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Tsolaki, V., Mantzarlis, K., Mpakalis, A., Malli, E., Tsimpoukas, F., Tsirogianni, A., Papagiannitsis, K., Zygoulis, P., Papadonta, M.-E., Petinaki, E., Makris, D., Zakynthinos, E.

Data on the effectiveness of ceftazidime-avibactam (CAZ-AVI) in critically ill, mechanically ventilated patients are limited. The present retrospective observational cohort study, which was conducted in two general Intensive Care Units (ICUs) in central Greece, compared critically-ill, mechanically ventilated patients suffering from carbapenem-resistant enterobacteriaceae (CRE) infections receiving CAZ-AVI to patients who received appropriate available antibiotic therapy. Clinical, microbiological outcomes and safety issues were evaluated. A secondary analysis in patients with blood stream infections (BSI) was conducted. Forty-one patients that received CAZ-AVI (CAZ-AVI group) were compared to thirty-six patients receiving antibiotics other than CAZ-AVI (control group). There was significant improvement in the SOFA score on Day 4 and 10 in the CAZ-AVI compared to the control group (p=0.006, and p=0.003 respectively). Microbiological eradication was accomplished in 33/35 (94.3%) in CAZ-AVI group vs 21/31 (67.7%) patients in control group (p=0.021) and clinical cure was observed in 33/41 (80.5%) vs 19/36 (52.8%) patients (p=0.010), respectively. The results were similar in BSI subgroups for both outcomes (p=0.038 and p=0.014, respectively). 28-day survival was 85.4% in the CAZ-AVI and 61.1% in the control group (log Rank=0.035), while there were 2 and 12 relapses in each group (p=0.042). A CAZ-AVI containing regime was independent predictor of survival and clinical cure (OR 5.575, p=0.012 and OR 5.125, p=0.004, respectively) along with illness severity. In conclusion, no significant side effects were reported. A CAZ-AVI containing regime is more effective than other available antibiotic agents for the treatment of CRE infections in the high-risk, mechanically-ventilated, ICU population.…

Hiemstra, Bart; Eck, Ruben J.; Wiersema, Renske; Kaufmann, Thomas; Koster, Geert; Scheeren, Thomas W.L.; Snieder, Harold; Perner, Anders; Pettilä, Ville; Wetterslev, Jørn; Keus, Frederik; van der Horst, Iwan C.C.; SICS Study Group

Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves (AUC). Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. Main Results: A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (AUC = 0.74; 95% CI, 0.71–0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (SAPS-II) (AUC = 0.76; 95% CI, 0.73–0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (APACHE-IV) (AUC = 0.77; 95% CI, 0.74–0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (SOFA) (AUC = 0.67; 95% CI, 0.64–0.71; p < 0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the SAPS-II and APACHE-IV and outperformed the SOFA score. New affiliation for Dr. Eck: Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Drs. Hiemstra, van der Horst, and Keus drafted the manuscript and conducted the analyses. Drs. van der Horst and Keus created the idea of the study. Drs. Eck and Koster developed the protocol and implemented the study. Mr. Wiersema and Dr. Kaufmann contributed substantially to the data collection. Drs. Wetterslev and Snieder contributed to the statistical analyses and design of the detailed statistical analyses plan. Professors Scheeren, Perner, and Pettilä critically reviewed the article. All authors critically reviewed the article and agreed with the final version and findings. 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). Prof dr. Scheeren received research funding and honoraria from Edwards Lifesciences and Masimo Inc. (Irvine, CA) for consulting and lecturing and from Pulsion Medical Systems SE for lecturing in the past. The remaining authors have disclosed that they do not have any potential conflicts of interest. Ethics approval: Medisch Ethische Toetsingscommissie, University Medical Center Groningen; METc M15.168207. ORCID IDs: Dr. Hiemstra: 0000-0001-6547-2138; Dr. Eck: 0000-0001-7440-2465; Mr. Wiersema: 0000-0003-2413-2852; Dr. Kaufmann: 0000-0003-0589-8879; Dr. Koster: 0000-0002-8927-3077; Dr. Scheeren: 0000-0002-9184-4190; Dr. Snieder; 0000-0003-1949-2298; Dr. Perner: 0000-0002-4668-0123; Dr. Wetterslev: 0000-0001-7778-1771; Dr. Keus: 0000-0003-1516-1475; Dr. van der Horst: 0000-0003-3891-8522. For information regarding this article, E-mail: b.hiemstra01@umcg.nl 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 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Abstract Background Intravenous (IV) zanamivir could be a suitable alternative for the treatment of severe influenza A(H1N1)pdm09 infection in patients who are unable to take oral or inhaled medication, for example, those on mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, data on the clinical outcomes of such patients is limited. Case presentation We report the clinical outcomes of four patients who were admitted at the intensive care unit during the 2017–2018 influenza season with severe sepsis (SOFA score > 11) and acute respiratory distress syndrome requiring ECMO and mechanical ventilation. Two patients were immune-compromised. The A(H1N1)pdm09 genome was confirmed by polymerase chain reaction (PCR) on nasopharyngeal specimen swabs prior to administration of IV zanamivir at a dose of 600 mg twice daily. Weekly qualitative PCR analysis was done to monitor viral clearance, with zanamivir treatment being discontinued upon receipt of negative results. In addition, the patients were managed for concomitant multidrug-resistant bacterial infections, with infection resolution confirmed with blood cultures. The median time for zanamivir treatment was 10 days (IQR 10–17). The clinical outcome was favourable with all four patients surviving and improving clinically. All four patients achieved viral clearance of A(H1N1)pdm09 genome, and resolution of multidrug-resistant bacterial infections. Conclusions IV zanamivir could be a good therapeutic option in patients with severe influenza A(H1N1)pdm09 infection who are unable to take oral or aerosolised antiviral medication. We recommend prospective randomized control trials to support this hypothesis.…

