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Søgeord (sepsis) valgt. Opdateret for 2 timer siden.
50 emner vises.
M. Isabel García‐Laorden, Arie J. Hoogendijk, Maryse A. Wiewel, Lonneke A. van Vught, Marcus J. Schultz, Niels Bovenschen, Alex F. de Vos, Tom van der Poll
Clinical & Experimental Immunology, 18.04.2021 Tilføjet 19.04.2021 11:57Infection, 15.04.2021 Tilføjet 15.04.2021 19:50
Abstract In patients who develop sepsis, whether due to primary, secondary or metastatic lesions, the skin is frequently affected. However, there are unresolved aspects regarding the general clinical manifestations in the skin or the prognosis and/or therapeutic implications. The main challenge in the approach to sepsis is its early diagnosis and management. In this review, we address the sepsis–skin relationship and the potential impact of early dermatological intervention on the septic patient through ten basic questions. We found little evidence of the participation of the dermatologist in sepsis alert programs. There are early skin changes that may alert clinicians on a possible sepsis, such as skin mottling or variations in acral skin temperature. In addition, the skin is an accessible and highly cost-effective tissue for etiological studies of some forms of sepsis (e.g., meningococcal purpura) and its involvement defines the prognosis of certain patients (e.g., infective endocarditis).
Læs mere Tjek på PubMedOh, Tak Kyu; Park, Hye Youn; Song, In-Ae
Critical Care Medicine, 8.04.2021 Tilføjet 13.04.2021 13:40Objectives: We investigated the prevalence of pre- and postsepsis depression and examined the association between diagnosis of pre- and postsepsis depression and 5-year all-cause mortality among survivors of sepsis. Design: A population-based cohort study. Setting: Data were obtained from the National Health Insurance Service database in South Korea. Patients: Sepsis survivors were defined as those who were admitted with a main diagnosis of sepsis or septic shock and had survived for over 365 days. Measurements and Main Results: Sepsis survivors who were diagnosed with depression before sepsis were defined as the presepsis depression group, whereas those who had no history of depression but were newly diagnosed with depression within 1 year of diagnosis of sepsis were defined as the postsepsis depression group. All other participants comprised the control group. A total of 45,826 sepsis survivors were included in the final analysis. Among the survivors, 1,105 (2.4%) were in the postsepsis depression group, whereas 9,626 (21.0%) were in the presepsis depression group. The 5-year all-cause mortality rate in the pre- and postsepsis depression group was 44.1% and 46.2%, whereas that in the control group was 30.4%. Multivariable Cox regression modeling revealed that the risk of 5-year all-cause mortality rate in the postsepsis depression group was 1.29-fold (hazard ratio = 1.29; 95% CI = 1.18–1.41; p < 0.001) higher than that of the control group, whereas the presepsis depression group was not significantly associated with 5-year all-cause mortality (p = 0.509). Conclusions: Among sepsis survivors in South Korea, 2.4%% were newly diagnosed with depression within 1 year after their sepsis diagnosis. In addition, postsepsis depression was independently associated with higher 5-year all-cause mortality among sepsis survivors. Our results suggest that patients with a history of sepsis and associated depression may be a high-risk group that interventions may be directed toward. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: songoficu@outlook.kr Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedPrest, Jonathan; Sathananthan, Matheni; Jeganathan, Niranjan
Critical Care Medicine, 8.04.2021 Tilføjet 13.04.2021 13:40Objectives: Sepsis is a life-threatening condition and is one of the leading causes of death in the United States. The burden of sepsis-related mortality in the United States in recent years is not well characterized. We sought to describe sepsis-related mortality rates and mortality trends in the United States from 2005 to 2018. Design: Retrospective population-based study. Setting: We used the Multiple Cause of Death Database available through the Centers for Disease Control and Prevention website. Patients: Decedents with sepsis-related deaths were identified using previously validated International Classification of Diseases codes. Interventions: None. MEASUREMENTS AND Main Results: From 2005 to 2018, 6.7% of decedents had a diagnosis of sepsis. The overall sepsis-related mortality rates remained stable in both males (57 deaths per 100,000) and females (45.1 deaths per 100,000) during this period. Compared with Whites, the sepsis-related mortality rates were higher in Blacks (rate ratio = 1.78), Native Americans (rate ratio = 1.43), and Hispanics (rate ratio = 1.04) and were lower in Asians (rate ratio = 0.73). Sepsis-related mortality rates declined in Blacks, Hispanics, and Asians but increased in Whites and Native Americans. The majority of sepsis-related deaths occurred in the hospital. The percentage of deaths in the nursing home decreased, whereas deaths occurring at home and hospice increased. Conclusions: From 2005 to 2018, the overall sepsis-related mortality rates were stable, but there were significant racial and gender disparities in mortality trends. Further research is needed to evaluate the genetic and environmental contributors to these differences. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: njeganathan@llu.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedChurpek, Matthew M.; Dumanian, Jay; Dussault, Nicole; Bhavani, Sivasubramanium V.; Carey, Kyle A.; Gilbert, Emily R.; Arain, Erum; Ye, Chen; Winslow, Christopher J.; Shah, Nirav S.; Afshar, Majid; Edelson, Dana P.
Critical Care Medicine, 8.04.2021 Tilføjet 13.04.2021 13:40Objectives: Recent sepsis studies have defined patients as “infected” using a combination of culture and antibiotic orders rather than billing data. However, the accuracy of these definitions is unclear. We aimed to compare the accuracy of different established criteria for identifying infected patients using detailed chart review. Design: Retrospective observational study. Setting: Six hospitals from three health systems in Illinois. Patients: Adult admissions with blood culture or antibiotic orders, or Angus International Classification of Diseases infection codes and death were eligible for study inclusion as potentially infected patients. Nine-hundred to 1,000 of these admissions were randomly selected from each health system for chart review, and a proportional number of patients who did not meet chart review eligibility criteria were also included and deemed not infected. Interventions: None. Measurements and Main Results: The accuracy of published billing code criteria by Angus et al and electronic health record criteria by Rhee et al and Seymour et al (Sepsis-3) was determined using the manual chart review results as the gold standard. A total of 5,215 patients were included, with 2,874 encounters analyzed via chart review and a proportional 2,341 added who did not meet chart review eligibility criteria. In the study cohort, 27.5% of admissions had at least one infection. This was most similar to the percentage of admissions with blood culture orders (26.8%), Angus infection criteria (28.7%), and the Sepsis-3 criteria (30.4%). Sepsis-3 criteria was the most sensitive (81%), followed by Angus (77%) and Rhee (52%), while Rhee (97%) and Angus (90%) were more specific than the Sepsis-3 criteria (89%). Results were similar for patients with organ dysfunction during their admission. Conclusions: Published criteria have a wide range of accuracy for identifying infected patients, with the Sepsis-3 criteria being the most sensitive and Rhee criteria being the most specific. These findings have important implications for studies investigating the burden of sepsis on a local and national level. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Churpek and Edelson received funding from National Institute of General Medical Sciences R01 GM123193; disclosed a patent pending (ARCD. P0535US. P2) for risk stratification algorithms for hospitalized patients and have received research support from EarlySense (Tel Aviv, Israel). Drs. Churpek, Winslow, Shah, and Afshar received support for article research from the National Institutes of Health. Dr. Afshar also received support from a K23 from National Institute on Alcohol Abuse and Alcoholism K23 AA024503. Dr. Edelson received support for article research from the American Heart Association (Dallas, TX) and Laerdal Medical (Stavanger, Norway), and she received research support from Philips Healthcare (Andover, MA). She disclosed ownership interest in Quant HC (Chicago, IL), which is developing products for risk stratification of hospitalized patients; she is president/co-founder and shareholder of AgileMD with licensing agreements with Philips Healthcare and EarlySense; and she is the chair for the American Heart Association Get with The Guidelines adult research task force. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: mchurpek@medicine.wisc.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedDuprey, Matthew S.; Devlin, John W.; van der Hoeven, Johannes G.; Pickkers, Peter; Briesacher, Becky A.; Saczynski, Jane S.; Griffith, John L.; van den Boogaard, Mark
Critical Care Medicine, 8.04.2021 Tilføjet 13.04.2021 13:40Objectives: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality. Design: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial. Setting: Fourteen Dutch ICUs between July 2013 and December 2016. Patients: One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days. Interventions: Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion. Measurements and Main Results: Patients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2–7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0–3.8 mg] daily) for 6 days (3–11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91–0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96–0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence. Conclusions: Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by ZonMw program Goed Gebruik Geneesmiddelen (dossier number 836031004). ZonMw had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr. Duprey’s efforts are supported by the National Institute of Aging 1F31AG066460-01. Drs. Duprey, Devlin, Briesacher, and Saczynski received support for article research from the National Institutes of Health. Dr. Duprey disclosed off-label product use of haloperidol for delirium. Dr. van den Boogaard’s institution received funding and support for research from ZonMw. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this aticle, E-mail: j.devlin@neu.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedAurelia H.M. de Vries Schultink, Bastiaan T.G.M. Sallevelt, Arend Jan Meinders, Ewoudt M.W. van de Garde, Nienke Roescher
Clinical Microbiology and Infection, 9.04.2021 Tilføjet 09.04.2021 20:25The updated national Dutch Working Party on Antibiotic Policy (SWAB) guideline for antibacterial therapy of adult patients with sepsis recommends against the addition of an aminoglycoside to a beta-lactam agent for patients with sepsis or septic shock unless local distribution of pathogens associated with sepsis and their antimicrobial susceptibilities justify its additional use. [1] However, this data is generally not readily available and adjunctive gentamicin is often given. From an antimicrobial stewardship perspective, we evaluated our local sepsis protocol by assessing the potential benefit and risk of gentamicin adjunctive to cefuroxime by studying blood culture results and incidence of acute kidney injury (AKI).
Læs mere Tjek på PubMedAbboud H.
