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  • 1
    Online Resource
    Online Resource
    International Epidemiology of Carbapenemase-Producing Escherichia coli
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases Vol. 77, No. 4 ( 2023-08-22), p. 499-509
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), Vol. 77, No. 4 ( 2023-08-22), p. 499-509
    Abstract: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. Methods Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. Results Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non–MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non–MBL-Ec was 62% (95% CI: 48.2–74.3%). Among infected patients, non–MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. Conclusions Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non–MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations.
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciad288
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study
    Elsevier BV ; 2023
    In:  The Lancet Microbe Vol. 4, No. 3 ( 2023-03), p. e159-e170
    Details
    In: The Lancet Microbe, Elsevier BV, Vol. 4, No. 3 ( 2023-03), p. e159-e170
    Type of Medium: Online Resource
    ISSN: 2666-5247
    URL: Article
    DOI: 10.1016/S2666-5247(22)00329-9
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 3028547-1
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  • 3
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    Online Resource
    Clinical Outcomes and Bacterial Characteristics of Carbapenem-Resistant Acinetobacter baumannii Among Patients from Different Global Regions
    Oxford University Press (OUP) ; 2023
    In:  Clinical Infectious Diseases ( 2023-09-20)
    Details
    In: Clinical Infectious Diseases, Oxford University Press (OUP), ( 2023-09-20)
    Abstract: Carbapenem-resistant Acinetobacter baumannii (CRAb) is one of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. Methods In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. Results Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs. 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. Conclusions CRAb infection types and clinical outcomes differed significantly across regions. While CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. ClinicalTrials.gov #NCT03646227
    Type of Medium: Online Resource
    ISSN: 1058-4838 , 1537-6591
    URL: Article
    DOI: 10.1093/cid/ciad556
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 4
    Online Resource
    Online Resource
    229. Molecular and Clinical Epidemiology of Carbapenemase-Producing E. coli Isolates from Different Global Regions (CRACKLE-2)
    Oxford University Press (OUP) ; 2022
    In:  Open Forum Infectious Diseases Vol. 9, No. Supplement_2 ( 2022-12-15)
    Details
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Carbapenemase-producing (CP) Escherichia coli (CPEc) are a global public health threat. We describe the epidemiology and outcomes of patients with CPEc isolates obtained in CRACKLE 2, a prospective cohort study of hospitalized patients with positive cultures for CP Enterobacteriaceae. Methods In CRACKLE-2, patients with CPEc were enrolled from 26 hospitals in 6 countries (ClinicalTrials.gov NCT03646227). Clinical data were collected, and bacterial isolates underwent whole genome sequencing (WGS). Here, we included unique patients with CPEc by WGS (n=114). The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Chi squared tests with alpha = 0.05 were used to evaluate differences in culture source and outcomes between metallo-beta-lactamase (MBL) and non-MBL isolates. Results Of 114 CPEc isolates, 57 (50%) represented infection (Table 1). Isolates primarily arose from urine (34%) and blood (21%). Compared to non-MBL isolates, isolates containing MBL were more often from urine (41% vs 29%) and less frequently from blood (6% vs 32%); p=0.02. We observed strong regional variations in CP (Figure 1) and MBL (p & lt; 0.0001). Sequence type (ST) 167 was more common among MBL than non-MBL isolates (31% vs 2%, p & lt; 0.0001); non-MBL isolates were more often ST410 and ST131 (17% and 20%). Extended-spectrum beta-lactamases (ESBL) were present in 52% of isolates; most commonly, CTX-M-15 in both MBL (33%) and non-MBL isolates (34%). Phylogenetic analysis of the isolates and corresponding region, bacterial characteristics, and DOOR outcomes are in Figure 1. Death at 30 days occurred in 18 (16%) of patients, more commonly among non-MBL than MBL CPEc (23% vs 6%; p=0.01). The probability of a better DOOR outcome for a randomly selected MBL was 58% [95% CI: 48.2, 67.4], indicating no significant difference between the groups. Figure 1:Phylogenetic population structures of Carbapenemase-producing Escherichia coli (CPEc) isolates Legend: Infection = categorization as infection or colonization. ST = sequence type. BlaCarb = Carbapenemase gene. BlaESBL = acquired ESBL enzymes. DOOR = desirability of outcome ranking. DOOR rankings: 1 = Alive without events; DOOR 2 = Alive with 1 event; DOOR 3 = Alive with 2 or 3 events; DOOR 4 = dead. Conclusion Emergence of carbapenem resistance with important geographic variations was observed in E coli including among high-risk clones such as ST131. Mortality was higher among non-MBL isolates, which were more frequently from blood, but these findings may be confounded by region. Disclosures Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds Cesar A. Arias, MD, PhD, Entasis Phramceuticals: Grant/Research Support|MeMed Diagnostics: Grant/Research Support|Merck: Grant/Research Support David Paterson, MBBS, Accelerate: Honoraria|bioMerieux: Honoraria|Entasis: Advisor/Consultant|Janssen-Cilag: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|PPD: Grant/Research Support|Shionogi: Grant/Research Support|VenatoRx: Advisor/Consultant Karen M. Ordonez, MD, AstraZeneca: Expert Testimony|Biomerieux: Expert Testimony|Farma de Colombia: Expert Testimony|MSD: Expert Testimony|Pfizer: Expert Testimony Souha S. Kanj, Pr, MSD, Pfizer, Gilead, Menarini, Astellas: Advisor/Consultant|MSD, Pfizer, Gilead, Menarini, Astellas: Honoraria Robert Bonomo, MD, Cystic Fibrosis Foundation: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|VA: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt: Grant/Research Support David van Duin, MD, PhD, Achaogen: Advisor/Consultant|Allergan: Advisor/Consultant|Astellas: Advisor/Consultant|MedImmune: Advisor/Consultant|Melinta: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NeuMedicine: Advisor/Consultant|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|T2 Biosystems: Advisor/Consultant|Tetraphase: Advisor/Consultant.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    URL: Article
    DOI: 10.1093/ofid/ofac492.307
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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