Kan F, Tan C, von Bahr Greenwood T, et al.

AbstractBackgroundGlobally approximately 500,000 people with severe dengue (SD) require hospitalization yearly; about 12,500 (2.5%) die. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal hyperinflammatory condition for which HLH-directed therapy (as etoposide and dexamethasone) can be life-saving. Prompted by the high mortality in SD and the increasing awareness that patients with SD may develop sHLH, our objectives were to i) determine the frequency of dengue-HLH in SD, ii) describe clinical features of dengue-HLH, iii) assess mortality rate in SD and dengue-HLH, and iv). identify mortality-associated risk factors in SD.MethodsA 5-year retrospective single-center study on all adult patients with SD admitted to a tertiary ICU in Malaysia.ResultsThirty-nine/180 (22%) patients with SD died. Twenty-one/180 (12%) had HLH defined as HLH-probability ≥70% according to HScore; nine (43%) died. Similarly, 12/31 (39%) fulfilling ≥4 and 7/9 (78%) fulfilling ≥5 HLH-2004 diagnostic criteria died. Peak values of AST, ALT, LDH, and creatinine correlated to fatality (OR=2.9, 3.4, 5.8, and 31.9; all p

Nobuhiro Asai, Hiroki Watanabe, Arufumi Shiota, Hideo Kato, Daisuke Sakanashi, Mao Hagihara, Yusuke Koizumi, Yuka Yamagishi, Hiroyuki Suematsu, Hiroshige Mikamo

Emily Herrett, Sarah Gadd, Rod Jackson, Krishnan Bhaskaran, Elizabeth Williamson, Tjeerd van Staa, Reecha Sofat, Adam Timmis, Liam Smeeth

A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided.

John F. McNamara, Patrick NA. Harris, Mark D. Chatfield, Penelope Lorenc, David L. Paterson

To evaluate the sequential organ failure assessment (SOFA), modified SOFA scoring and a novel performance score based on the Karnofsky score for measuring outcome following a bloodstream infection.

Abstract Background The sepsis-induced immunodepression contributes to impaired clinical outcomes of various stress conditions. This syndrome is well documented and characterized by attenuated function of innate and adaptive immune cells. Several pharmacological interventions aimed to restore the immune response are emerging of which interferon-gamma (IFNγ) is one. It is of paramount relevance to obtain clinical information on optimal timing of the IFNγ-treatment, −tolerance, −effectiveness and outcome before performing a RCT. We describe the effects of IFNγ in a cohort of 18 adult and 2 pediatric sepsis patients. Methods In this open-label prospective multi-center case-series, IFNγ treatment was initiated in patients selected on clinical and immunological criteria early ( 7 days) following the onset of sepsis. The data collected in 18 adults and 2 liver transplanted pediatric patients were: clinical scores, monocyte expression of HLA-DR (flow cytometry), lymphocyte immune-phenotyping (flow cytometry), IL-6 and IL-10 plasma levels (ELISA), bacterial cultures, disease severity, and mortality. Results In 15 out of 18 patients IFNγ treatment was associated with an increase of median HLA-DR expression from 2666 [IQ 1547; 4991] to 12,451 [IQ 4166; 19,707], while the absolute number of lymphocyte subpopulations were not affected, except for the decrease number of NK cells 94.5 [23; 136] to 32.5 [13; 90.8] (0.0625)]. Plasma levels of IL-6 464 [201–770] to 108 (89–140) ng/mL (p = 0.04) and IL-10 from IL-10 from 29 [12–59] to 9 [1–15] pg/mL decreased significantly. Three patients who received IFNγ early after ICU admission (

Abstract Background This study aimed to determine the prevalence of infectious diseases and risk factors for one-year mortality in elderly emergency department (ED) patients. Methods A retrospective cohort study of patients aged 65 and over who visited the ED of one urban teaching hospital in Bangkok, Thailand and who were diagnosed with infectious diseases between 1 January 2016 and 30 June 2016. Results There were 463 elderly patients who visited ED with infectious diseases, accounting for 14.5% (463/3,196) of all elderly patients’ visits. The most common diseases diagnosed by emergency physicians (EPs) were pneumonia [151 (32.6%) patients] followed by pyelonephritis [107 (23.1%) patients] and intestinal infection [53 (11.4%) patients]. Moreover, 286 (61.8%) patients were admitted during the study period. The in-hospital mortality rate was 22.7%. 181 (39.1%) patients died within 1 year. Our multivariate analysis showed that age 85 years and older [odds ratio (OR) = 1.89; 95% confidence interval (CI): 1.36–2.63], Charlson Co-morbidity Index score ≥ 5 (OR = 3.51; 95% CI2.14–5.77), lactate ≥4 mmol/l (OR = 2.66;95% CI 1.32–5.38), quick Sequential Organ Failure Assessment (qSOFA) score ≥ 2 (OR = 5.46; 95% CI 2.94–10.12), and platelet count

Richard-Greenblatt M, Boillat-Blanco N, Zhong K, et al.

