international Epidemiology of Carbapenemase-Producing Escherichia Coli

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

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

BACKGROUND: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. METHODS: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. RESULTS: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P \u3c .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P \u3c .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). CONCLUSIONS: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p\u3c0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health

Epidemiología mundial y resultados clínicos de Pseudomonas aeruginosa resistente a carbapenemes y carbapenemasas asociadas (POP): un estudio prospectivo de cohortes

Antecedentes: La Pseudomonas aeruginosa resistente a los carbapenemes (CRPA) es una amenaza mundial, pero la distribución y la importancia clínica de las carbapenemasas no están claras. El objetivo de este estudio fue definir las características y los resultados de las infecciones por CRPA, así como la frecuencia global y el impacto clínico de las carbapenemasas albergadas por CRPA. Métodos: Llevamos a cabo un estudio de cohortes observacional y prospectivo de CRPA aislados de cultivos de torrente sanguíneo, respiratorio, orina o heridas de pacientes en 44 hospitales (10 países) entre el 1 de diciembre de 2018 y el 30 de noviembre de 2019. Los datos clínicos se extrajeron de los registros de salud y los aislados de CRPA se secuenciaron en todo el genoma. El resultado primario fue la mortalidad a 30 días a partir del día en que se recolectó el cultivo índice. Se compararon los resultados de los pacientes con infecciones por CRPA por tipo de infección y entre regiones geográficas y se realizó un análisis ponderado de probabilidad inversa para evaluar la asociación entre la producción de carbapenemasas y la mortalidad a 30 días. Resultados: Se incluyeron 972 pacientes (EE.UU. n=527, China n=171, América del Sur y Central n=127, Oriente Medio n=91, Australia y Singapur n=56), de los cuales 581 (60%) tenían infecciones por CRPA. La mortalidad a los 30 días difería según el tipo de infección (torrente sanguíneo 21 [30%] de 69, respiratoria 69 [19%] de 358, herida nueve [14%] de 66, orina seis [7%] de 88; p=0-0012) y la región geográfica (Oriente Medio 15 [29%] de 52, América del Sur y Central 20 [27%] de 73, EE.UU. 60 [19%] de 308, Australia y Singapur tres [11%] de 28, China siete [6%] de 120; p=0-0002). La prevalencia de genes carbapenemasa entre los aislados CRPA también varió según la región (América del Sur y Central 88 [69%] de 127, Australia y Singapur 32 [57%] de 56, China 54 [32%] de 171, Oriente Medio 27 [30%] de 91, EE.UU. diez [2%] de 527; p<0-0001). KPC-2 (n=103 [49%]) y VIM-2 (n=75 [36%]) fueron las carbapenemasas más comunes en 211 aislados productores de carbapenemasas. Después de excluir a los pacientes de EE.UU., porque pocos aislados de EE.UU. tenían carbapenemasas, los pacientes con infecciones por CRPA productoras de carbapenemasas tuvieron una mayor mortalidad a los 30 días que aquellos con infecciones por CRPA no productoras de carbapenemasas, tanto en los análisis no ajustados (26 [22%] de 120 frente a 19 [12%] de 153; diferencia 9%, IC 95% 3-16) como ajustados (diferencia 7%, IC 95% 1-14). Interpretación: La aparición de diferentes carbapenemasas entre los aislados de CRPA en diferentes regiones geográficas y el aumento de la mortalidad asociada a las infecciones por CRPA productores de carbapenemasas ponen de manifiesto los retos terapéuticos que plantean estos organismos. Financiación: Institutos Nacionales de Salud.Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. Methods: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. Findings: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p<0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3–16) and adjusted (difference 7%, 95% CI 1–14) analyses. Interpretation: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. Funding: National Institutes of Health

Measuring the Value of Data Curation: Preliminary Results from the Data Curation Network

April 2019 poster presented at the Research Data Alliance 13th Plenary in Philadelphia, Pennsylvania.Alfred P Sloan Foundatio

Effect of γ‑Ray-Radiation-Modified Graphene Oxide on the Integrated Mechanical Properties of PET Blends

The surface modification of graphene oxide (GO) determines the interactions between GO and polymers, which possibly produces a significant impact on the mechanical properties of polymer. Here, GO was first modified with poly­(glycidyl methacrylate) (PGMA) and triethylenetetramine (TTA) through γ-ray radiation. Then, a tiny small amount (0.04%) of the prepared modified GO was filled with a PET/ethylene-methyl acrylate-glycidyl methacrylate random terpolymer (PET/ST2000) blend. The morphological analyses on these filled PET blends confirmed that the surface chemical structure of GO had a crucial impact on the mechanical property of the blend. The chemical bonding between GO and ST2000 was more efficient in improving the dispersibility of GO and the compatibility between PET and ST2000, leading to a 2.5-fold increase in the impact strength, along with a slight increase in tensile strength. However, the addition of reduced GO lacking polar groups caused fatal damage in the mechanical property of the blend

Poor Sensitivity of the MALDI Biotyper^® MBT Subtyping Module for Detection of <i>Klebsiella pneumoniae</i> Carbapenemase (KPC) in <i>Klebsiella</i> Species

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates

Poor Sensitivity of the Maldi Biotyper® Mbt Subtyping Module For Detection of Klebsiella Pneumoniae Carbapenemase (Kpc) in Klebsiella Species

Rapid detection of Klebsiella pneumoniae carbapenemase (KPC) in the Klebsiella species is desirable. The MALDI Biotyper® MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the p019 gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical Klebsiella isolates, with whole genome sequences used to assess for blaKPC and p019. For the isolates identified as KPC positive by sequencing, the overall sensitivity of the MALDI-ToF MS subtyping module was 239/574 (42%) with 100% specificity. For the isolates harboring p019, the subtyping module showed a sensitivity of 97% (239/246) and a specificity of 100%. The subtyping module had poor sensitivity for the detection of blaKPC-positive Klebsiella isolates, albeit exhibiting excellent specificity. The poor sensitivity was a result of p019 being present in only 43% of the blaKPC-positive Klebsiella isolates

International epidemiology of carbapenemase-producing Escherichia coli

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 (MBL) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. RESULTS: Of the 114 CP-Ec isolates in 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 source (49% vs. 29%), less often met criteria for infection (39% vs 58%, p=0.04), and had lower acuity of illness when compared to non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared to 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=0.02) and 90-day (39% vs 0%, p=0.001) mortality compared with MBL-Ec. CONCLUSION: 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

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study

BackgroundCeftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common.MethodsThis is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding.ResultsNotable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P &lt; .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P &lt; .001), and incident admission to a long-term care facility (22% vs 12%, P = .045).ConclusionsPatients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders