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

Gold Microelectrode Arrays Based Electrode for Determination of Trace Copper in Seawater

We report a novel and facile gold microelectrode array (Au MEA) for the determination of trace Cu2+ by differential pulse anodic stripping voltammetry (DPASV). The gold microelectrode array was fabricated by a multi-step micro-fabrication approach combining sputtering for the deposition of metals and the dielectric material (SiO2) on the surface of a silicon wafer and photolithography for the definition of the geometry of the electrode. Due to the rapid mass transporting and low background current of gold microelectrode array, low detection limit (1.3 pM) and wide linear range (10-150 pM) can be obtained for the determination of Cu2+. The practical application of the proposed electrode has been carried out for the determination of trace level of Cu2+ in real seawater sample

Lunar rock investigation and tri-aspect characterization of lunar farside regolith by a digital twin

Abstract Yutu-2 rover conducted an exciting expedition on the 41st lunar day to investigate a fin-shaped rock at Longji site (45.44°S, 177.56°E) by extending its locomotion margin on perilous peaks. The varied locomotion encountered, especially multi-form wheel slippage, during the journey to the target rock, established unique conditions for a fin-grained lunar regolith analysis regarding bearing, shear and lateral properties based on terramechanics. Here, we show a tri-aspect characterization of lunar regolith and infer the rock’s origin using a digital twin. We estimate internal friction angle within 21.5°−42.0° and associated cohesion of 520-3154 Pa in the Chang’E-4 operational site. These findings suggest shear characteristics similar to Apollo 12 mission samples but notably higher cohesion compared to regolith investigated on most nearside lunar missions. We estimate external friction angle in lateral properties to be within 8.3°−16.5°, which fills the gaps of the lateral property estimation of the lunar farside regolith and serves as a foundational parameter for subsequent engineering verifications. Our in-situ spectral investigations of the target rock unveil its composition of iron/magnesium-rich low-calcium pyroxene, linking it to the Zhinyu crater (45.34°S, 176.15°E) ejecta. Our results indicate that the combination of in-situ measurements with robotics technology in planetary exploration reveal the possibility of additional source regions contributing to the local materials at the Chang’E-4 site, implying a more complicated geological history in the vicinity

Gold Microelectrode Arrays Based Electrode for Determination of Trace Copper in Seawater

We report a novel and facile gold microelectrode array (Au MEA) for the determination of trace Cu2+ by differential pulse anodic stripping voltammetry (DPASV). The gold microelectrode array was fabricated by a multi-step micro-fabrication approach combining sputtering for the deposition of metals and the dielectric material (SiO2) on the surface of a silicon wafer and photolithography for the definition of the geometry of the electrode. Due to the rapid mass transporting and low background current of gold microelectrode array, low detection limit (1.3 pM) and wide linear range (10-150 pM) can be obtained for the determination of Cu2+. The practical application of the proposed electrode has been carried out for the determination of trace level of Cu2+ in real seawater sample

Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases