeruginosa</i>
    clinical isolates
    (Oxford University Press (OUP), 2026-07-02)
    Mystakelis, Harry
    ;
    Shields, Ryan K
    ;
    Mathers, Amy J
    ;
    Bergman, Yehudit
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    Objectives This study aimed to characterize susceptibility profiles of both currently approved and investigational β-lactam agents against difficult-to-treat resistant Pseudomonas aeruginosa (DTR P. aeruginosa) clinical isolates, including carbapenemase-producing strains. Patients and methods A total of 502 consecutive DTR P. aeruginosa clinical isolates were collected from unique hospitalized patients between 2022 and 2024 across three tertiary care centres. Isolates originated from bloodstream, respiratory, urinary and intra-abdominal infections. Minimum inhibitory concentrations (MICs) for seven β-lactam agents were determined using triplicate reference broth microdilution. Susceptibility interpretations were based on CLSI criteria or, where applicable, investigational breakpoints. Whole-genome sequencing was performed to detect β-lactamase genes. Results Among the 502 isolates, cefepime-zidebactam exhibited the highest in vitro activity (100% susceptibility), followed by cefiderocol-xeruborbactam (98%), cefiderocol (95%), ceftolozane-tazobactam (90%), cefepime-taniborbactam (86%), ceftazidime-avibactam (85%), and imipenem-relebactam (41%). Notably, only 35% of isolates were susceptible to all seven agents. Carbapenemase genes were identified in 4% of isolates, including blaGES (n = 13), blaVIM (n = 7), blaKPC (n = 1) and blaIMP (n = 1). Among carbapenemase-producing isolates, cefepime-zidebactam retained activity against all isolates (100%), exceeding that of other approved β-lactam/β-lactamase inhibitor combinations (0%–24% susceptible), cefiderocol (76%), cefiderocol-xeruborbactam (86%) and cefepime-taniborbactam (81%). Conclusions While currently approved β-lactam agents retained activity against many DTR P. aeruginosa isolates, their performance was markedly compromised in the presence of carbapenemases, with the notable exceptions of cefepime-zidebactam and cefiderocol. Investigational β-lactam/β-lactamase inhibitor combinations exhibited consistently robust activity across resistance phenotypes, including carbapenemase-producing isolates, representing promising options for DTR P. aeruginosa infections.
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    Resistance to novel β-lactam/β-lactamase inhibitors among carbapenem-resistant
    <i>Pseudomonas aeruginosa</i>
    and clinical implications in the prospective observational
    <i>Pseudomonas</i>
    study
    (American Society for Microbiology, 2026-06-03)
    Lee S. Gottesdiener
    ;
    Yixuan Li
    ;
    Kerryl E. Greenwood-Quaintance
    ;
    Lauren Komarow
    ;
    Cesar A. Arias
      6
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    Comparative outcomes of ceftazidime-avibactam versus meropenem-vaborbactam for KPC-producing Enterobacterales infections
    (American Society for Microbiology, 2026-03-23)
    Sara M. Karaba
    ;
    Dariusz A. Hareza
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    ;
    MARTINEZ SOLIS, JOSE RODRIGO WALDEMAR  
    ;
    Yehudit Bergman
    <jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title/> <jats:p> Thirty-day mortality was similar in a propensity-score-weighted cohort of 73 patients with KPC-producing Enterobacterales infections treated with ceftazidime-avibactam or meropenem-vaborbactam. Emergence of resistance was higher in the ceftazidime-avibactam group (12% vs 0%); putative resistance mechanisms included porin mutations ( <jats:italic toggle="yes">Klebsiella pneumoniae</jats:italic> ) and R2 loop structural changes in AmpC ( <jats:italic toggle="yes">Enterobacter cloacae</jats:italic> complex). </jats:p> </jats:sec>
      1Scopus© Citations 1
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    Cross-sectional survey to assess the status of antimicrobial stewardship programs in public Chilean hospitals
    (Springer Science and Business Media LLC, 2026-03-17)
    Ruth Rosales
    ;
    Claudio González
    ;
    José Valderrama
    ;
    Tomás Reyes-Barros
    ;
    Carmen Gloria Núñez
    Antimicrobial resistance is a leading cause of death worldwide, with the highest burdens in low-resource settings. Antimicrobial stewardship programs (ASP) are coordinated interventions designed to improve and measure the appropriate use of antimicrobials. In December 2020, the Ministry of Health of Chile mandated that all hospitals in the country implement an ASP, but there has been little rigorous, comparable information on the prevalence and types of ASP activities currently occurring in Chilean hospitals, which is critical for infection control officials and health decision-makers.