Journal of Infectious Diseases, 7.01.2021 Tilføjet 08.04.2021 18:55To the Editor—In their article “Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2–Related Encephalitis,” Pilotto and colleagues reported on the incidence of encephalitis in a multicenter cohort of coronavirus disease 2019 (COVID-19) patients [1]. The reported incidence of 50 per 100 000 may be overestimated. Their definition of encephalitis corresponds to the designation of “possible encephalitis” as proposed by Venkatesan et al in their 2013 consensus article [2]. The diagnosis of probable encephalitis requires presentation with altered mental status (AMS) and at least 3 minor criteria relating to cerebrospinal fluid (CSF) pleocytosis, magnetic resonance imaging (MRI) changes, electroencephalogram changes, new-onset seizures, or focal neurologic deficits [2]. The diagnosis of confirmed encephalitis further requires pathological confirmation or laboratory evidence of a causative organism or highly clinically relevant neuronal autoantibody. The definition used by Pilotto et al (AMS and 2 minor criteria) allows for overestimation of encephalitis. In fact, 8 of their 25 patients (32%) had unremarkable brain MRI and CSF. The diagnosis of encephalitis in those 8 patients was based solely on the clinical picture, which makes the diagnosis questionable at best. Generalized seizures and AMS can occur in the setting of viral sepsis or metabolic derangements associated with COVID-19 infection [3]. They should not be utilized as evidence of encephalitis in this setting. In addition, aphasia and dysarthria are difficult to ascertain in the setting of AMS and should not be considered as focal deficits in altered patients. The fact that nearly half the patients were not tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) in the CSF or for neuronal autoantibodies adds to the limitations of this study by allowing significant misclassification of infectious versus parainfectious versus autoimmune etiologies. The authors concluded that most cases of COVID-19–related encephalitis were parainfectious in nature, secondary to the associated cytokine storm. This claim cannot be made if half the patients were not tested for SARS-CoV-2 PCR in the CSF nor for neuronal autoantibodies in both the serum and CSF. Moreover, the authors did not report on cancer screening in their cohort, possibly missing patients with an incidental paraneoplastic etiology, a major cause of encephalitis [4]. With modern epidemiological data suggesting that autoimmune encephalitis may be as common as viral encephalitis [5], scientific reports addressing encephalitis related to COVID-19 (or any cause) should adhere to certain reporting standards to avoid etiological misclassification. At a minimum, all patients should be tested for common microbiological pathogens of encephalitis as well as clinically relevant neuronal autoantibodies [6]. Patients without evidence of direct CNS infection should undergo cancer screening to rule out paraneoplastic etiologies. Administering unnecessary immunomodulating therapies to encephalopathic patients with COVID-19 can have negative effects, especially in cases complicated by secondary bacterial infections. In addition, overestimating the incidence of COVID-19–related encephalitis may result in missing important alternative causes of encephalitis (eg, cancer or antibody mediated) if full encephalitis workup is not pursued in each case.
Læs mere Tjek på PubMedTsai C, Soper N, Bennett M, et al.
Journal of Infectious Diseases, 6.08.2020 Tilføjet 08.04.2021 18:55AbstractA successful Staphylococcus aureus vaccine remains elusive, and one controversy in the field is whether humans generate a protective adaptive immune response to infection. We developed a bacterial challenge murine assay that directly assesses the protective capacity of adoptively transferred human serum samples. We first validated the model by showing that postpneumococcal vaccine serum samples from humans induced effective clearance of Streptococcus pneumoniae in mice. We then found that human serum samples adoptively transferred from children with invasive S. aureus infections exhibited protection from disease in a murine model, with some samples conferring near complete protection. These findings demonstrate that human serum samples are capable of conferring a protective adaptive response generated by humans during invasive staphylococcal disease, allowing for the study of protective factors in a murine model. Identification of the protective factors present in the most efficacious serum samples would be of high interest as potential staphylococcal vaccine candidates or passive therapeutics.
Læs mere Tjek på PubMedKakkar A, Shafiq N, Malhotra S.
Clinical Infectious Diseases, 24.06.2020 Tilføjet 08.04.2021 14:46To the Editor—We read with interest the article by Honda et al [1] highlighting the critical shortages of cefazolin in Japan. While it is commendable that the Ministry of Health, Labor, and Welfare of Japan issued a list suggesting potential substitute drugs for surgical prophylaxis and for specific infections, we find the lists are quite similar and thus disconcerting. As is evident in their report, the use of third-generation cephalosporins—cefotaxime and ceftriaxone, both “watch” group antibiotics—increased by more than 60-fold following cefazolin shortages [2]. Given that gram-positive cocci continue to be the predominant pathogens in most surgical site infections, routine use of broad-spectrum agents for surgical prophylaxis promotes the selection of multidrug-resistant species as well as limits the choice of effective agents in case the patients develop severe sepsis. Moreover, several studies including pharmacokinetic-pharmacodynamic analysis have demonstrated superior activity of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) when compared with ceftriaxone [3–6]. This could be ascribed to the latter’s concentration-dependent significant protein binding (>90%), resulting in relatively low serum-free drug concentrations that are responsible for its antimicrobial activity [4, 7]. Even vancomycin is less effective than cefazolin for surgical prophylaxis against MSSA, hence the recommendation of using it in combination with cefazolin when there is a risk of both MSSA and methicillin-resistant S. aureus surgical site infections [8].
Læs mere Tjek på PubMedStohs E, Kalil A.
Clinical Infectious Diseases, 5.03.2020 Tilføjet 08.04.2021 14:46Lind M, Phipps A, Mooney S, et al.
Clinical Infectious Diseases, 4.03.2020 Tilføjet 08.04.2021 14:46AbstractBackgroundSepsis disproportionately affects allogeneic hematopoietic cell transplant (HCT) recipients and is challenging to define. Clinical criteria that predict mortality and intensive care unit end-points in patients with suspected infections (SIs) are used in sepsis definitions, but their predictive value among immunocompromised populations is largely unknown. Here, we evaluate 3 criteria among allogeneic HCT recipients with SIs.MethodsWe evaluated Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and National Early Warning Score (NEWS) in relation to short-term mortality among recipients transplanted between September 2010 and July 2017. We used cut-points of ≥ 2 for qSOFA/SIRS and ≥ 7 for NEWS and restricted to first SI per hospital encounter during patients’ first 100 days posttransplant.ResultsOf the 880 recipients who experienced ≥ 1 SI, 58 (6.6%) died within 28 days and 22 (2.5%) within 10 days of an SI. In relation to 10-day mortality, SIRS was the most sensitive (91.3% [95% confidence interval {CI}, 72.0%–98.9%]) but least specific (35.0% [95% CI, 32.6%–37.5%]), whereas qSOFA was the most specific (90.5% [95% CI, 88.9%–91.9%]) but least sensitive (47.8% [95% CI, 26.8%–69.4%]). NEWS was moderately sensitive (78.3% [95% CI, 56.3%–92.5%]) and specific (70.2% [95% CI, 67.8%–72.4%]).ConclusionsNEWS outperformed qSOFA and SIRS, but each criterion had low to moderate predictive accuracy, and the magnitude of the known limitations of qSOFA and SIRS was at least as large as in the general population. Our data suggest that population-specific criteria are needed for immunocompromised patients.
Læs mere Tjek på PubMedXia, Y., He, F., Wu, X., Tan, B., Chen, S., Liao, Y., Qi, M., Chen, S., Peng, Y., Yin, Y., Ren, W.
Science Advances, 7.04.2021 Tilføjet 07.04.2021 23:15Accumulating evidence shows that nervous system governs host immune responses; however, how -aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1β (IL-1β) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region. KID3 regulates oxidative phosphorylation (OXPHOS) via targeting the expression of OXPHOS-related genes and is also critical for NLRP3–ASC–caspase-1 complex formation. Likewise, GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo, including lipopolysaccharide-induced sepsis, infection-induced pneumonia, and high-fat diet-induced obesity. Together, we propose that targeting GABAergic system (e.g., GABA transporter) could provide previously unidentified therapeutic opportunities for the macrophage-associated diseases.
Læs mere Tjek på PubMedLisa Mellhammar, Louise Thelaus, Sixten Elén, Jane Fisher, Adam Linder
PLoS One Infectious Diseases, 6.04.2021 Tilføjet 06.04.2021 20:08by Lisa Mellhammar, Louise Thelaus, Sixten Elén, Jane Fisher, Adam Linder Background and aims Neutrophil-derived heparin binding protein (HBP; also known as azurocidin or CAP-37) is a key player in bacterial sepsis and a promising biomarker in severe infections.The aims of this study were to assess whether HBP is involved in the pathophysiology of COVID-19 and, if so, whether it can be used to predict severe disease preferably using a point-of-care test. Methods This was a prospective convenience sample study of biomarkers in patients admitted to Skåne University hospital in Sweden with a confirmed COVID-19 diagnosis. Plasma samples and clinical data were collected within 72h after admission, during hospital stay and at discharge. Plasma HBP concentrations samples were measured both with enzyme-linked immunosorbent assay (ELISA) and with a novel dry immunofluorescence analyzer (Joinstar) point-of-care test. Results Thirty-five COVID-19 patients were enrolled in the study. Twenty-nine patients had blood samples taken within 72h after admission. We compared the highest HBP value taken within 72h after admission in patients who eventually developed organ dysfunction (n = 23) compared to those who did not (n = 6), and found that HBP was significantly elevated in those who developed organ dysfunction (25.0 ng/mL (interquartile range (IQR) 16.6–48.5) vs 10.6 ng/mL (IQR 4.8–21.7 ng/mL), p = 0.03). Point-of-care test measurements correlated well with ELISA measurements (R = 0.83). HBP measured by the POC device predicted development of COVID-induced organ dysfunction with an AUC of 0.88 (95% confidence interval (CI) 0.70–1.0). Conclusions HBP is elevated prior to onset of organ dysfunction in patients with severe COVID-19 using a newly developed point-of-care test and hence HBP could be used in a clinical setting as a prognostic marker in COVID-19.
Læs mere Tjek på PubMedRoshika, R., Jain, I., Medicielo, J., Wächter, J., Danger, J. L., Sumby, P.
Infection and Immunity, 5.04.2021 Tilføjet 06.04.2021 04:46Serotype M28 isolates of the group A Streptococcus (GAS; Streptococcus pyogenes) are non-randomly associated with cases of puerperal sepsis, a potentially life-threatening infection that can occur in women following childbirth. Previously, we discovered that the 36.3 kb RD2 pathogenicity island, which is present in serotype M28 isolates but lacking from most other isolates, promotes the ability of M28 GAS to colonize the female reproductive tract. Here, we performed a gain-of-function study in which we introduced RD2 into representative serotype M1, M49, and M59 isolates and assessed the phenotypic consequences of RD2 acquisition. All RD2-containing derivatives colonized a higher percentage of mice, and at higher colony-forming-unit levels, than did the parental isolates in a mouse vaginal colonization model. However, for two additional phenotypes, survival in heparinized whole human blood and adherence to two human vaginal epithelial cell lines, there were serotype-specific differences to RD2-acquisition. Using transcriptomic comparisons, we identified that such differences may be a consequence of RD2 altering the abundance of transcripts from select core genome genes along serotype-specific lines. Our study is the first that interrogates RD2 function in GAS serotypes other than M28 isolates, shedding light on variability in the phenotypic consequences of RD2 acquisition, and informing on why this mobile genetic element is not ubiquitous in the GAS population.
Læs mere Tjek på PubMedBMC Infectious Diseases, 2.04.2021 Tilføjet 02.04.2021 16:07
Abstract Background Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score. Methods Adult patients (≥ 18 years) presenting at the emergency department (ED) with suspected BSI were prospectively included between 2014 and 2016 at Örebro University Hospital. Besides extra blood sampling, all study patients were treated according to ED routines. Electronic patient charts were retrospectively reviewed. A modified Shapiro score (MSS) and NLCR were extracted and compiled. Continuous score variables were analysed with area under receiver operator characteristics curves (AUC) to evaluate the ability of BSI prediction. Results The final cohort consisted of 484 patients where 84 (17%) had positive blood culture judged clinically significant. At optimal cut-offs, MSS (≥3 points) and NLCR (> 12) showed equal ability to predict BSI in the whole cohort (AUC 0.71/0.74; sensitivity 69%/67%; specificity 64%/68% respectively) and in a subgroup of 155 patients fulfilling Sepsis-3 criteria (AUC 0.71/0.66; sensitivity 81%/65%; specificity 46%/57% respectively). In BSI cases only predicted by NLCR> 12 the abundance of Gram-negative to Gram-positive pathogens (n = 13 to n = 4) differed significantly from those only predicted by MSS ≥3 p (n = 7 to n = 12 respectively) (p < 0.05). Conclusions MSS and NLCR predicted BSI in the RISE cohort with similar cut-offs as shown in previous studies. Combining the MSS and NLCR did not increase the predictive performance. Differences in BSI prediction between MSS and NLCR regarding etiology need further evaluation.
Læs mere Tjek på PubMedBMC Infectious Diseases, 1.04.2021 Tilføjet 01.04.2021 18:01
Abstract Background The primary objective of our study was to examine predictors for readmission in a prospective cohort of sepsis patients admitted to an emergency department (ED) and identified by the new Sepsis-3 criteria. Method A single-center observational population-based cohort study among all adult (≥18 years) patients with sepsis admitted to the emergency department of Slagelse Hospital during 1.10.2017–31.03.2018. Sepsis was defined as an increase in the sequential organ failure assessment (SOFA) score of ≥2. The primary outcome was 90-day readmission. We followed patients from the date of discharge from the index admission until the end of the follow-up period or until the time of readmission to hospital, emigration or death, whichever came first. We used competing-risks regression to estimate adjusted subhazard ratios (aSHRs) with 95% confidence intervals (CI) for covariates in the regression models. Results A total of 2110 patients were admitted with infections, whereas 714 (33.8%) suffered sepsis. A total of 52 patients had died during admission and were excluded leaving 662 patients (44.1% female) with a median age of 74.8 (interquartile range: 66.0–84.2) years for further analysis. A total of 237 (35,8%; 95% CI 32.1–39.6) patients were readmitted within 90 days, and 54(8.2%) had died after discharge without being readmitted. We found that a history of malignant disease (aSHR 1,61; 1.16–2.23), if previously admitted with sepsis within 1 year before the index admission (aSHR; 1.41; 1.08–1.84), and treatment with diuretics (aSHR 1.51; 1.17–1.94) were independent predictors for readmission. aSHR (1.49, 1.13–1.96) for diuretic treatment was almost unchanged after exclusion of patients with heart failure, while aSHR (1.47, 0.96–2.25) for malignant disease was slightly attenuated after exclusion of patients with metastatic tumors. Conclusions More than one third of patients admitted with sepsis, and discharged alive, were readmitted within 90 days. A history of malignant disease, if previously admitted with sepsis, and diuretic treatment were independent predictors for 90-day readmission.
Læs mere Tjek på PubMedBentounsi, Z., Sheik-Ali, S., Drury, G., Lavy, C.
BMJ Open, 25.03.2021 Tilføjet 25.03.2021 19:09Objective To provide a general overview of the reported current surgical capacity and delivery in order to advance current knowledge and suggest targets for further development and research within the region of sub-Saharan Africa. Design Scoping review. Setting District hospitals in sub-Saharan Africa. Data sources PubMed and Ovid EMBASE from January 2000 to December 2019. Study selection Studies were included if they contained information about types of surgical procedures performed, number of operations per year, types of anaesthesia delivered, cadres of surgical/anaesthesia providers and/or patients’ outcomes. Results The 52 articles included in analysis provided information about 16 countries. District hospitals were a group of diverse institutions ranging from 21 to 371 beds. The three most frequently reported procedures were caesarean section, laparotomy and hernia repair, but a wide range of orthopaedics, plastic surgery and neurosurgery procedures were also mentioned. The number of operations performed per year per district hospital ranged from 239 to 5233. The most mentioned anaesthesia providers were non-physician clinicians trained in anaesthesia. They deliver mainly general and spinal anaesthesia. Depending on countries, articles referred to different surgical care providers: specialist surgeons, medical officers and non-physician clinicians. 15 articles reported perioperative complications among which surgical site infection was the most frequent. Fifteen articles reported perioperative deaths of which the leading causes were sepsis, haemorrhage and anaesthesia complications. Conclusion District hospitals play a significant role in sub-Saharan Africa, providing both emergency and elective surgeries. Most procedures are done under general or spinal anaesthesia, often administered by non-physician clinicians. Depending on countries, surgical care may be provided by medical officers, specialist surgeons and/or non-physician clinicians. Research on safety, quality and volume of surgical and anaesthesia care in this setting is scarce, and more attention to these questions is required.
Læs mere Tjek på PubMedBMC Infectious Diseases, 23.03.2021 Tilføjet 23.03.2021 17:55
Abstract Background Escherichia coli (E. coli) is one of the important causative pathogens of neonatal invasive infection. The epidemiological and clinical profile of invasive E. coli infection in Chinese newborns is not well characterized. Methods Ninety-four infants with invasive E. coli infection were categorized into E. coli early onset disease (EOD) group (onset ≤72 h after birth) (n = 46) and E. coli late onset disease (LOD) group (onset > 72 h) (n = 48). We compared and analyzed the clinical characteristics and drug sensitivity profile of early-onset and late-onset E. coli invasive infection in neonates. Results The incidence of E. coli-EOD and E.coli-LOD was 0.45/1000 live births (LBs) and 0.47/1000 LBs, respectively. The incidence of gestational diabetes mellitus, perinatal fever, urinary tract infection, chorioamnionitis, and positive E. coli culture among mothers in the E. coli-EOD group were significantly higher than that in E. coli-LOD group. The incidence of premature birth, low-birth-weight, nosocomial infection, and hospitalization time were significantly higher in the E. coli-LOD group. The main disease in E. coli-EOD group was pneumonia (main clinical manifestation: dyspnea). The main disease in E. coli-LOD group was sepsis (main clinical manifestation: fever). The sensitivity rates of E. coli strains to ampicillin and piperacillin were low (25.00–28.79%); sensitivity to cephalosporins was also low except ceftazidime (lowest sensitivity rate: 57.14%). Sensitivity to compound preparations containing β-lactamase inhibitors was high, even for extended spectrum β-lactamase-positive strains (nearly 100%). Conclusion E. coli is an important cause of invasive infection of newborns in Xiamen, China. E. coli-EOD was largely attributable to perinatal factors, while E. coli-LOD was largely related to nosocomial infection. Compound preparations containing β-lactamase inhibitor or carbapenem antibiotics should be preferred for neonatal invasive infection by E. coli.
Læs mere Tjek på PubMedBabowicz, F., LaPlante, R., Mitchell, C., ODonnell, J. N., Tobin, E., George, M., Carreno, J. J.
Antimicrobial Agents And Chemotherapy, 22.03.2021 Tilføjet 23.03.2021 03:59Background: Accelerate Pheno system and BacT/ALERT VIRTUO may improve bacteremia management. This study evaluated the impact of both devices on outcomes in patients with sepsis and concurrent gram-negative bacteremia. Methods: This quasi-experimental study included a retrospective pre-implementation and a prospective post-implementation group. Patients ≥18 years old with gram-negative bacteremia were included. Patients with neutropenia, pregnancy, were transferred from an outside hospital with active bloodstream infection, or polymicrobial bacteremia were excluded. Blood culture incubation in the BacT/ALERT 3D and microdilution antimicrobial susceptibility testing from culture plate growth was used prior to implementation of BacT/ALERT VIRTUO and Accelerate Pheno. MALDI-TOF identification directly from blood culture was used pre- and post-implementation. Time to gram-stain, identification, susceptibility reporting, initiation of narrow spectrum gram-negative therapy at 72 hours, 30-day inpatient mortality, sepsis resolution, and hospital length of stay were evaluated. Results: 116 patients were included (63 pre-implementation, 53 post-implementation). Median time to gram-stain and susceptibility results were significantly shorter post-implementation (P < 0.001). The post-implementation group had an improved hazard for narrow spectrum gram-negative therapy at 72 hours (HR [95% CI] = 2.685 [1.348 – 5.349]), reduced hazard for 30-day inpatient mortality (aHR: 0.150 [0.026 – 0.846]) and improved sepsis resolution (77.8% vs. 92.5%, P = 0.030). Hospital length of stay was unchanged between groups. Conclusion: The implementation of BacT/Alert VIRTUO and the Accelerate Pheno system improved microbiology laboratory processes, antibiotic utilization processes and clinical outcomes. These data support the use of rapid diagnostics in sepsis with concurrent gram-negative bacteremia.
Læs mere Tjek på PubMedAo, X., Yang, Y., Okiji, T., Azuma, M., Nagai, S.
Infection and Immunity, 22.03.2021 Tilføjet 23.03.2021 03:36Immune paralysis is a protracted state of immune suppression following the early/acute inflammatory phase of sepsis. CD11b+Gr-1+ cells induced during sepsis are heterogeneous myeloid-derived cells (MDCs). This study investigated the contribution of MDCs to immune paralysis. Treatment of mice with zymosan (ZM) induced a marked increase in the total number of splenocytes with an increase in the ratio of Gr-1hi cells and a decease in the ratio of T cells on day 7, eventually returning to levels similar to those of control mice on day 21. T cell activation and IFN- expression by CD8+ T cells were clearly impaired in ZM-treated mice on day 21 (d21-ZM mice). Gr-1hi cells showed a CD11b+Ly6Ghi polymorphonuclear phenotype. Injection of lipopolysaccharide (LPS) into d21-ZM mice impaired IL-6 production in serum, accompanied by accumulation of CD11b+Gr-1hi cells in the peripheral blood. Transfer of Gr-1hi cells from d21-ZM mice into intact mice impaired IL-6 production, but similar transfer of Gr-1hi cells from PD-1/PD-L1-deficient d21-ZM mice showed no such suppressive effect. Conversely, either depletion of Gr-1hi cells by treatment with anti-Gr-1 monoclonal antibody (mAb) or neutralization of the PD-1/PD-L1 pathway by anti-PD-1 and anti-PD-L1 mAbs during the induction phase of sepsis ameliorated ZM-induced immune suppression. Our results suggest that the PD-1/PD-L1-mediated generation of Gr-1hi cells in the early phase of sepsis is required for late-phase of immune paralysis.
