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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>
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    Impact of inappropriate empirical antibiotic therapy on in-hospital mortality: a retrospective multicentre cohort study of patients with bloodstream infections in Chile, 2018–2022
    (BMJ, 2024-11)
    Kasim Allel
    ;
    Anne Peters
    ;
    Luis Furuya-Kanamori
    ;
    Maria Spencer-Sandino
    ;
    Emma Pitchforth
    Introduction Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. Methods We used a retrospective multicentre cohort study of BSI cases in three Chilean tertiary hospitals (2018-2022) to assess the impact of IEAT on 30-day and overall in-hospital mortality and quantify excess disease and economic burdens associated with IEAT. We determined the appropriateness of pathogen-antimicrobial pairings based on in vitro susceptibilities and pathogen-corresponding antibiotic treatment, allowing a 48-hour window after the initial blood culture. We addressed confounding using propensity scores and inverse probability weights (IPW). We used IPW-weighted logistic competing-risk survival models, including time-varying independent variables after blood tests as controls. Results Among 1323 BSI episodes, 432 (33%) received IEAT, with an average time to adequate therapy of 4.6 days. Compared with adequate treatment, IEAT was associated with 30-day and overall mortality risks that were 1.31 and 1.24 times higher, respectively. These risks were further inflated between twofold and fourfold when antibiotic-resistant bacteria (ARB) was included. Competing-risk models showed associations between IEAT and IEAT-ARB combinations with in-hospital mortality. Accounting for time-varying variables yielded similar results. The economic burden of IEAT resulted in an additional cost of similar to US$9900 from premature mortality and 0.46 disability-adjusted life-years per patient with BSI. Conclusion Approximately one in three patients received IEAT, often associated with ARB. IEAT was linked to increased mortality risk and higher economic costs. Timely appropriate treatment, early pathogen detection and resistance profiling are likely to improve health and financial outcomes at the population level.
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      2
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    Multispecies emergence of dual blaKPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile
    (American Society for Microbiology, 2025-01-31)
    QUESILLE VILLALOBOS, ANA MARIA  
    ;
    Camila Solar
    ;
    Jose R. W. Martínez
    ;
    RIVAS JIMENEZ, LINA MARIA  
    ;
    Valeria Quiroz
    Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring
    Scopus© Citations 10  15
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    Excess burden of antibiotic-resistant bloodstream infections: evidence from a multicentre retrospective cohort study in Chile, 2018–2022
    (2024)
    Kasim Allel
    ;
    Anne Peters
    ;
    Hassan Haghparast-Bidgoli
    ;
    Maria Spencer-Sandino
    ;
    Jose Conejeros
    Scopus© Citations 2  4
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    Colonization With Antibiotic-Resistant Gram-Negative Bacteria in Population-Based Hospital and Community Settings in Chile
    (2020)
    ARAOS BRALIC, RAFAEL IGNACIO  
    ;
    Anne Peters
    ;
    Felipe Sanchez
    ;
    Danilo Alvares
    ;
    RIVAS JIMENEZ, LINA MARIA  
    <jats:p><jats:bold>Background:</jats:bold> Estimating the burden of intestinal colonization with antibiotic-resistant gram-negative bacteria (AR-GNB) is critical to understanding their global epidemiology and spread. We aimed to determine the prevalence of, and risk factors for, intestinal colonization due to AR-GNB in population-based hospital and community settings in Chile. <jats:bold>Methods:</jats:bold> Between December 2018 and May 2019, we enrolled randomly selected hospitalized adults in 4 tertiary-care public hospitals (Antofagasta, Santiago, Curico and Puerto Montt), and adults residing in a community-based cohort in the rural town of Molina. Following informed consent, we collected rectal swabs and epidemiological information through a standardized questionnaire. Swabs were plated onto MacConkey agar with 2 &amp;micro;g/mL ciprofloxacin or ceftazidime. All recovered morphotypes were identified, and antibiotic susceptibility testing was performed via disk diffusion. The primary outcome was the prevalence of colonization with fluoroquinolone (FQ)- or third-generation cephalosporin (3GC)&amp;ndash;resistant GNB. The secondary outcome was the prevalence of colonization with multidrug-resistant (MDR) GNB, defined as GNB resistant to &amp;ge;3 antibiotic classes. Categories were not mutually exclusive. Bivariate and multivariate analyses were performed to describe risk factors for colonization with these categories. <jats:bold>Results:</jats:bold> In total, 775 hospitalized adults and 357 community participants were enrolled, with a median age of 60 years (IQR, 42&amp;ndash;72) and 55 years (IQR, 48&amp;ndash;62) years, respectively. Among hospitalized participants, the prevalence of colonization with FQ- or 3GC-resistant GNB was 47% (95% CI, 43%&amp;ndash;50%) and 41% (95% CI, 38%&amp;ndash;45%), respectively, whereas the prevalence of MDR-GNB colonization was 27% (95% CI, 24%&amp;ndash;31%). In the community setting, the prevalence of colonization with either FQ-, 3GC-resistant GNB, or MDR-GNB was 40% (95% CI, 34%&amp;ndash;45%), 29% (95% CI, 24%&amp;ndash; 34%), and 5% (95% CI, 3%&amp;ndash;8%), respectively. Independent risk factors for hospital MDR-GNB colonization included the hospital of admission, unit of hospitalization (intensive care units carried the highest risk), in-hospital antimicrobial exposure, comorbidities (Charlson index), and length of stay. In the community setting, recent antibiotic exposure (&amp;lt;3 months) predicted colonization with either FQ- or 3GC-resistant GNB, and alcohol consumption was inversely associated with MDR GNB colonization. <jats:bold>Conclusions:</jats:bold> A high burden of colonization with AR-GNB was observed in this sample of hospitalized and community-dwelling adults in Chile. The high burden of colonization with GNB resistant to commonly used antibiotics such as FQ and 3GC found in community dwellers, suggests that the community may be a relevant source of antibiotic resistance. Efforts to understand relatedness between resistant strains circulating in the community and the hospital are needed.</jats:p><jats:p><jats:bold>Funding:</jats:bold> None</jats:p><jats:p><jats:bold>Disclosures:</jats:bold> None</jats:p>
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    Scopus© Citations 1  3
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      7
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      2Scopus© Citations 4
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    High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study
    (2023)
    ARAOS BRALIC, RAFAEL IGNACIO  
    ;
    Rachel M Smith
    ;
    Ashley Styczynski
    ;
    Felipe Sánchez
    ;
    Lea Maureira
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9–50.0), 41.2% (95% CI, 37.7–44.6), 14.5% (95% CI, 12.0–16.9), and 26.3% (95% CI, 23.2–29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4–44.6), 28.9% (95% CI, 24.2–33.6), 5.6% (95% CI, 3.2–8.0), and 4.8% (95% CI, 2.6–7.0), respectively.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.</jats:p> </jats:sec>
    Scopus© Citations 10  2