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    Antimicrobial use and documented infection among hospitalized adults in South American acute care facilities during the coronavirus disease 2019 (COVID-19) pandemic
    (Public Library of Science (PLoS), 2026-02-27)
    Lauren F. Dempsey
    ;
    Hanako Osuka
    ;
    Olivia L. McGovern
    ;
    MUNITA SEPULVEDA, JOSE MANUEL  
    ;
    Maria Isabel Garzon
    <jats:sec id="sec001"> <jats:title>Background</jats:title> <jats:p>Despite low bacterial and fungal infection rates, increased antimicrobial use (AU) among hospitalized patients has been reported during the Coronavirus Disease 2019 (COVID-19) pandemic. We evaluated whether COVID-19 was a driver of AU and documented bacterial or fungal infection.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>We conducted a retrospective cohort study in two hospitals each in Argentina, Brazil, and Chile. We included hospitalized adults with and without COVID-19 admitted during the pandemic (March 2020-February 2021) as well as a cohort admitted prior to the pandemic (March 2019-February 2020) with similar age and length of hospitalization. We performed multivariable logistic regressions to compare 1) patients with COVID-19 to those without who were admitted during the pandemic, and 2) patients without COVID-19 who were admitted during the pandemic to a similar patient population before the pandemic to characterize the association of COVID-19 or admission during the pandemic with rates of AU and infections.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>A total of 1116 patients were included. During the pandemic, COVID-19 was not associated with receiving antimicrobials or receiving antimicrobials for a duration &gt;48 hours, but it was associated with reduced likelihood of culture-positive bacterial or fungal infection (aOR=0.35, 95% CI: 0.19–0.64, p &lt; 0.001). Compared to patients without COVID-19 admitted during the pandemic, patients admitted prior to the pandemic were more likely to have received antimicrobials (aOR=1.54, 95% CI: 1.15–2.07, p &lt; 0.01), but there was no association with receiving antimicrobials for duration&gt;48 hours or having a culture-positive bacterial or fungal infection.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>COVID-19 was not associated with an increased likelihood of AU in this cohort of hospitalized adults.</jats:p> </jats:sec>
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      11
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    Activity of novel antibiotics against dual metallo-Beta-lactamase producing
    <i>Enterobacter hormaechei</i>
    clinical isolates
    (Oxford University Press (OUP), 2026-01-07)
    Camila Solar
    ;
    LORENA DIAZ BAYO
    ;
    Katherine Soto
    ;
    Jose R W Martínez
    ;
    Nicolas Canales
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Metallo-β-lactamase (MBL)-producing carbapenemase-resistant Enterobacterales infections are associated with significant mortality. Several β-lactam/β-lactamase inhibitor combinations (BL/BLI) with promising activity against MBLs are in the pipeline.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To investigate the in vitro activity of upcoming BL/BLI agents against Enterobacter hormaechei clinical isolates co-producing NDM and VIM enzymes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Eleven E. hormaechei isolates co-harbouring blaNDM-7 and blaVIM-1 were identified from 10 patients admitted to a tertiary hospital in Santiago, Chile, between July 2022 and July 2023. Reference broth microdilution (BMD) panels were developed to determine minimum inhibitory concentrations (MICs) to aztreonam/avibactam, cefepime/taniborbactam, cefepime/zidebactam, cefiderocol and cefiderocol/xeruborbactam. Cefiderocol population analysis profile–area under the curve (PAP–AUC) was performed in strains exhibiting cefiderocol susceptibility to assess for cefiderocol heteroresistance. Long-read sequencing, using the Oxford Nanopore Technologies platform, was conducted on all isolates to characterize the genomic background of blaNDM-7 and blaVIM-1.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Among the 11 E. hormaechei isolates assemblies revealed blaNDM-7 and blaVIM-1 were located on separate plasmids. All isolates were susceptible to aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. Cefiderocol susceptibility was variable; the addition of xeruborbactam restored susceptibility.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our findings indicate that E. hormaechei clinical isolates co-producing NDM and VIM metallo-carbapenemases exhibited susceptibility to all tested novel BL/BLIs, including aztreonam/avibactam, cefepime/taniborbactam and cefepime/zidebactam. The combination of cefiderocol and xeruborbactam restored the activity of cefiderocol.</jats:p> </jats:sec>
      1