Læs mere Tjek på PubMedRen, Xinyong
Critical Care Medicine, 17.03.2021 Tilføjet 20.03.2021 09:07Fleischmann-Struzek, C., Kesselmeier, M., Ouart, D., Hartog, C. S., Bauer, M., Bercker, S., Bucher, M., Meier-Hellmann, A., Petros, S., Schreiber, T., Simon, P., Weidhase, L., Born, S., Braune, A., Chkirni, H., Eichhorn, C., Fiedler, S., Gampe, C., König, C., Platzer, S., Romeike, H., Töpfer, K., Reinhart, K., Scherag, A.
BMJ Open, 18.03.2021 Tilføjet 18.03.2021 06:39Purpose The Mid-German Sepsis Cohort (MSC) aims to investigate mid-term and long-term functional disabilities in sepsis survivors from intensive care unit (ICU) discharge until 1 year after. Secondary, post-acute mortality and morbidity, health-related quality of life and healthcare utilisation will be investigated. Participants The MSC comprises adult (aged ≥18 years) patients who were treated for (severe) sepsis or septic shock on ICU. The participants were recruited between 15 April 2016 and 30 November 2018 from five German centres. Three thousand two hundred and ten patients with sepsis were identified, of which 1968 survived their ICU stay and were eligible for enrolment in the follow-up cohort. Informed consent for follow-up assessment was provided by 907 patients (46.1% of eligible patients). Findings to date The recruitment of the participants for follow-up assessments and the baseline data collection is completed. Incidence of sepsis was 116.7 patients per 1000 ICU patients. In this cohort profile, we provide an overview of the demographics and the clinical characteristics of both the overall sepsis cohort and the ICU survivors who provided informed consent for follow-up assessment (907 out of 1968 ICU survivors (46.1%)). Future plans The follow-ups are conducted 3, 6 and 12 months after ICU discharge. Another yearly follow-up up to 5 years after ICU discharge is pursued. Several cooperation and satellite projects were initiated. This prospective cohort offers a unique resource for research on long-term sequelae of sepsis survivors. Trial registration number German Clinical Trials Registry (DRKS00010050).
Læs mere Tjek på PubMedAl-Shaer, M. H., Philpott, C. D., Droege, C. A., Courter, J. D., Healy, D. P., Droege, M. E., Ernst, N. E., Mueller, E. W., Peloquin, C. A.
Antimicrobial Agents And Chemotherapy, 15.03.2021 Tilføjet 16.03.2021 03:26Sepsis causes half of acute kidney injuries in the intensive care unit (ICU). ICU patients may need continuous renal replacement therapy (CRRT) which will affect their antimicrobial exposure. We aim to build a cefepime population pharmacokinetic (PK) model in CRRT ICU patients and perform simulations to assess target attainment. Patients who were ≥18 years old, admitted to the ICU, and received cefepime 2 g every 8 hours as 4-hour infusion while on CRRT were enrolled prospectively. Samples were collected from the predialyzer, postdialyzer ports, and effluent fluid at times 1, 2, 3, 4, and 8 hours after the first dose and at steady state. Age, sex, weight, urine output, and CRRT parameters were recorded. Pmetrics was used for population PK and simulations. The target exposure was 100% fT>MIC. Ten patients were included and their mean age was 53 years and weight 119 kg. Seventy percent were males. Cefepime was described by a five-compartment model. The downtime was applied to the CRRT flow rates which were used to describe the rates of transfer between the compartments. At MIC of ≤8 mg/L, cefepime 2g intermittent infusion every 8 hours achieved good target attainment both early in therapy and at steady state. Only extended and continuous infusion regimens achieved good target attainment at MIC 16 mg/L. In conclusion, cefepime 2g infused over 30 minutes followed by 2g extended infusion every 8 hours achieved good target attainment at MIC ≤16 mg/L with different CRRT flow rates and may be considered in resistant bacterial infections.
Læs mere Tjek på PubMedCarmo T, Ferreira I, Menezes R, et al.
Clinical Infectious Diseases, 8.03.2020 Tilføjet 15.03.2021 15:47AbstractBackgroundSeverity stratification scores developed in intensive care units (ICUs) are used in interventional studies to identify the most critically ill. Studies that evaluate accuracy of these scores in ICU patients admitted with pneumonia are lacking. This study aims to determine performance of severity scores as predictors of mortality in critically ill patients admitted with pneumonia.MethodsProspective cohort study in a general ICU in Brazil. ICU severity scores (Simplified Acute Physiology Score 3 [SAPS 3] and Sepsis-Related Organ Failure Assessment [qSOFA]), prognostic scores of pneumonia (CURB-65 [confusion, urea, respiratory rate, blood pressure, age] and CRB-65 [confusion, respiratory rate, blood pressure, age]), and clinical and epidemiological variables in the first 6 hours of hospitalization were analyzed.ResultsTwo hundred patients were included between 2015 and 2018, with a median age of 81 years (interquartile range, 67–90 years) and female predominance (52%), primarily admitted from the emergency department (65%) with community-acquired pneumonia (CAP, 80.5%). SAPS 3, CURB-65, CRB-65,and qSOFA all exhibited poor performance in predicting mortality. Multivariate regression identified variables independently associated with mortality that were used to develop a novel pneumonia-specific ICU severity score (Pneumonia Shock score) that outperformed SAPS 3, CURB-65, and CRB-65. The Shock score was validated in an external multicenter cohort of critically ill patients admitted with CAP.ConclusionsWe created a parsimonious score that accurately identifies patients with pneumonia at highest risk of ICU death. These findings are critical to accurately stratify patients with severe pneumonia in therapeutic trials that aim to reduce mortality.
Læs mere Tjek på PubMedMcGee L, Chochua S, Li Z, et al.
Clinical Infectious Diseases, 15.02.2020 Tilføjet 15.03.2021 15:47AbstractBackgroundGroup B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development.MethodsUsing whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015–2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states.ResultsSix serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1–2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed.ConclusionsThis first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The β-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.
Læs mere Tjek på PubMedShah, Parth K.; Ginestra, Jennifer C.; Ungar, Lyle H.; Junker, Paul; Rohrbach, Jeff I.; Fishman, Neil O.; Weissman, Gary E.
Critical Care Medicine, 15.03.2021 Tilføjet 13.03.2021 08:10Objectives: The National Early Warning Score, Modified Early Warning Score, and quick Sepsis-related Organ Failure Assessment can predict clinical deterioration. These scores exhibit only moderate performance and are often evaluated using aggregated measures over time. A simulated prospective validation strategy that assesses multiple predictions per patient-day would provide the best pragmatic evaluation. We developed a deep recurrent neural network deterioration model and conducted a simulated prospective evaluation. Design: Retrospective cohort study. Setting: Four hospitals in Pennsylvania. Patients: Inpatient adults discharged between July 1, 2017, and June 30, 2019. Interventions: None. Measurements and Main Results: We trained a deep recurrent neural network and logistic regression model using data from electronic health records to predict hourly the 24-hour composite outcome of transfer to ICU or death. We analyzed 146,446 hospitalizations with 16.75 million patient-hours. The hourly event rate was 1.6% (12,842 transfers or deaths, corresponding to 260,295 patient-hours within the predictive horizon). On a hold-out dataset, the deep recurrent neural network achieved an area under the precision-recall curve of 0.042 (95% CI, 0.04–0.043), comparable with logistic regression model (0.043; 95% CI 0.041 to 0.045), and outperformed National Early Warning Score (0.034; 95% CI, 0.032–0.035), Modified Early Warning Score (0.028; 95% CI, 0.027– 0.03), and quick Sepsis-related Organ Failure Assessment (0.021; 95% CI, 0.021–0.022). For a fixed sensitivity of 50%, the deep recurrent neural network achieved a positive predictive value of 3.4% (95% CI, 3.4–3.5) and outperformed logistic regression model (3.1%; 95% CI 3.1–3.2), National Early Warning Score (2.0%; 95% CI, 2.0–2.0), Modified Early Warning Score (1.5%; 95% CI, 1.5–1.5), and quick Sepsis-related Organ Failure Assessment (1.5%; 95% CI, 1.5–1.5). Conclusions: Commonly used early warning scores for clinical decompensation, along with a logistic regression model and a deep recurrent neural network model, show very poor performance characteristics when assessed using a simulated prospective validation. None of these models may be suitable for real-time deployment. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Mr. Shah’s institution received funding from America Thoracic Society Research Foundation and the National Institutes of Health (NIH), and he received funding from Medical Student Health Services and Policy Research Summer Research Fellowship through the Master of Science in Health Policy Research Program at the Perelman School of Medicine, University of Pennsylvania. Dr. Ungar received support for article research from the NIH. Dr. Weissman was supported in part by NIH K23HL141639 and a grant from the America Thoracic Society Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: parth.shah@pennmedicine.upenn.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedKyriazopoulou, Evdoxia; Poulakou, Garyfallia; Giamarellos-Bourboulis, Evangelos J.
Current Opinion in Infectious Diseases, 1.04.2021 Tilføjet 13.03.2021 08:09Purpose of review Biomarkers, mainly procalcitonin, are commonly used in sepsis diagnosis, prognosis and treatment follow-up. This review summarizes the potential benefit of their use for the critically ill. Recent findings Increased clinical evidence from randomized clinical trials of biomarker-guided treatment suggests a trend for appropriate but short antimicrobial treatment for the critically ill. Procalcitonin (PCT) is the most studied biomarker; in the majority of randomized clinical trials, the use of a stopping rule of antibiotics on the day when PCT is below 80% from baseline or less than 0.5 ng/ml was proven effective to reduce length of antimicrobial treatment, antibiotic-associated adverse events and infectious complications like infections by multidrug-resistant organisms and Clostridium difficile. Survival benefit was also noted. Summary Biomarkers, mainly PCT, may help improve sepsis outcome by restriction of injudicious antimicrobial use.
Læs mere Tjek på PubMedJochem B. Buil, Peter Pickkers, Henrich A.L. van der Lee, Paul E. Verweij
Clinical Microbiology and Infection, 26.11.2020 Tilføjet 11.03.2021 16:48A female was admitted to our hospital with a penetrating abdominal lesion. A foreign body was removed surgically from the abdominal cavity. She developed severe sepsis necessitating repeated surgical explorations of the abdomen. Despite these surgical interventions and initiation of broad-spectrum antibacterial therapy septic shock developed. A blood culture became positive, showing a yeast-like cell with a germ tube in the Gram stain (Fig. 1a). The same day stool cultures became positive with the mould Lomentospora prolificans.
Læs mere Tjek på PubMedMichael Hogardt, Silke Besier, Lisa Vorbeck, Stephan Göttig, Thomas A. Wichelhaus, David Villinger, Daniel Hack, Julian Sommer, Valentina Ilievski, Volkhard A.J. Kempf
Clinical Microbiology and Infection, 23.10.2020 Tilføjet 11.03.2021 16:48Since 31st December 2019, and as of 29th September 2020, 5 011 669 cases of coronavirus disease 2019 (COVID-19) have been reported in Europe (worldwide 33 423 469, including 1 002 678 deaths). In Germany, 287 421 cases and 9471 deaths have been recorded [1]. COVID-19 presents as a mild to severe disease, and the outcome is potentially fatal [2,3]. The course of infection might be complicated by nosocomial infections (e.g. ventilator-associated pneumonia, sepsis, etc.), eventually caused by multidrug-resistant organisms (MDRO).
Læs mere Tjek på PubMedMiriam Kesselmeier, Mathias W. Pletz, Anna Leona Blankenstein, André Scherag, Torsten Bauer, Santiago Ewig, Martin Kolditz
Clinical Microbiology and Infection, 10.10.2020 Tilføjet 11.03.2021 16:48The qSOFA (quick sepsis-related organ failure assessment) score shows similarities to the CRB-65 pneumonia score, but its prognostic accuracy in patients with community-acquired pneumonia (CAP) has not been extensively evaluated. Our aim was to validate the qSOFA (-65) score in a large cohort of CAP patients.
Læs mere Tjek på PubMedM. Cobussen, M.B. Haeseker, J. Stoffers, V.H.M. Wanrooij, P.H.M. Savelkoul, P.M. Stassen
Clinical Microbiology and Infection, 1.07.2020 Tilføjet 11.03.2021 16:48To determine the effect of a single dose of gentamicin on the incidence and persistence of acute kidney injury (AKI) in patients with sepsis in the emergency department (ED).
Læs mere Tjek på PubMedUffen, J. W., van Goor, H., Reitsma, J., Oosterheert, J. J., de Regt, M., Kaasjager, K.
BMJ Open, 11.03.2021 Tilføjet 11.03.2021 16:48Objective The quick Sequential Organ Failure Assessment (qSOFA) is developed as a tool to identify patients with infection with increased risk of dying from sepsis in non-intensive care unit settings, like the emergency department (ED). An abnormal score may trigger the initiation of appropriate therapy to reduce that risk. This study assesses the risk of a treatment paradox: the effect of a strong predictor for mortality will be reduced if that predictor also acts as a trigger for initiating treatment to prevent mortality. Design Retrospective analysis on data from a large observational cohort. Setting ED of a tertiary medical centre in the Netherlands. Participants 3178 consecutive patients with suspected infection. Primary outcome To evaluate the existence of a treatment paradox by determining the influence of baseline qSOFA on treatment decisions within the first 24 hours after admission. Results 226 (7.1%) had a qSOFA ≥2, of which 51 (22.6%) died within 30 days. Area under receiver operating characteristics of qSOFA for 30-day mortality was 0.68 (95% CI 0.61 to 0.75). Patients with a qSOFA ≥2 had higher odds of receiving any form of intensive therapy (OR 11.4 (95% CI 7.5 to 17.1)), such as aggressive fluid resuscitation (OR 8.8 95% CI 6.6 to 11.8), fast antibiotic administration (OR 8.5, 95% CI 5.7 to 12.3) or vasopressic therapy (OR 17.3, 95% CI 11.2 to 26.8), compared with patients with qSOFA <2. Conclusion In ED patients with suspected infection, a qSOFA ≥2 was associated with more intensive treatment. This could lead to inadequate prediction of 30-day mortality due to the presence of a treatment paradox. Trial registration number 6916.
Læs mere Tjek på PubMedChalker, V. J., Sharratt, M. G., Rees, C., Bell, O. H., Portal, E., Sands, K., Payne, M. S., Spiller, O. B.
Antimicrobial Agents And Chemotherapy, 19.01.2021 Tilføjet 11.03.2021 16:47A minimal genome and absent bacterial cell wall renders Mycoplasma hominis inherently resistant to most antimicrobials except lincosamides, tetracyclines and fluoroquinionlones. Often dismissed as a commensal (except where linked to preterm birth), it causes septic arthritis in immunodeficient patients and is increasingly associated with transplant failure (particularly lung) accompanying immunosuppression. We examined antimicrobial susceptibility (AST) on strains archived between 2005-2015 submitted to the Public Health England reference laboratory and determined the underlying mechanism of resistance by whole genome sequencing (WGS). Archived M. hominis strains included 32/115 from invasive infection (sepsis, CSF, peritoneal and pleural fluid) over the 10-year period (6.4% of all samples submitted between 2010-2015 were positive). No clindamycin resistance was detected, while two strains were resistant to moxifloxacin and levofloxacin (resistance mutations: S83L or E87G in gyrA and S81I or E84V in parC). One of these strains and 11 additional strains were tetracycline resistant, mediated by tet(M) carried within an integrative conjugative element (ICE) consistently integrated at the somatic rumA gene; however, the ICEs varied widely in 5-19 associated accessory genes. WGS analysis showed tet(M)-carrying strains were not clonal, refuting previous speculation that the ICE was broken and immobile. We found tet(M)-positive and -negative strains (including the multi-resistant 2015 strain) to be equally susceptible to tigecycline and josamycin, however, the British National Formulary does not include guidance for these. Continued M. hominis investigation and AST surveillance (especially immunocompromised patients) is warranted, and expansion of the limited therapeutics needs to be expanded in the UK.
Læs mere Tjek på PubMedSi-Ho Kim, Jin Gu Yun, Hyo Jung Park, Hojeong Won, Sung Suk Ryoo, Eunsil Choi, Eun-Kyung Park, Kyungmin Huh, Chi-Min Park
International Journal of Infectious Diseases, 24.02.2021 Tilføjet 11.03.2021 16:47Antimicrobial resistance in intensive care units (ICUs) is one of the most challenging problems for managing critically ill patients (Johnson et al., 2020; Weiner-Lastinger et al., 2020). It is known that more than one-third of patients admitted to the ICU have sepsis; thus, antimicrobial agents could be over- and mis-prescribed to increase the chance of administering appropriate antibiotics or simply to relieve the anxiety of clinicians (Luyt et al., 2014; Vincent et al., 2006). Therefore, the antimicrobial stewardship program (ASP) is highly recommended in critical care to improve antibiotic utilization and patient outcome (Barlam et al., 2016; Luyt et al., 2014; Pickens and Wunderink, 2019; Zhang and Singh, 2015).
Læs mere Tjek på PubMedDeMerle, Kimberley M.; Angus, Derek C.; Baillie, J. Kenneth; Brant, Emily; Calfee, Carolyn S.; Carcillo, Joseph; Chang, Chung-Chou H.; Dickson, Robert; Evans, Idris; Gordon, Anthony C.; Kennedy, Jason; Knight, Julian C.; Lindsell, Christopher J.; Liu, Vincent; Marshall, John C.; Randolph, Adrienne G.; Scicluna, Brendon P.; Shankar-Hari, Manu; Shapiro, Nathan I.; Sweeney, Timothy E.; Talisa, Victor B.; Tang, Benjamin; Thompson, B. Taylor; Tsalik, Ephraim L.; van der Poll, Tom; van Vught, Lonneke A.; Wong, Hector R.; Yende, Sachin; Zhao, Huiying; Seymour, Christopher W.
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or “subclasses” with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent “truth.” We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and social care. The funding source did not have any role in the design, conduct or interpretation of study results. Dr. Seymour helped in designing the concept. Drs. DeMerle, Angus, and Seymour helped in designing. Drs. DeMerle, Baille, Brant, Calfee, Carcillo, Chang, Dickson, Evans, Gordon, Kennedy, Knight, Lindsell, Liu, Marshall, Randolph, Scicluna, Shankar-Hari, Shapiro, Sweeney, Talis, Tang, Thompson, Tsalik, van der Poll, van Vught, Wong, Yende, Zhao, and Seymour drafted the article and critically revised the article for important intellectual content. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. DeMerle’s institution received funding from R35 GM119519-03 and T32HL007820. Dr. Calfee is supported in part by grants from the National Institutes of Health (NIH; HL140026). Dr. Carcillo is supported in part by grants from the National Institutes of Health (R01GM108618). Dr. DeMerle is supported in part by grants from the National Institutes of Health (T32HL007820). Dr. Angus received funding from Ferring Pharmaceuticals, Bristol-Myers Squibb, Bayer AG, and Alung Technologies. Drs. Angus, Brant, Carcillo, Chang, Dickson, Kennedy, Lindsell, Liu, Randolph, Thompson, Tsalik, Wong, and Seymour received support for article research from the NIH. Dr. Baillie received support for article research from Wellcome Trust/Charity Open Access Fund (COAF), and Research Councils UK. Dr. Calfee’s institution received funding from Roche/Genentech and Bayer, and she received funding from Roche/Genentech, Quark, CSL Behring, Bayer, Gen1e Life Sciences, and Vasomune. Drs. Carcillo’s and Seymour’s institutions received funding from the National Institute of General Medical Sciences. Drs. Chang’s, Lindsell’s, Liu’s, Randolph’s, Shapiro’s, and Wong’s institutions received funding from the NIH. Dr. Gordon’s institution received funding from the National Institute for Health Research (NIHR) Research Professorship (RP-2015-06-18), NIHR Imperial Biomedical Research Centre, GlaxoSmithKline, and Bristol Myers Squibb. Dr. Knight received support for article research from Wellcome Trust/COAF. Dr. Lindsell’s institution received funding from the Centers for Disease Control and Prevention (CDC), Department of Defense, Marcus Foundation, Entegrion, Endpoint Health, and bioMerieux, and he disclosed he is a coinventor on patents related to risk stratification in septic shock. Dr. Marshall received funding from AM Pharma, AKPA Pharma, and the Society of Critical Care Medicine (Critical Care Medicine Associate Editor). Dr. Randolph’s institution received funding from the CDC, and she received funding from La Jolla Pharma. Dr. Shapiro’s institution received funding from rapid pathogen screening, Baxter, and Inflammatix, and he received funding from Diagnostic Robotics. Dr. Sweeney received funding from Inflammatix. Dr. Thompson’s institution received funding from the National Heart, Lung, and Blood Institute, and he received funding from Bayer and Thetis. Dr. Tsalik disclosed that he is a founder and holds equity in Predigen; he receives salary support from the Durham VA Healthcare System and Duke University; and he has received salary support and/or grant funding (paid to his university) from the NIH, DARPA, DTRA, Karius, and Sanofi US. Dr. Wong disclosed that he and his institutions hold U.S. patents for sepsis biomarkers. Dr. Yende received funding from serving as consultant for expert testimony and he disclosed government work. Dr. Knight is supported by a Wellcome Trust Investigator Award (204969/Z/16/Z) and the NIHR Oxford Biomedical Research Centre. Dr. Lindsell was supported in part by grants from the National Institutes of Health (R35GM126943, R01HL149422), a research grant to VUMC from Endpoint Health, and is also listed as co-inventor on patents for endotyping and risk-stratification in pediatric septic shock. Dr. Liu is supported in part by grants from the National Institutes of Health (R35GM128672). Dr. Marshall is supported in part by grants from the Canadian Institutes of Health Research. Dr. Randolph is supported in part by grants from the National Institutes of Health (R21HD095228). Dr. Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16-011). Dr. Wong is supported in part by grants from the National Institutes of Health (R35 GM126943). Dr. Sweeney is an employee of, and shareholder in, Inflammatix. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: demerlekm@upmc.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedTaylor, Stephanie Parks; Anderson, William E.; Beam, Kent; Taylor, Brice; Ellerman, Justin; Kowalkowski, Marc A.
