The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis.

Table of contentsP001 - Sepsis impairs the capillary response within hypoxic capillaries and decreases erythrocyte oxygen-dependent ATP effluxR. M. Bateman, M. D. Sharpe, J. E. Jagger, C. G. EllisP002 - Lower serum immunoglobulin G2 level does not predispose to severe flu.J. Solé-Violán, M. López-Rodríguez, E. Herrera-Ramos, J. Ruíz-Hernández, L. Borderías, J. Horcajada, N. González-Quevedo, O. Rajas, M. Briones, F. Rodríguez de Castro, C. Rodríguez GallegoP003 - Brain protective effects of intravenous immunoglobulin through inhibition of complement activation and apoptosis in a rat model of sepsisF. Esen, G. Orhun, P. Ergin Ozcan, E. Senturk, C. Ugur Yilmaz, N. Orhan, N. Arican, M. Kaya, M. Kucukerden, M. Giris, U. Akcan, S. Bilgic Gazioglu, E. TuzunP004 - Adenosine a1 receptor dysfunction is associated with leukopenia: A possible mechanism for sepsis-induced leukopeniaR. Riff, O. Naamani, A. DouvdevaniP005 - Analysis of neutrophil by hyper spectral imaging - A preliminary reportR. Takegawa, H. Yoshida, T. Hirose, N. Yamamoto, H. Hagiya, M. Ojima, Y. Akeda, O. Tasaki, K. Tomono, T. ShimazuP006 - Chemiluminescent intensity assessed by eaa predicts the incidence of postoperative infectious complications following gastrointestinal surgeryS. Ono, T. Kubo, S. Suda, T. Ueno, T. IkedaP007 - Serial change of c1 inhibitor in patients with sepsis – A prospective observational studyT. Hirose, H. Ogura, H. Takahashi, M. Ojima, J. Kang, Y. Nakamura, T. Kojima, T. ShimazuP008 - Comparison of bacteremia and sepsis on sepsis related biomarkersT. Ikeda, S. Suda, Y. Izutani, T. Ueno, S. OnoP009 - The changes of procalcitonin levels in critical patients with abdominal septic shock during blood purificationT. Taniguchi, M. OP010 - Validation of a new sensitive point of care device for rapid measurement of procalcitoninC. Dinter, J. Lotz, B. Eilers, C. Wissmann, R. LottP011 - Infection biomarkers in primary care patients with acute respiratory tract infections – Comparison of procalcitonin and C-reactive proteinM. M. Meili, P. S. SchuetzP012 - Do we need a lower procalcitonin cut off?H. Hawa, M. Sharshir, M. Aburageila, N. SalahuddinP013 - The predictive role of C-reactive protein and procalcitonin biomarkers in central nervous system infections with extensively drug resistant bacteriaV. Chantziara, S. Georgiou, A. Tsimogianni, P. Alexandropoulos, A. Vassi, F. Lagiou, M. Valta, G. Micha, E. Chinou, G. MichaloudisP014 - Changes in endotoxin activity assay and procalcitonin levels after direct hemoperfusion with polymyxin-b immobilized fiberA. Kodaira, T. Ikeda, S. Ono, T. Ueno, S. Suda, Y. Izutani, H. ImaizumiP015 - Diagnostic usefullness of combination biomarkers on ICU admissionM. V. De la Torre-Prados, A. Garcia-De la Torre, A. Enguix-Armada, A. Puerto-Morlan, V. Perez-Valero, A. Garcia-AlcantaraP016 - Platelet function analysis utilising the PFA-100 does not predict infection, bacteraemia, sepsis or outcome in critically ill patientsN. Bolton, J. Dudziak, S. Bonney, A. Tridente, P. NeeP017 - Extracellular histone H3 levels are in...

ClinicalTrials.gov (NCT02127749; Pre-results).

IMPORTANCECellulitis is a commonly occurring skin and soft tissue infection and one of the most frequently seen dermatological diseases in the intensive care unit (ICU). However, clinical characteristics of patients with cellulitis requiring intensive care treatment are poorly defined. Necrotizing fasciitis is often confused for cellulitis at initial presentation and is considered to be more severe and thus has previously been described in more detail.OBJECTIVE To describe the clinical presentation and outcomes of patients with ICU-necessitating cellulitis and to compare them with patients with necrotizing fasciitis. DESIGN, SETTING, AND PARTICIPANTS This prospective cohort study includes all ICU admissions from 2 tertiary hospitals in the Netherlands. Of 2562 sepsis admissions, 101 had possible, probable, or definite cellulitis or soft tissue infections. Retrospective review identified severe cellulitis was the reason for ICU admission in 23 patients, necrotizing fasciitis in 31 patients, and other diagnoses in 47 patients. MAIN OUTCOMES AND MEASURES Patient and disease characteristics, cultured pathogens, lengths of stay, and short-term and long-term mortality. RESULTS Overall, 54 patients with cellulitis (n = 23; mean [SD] age, 57.2 [17.7] years) or necrotizing fasciitis (n = 31; mean [SD] age, 54.3 [13.5]) were included in this study. Patients with cellulitis were found to be less severely ill than patients with necrotizing fasciitis. This is reflected in rates of shock (7 [30.4%] vs 19 [61.3%]; P = .03), need for mechanical ventilation (12 [52.2%] vs 19 [93.5%]; P = .003) and slightly lower mean Sequential Organ Failure Assessment scores (8 vs 10; P = .046). Median (interquartile range [IQR]) Acute Physiology and Chronic Health Evaluation IV scores did not differ significantly (82 [75-98] vs 76 [70-96]; P = .16). Patients with cellulitis had more chronic comorbidities than patients with necrotizing fasciitis (20 [87.0%] vs 17 [54.8%]; P = .02), especially cardiovascular insufficiencies (10 [43.5%] vs 4 [12.9%]; P = .02) and immunodeficiencies (9 [39.1%] vs 3 [9.7%]; P = .02). Among patients with cellulitis and patients with patients with necrotizing fasciitis, Staphylococcus aureus (10 [43.5%] vs 4 [12.9%]; P = .02), Streptococcus pyogenes (2 [8.7%] vs 19 [61.3%]; P < .001) and Escherichia coli (4 [17.4%] vs 5 [16.2%]; P = .90) were the most frequently observed pathogens. Median (IQR) length of ICU stay was shorter for patients with cellulitis vs patients with necrotizing fasciitis (3 [2-5] vs 5 [3][4][5][6][7][8][9][10][11]; P = .01), while median (IQR) hospital length of stay did not differ significantly (22 [10.25-32] vs 36 [14.25-40]; P = .16); and the in-hospital mortality rate (26.1% vs 22.6%, P > .99) and 90-day mortality rate (30.4% vs 22.6%; P = .54) were similar.CONCLUSIONS AND RELEVANCE Patients with cellulitis patients are seldom admitted to the ICU. However, while these patients are less critically ill on admission than patients with necrotizing fasciitis, they have more chronic comorbidities an...

a b s t r a c tObjectives: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. Methods: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. Results: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12-and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: e15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI:e8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). Conclusions: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies. D.R. Cranendonk, Clin Microbiol Infect 2020;26:606

BackgroundRecommended therapy duration for patients hospitalized with cellulitis is 10–14 days. Unnecessary use of antibiotics is one of the key factors driving resistance. Recent studies have shown that antibiotic therapy for cellulitis in outpatients can safely be shortened, despite residual inflammation. This study will compare in hospitalized patients the safety and effectiveness of shortening antibiotic therapy for cellulitis from 12 to 6 days.Methods/designIn a multicenter, randomized, double-blind, non-inferiority trial, adult patients admitted with cellulitis will be included. Cellulitis is defined as warmth, erythema, and induration of the skin and/or subcutaneous tissue, with or without pain (including erysipelas). All patients will initially be treated with intravenous flucloxacillin, and will be evaluated after 5–6 days. Those who have improved substantially (defined as being afebrile, and having a lower cellulitis severity score) will be randomized at day 6 between additional 6 days of oral flucloxacillin (n = 198) or placebo (n = 198). Treatment success is defined as resolution of cellulitis on day 14 (disappearance of warmth and tenderness, improvement of erythema and edema), without the need of additional antibiotics for cellulitis by day 28. Secondary endpoints are relapse rate (up to day 90), speed of recovery (using a cellulitis severity score until day 28, and VAS scores on pain and swelling until day 90), quality of life (using the SF-36 and EQ-5D questionnaires) and costs (associated with total antibiotic use and health-care resource utilization up to day 90).DiscussionInclusion is planned to start in Q2 2014.Trial registrationClinicalTrials.gov (NCT02032654) and the Netherlands Trial Register (NTR4360).

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Neither ciprofloxacin nor amoxicillin should be used as empirical therapy in patients with a presumed E. coli bacteraemia.