Boutzoukas, Angelique E

Abstract Background Ceftriaxone-resistant Escherichia coli infections are increasingly common, partially because of the emergence of E. coli sequence type 131 (ST131), including its subclade C2/H30Rx, which produce extended-spectrum β-lactamases. Methods A prospective cohort including 14 US sites, which enrolled monomicrobial ceftriaxone-resistant and susceptible E. coli bloodstream infection (BSI) cases in a 1:1 ratio, was used to compare ST131 versus non-ST131 E. coli BSI, with specific attention to E. coli ST131 C2/H30Rx. Desirability of outcome ranking was determined at 30 days after infection onset. Results This analysis included 282 patients with E. coli BSI; 43% (121/282) were E. coli ST131 and 23% (66/282) belonged to the C2/H30Rx subclade. Resistance to ceftriaxone was present in 79% (96/121) ST131, 86% (57/66) E. coli ST131 C2/H30Rx, and 27% (43/161) E. coli non-ST131. Compared to patients with non-ST131 E. coli BSI, patients with ST131 BSI were older (median 70 years, [Q1 62, Q3 76] years vs 65 years, [51, 74]; P = .005) and more often admitted from long-term care facilities (21/121 [17%] vs 7/161 [4%], P < .001). Overall and empiric carbapenem use was more frequent in the treatment of patients with ST131 BSI compared with non-ST131 BSI (overall 89/121 [74%] vs 50/161 [31%]; empiric: 58/121 [48%] vs 31/161 [19%], P < .001). Desirability of outcome ranking outcomes were similar between groups. Conclusions Most ceftriaxone-resistant E. coli from US patients with E. coli BSI belong to ST131, particularly E. coli ST131 C2/H30Rx, serving as an important driver of carbapenem use.

Abstract Background Drug-resistant E. coli is a leading cause of antimicrobial resistance-associated deaths globally. Specifically, resistance to ceftriaxone (CRO-R) is increasing in E. coli. High-risk clonal group ST131 and its pandemic H30 subclone are of high concern yet studies characterizing these infections are limited. We evaluated baseline characteristics and clinical outcomes associated with H30 ST131, non-H30 ST131 and non-ST131 E. coli bloodstream infections (BSI). Methods Patients with monomicrobial carbapenem-susceptible E. coli BSI that were matched 1:1 by study site (CRO-R and CRO-susceptible community-acquired and hospital onset cases) were prospectively enrolled from 14 United States hospitals between November 12, 2020 to April 28, 2021 in the multicenter Study of Highly Resistant E. coli (SHREC). Isolates underwent whole genome sequencing. The primary outcome was a 30-day Desirability of Outcome Ranking (DOOR) after index culture including clinical response to treatment and all-cause mortality. Results There were 92 (33%) H30 ST131, 29 (10%) non-H30 ST131, and 161 (57%) non-ST131 isolates in 282 E. coli BSI (Table 1). Most ceftriaxone resistance was conferred by CTX-M-15 produced by H30 ST131 isolates (Figure 1, Table 1). H30 ST131 BSI patients were older (median age [IQR] 70.5 [63,76] vs. 67 [56,77] vs 65 [51,74] years, p = 0.017), had higher Charlson comorbidity indices (3 [2,5] vs. 2 [1,4] vs. 2 [1,4], p=0.009), and were more often admitted from long-term care facilities (18/92 [20%] vs. 3/29 [10%] vs. 7/161 [4%], p = 0.003) compared to non-H30 ST131 and non-ST131 BSI patients. Among H30 ST131 isolates, high rates of antibiotic resistance were observed to cephalosporins and fluoroquinolones, resulting in significantly more carbapenem use compared with non-H30 ST131 and non-ST131 isolates (75/92 [82%] vs. 14/29 [48%] vs. 50/161 [31%], p < 0.001) (Figure 2). 30-day DOOR and hospital length of stay did not differ between groups (Table 2). Conclusion Compared with non-H30 ST131 and non-ST131 E. coli BSI, H30 ST131 E. coli BSI have a unique epidemiology with more healthcare exposures, comorbidities and antibiotic resistance and are more likely to be treated with carbapenems, though no significant difference in clinical outcomes was observed. Disclosures Yohei Doi, MD, PHD, AbbVie: Honoraria|Entasis: Grant/Research Support|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Meiji Seika: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Honoraria Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Loren G. Miller, MD MPH, Armata: Grant/Research Support|Contrafect: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds (Public Company)|Zimmer Biomet: Stocks/Bonds (Public Company) Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

Abstract Background The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI). Methods Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible. Infections were defined as CO or HO by CDC guidelines, and clinical characteristics and outcomes were compared. The primary outcome was desirability of outcome ranking (DOOR) 30 days after index culture. Difference in 30-day mortality was calculated with 95% CI. Results Among 891 patients with CRE BSI, 65% were HO (582/891). Compared to those with CO CRE, patients with HO CRE were younger [median 60 (Q1 42, Q3 70) years versus 65 (52, 74); P < 0.001], had fewer comorbidities [median Charlson comorbidity index 2 (1, 4) versus 3 (1, 5); P = 0.002] and were more acutely ill (Pitt bacteraemia score ≥4: 47% versus 32%; P < 0.001). The probability of a better DOOR outcome in a randomly selected patient with CO BSI compared to a patient with HO BSI was 60.6% (95% CI: 56.8%–64.3%). Mortality at 30-days was 12% higher in HO BSI (192/582; 33%) than CO BSI [66/309 (21%); P < 0.001]. Conclusion We found a disproportionately greater impact on patient outcomes with HO compared to CO CRE BSIs; thus, the recently reported increases in HO CRE infections by CDC requires rigorous surveillance and infection prevention methods to prevent added mortality.

Abstract Background 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.