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Rapid delivery of antibiotics is a cornerstone of sepsis therapy, although time targets for specific components of antibiotic delivery are unknown. We quantified time intervals comprising the task of antibiotic delivery and evaluated the association between interval delays and hospital mortality among patients treated in the emergency department for suspected sepsis. Design: Retrospective cohort. Setting: Twelve hospitals in Southeastern United States from 2014 to 2017. Patients: Twenty-four thousand ninety-three encounters among 20,026 adults with suspected sepsis in 12 emergency departments. Measurements and Main Results: We divided antibiotic administration into two intervals: time from emergency department triage to antibiotic order (recognition delay) and time from antibiotic order to infusion (administration delay). We used generalized linear mixed models to evaluate associations between these intervals and hospital mortality. Median time from emergency department triage to antibiotic administration was 3.4 hours (interquartile range, 2.0–6.0 hr), separated into a median recognition delay (time from emergency department triage to antibiotic order) of 2.7 hours(interquartile range, 1.5–4.7 hr) and median administration delay (time from antibiotic order to infusion) of 0.6 hours (0.3–1.2 hr). Adjusting for other risk factors, both recognition delay and administration delay were associated with mortality, but pairwise comparison with a no-delay reference group was not significant for up to 6 hours of recognition delay or up to 1.5 hours of administration delay. Conclusions: Both recognition delays and administration delays were associated with increased hospital mortality, but only for longer delays. These results suggest that both metrics may be important to measure and improve for patients with suspected sepsis but do not support targets less than 1 hour. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Presented, in part, at the annual meeting of the Society Critical Care Medicine, San Antonio, TX, February 2018. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Stephanie.p.taylor@atriumhealth.org Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedBeesley, Sarah J.; Sorensen, Jeff; Walkey, Allan J.; Tonna, Joseph E.; Lanspa, Michael J.; Hirshberg, Ellie; Grissom, Colin K.; Horne, Benjamin D.; Burk, Rebecca; Abraham, Theodore P.; Paine, Robert; Brown, Samuel M.
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Septic cardiomyopathy develops frequently in patients with sepsis and likely increases short-term mortality. However, whether septic cardiomyopathy is associated with long-term outcomes after sepsis is unknown. We investigated whether septic patients with septic cardiomyopathy have worse long-term outcomes than septic patients without septic cardiomyopathy. Design: Retrospective cohort study. SETTING: Adult ICU. PATIENTS: Adult ICU patients with sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Left ventricular global longitudinal systolic strain was our primary measure of septic cardiomyopathy. We employed a suite of multivariable survival analyses to explore linear and nonlinear associations between left ventricular global longitudinal systolic strain and major adverse cardiovascular events, which included death, stroke, and myocardial infarction. Our primary outcome was major adverse cardiovascular event through 24 months after ICU discharge. Among 290 study patients, median left ventricular global longitudinal systolic strain was –16.8% (interquartile range, –20.4% to –12.6%), and 38.3% of patients (n = 111) experienced a major adverse cardiovascular event within 24 months after discharge. On our primary, linear analysis, there was a trend (p = 0.08) toward association between left ventricular global longitudinal systolic strain and major adverse cardiovascular event (odds ratio, 1.03; CI, < 1 to 1.07). On our nonlinear analysis, the association was highly significant (p < 0.001) with both high and low left ventricular global longitudinal systolic strain associated with major adverse cardiovascular event among patients with pre-existing cardiac disease. This association was pronounced among patients who were younger (age < 65 yr) and had Charlson Comorbidity Index greater than 5. Conclusions: Among patients with sepsis and pre-existing cardiac disease who survived to ICU discharge, left ventricular global longitudinal systolic strain demonstrated a U-shaped association with cardiovascular outcomes through 24 months. The relationship was especially strong among younger patients with more comorbidities. These observations are likely of use to design of future trials. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The Intermountain Institutional Review Board approved this study with waiver of informed consent. Drs Beesley, Tonna, Paine, Grissom, and Brown designed the study. Drs. Beesley, Sorensen, Tonna, Paine, and Brown analyzed and interpreted the data. Dr. Beesley drafted the report, and all other authors revised it. All authors gave final approval of the report to be published. Supported (in part or in full) by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR001067. Dr. Walkey received funding from UptoDate. Dr. Tonna’s institution received funding from National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences, and LivaNova; he received funding from Philips Healthcare; he received support for article research from National Institutes of Health; and he was supported by a career development award (K23HL141596) from the NHLBI of the National Institutes of Health. Dr. Burk received funding from Intermountain Research and Medical Foundation. Dr. Paine’s institution received funding from NHLBI and the Department of Veterans Affairs. The remaining authors have disclosed that they do not have any potential conflicts of interest. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. For information regarding this article, E-mail: Sarah.beesley@imail.org Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedCoopersmith, Craig M.; Antonelli, Massimo; Bauer, Seth R.; Deutschman, Clifford S.; Evans, Laura E.; Ferrer, Ricard; Hellman, Judith; Jog, Sameer; Kesecioglu, Jozef; Kissoon, Niranjan; Martin-Loeches, Ignacio; Nunnally, Mark E.; Prescott, Hallie C.; Rhodes, Andrew; Talmor, Daniel; Tissieres, Pierre; De Backer, Daniel
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: To identify research priorities in the management, pathophysiology, and host response of coronavirus disease 2019 in critically ill patients. Design: The Surviving Sepsis Research Committee, a multiprofessional group of 17 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine, was virtually convened during the coronavirus disease 2019 pandemic. The committee iteratively developed the recommendations and subsequent document. Methods: Each committee member submitted a list of what they believed were the most important priorities for coronavirus disease 2019 research. The entire committee voted on 58 submitted questions to determine top priorities for coronavirus disease 2019 research. Results: The Surviving Sepsis Research Committee provides 13 priorities for coronavirus disease 2019. Of these, the top six priorities were identified and include the following questions: 1) Should the approach to ventilator management differ from the standard approach in patients with acute hypoxic respiratory failure?, 2) Can the host response be modulated for therapeutic benefit?, 3) What specific cells are directly targeted by severe acute respiratory syndrome coronavirus 2, and how do these cells respond?, 4) Can early data be used to predict outcomes of coronavirus disease 2019 and, by extension, to guide therapies?, 5) What is the role of prone positioning and noninvasive ventilation in nonventilated patients with coronavirus disease?, and 6) Which interventions are best to use for viral load modulation and when should they be given? Conclusions: Although knowledge of both biology and treatment has increased exponentially in the first year of the coronavirus disease 2019 pandemic, significant knowledge gaps remain. The research priorities identified represent a roadmap for investigation in coronavirus disease 2019. Drs. Coopersmtih and De Backer are cochairs of the committee who contributed equally to the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Coopersmith is past president of the Society of Critical Care Medicine. Dr. Antonelli is immediate past president of European Society of Intensive Care Medicine and received consulting fees from Toray, Intersurgical, and Fisher & Paykel and unrestricted research grants from GE and Estor. Dr. Bauer is a consultant for Wolters Kluwer, and he received funding from Wolters Kluwer. Dr. Deutschman is past president of the Society of Critical Care Medicine scientific editor for Critical Care Medicine, consultant for Enlivex and Lowell Therapeutics; his institution received funding from National Institute of General Medical Sciences; he received funding from the Society of Critical Care Medicine, Elsevier, Enlivex, Sage Therapeutics, and La Jolla Pharmaceuticals; and he received support for article research from the National Institutes of Health (NIH). Dr. Evans disclosed that she serves as the cochair of the Surviving Sepsis Committee and as the adult Surviving Sepsis Campaign Guidelines for the management of sepsis and septic shock. Dr. Ferrer received funding from MSD, Pfizer, and Gilead. Dr. Kesecioglu is president of the European Society of Intensive Care Medicine. Dr. Kissoon is the pediatrics guidelines cochair of the Surviving Sepsis Committee. Dr. Martin-Loeches received honoraria from MSD, Gilead, and Aspen. Dr. Nunnally is Treasurer of the Society of Critical Care Anesthesiologists. Dr. Prescott is the sepsis lead for a Michigan statewide sepsis quality improvement initiative sponsored by Blue Cross Blue Shield of Michigan, and his institution received funding from Agency for Healthcare Research and Quality, the Department of Veterans Affairs, and the NIH, and she disclosed government work. Dr. Rhodes is the adult guidelines cochair of the Surviving Sepsis Committee and a member of the Executive Committee. Dr. Talmor received speaking fees from Hamilton Medical, Clew, and Mindray. Dr Tissieres is president of the European Society of Pediatric and Neonatal Intensive Care, is the pediatrics guidelines cochair of the Surviving Sepsis Committee, and has received consulting fees or research grant from Baxter, bioMerieux, Sanofi. Dr. DeBacker is past president of the European Society of Intensive Care Medicine and has received consulting fees from Fresenius Kabi. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedHariri, Geoffroy; Urbina, Tomas; Lavillegrand, Jean-Rémi; Gasperment, Maxime; Mazerand, Sandie; Abdelmalek, Abdelkrim; Bigé, Naïke; Baudel, Jean-Luc; Guidet, Bertrand; Maury, Eric; Ait-Oufella, Hafid