AbstractBackgroundThe inability to identify individuals with acute fever at risk of death is a barrier to effective triage and management of severe infections, especially in low-resource settings. Since endothelial and immune activation contribute to the pathogenesis of various distinct life-threatening infections, we hypothesized that measuring mediators of these pathways at clinical presentation would identify febrile adults at risk of death.MethodsPlasma concentrations of markers of endothelial (Angpt-2, sFlt-1, sVCAM-1, sICAM-1) and immune (sTREM-1, IL-6, IL-8, CHI3L1, sTNFR1, PCT, CRP) activation pathways were determined in consecutive adults with acute fever (>38°C) at presentation to outpatient clinics in Dar es Salaam, Tanzania. We evaluated the accuracy of these mediators in predicting all-cause mortality, and examined whether markers could improve the prognostic accuracy of clinical scoring systems, including the quick Sequential Organ Failure Assessment (qSOFA) and Glasgow Coma Scale (GCS).ResultsOf 507 febrile adults, 32 died (6.3%) within 28 days of presentation. sTREM-1 was the best prognostic marker for 28-day mortality (area under the receiver operating characteristic [AUROC] 0.87, 95% CI 0.81-0.92) and was significantly better than CRP (P

Fei Peng, Wei Chang, Chun Pan, Yi Yang

We appreciated the comments by Dr van Oers and colleagues concerning the effect of PCT-guided cessation of antibiotics in patients with the SOFA score less than 8. Our meta-analysis revealed that PCT-guided cessation of antibiotic therapy decreased the short-term mortality in patients with an average SOFA score < 8, suspected sepsis or lower algorithm adherence (< 70%), but not in those with a score > 8, confirmed sepsis or higher adherence(Peng et al., 2019). Compared to the standard care group, PCT-guided antibiotic therapy failed to decrease the mortality or shorten the ICU length of stay, as previous trials reported(Bouadma et al., 2010; Jensen et al., 2011; Bloos et al., 2016).

Challener DW, Prokop LJ, Abu-Saleh O.

This Viewpoint charts the rise in publications describing risk prediction tools, such as the FRAX, CHADS2, and SOFA scores, and discusses the implications of using algorithms for clinical decisions in the absence of evidence about the effects of the tools on patient care and outcomes.

Ymkje Stienstra, Dorien T Beeres, Richard Phillips, Machiel Vonk, Sofanne J Ravensbergen

We read the Article by David Engelman and colleagues1 with interest. Their overview of the key operational research questions to develop a global control programme for scabies provides a clear research agenda for the years to come.1 Mass drug administration (MDA) using ivermectin reduced the prevalence of both scabies and impetigo tremendously in Fiji with a sustained effect even 24 months after the intervention.2 Future studies should prioritise the inclusion of non-island populations.

Satoshi Koyama, Yutaka Yamaguchi, Koichiro Gibo, Izumi Nakayama, Shinichiro Ueda

by Satoshi Koyama, Yutaka Yamaguchi, Koichiro Gibo, Izumi Nakayama, Shinichiro Ueda Background The quick sequential organ failure assessment (qSOFA) score has recently been introduced to the emergency department (ED) and wards, and it predicted a higher number of deaths among patients with sepsis compared with baseline risk. However, studies about the application of the qSOFA score are limited in prehospital settings. Thus, this study aimed to assess the performance of prehospital qSOFA score in predicting the risk of mortality among patients with infection. Methods This single center, retrospective cohort study was conducted in a Japanese tertiary care teaching hospital between April 2016 and March 2017. We enrolled all consecutive adult patients transported to the hospital by ambulance and admitted to the ED due to a suspected infection. We calculated the prehospital qSOFA score using the first vital sign obtained at the scene by emergency medical service (EMS) providers. The primary outcome was in-hospital mortality. The Cox proportional hazards model was used to assess the association between prehospital qSOFA positivity and in-hospital mortality. Results Among the 925 patients admitted to the ED due to a suspected infection, 51.1% (473/925) were prehospital qSOFA-positive and 48.9% (452/925) were prehospital qSOFA-negative. The in-hospital mortality rates were 14.0% (66/473) in prehospital qSOFA-positive patients and 6.0% (27/452) in prehospital qSOFA-negative patients. The Cox proportional hazard regression model revealed a strong association between prehospital qSOFA score and in-hospital mortality (adjusted hazard ratio: 2.41, 95% confidence interval: 1.51–3.98; p…

Jos A.H. van Oers, Maarten W Nijsten, Evelien de Jong, Albertus Beishuizen, Dylan W de Lange