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Cirrhosis is associated with hemodynamic and vascular disorders. However, microvascular reactivity of cirrhotic patients in the context of sepsis has poorly been investigated. Design: Prospective observational study. Setting: Medical ICU in a tertiary teaching hospital. Patients: We prospectively included adult patients admitted in the ICU for septic shock with and without cirrhosis. After initial resuscitation, global hemodynamic parameters were recorded and skin microvascular reactivity to local acetylcholine iontophoresis was measured. Interventions: None. Measurements and Main Results: Thirty patients with septic shock were included (60% male), 10 with cirrhosis and 20 without, with a median age of 61 years (54–74 yr). Cirrhotic patients were mainly classed as Child-Pugh C (80%) and all of them had ascites. Sequential Organ Failure Assessment score and ICU mortality of cirrhotic patients were higher than the noncirrhotic patients, respectively (6.5 [5.0–8.3] vs 11.5 [9.0–14.0]; p < 0.01; 15% vs 70%; p < 0.01). Peripheral tissue perfusion and global hemodynamic parameters were not different between the cirrhotic and noncirrhotic patients but arterial lactate level was three times higher in patients with cirrhosis (6.0 mmol/L [3.9–8.0 mmol/L] vs 2.0 mmol/L [0.9–3.5 mmol/L]; p < 0.01). Basal skin microvascular blood flow was not statistically different between the groups (4.94 perfusion units [3.45–8.73 perfusion units] vs 6.95 perfusion units [5.24–8.38 perfusion units]; p = 0.29). After acetylcholine simulation, skin microvascular blood flow increased more in cirrhotic patients than in noncirrhotic patients (644% [217–966%] vs 169% [73–505%], p = 0.03). Global microvascular reactivity was seven times higher in cirrhotic patients (area under the curve, 16,412 perfusion units [13,898–19,041 perfusion units] vs 2,664 perfusion units [969–4,604 perfusion units]; p < 0.001). Conclusions: We identified an exaggerated vasodilating microvascular response in cirrhotic patients with septic shock. Such a result may explain vasopressor resistance and paves the way for future therapeutic trials, targeting nitric oxide pathway specifically in this population. All authors are involved in study concept and design, and critical revision of article. Drs. Hariri, Urbina, Lavillegrand, and Ait-Oufella helped in acquisitions of data. Drs. Hariri, Urbina, Gasperment, Guidet, Maury, and Ait-Oufella drafted of the article. Drs. Hariri and Ait-Oufella are involved in statistical analysis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: hafid.aitoufella@aphp.fr Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedDemiselle, Julien; Seegers, Valérie; Lemerle, Marie; Meziani, Ferhat; Grelon, Fabien; Megarbane, Bruno; Anguel, Nadia; Mira, Jean-Paul; Dequin, Pierre-François; Gergaud, Soizic; Weiss, Nicolas; Legay, Francçois; Le Tulzo, Yves; Conrad, Marie; Robert, René; Gonzalez, Frédéric; Guitton, Christophe; Tamion, Fabienne; Tonnelier, Jean-Marie; Bédos, Jean-Pierre; Van Der Linden, Thierry; Vieillard-Baron, Antoine; Mariotte, Eric; Pradel, Gaël; Lesieur, Olivier; Ricard, Jean-Damien; Hervé, Fabien; du Cheyron, Damien; Guerin, Claude; Teboul, Jean-Louis; Helms, Julie; Radermacher, Peter; Asfar, Pierre
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Individualizing a target mean arterial pressure is challenging during the initial resuscitation of patients with septic shock. The SEPSISPAM trial suggested that targeting high mean arterial pressure might reduce the occurrence of acute kidney injury among those included patients with a past history of chronic hypertension. We investigated whether the class of antihypertensive medications used before the ICU stay in chronic hypertensive patients was associated with the severity of acute kidney injury occurring after inclusion, according to mean arterial pressure target. Design: Post hoc analysis of the SEPSISPAM trial. Setting: The primary outcome was the occurrence of severe acute kidney injury during the ICU stay defined as kidney disease improving global outcome stage 2 or higher. Secondary outcomes were mortality at day 28 and mortality at day 90. Patients: All patients with chronic hypertension included in SEPSISPAM with available antihypertensive medications data in the hospitalization report were included. Measurements and Main Results: We analyzed 297 patients. Severe acute kidney injury occurred in 184 patients, without difference according to pre-ICU exposure to antihypertensive medications. Patients with pre-ICU exposure to angiotensin II receptor blockers had significantly less severe acute kidney injury in the high mean arterial pressure target group (adjusted odd ratio 0.24 with 95% CI [0.09–0.66]; p = 0.006). No statistically significant association was found after adjustment for pre-ICU exposure to antihypertensive medications and survival. Conclusions: Our results suggest that patients with septic shock and chronic hypertension treated with angiotensin II receptor blocker may benefit from a high mean arterial pressure target to reduce the risk of acute kidney injury occurrence. Drs. Demiselle and Asfar designed the study. Drs. Demiselle and Lemerle collected data in hospitalization reports. Drs. Demiselle and Seegers performed statistical analysis. Drs. Demiselle, Seegers, Guitton, Ricard, Radermacher, and Asfar drafted the article. Drs. Meziani, Grelon, Megarbane, Anguel, Mira, Dequin, Gergaud, Weiss, Legay, Le Tulzo, Conrad, Robert, Gonzalez, Guitton, Tamion, Tonnelier, Bédos, Van Der Linden, Vieillard-Baron, Mariotte, Pradel, Lesieur, Ricard, Hervé, du Cheyron, and Helms included patients in the SEPSISPAM trial and helped to have access to hospitalization reports. All the authors have revised and approved the final version of the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The SEPSISPAM trial was supported by the French Ministry of Health. Dr. Weiss perceived consultant fees from Med-Day Pharmaceuticals outside of the scope of this article. Dr. Dequin’s institution received funding from Angers University Hospital, the French Ministry of Health, Abionic, Atox Bio, Sphingotec GMBH, Adrenomed, Medspace, Aridis, Merck, Combioxin, GSK, Med-Immune, Genentech INH, Rev-Immune, Faron, Kenta, and Tigenix, and he received support for article research from the French Ministry of Health. Dr. Gonzalez disclosed work for hire. Dr. Teboul received funding from Getinge/Pulsion. Dr. Radermacher’s institution received funding from Deutsche Forschungsgemeinschaft and the German Ministry of Defense. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: piasfar@chu-angers.fr Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedYu, Sean C.; Betthauser, Kevin D.; Gupta, Aditi; Lyons, Patrick G.; Lai, Albert M.; Kollef, Marin H.; Payne, Philip R. O.; Michelson, Andrew P.
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Assess the impact of heterogeneity among established sepsis criteria (Sepsis-1, Sepsis-3, Centers for Disease Control and Prevention Adult Sepsis Event, and Centers for Medicare and Medicaid severe sepsis core measure 1) through the comparison of corresponding sepsis cohorts. Design: Retrospective analysis of data extracted from electronic health record. Setting: Single, tertiary-care center in St. Louis, MO. Patients: Adult, nonsurgical inpatients admitted between January 1, 2012, and January 6, 2018. Interventions: None. Measurements and Main Results: In the electronic health record data, 286,759 encounters met inclusion criteria across the study period. Application of established sepsis criteria yielded cohorts varying in prevalence: Centers for Disease Control and Prevention Adult Sepsis Event (4.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (4.8%), International Classification of Disease code (7.2%), Sepsis-3 (7.5%), and Sepsis-1 (11.3%). Between the two modern established criteria, Sepsis-3 (n = 21,550) and Centers for Disease Control and Prevention Adult Sepsis Event (n = 12,494), the size of the overlap was 7,763. The sepsis cohorts also varied in time from admission to sepsis onset (hr): Sepsis-1 (2.9), Sepsis-3 (4.1), Centers for Disease Control and Prevention Adult Sepsis Event (4.6), and Centers for Medicare and Medicaid severe sepsis core measure 1 (7.6); sepsis discharge International Classification of Disease code rate: Sepsis-1 (37.4%), Sepsis-3 (40.1%), Centers for Medicare and Medicaid severe sepsis core measure 1 (48.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (54.5%); and inhospital mortality rate: Sepsis-1 (13.6%), Sepsis-3 (18.8%), International Classification of Disease code (20.4%), Centers for Medicare and Medicaid severe sepsis core measure 1 (22.5%), and Centers for Disease Control and Prevention Adult Sepsis Event (24.1%). Conclusions: The application of commonly used sepsis definitions on a single population produced sepsis cohorts with low agreement, significantly different baseline demographics, and clinical outcomes. Washington University in St. Louis, St. Louis, MO. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Michelson received funding as a shareholder of Pfizer. Dr. Lai received funding as a shareholder of Altria Group, Apple, Berkshire Hathaway, Barnes Group, Carnival Corp, Citigroup, Johnson & Johnson, Verizon Communications, Walt Disney, Royal Caribbean Cruises, Caterpillar, McDonald’s Corp, Ubiquiti, Westinghouse Air Brake Technologies, and Yum! Brands. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: amichels@wustl.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedFaustino, E. Vincent S.; Raffini, Leslie J.; Hanson, Sheila J.; Cholette, Jill M.; Pinto, Matthew G.; Li, Simon; Kandil, Sarah B.; Nellis, Marianne E.; Shabanova, Veronika; Silva, Cicero T.; Tala, Joana A.; McPartland, Tara; Spinella, Philip C.; for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Inve
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children. Design: Post hoc analysis of a Bayesian phase 2b randomized clinical trial. Setting: Seven PICUs. Patients: Children less than 18 years old with newly inserted central venous catheter. Interventions: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2–0.5 international units/mL versus usual care. Measurements and Main Results: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37–2.44) in infants and 0.24 (95% credible interval, 0.04–0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78–437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7–74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17–61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count. Conclusions: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Drs. Faustino and Spinella received funding to conduct the Catheter-Related Early Thromboprophylaxis with Enoxaparin Trial. Dr. Faustino’s institution received funding from National Institutes of Health (NIH) and the American Heart Association to conduct the trial (16RNT31180018). Drs. Faustino and Spinella received funding from the NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to conduct the trial (R21HD089131). Drs. Faustino, Hanson, Pinto, Shabanova, and McPartland received support for article research from the NIH. Drs. Faustino, Raffini, Hanson, Kandil, McPartland, and Spinella disclosed off-label product use of enoxaparin (investigational new drug approval from the U.S. Food and Drug Administration was received). Dr. Raffini received funding from Bayer, Genetech, Xa-Tek, and HemaBiologics. Dr. Hanson’s institution received funding from the NIH. Dr. Kandil received funding from Children’s Hospital Collaborative, Improving Pediatric Sepsis Outcomes. Dr. Shabanova’s institution received funding from Prevention of Central Venous Catheter-Associated Thrombosis in Critically Ill Children NICHD: R21HD089131; she received funding through the Clinical and Translational Science Award Grant Number UL1 RR024139 from the National Center for Research Resources and the National Center for Advancing Translational Science, components of the NIH, and NIH Roadmap for Medical Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. The CRETE Trial Investigators are listed in the Appendix. ClinicalTrials.gov Identifier: NCT03003390. For information regarding this article, E-mail: vince.faustino@yale.edu Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedKellum, John A.; Artigas, Antonio; Gunnerson, Kyle J.; Honore, Patrick M.; Kampf, J. Patrick; Kwan, Thomas; McPherson, Paul; Nguyen, H. Bryant; Rimmelé, Thomas; Shapiro, Nathan I.; Shi, Jing; Vincent, Jean-Louis; Chawla, Lakhmir S.; for the Sapphire Investigators
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: Although early recognition of sepsis is vital to improving outcomes, the diagnosis may be missed or delayed in many patients. Acute kidney injury is one of the most common organ failures in patients with sepsis but may not be apparent on presentation. Novel biomarkers for acute kidney injury might improve organ failure recognition and facilitate earlier sepsis care. Design: Retrospective, international, Sapphire study. Setting: Academic Medical Center. Patients: Adults admitted to the ICU without evidence of acute kidney injury at time of enrollment. Interventions: None. Measurements and Main Results: We stratified patients enrolled in the Sapphire study into three groups—those with a clinical diagnosis of sepsis (n = 216), those with infection without sepsis (n = 120), and those without infection (n = 387) at enrollment. We then examined 30-day mortality stratified by acute kidney injury within each group. Finally, we determined the operating characteristics for kidney stress markers (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) for prediction of acute kidney injury as a sepsis-defining organ failure in patients with infection without a clinical diagnosis of sepsis at enrollment. Combining all groups, 30-day mortality was 23% for patients who developed stage 2–3 acute kidney injury within the first 3 days compared with 14% without stage 2–3 acute kidney injury. However, this difference was greatest in the infection without sepsis group (34% vs 11%; odds ratio, 4.09; 95% CI, 1.53–11.12; p = 0.005). Using a (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) cutoff of 2.0 units, 14 patients (11.7%), in the infection/no sepsis group, tested positive of which 10 (71.4%) developed stage 2–3 acute kidney injury. The positive test result occurred a median of 19 hours (interquartile range, 0.8–34.0 hr) before acute kidney injury manifested by serum creatinine or urine output. Similar results were obtained using a cutoff of 1.0 for any stage of acute kidney injury. Conclusions: Use of the urinary (tissue inhibitor of metalloproteinases-2) × (insulin-like growth factor binding protein 7) test could identify acute kidney injury in patients with infection, possibly helping to detect sepsis, nearly a day before acute kidney injury is apparent by clinical criteria. A complete list of Sapphire Investigators is provided in the Appendix (Supplemental Digital Content 1, http://links.lww.com/CCM/G111). Clinical Trial Registration: NCT01209169. The parent study was designed by Drs. Kellum, Kampf, McPherson and Chawla and was conducted by Drs. Artigas, Gunnerson, Honore, Nguyen, Rimmel,o Shapiro, and Vincent. Dr. Kellum conceived of the current study and drafted the article. Dr. Shi performed the statistical analysis. Drs. Kellum, Kampf, Kwan, and McPherson interpreted the results, and all authors reviewed and revised the article. Dr. Kellum takes responsibility for the content of the article, including the data and analysis. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The study sponsor (Astute Medical) was primarily responsible for design of the parent study and data collection; the current study was designed and interpreted by the authors. Dr. Kellum’s institution received funding from Astute Medical and bioMerieux. Drs. Kellum, Rimmelé, Shi, and Chawla received funding from Astute Medical. Drs. Kampf, Kwan, and McPherson are employees of Astute Medical/bioMerieux; Drs. Kellum, Rimmelé, Shi, and Chawla are paid consultants of Astute Medical/bioMerieux; and Dr. Kellum has received grant support from Astute Medical/ bioMerieux apart from the current work. Dr. Artigas’s institution received funding from Lilly Foundation, and he received funding from Grifols, Fisher & Paykel. Drs. Kampf, Kwan, and McPherson received funding from Astute Medical (employee). Drs. Nguyen’s and Shapiro’s institutions received funding from Astute Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: kellum@pitt.edu This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedMuttalib, Fiona; González-Dambrauskas, Sebastián; Lee, Jan Hau; Steere, Mardi; Agulnik, Asya; Murthy, Srinivas; Adhikari, Neill K. J.; for the PALISI Global Health Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Objectives: To describe the infrastructure and resources for pediatric emergency and critical care delivery in resource-limited settings worldwide. Design: Cross-sectional survey with survey items developed through literature review and revised following piloting. Setting: The electronic survey was disseminated internationally in November 2019 via e-mail directories of pediatric intensive care societies and networks and using social media. PATIENTS: Healthcare providers who self-identified as working in resource-limited settings. Interventions: None. Measurements and Main Results: Results were summarized using descriptive statistics and resource availability was compared across World Bank country income groups. We received 328 responses (238 hospitals, 60 countries), predominantly in Latin America and Sub-Saharan Africa (n = 161, 67.4%). Hospitals were in low-income (28, 11.7%), middle-income (166, 69.5%), and high-income (44, 18.4%) countries. Across 174 PICU and adult ICU admitting children, there were statistically significant differences in the proportion of hospitals reporting consistent resource availability (“often” or “always”) between country income groups (p < 0·05). Resources with limited availability in lower income countries included advanced ventilatory support, invasive and noninvasive monitoring, central venous access, renal replacement therapy, advanced imaging, microbiology, biochemistry, blood products, antibiotics, parenteral nutrition, and analgesic/sedative drugs. Seventy-seven ICUs (52.7%) were staffed 24/7 by a pediatric intensivist or anesthetist. The nurse-to-patient ratio was less than 1:2 in 71 ICUs (49.7%). Conclusions: Contemporary data demonstrate significant disparity in the availability of essential and advanced human and material resources for the care of critically ill children in resource-limited settings. Minimum standards for essential pediatric emergency and critical care in resource-limited settings are needed. The PALISI Global Health Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) are as follows: Jonah Attebery, MD; Adnan T. Bhutta, MBBS; Alden Blair, PhD, MS; Timothy Thomas Cornell, MD; Ericka Fink, MD, MS; Adrian J. Holloway, MD; Shubhada Hooli, MD, MPH; Teresa Kortz, MD, MS; Niranjan (Tex) Kissoon, MD; Katie Nielsen, MD, MPH; Kenneth E. Remy, MD, MHSc, MSCI; and Amelie von Saint Andre-von Arnim, MD. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Muttalib received research fellowship funding from the Centre for Global Child Health (Hospital for Sick Children). The Hospital for Sick Children had no role in the design, conduct, or analysis of the study, or the decision to publish. Dr. Lee received funding from KK Women’s and Children’s Hospital. Dr. Agulnik’s institution received funding from Conquer Cancer Foundation Global Oncology Young Investigator Award. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: Fiona.muttalib@mail.utoronto.ca Copyright © by 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
Læs mere Tjek på PubMedPlata-Menchaca, Erika P.; Ferrer, Ricard
Critical Care Medicine, 3.03.2021 Tilføjet 11.03.2021 16:47Jérémy Guenezan, Nicolas Marjanovic, Bertrand Drugeon, Rodérick O Neill, Evelyne Liuu, France Roblot, Paola Palazzo, Vanessa Bironneau, Frederique Prevost, Julie Paul, Maxime Pichon, Matthieu Boisson, Denis Frasca, Olivier Mimoz, CLEAN-3 trial investigators
Lancet Infectious Diseases, 2.02.2021 Tilføjet 11.03.2021 16:47For skin antisepsis, chlorhexidine plus alcohol provides greater protection of peripheral venous catheter-related infectious complications than does povidone iodine plus alcohol. Use of innovative devices extends the catheter complication-free dwell time.
Læs mere Tjek på PubMedSonali D Advani, Deverick J Anderson
Lancet Infectious Diseases, 2.02.2021 Tilføjet 11.03.2021 16:47Peripheral venous catheters are the most frequently used invasive devices in health care.1 A French prevalence survey found that peripheral venous catheters account for 80% of all intravascular catheters.2 Although peripheral venous catheters are considered low risk to the patient, they rarely can cause substantial adverse events, including mechanical, vascular, and infectious complications.3 However, little research has been done on strategies and interventions focused on decreasing the risk of complications related to peripheral venous catheters.
Læs mere Tjek på PubMedWilliam E Benitz, Niek B Achten
Lancet Infectious Diseases, 30.10.2020 Tilføjet 11.03.2021 16:47The use of the neonatal early-onset sepsis risk calculator, developed by Kaiser Permanente Northern California (CA, USA), is increasing for the management of late preterm and full term newborn babies at risk for early-onset sepsis. The calculator is based on a robust logistic regression model that provides quantitative individualised estimates of early-onset sepsis risk. Low sensitivity for prediction of sepsis at birth shows that standard perinatal risk factors alone are insufficient for ascertainment of neonatal early-onset sepsis.
Læs mere Tjek på PubMedWright S, Kaewarpai T, Lovelace-Macon L, et al.
Clinical Infectious Diseases, 8.02.2020 Tilføjet 11.03.2021 16:47AbstractBackgroundMelioidosis, infection caused by Burkholderia pseudomallei, is a common cause of sepsis with high associated mortality in Southeast Asia. Identification of patients at high likelihood of clinical deterioration is important for guiding decisions about resource allocation and management. We sought to develop a biomarker-based model for 28-day mortality prediction in melioidosis.MethodsIn a derivation set (N = 113) of prospectively enrolled, hospitalized Thai patients with melioidosis, we measured concentrations of interferon-γ, interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-ɑ, granulocyte-colony stimulating factor, and interleukin-17A. We used least absolute shrinkage and selection operator (LASSO) regression to identify a subset of predictive biomarkers and performed logistic regression and receiver operating characteristic curve analysis to evaluate biomarker-based prediction of 28-day mortality compared with clinical variables. We repeated select analyses in an internal validation set (N = 78) and in a prospectively enrolled external validation set (N = 161) of hospitalized adults with melioidosis.ResultsAll 8 cytokines were positively associated with 28-day mortality. Of these, interleukin-6 and interleukin-8 were selected by LASSO regression. A model consisting of interleukin-6, interleukin-8, and clinical variables significantly improved 28-day mortality prediction over a model of only clinical variables [AUC (95% confidence interval [CI]): 0.86 (.79–.92) vs 0.78 (.69–.87); P = .01]. In both the internal validation set (0.91 [0.84–0.97]) and the external validation set (0.81 [0.74–0.88]), the combined model including biomarkers significantly improved 28-day mortality prediction over a model limited to clinical variables.ConclusionsA 2-biomarker model augments clinical prediction of 28-day mortality in melioidosis.
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